SIOP ABSTRACTS
Identifieur interne : 000159 ( Pmc/Corpus ); précédent : 000158; suivant : 000160SIOP ABSTRACTS
Auteurs :Source :
- Pediatric Blood & Cancer [ 1545-5009 ] ; 2017.
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DOI: 10.1002/pbc.26772
PubMed: 28863244
PubMed Central: 7167988
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">SIOP ABSTRACTS</title></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28863244</idno><idno type="pmc">7167988</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167988</idno><idno type="RBID">PMC:7167988</idno><idno type="doi">10.1002/pbc.26772</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000159</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000159</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">SIOP ABSTRACTS</title></analytic><series><title level="j">Pediatric Blood & Cancer</title><idno type="ISSN">1545-5009</idno><idno type="eISSN">1545-5017</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader></TEI><pmc article-type="abstract"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Pediatr Blood Cancer</journal-id><journal-id journal-id-type="iso-abbrev">Pediatr Blood Cancer</journal-id><journal-id journal-id-type="doi">10.1002/(ISSN)1545-5017</journal-id><journal-id journal-id-type="publisher-id">PBC</journal-id><journal-title-group><journal-title>Pediatric Blood & Cancer</journal-title></journal-title-group><issn pub-type="ppub">1545-5009</issn><issn pub-type="epub">1545-5017</issn><publisher><publisher-name>John Wiley and Sons Inc.</publisher-name><publisher-loc>Hoboken</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28863244</article-id><article-id pub-id-type="pmc">7167988</article-id><article-id pub-id-type="doi">10.1002/pbc.26772</article-id><article-id pub-id-type="publisher-id">PBC26772</article-id><article-categories><subj-group subj-group-type="overline"><subject>Abstracts</subject></subj-group><subj-group subj-group-type="heading"><subject>Abstracts</subject></subj-group></article-categories><title-group><article-title>SIOP ABSTRACTS</article-title><alt-title alt-title-type="left-running-head">SIOP ABSTRACTS</alt-title><alt-title alt-title-type="right-running-head">SIOP ABSTRACTS</alt-title></title-group><pub-date pub-type="epub"><day>01</day><month>9</month><year>2017</year></pub-date><pub-date pub-type="ppub"><month>11</month><year>2017</year></pub-date><volume>64</volume><issue>Suppl 3</issue><issue-id pub-id-type="doi">10.1002/pbc.v64.S3</issue-id><elocation-id>e26772</elocation-id><permissions><pmc-comment> © 2017 Wiley Periodicals, Inc. </pmc-comment>
<copyright-statement content-type="article-copyright">© 2017 Wiley Periodicals, Inc.</copyright-statement><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="file:PBC-64-e26772.pdf"></self-uri><counts><fig-count count="0"></fig-count><table-count count="4"></table-count><page-count count="496"></page-count><word-count count="373942"></word-count></counts><custom-meta-group><custom-meta><meta-name>source-schema-version-number</meta-name><meta-value>2.0</meta-value></custom-meta><custom-meta><meta-name>cover-date</meta-name><meta-value>November 2017</meta-value></custom-meta><custom-meta><meta-name>details-of-publishers-convertor</meta-name><meta-value>Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:16.04.2020</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="pbc26772-sec-0010"><title>SIOP Awards</title><sec id="pbc26772-sec-0020"><label>AW-01</label><title>Procedural Sedation in Pediatric Oncology by non Anaesthesiologists‐ A Randomized Comparative Trial of Ketamine ‐ Midazolam Combination vs Propofol</title><p><underline underline-style="single">M. Kalra</underline><sup>1</sup>, V. C<sup>2</sup>, A. Bakshi<sup>2</sup>, G. Mandhani<sup>1</sup>, A. Mahajan<sup>1</sup></p><p><italic><sup>1</sup>Indraprastha Apollo Hospital, Pediatric Hematology Oncology, Delhi, India; <sup>2</sup>Indraprastha Apollo Hospital, Pediatrics, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Both ketamine‐midazolam and propofol are frequently used in pediatric‐oncology units for procedural sedation. However, there are no prospective, randomized comparative trials (RCT) comparing them. This is especially important for developing countries where due to limited resources; non‐anesthesiologists (trained pediatricians) usually perform the procedural sedation.</p><p>Objective is to compare ketamine+midazolam (Group A) and propofol (Group B) as sedative agents for intrathecal chemotherapy.</p><p><bold>Design/Methods</bold>: A partially‐blinded, RCT was conducted between July 2015‐February 2017 after institutional ethics approval. Children aged 1‐12 years requiring intravenous sedation for intrathecal chemotherapy were included. Patients were randomized using computer generated randomization tables after obtaining written consent. Initial doses used were, ketamine at 2mg/kg, midazolam at 0.2 mg/kg and propofol at 2.5mg/kg as per standard recommendations. Time to sedation, dose required, depth of sedation (using Modified Ramsey scale), vital parameters, time and smoothness of recovery and emergence phenomenon were documented.</p><p><bold>Results</bold>: A total of 152 patients were enrolled (Group A: 76, Group B: 76). Nine patients had failure of sedation (all in Group B). Thirteen in group A and 51 in‐group B required top up sedation. Mean time to sedation in‐group B was shorter (<bold>p=0.000)</bold>. Mean heart rate in‐group A was higher (<bold>p=0.000)</bold>. Transient drop in saturation was noted in 10 patients in‐group A and in 20 in‐group B <bold>(p=0.174)</bold>. Mean depth of sedation in‐group A was greater than in‐group B (<bold>p=0.000)</bold>. Mean time to recovery in‐group B was shorter than in‐group A (<bold>p=0.000)</bold>. Emergence symptoms were experienced by 38 patients in‐group A and 7 in‐group B (<bold>p=0.000)</bold>.</p><p><bold>Conclusions</bold>: Ketamine‐Midazolam combination appears to be safer and more effective when used by non‐anaesthesiologists. Propofol has a significantly faster onset, quicker recovery, smoother emergence from sedation, but at the recommended initial doses it provides inadequate sedation.</p></sec><sec id="pbc26772-sec-0030"><label>AW-02</label><title>Treatment Results of a Strategy for the Management of Mature B‐Cell Malignancies in Central America. A Report of the Cooperative Group AHOPCA</title><p>A. Pena‐Hernandez<sup>1</sup>, <underline underline-style="single">R. Ortiz</underline><sup>2</sup>, C. Garrido<sup>3</sup>, W. Gomez‐Garcia<sup>4</sup>, S. Fuentes‐Alabi<sup>5</sup>, R. Martinez<sup>6</sup>, M. Metzger<sup>7</sup>, R.C. Ribeiro<sup>7</sup>, G. Chantada<sup>8</sup></p><p><italic><sup>1</sup>Hospital Escuela, Oncology, Tegucigalpa, Honduras; <sup>2</sup>Hospital La Mascota, Oncology, Managua, Nicaragua; <sup>3</sup>UNOP, Oncology, Guatemala, Guatemala; <sup>4</sup>Hospital Infantil Reid Cabral, Oncology, Santo Domingo, Dominican Republic; <sup>5</sup>Hospital Bloom, Oncology, El Salvador, El Salvador; <sup>6</sup>Hospital de San Pedro Sula, Oncology, San Pedro Sula, Honduras; <sup>7</sup>St Jude Children's Research Hospital, Oncology, memphis, USA; <sup>8</sup>St Jude Children's Research Hospital, International Outreach, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Treatment of mature B‐cell malignancies in lower‐middle income countries is challenging because of increased risk of toxicity associated with advanced disease at presentation and limited supportive care. AHOPCA, a collaborative group in Central America, implemented a modified BFM‐based treatment regimen.</p><p><bold>Design/Methods</bold>: Newly diagnosed patients with histologically or immunocytological diagnosis of mature B‐cell malignancies diagnosed between 03/2004 and 06/2016 at 6 institutions. reatment: Murphy's Stages I‐II, prephase and blocks A, B, A (methotrexate dose 1 g/m2 in 3 hour infusion); Stage III, prephase and blocks A,B,A,B,A,B; Stage IV, prephase and blocks A,B,A,B,A,B (methotrexate dose 3 g/m2 in 3 hour infusion). Patients in poor clinical conditions during induction were given a second prephase before proceeding with Blocks A or AA. Poor responders to the first 2 cycles were given AA and BB blocks for the remaining cycles. Ifosfamide dose was 400 mg/m2 in blocks A or AA. Difficult cases were discussed at Cure4kids.org.</p><p><bold>Results</bold>: With a median follow‐up of 49 months, 405 patients were registered (386 eligible). Four patients with HIV, eight previously treated, three cases with wrong diagnosis and three cases treated with another treatment protocol were excluded.177 cases had immunohistochemical characterization. Distribution was Stages I‐II, 30; III, 248; IV, 99; NA, 9. The 3‐year overall survival was 70% for the whole group (86% for stages I‐II, 75% for stage III and 58% for stage IV‐B‐ALL). Events included: Death on induction (n=32), abandonment (n=23), relapse/progression (n=23), death in complete remission (n=9), second malignancy (n=1) and death of unknown cause (n=1).</p><p><bold>Conclusions</bold>: This simplified adapted treatment is feasible and associated with acceptable results in settings with limited resources. Efforts to improve results should focus on educating the community providers about the early signs of the disease and prompt referral. Improving histologic techniques is critical to decrease the number of wrong diagnosis and allow proper classification.</p></sec><sec id="pbc26772-sec-0040"><label>AW-03</label><title>Mapping Relapse and Relapse Detection of Wilms Tumour ‐ A Report from The SIOP Renal Tumour Study Group</title><p><underline underline-style="single">J. Brok</underline><sup>1</sup>, M. Lopez<sup>2</sup>, V.T. Harm<sup>2</sup>, T.D. Treger<sup>3</sup>, R. Furtwängler<sup>4</sup>, N. Graf<sup>4</sup>, C. Bergeron<sup>5</sup>, M.M. van den Heuvel‐Eibrink<sup>6</sup>, B. de Camargo<sup>7</sup>, A. Verschuur<sup>8</sup>, K. Pritchard‐Jones<sup>1</sup>, O. Olsen<sup>9</sup>, F. Spreafico<sup>10</sup></p><p><italic><sup>1</sup>University College Great Ormond Street Institute of Child Health, Cancer section, London, United Kingdom; <sup>2</sup>Netherlands Cancer Institute, Dept Biometrics, Amsterdam, The Netherlands; <sup>3</sup>University of Cambridge, Dept. of Paediatrics, Cambridge, United Kingdom; <sup>4</sup>Saarland University Hospital, Dept. Haematology and Oncology, Homburg, Germany; <sup>5</sup>Centre Léon Bérard‐, Institut d'haematology and d'oncology paediatric, Lyon, France; <sup>6</sup>Princess Maxima Center, Pediatric Oncology, Utrecht, The Netherlands; <sup>7</sup>Instituto Nacional do Cancer, Paediatric Haemato‐Oncology Program‐ Research Center, Rio de Janeiro, Brazil; <sup>8</sup>Hôpital de la Timone Enfant, Department of Pediatric Hematology and Oncology, Marseille, France; <sup>9</sup>University College Great Ormond Street Institute of Child Health, Dept Radiology, London, United Kingdom; <sup>10</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Dept. of Hematology and Pediatric Onco‐Hematology, Milano, Italy</italic></p><p><bold>Background/Objectives</bold>: Children with Wilms tumor (WT) require regular relapse surveillance, usually with abdominal ultrasound and chest X‐ray starting after surgery. We mapped the site, timing and mode of detection of first WT relapse using the SIOP WT 2001 study database and assessed prognostic factors for post‐relapse mortality. Data were used to evaluate current surveillance recommendations.</p><p><bold>Design/Methods</bold>: All patients with WTs registered (2001‐2016) in the SIOP WT 2001 study and treated with pre‐operative chemotherapy as per protocol were included in the analyses.</p><p><bold>Results</bold>: Of 4348 registered patients, 538 (12%) relapsed. Relapse site involved lung (65%) and/or abdomen (49%), liver (11%), bone (1%) and central nervous system (1%). Most relapses (80%) occurred within 2 years post‐surgery, with high‐risk histology tumours relapsing faster (89% by 2y). Post‐relapse overall 5‐year survival rate was 61% (95% CI: 57%‐66%). Surveillance imaging captured 78% of the relapses and the remaining relapses presented with clinical symptoms ‘outside’ of routine follow‐up. Relapse was identified by abdominal ultrasound (32%), chest X‐ray (30%), CT scan of chest/abdomen (23%/7%), abdominal MRI (4%) or other (4%). The majority (69%) of relapses were not detectable by medical examination and only 33% of relapses were accompanied by symptoms. In multivariable analyses, overall survival after relapse was statistically significantly (P < 0.05) poorer for; surgery to relapse interval < 6 months, symptomatic presentation ‘outside’ planned follow‐up, higher tumour volume at initial surgery, and advanced stage/histological risk group.</p><p><bold>Conclusions</bold>: WT relapses predominantly involve the lung and generally occur within 2 years of nephrectomy and without symptoms. Routine surveillance imaging captured the majority of relapses and these patients seemed to have better post‐relapse survival. In the absence of prospective trials, our evidence indicates that current recommendations for imaging follow‐up intervals are effective and duration should focus on the first 2‐3 years after nephrectomy.</p></sec><sec id="pbc26772-sec-0050"><label>AW-04</label><title>Perinatal and Familial Risk Factors for Soft‐Tissue Sarcomas in Children, Adolescents, and Young Adults: A Population‐Based Birth Cohort Study, Sweden, 1973‐2012</title><p><underline underline-style="single">P. Lupo</underline><sup>1</sup>, R. Luna‐Gierke<sup>1</sup>, B. Tavelin<sup>2</sup>, M. Scheurer<sup>1</sup>, B. Melin<sup>2</sup>, K. Papworth<sup>2</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>2</sup>Umeå University, Radiation Sciences, Umeå, Sweden</italic></p><p><bold>Background/Objectives</bold>: Perinatal factors have been associated with soft‐tissue sarcomas (STS) in case‐control studies. However, (1) the specific contributions of factors including fetal growth remain unknown, (2) these factors have not been examined in large cohort studies, and (3) few assessments have evaluated risk in specific STS subtypes. Therefore, we sought to identify the role of perinatal and familial factors on the risk of STS in a large population‐based birth cohort.</p><p><bold>Design/Methods</bold>: We identified 5,063,499 individuals in the Swedish Birth Registry born during 1973‐2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including: fetal growth, gestational age, presence of a congenital anomaly, and parental age. Poisson regression was used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for associations between selected factors and STS overall, as well as by common subtypes.</p><p><bold>Results</bold>: There were 673 children, adolescents, and young adults diagnosed with STS in 77.5 million person‐years of follow‐up. Having a congenital anomaly was associated with STS risk (IRR=1.70, 95% CI: 1.23‐2.35). This association was stronger (IRR=2.89, 95% CI: 1.25‐6.70) in more recent years (2000‐2012). High fetal growth was also associated with STS during the same time period (IRR=1.87, 95% CI: 1.06‐3.30). Being born preterm (<37 weeks) was associated with developing embryonal rhabdomyosarcoma (IRR=2.02, 95% CI: 1.01‐4.04). Notably, advanced paternal age (>35 years) was inversely associated with the risk of developing synovial sarcoma (IRR=0.50, 95% CI: 0.26‐0.94).</p><p><bold>Conclusions</bold>: In this cohort study, those with congenital anomalies and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways influencing the risk of STS. Our findings could implicate novel mechanisms underlying susceptibility to STS and may inform future surveillance, prevention, and treatment efforts.</p></sec><sec id="pbc26772-sec-0060"><label>AW-05</label><title>A Geography of Clones: Mapping Somatic Mutations Over Anatomic Space in Children with Cancer</title><p><underline underline-style="single">D. Gisselsson</underline><sup>1</sup>, J. Karlsson<sup>1</sup>, A. Valind<sup>1</sup>, C. Jansson<sup>1</sup></p><p><italic><sup>1</sup>Laboratory medicine ‐ Lund, Clinical Genetics, Lund, Sweden</italic></p><p><bold>Background/Objectives</bold>: To chart genetic intratumour diversity in childhood cancer over multiple anatomic locations and/or time points during treatment in order to (1) delineate common routes of cancer cell evolution, (2) reveal candidate mechanisms behind treatment resistance, and (3) gain information on intrapatient variability of clinical biomarkers.</p><p><bold>Design/Methods</bold>: Patients were included based on the availability of two or more informative samples from the primary tumour, taken with a minimum intersample distance of 10 mm. A total of 54 patients with neuroblastoma (n=24), Wilms tumour (n=20) or sarcoma (n=10) have so far been subjected to multiregional analysis of tumour tissue with high resolution whole genome genotyping arrays (all patients) complemented in selected cases by whole exome sequencing, targeted deep DNA sequencing, and RNA sequencing. Between two and 20 tumour samples were analyzed per patient with a total of 230 informative tumour samples genotyped so far.</p><p><bold>Results</bold>: The majority of cases exhibited intratumour genetic diversity with branching evolution, including variability of several suggested clinical biomarkers. Subclones were the major arena of genome evolution in most primary tumors. There were clear features of convergent evolution, including trisomies and monosomies of whole chromosomes as well as specific somatic gene alterations such as <italic>TP53</italic> mutation in Wilms tumors, <italic>CDKN2A/B</italic> deletion in neuroblastoma, and <italic>CDK4</italic> amplification in rhabdomyosarcoma. Genetic patterns unique to anatomic sub‐compartments in individual patients had functional consequences for gene expression at the RNA and protein levels. Four general patterns of tumour evolution were identified of which at least one strongly correlated to clinically aggressive.</p><p><bold>Conclusions</bold>: Even in very young patients, high‐risk cancer is a genetically dynamic disease over space and time. Intratumour genetic diversity is common and is a significant source of error in biomarker assessment. Certain evolutionary patterns may be useful as future clinical predictors.</p></sec><sec id="pbc26772-sec-0070"><label>AW-06</label><title>CRISPR/CAS9 Based Reverse Genetics Identifies Therapeutic Targets to Improve Therapy Response in Paediatric Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">M. Butler</underline><sup>1</sup>, L. van der Meer<sup>1</sup>, J. Yu<sup>2,3</sup>, T. Beeby<sup>1</sup>, R. Kuiper<sup>2,3</sup>, F. van Leeuwen<sup>2</sup></p><p><italic><sup>1</sup>Radboudumc Amalia Children's Hospital, Laboratory of Pediatric Oncology/ Pediatrics, Nijmegen, The Netherlands; <sup>2</sup>Princess Máxima Center for Pediatric Oncology, Pediatric Hema‐Oncology, Utrecht, The Netherlands; <sup>3</sup>Radboud university medical center and Radboud Insitute for Molecular Life Sciences, Department of Human Genetics, Nijmegen, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: The genomic characterization of ‘acute lymphoblastic leukemia’ (ALL) has greatly improved the recognition of patients with a high relapse risk. Despite the success of intensified treatment for ‘high‐risk’ patients, relapse and associated therapy resistance remain a significant problem. In this study we aimed to identify therapeutic targets that synergize with standard‐of‐care drugs in treating ALL.</p><p><bold>Design/Methods</bold>: We used a CRISPR/Cas9 based loss‐of‐function screen to identify novel genes that control tumor cell sensitivity towards prednisolone and asparaginase, key components of current ALL treatment protocols. To facilitate rapid translation to clinical practice, we focused our screen on kinases, as potential candidates for pharmacological inhibition. Results were validated using targeted knockout and small‐molecule inhibitors.</p><p><bold>Results</bold>: The CRISPR/Cas9 based screen has identified genes that modulate sensitivity towards the tested drugs, both inducing resistance as well as enhancing the susceptibility towards drug induced apoptosis. The anti‐tumor effects of asparaginase treatment impinge on changes in cell metabolism as a result of amino acid starvation. Consistent with this notion, we found genes either directly involved in the amino acid response route (TRIB3) or aminoacid metabolism (GCN2). Indeed, targeted knockout of GCN2 sensitizes cells to asparaginase treatment whereas depletion of TRIB3 was sufficient to render these cells more resistant.</p><p>Surprisingly, sensitivity for prednisolone was controlled by kinases involved in Toll‐like receptor signaling and beta‐adrenergic receptor signaling. Consistent with these findings, the use of clinically approved compounds that modulate these pathways dramatically potentiate the anti‐tumor effect of prednisolone. Inhibition of the beta‐adrenergic receptor‐increased sensitivity to prednisolone mediated apoptosis up to 30 fold.</p><p><bold>Conclusions</bold>: We conclude from these results that our CRISPR/Cas9 based screens can be used to (i) delineate pathways that contribute therapy resistance and (ii) identify targets that can be selectively inhibited to improve therapy response.</p></sec><sec id="pbc26772-sec-0080"><label>AW-07</label><title>Pseudoprogression in Pediatric Low‐Grade Glioma After Radiation Therapy</title><p><underline underline-style="single">D.S. Tsang</underline><sup>1</sup>, E.S. Murphy<sup>2</sup>, J.T. Lucas Jr.<sup>1</sup>, P. Lagiou<sup>3, 4</sup>, S. Acharya<sup>1</sup>, T.E. Merchant<sup>1</sup></p><p><italic><sup>1</sup>Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis TN, USA; <sup>2</sup>Department of Radiation Oncology, Cleveland Clinic, Cleveland OH, USA; <sup>3</sup>Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA; <sup>4</sup>Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens (NKUA), Athens, Greece</italic></p><p><bold>Background/Objectives</bold>: This goal of this study was to report the incidence, management and risk factors for pseudoprogression after radiation therapy (RT) in patients with pediatric low‐grade glioma (LGG).</p><p><bold>Design/Methods</bold>: This retrospective study included patients aged ≤21 years with intracranial LGG treated with curative‐intent RT at a single institution. Pseudoprogression was defined as an increase in tumour size by ≥10% in at least 2 dimensions between two or three consecutive MR imaging studies. Overall survival (OS) and event‐free survival (EFS) were measured from the first day of RT. EFS was defined as survival without true progression or secondary high‐grade glioma.</p><p><bold>Results</bold>: Sixty‐two of 221 patients developed pseudoprogression, with a 10‐year cumulative incidence of 29.0% (95% CI 23.0‐35.2). Median time to pseudoprogression was 6.1 months after RT (interquartile range [IQR] 3.5‐14.6). 68% of tumours with pseudoprogression were observed, with eventual stabilization (48%) or reduction in size (20%) over time. Symptomatic pseudoprogression was managed with subtotal resection, shunt/Ommaya reservoir placement, or corticosteroids in 11 (18%), 7 (11%), and 2 patients (3%), respectively. Patients with pilocytic astrocytoma (PA) had 5.4‐fold greater odds of developing pseudoprogression relative to other tumours (odds ratio 95% CI 2.5–11.4, P < 0.0001). Among 127 patients with PA, the 10‐year cumulative incidence of pseudoprogression was 42.9%. In this subgroup, pseudoprogression was associated with improved 10‐year EFS (84.5% vs. 58.5%, P = 0.008) and OS (98.0% vs. 91.2%, P = 0.03).</p><p><bold>Conclusion</bold>: Pseudoprogression after radiation therapy was common, particularly in patients with pilocytic astrocytoma, and was associated with improved survival. Awareness of the incidence and temporal dynamics of pseudoprogression may help avoid unnecessary salvage treatments.</p></sec><sec id="pbc26772-sec-0090"><label>AW-08</label><title>Mutations in CIC, DMD and PHOX2B Activate the RAS‐MAPK Pathway in Neuroblastoma and Activation of this Pathway Causes Tumor Progression</title><p><underline underline-style="single">T.F. Eleveld</underline><sup>1,2</sup>, L. Schild<sup>1</sup>, J. Koster<sup>2</sup>, D.A. Zwijnenburg<sup>2</sup>, L. Alles<sup>1</sup>, M.E. Ebus<sup>1</sup>, R. Volckmann<sup>2</sup>, G.A. Tijtgat<sup>3</sup>, P. van Sluis<sup>2</sup>, H.N. Caron<sup>3</sup>, R. Versteeg<sup>2</sup>, J.J. Molenaar<sup>1</sup>,</p><p><italic><sup>1</sup>Department of Translational Research, Princess Maxima Centre for Childhood Oncology, Utrecht, the Netherlands; <sup>2</sup>Department of Oncogenomics, Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands; <sup>3</sup>Department of Pediatric Oncology, Emma Children′s Hospital, Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands</italic></p><p><bold>Background/Objectives</bold>: It was recently shown that mutations affecting the RAS‐MAPK pathway occur frequently in neuroblastoma relapse tumors. We hypothesized that activation of this pathway could be associated with poor prognosis and tumor progression. Hence the objectives were to detect the activation state of the RAS‐MAPK pathway in tumors, correlate this to prognosis, and find and characterize additional mutations that can serve as biomarkers for pathway activation.</p><p><bold>Design/Methods</bold>: We generated a gene signature that can identify the activation state of the RAS‐MAPK pathway in cell lines and tumors. These data were correlated to Whole Genome Sequencing data to identify novel mutations that influence activation of this pathway. Candidate mutations were induced in cell lines using gene editing and characterized both in vitro and in vivo.</p><p><bold>Results</bold>: We show that in primary neuroblastoma tumors activation of the RAS‐MAPK pathway correlates with poor survival, and is associated with known activating mutations in ALK and other bona fide RAS‐MAPK pathway genes. From integrative analysis, we identify mutations in PHOX2B, CIC and DMD that activate the RAS‐MAPK pathway in vitro and we show that activation of this pathway causes tumor progression in vivo.</p><p><bold>Conclusion</bold>: These results identify novel biomarkers of RAS‐MAPK activation and reinforce this pathway as a promising target in high risk neuroblastoma. Further research should determine whether the identified mutations also function as biomarkers for sensitivity to MEK inhibition.</p></sec></sec><sec id="pbc26772-sec-0100"><title>Free Paper Session: Solid Tumours ‐ Biology</title><sec id="pbc26772-sec-0110"><label>O-001</label><title>Highly‐Accumulated HIF‐1Α is a Potential Therapeutic Target in the Treatment of Wilms Tumor</title><p><underline underline-style="single">M. Nelson</underline><sup>1</sup>, Y. Liu<sup>1</sup>, C. Bailey<sup>1</sup>, Y. Liu<sup>1</sup>, J. Dome<sup>1</sup>, Y. Wang<sup>1</sup></p><p><italic><sup>1</sup>Children's National Medical Center, Center for Cancer and Immunology Research, Washington‐ DC, USA</italic></p><p><bold>Background/Objectives</bold>: Five‐year survival of patients with Wilms tumor (WT) is over 90%. However, 40% of patients with anaplastic histology WT (AHWT) and 15% of patients with favorable histology WT (FHWT) will suffer recurrence. Patients who survive with additional therapy are at risk for toxicities such as infertility. Hypoxia‐inducible factor 1α (HIF‐1α) is upregulated in a number of malignancies and implicated in chemoresistance and recurrence. We investigate the prevalence of HIF‐1α accumulation, its role in WT growth, and response to treatment with echinomycin, a known HIF‐1α inhibitor, in pre‐clinical WT models.</p><p><bold>Design/Methods</bold>: Immunofluorescent staining for HIF‐1α was performed on 64 WT samples, which were scored on a scale according to percentage of cells positively stained. HIF‐1α was knocked‐out in the WiT49 cell line (WiT49‐HIF1α‐ko) employing the CRISPR/Cas9 system and tumor growth in NSG mice was compared to WiT49‐wild type (WiT49‐wt). The effect of echinomycin on viability was assessed in three patient‐derived WT cell lines, including two AHWT samples, using the MTT assay. The effect of liposomal echinomycin (Lipo‐E) on tumor growth was assessed in a patient‐derived AHWT xenograft model.</p><p><bold>Results</bold>: Fifty percent of WT samples (n=32) had the highest HIF 1α staining intensity score of 3 (>50% of cells staining positively). Mice injected WiT49‐wt cells resulted in tumors with incidence of 100%, while no tumors grew from injected WiT49‐HIF1α‐ko cells (P<0.001). Echinomycin was toxic against WiT49 and all three ex‐vivo WT cases in cell culture (IC50 at 1350 pM). AHWT xenografts treated with Lipo‐E showed significant growth inhibition compared to vehicle (P=0.04).</p><p><bold>Conclusions</bold>: HIF‐1α is prevalent in WT samples and its presence is essential for tumor growth in mice. Echinomycin treatment of AHWT xenografts impairs tumor growth. Therefore, echinomycin holds promise as a targeted agent against WT.</p></sec><sec id="pbc26772-sec-0120"><label>O-002</label><title>Insights from the Evolutionary Trajectories of Wilms Tumor</title><p><underline underline-style="single">G. Cresswell</underline><sup>1</sup>, T. Chagtai<sup>2</sup>, R. Al‐Saadi<sup>2</sup>, T. Treger<sup>2</sup>, R. Williams<sup>2</sup>, N.M. Luscombe<sup>1</sup>, K. Pritchard‐Jones<sup>2</sup>, W. Mifsud<sup>2</sup></p><p><italic><sup>1</sup>The Francis Crick Institute, Bioinformatics and Computational Biology Laboratory, London, United Kingdom; <sup>2</sup>UCL Great Ormond Street Institute of Child Health, Developmental Biology and Cancer, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: We previously demonstrated intra‐tumor genetic heterogeneity in multi‐sampled Wilms tumors (WT), which occurs despite a low number of genetic changes per tumor. Frequent multifocality or bilaterality are significant treatment challenges with poorly understood mechanisms. Furthermore, only circa 50% of relapses can be predicted with current stratification criteria. To address these issues, we need to understand better the evolutionary processes of WT development. Current experimental approaches to tumor evolution utilise whole‐genome/exome (WGS/WES) sequencing in multi‐sampled tumors, but WGS/WES may not be an efficient approach in tumors with relatively few mutations.</p><p><bold>Design/Methods</bold>: We combined targeted sequencing and Illumina CoreExome SNP arrays to assess genome‐wide, allele‐specific copy‐number profiles and mutational status in a panel of 181 genes. We developed a mixture model‐based method to model B‐allele frequencies and infer cellularities of copy‐number aberration (CNA) segments. We inferred per‐sample subclones by clustering segments with similar cellularities; subclones were compared across multiple samples, and an evolutionary trajectory was calculated for each tumor. Combined SNP array and sequencing data were available for 32 multi‐sampled WTs, and SNP array data only for an additional 30 WTs.</p><p><bold>Results</bold>: We inferred 1‐10 clones per WT, showing a wide range of evolutionary trajectories. A subset of cases show marked evolutionary divergence, and this may explain diagnostic difficulty in diffuse anaplasia. Another subset show striking convergent evolution for CNAs and point mutations.</p><p><bold>Conclusions</bold>: Accurate evolutionary trajectories can be inferred in multi‐sampled WT, regardless of tumor multifocality or bilaterality, and without resource‐intensive WGS/WES, despite the low number of passenger as well as driver mutations per tumor. Many tumors show a surprisingly high number of clones/tumor, comparable to adult cancers, and there is a wide range of evolutionary trajectories, generally unlike adult cancers. Cases with convergent evolution suggest a previously unsuspected strong selection pressure in a subset of WT.</p></sec><sec id="pbc26772-sec-0130"><label>O-003</label><title>Preclinical Rationale for Entinostat in Alveolar and Embryonal Rhabdomyosarcoma</title><p><underline underline-style="single">N. Bharathy</underline><sup>1</sup></p><p><italic><sup>1</sup>Children's Cancer Therapy Development Institute, Biotechnology, Beaverton, Usa</italic></p><p><bold>Background/Objectives</bold>: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood yet often also occurs in adolescents and young adults. Clinically, survival amongst metastatic RMS patients has remained dismal yet unimproved for years, if not several decades. We previously identified the class I specific histone deacetylase inhibitor, entinostat, as a pharmacological agent that transcriptionally suppresses the Pax3:Foxo1 tumor‐driving fusion gene found in many alveolar rhabdomyosarcomas. The purpose of this study is to examine whether entinostat may provide real therapeutic benefit for patients with embryonal rhabdomyosarcoma (eRMS) and alveolar rhabdomyosarcoma (aRMS).</p><p><bold>Design/Methods</bold>: We investigated the comparative efficacy of entinostat to other HDAC inhibitors for the full spectrum of Pax3:Foxo1/Pax7:Foxo1 positive aRMS and fusion negative eRMS using both <italic>in vitro</italic> and <italic>in vivo</italic> models that includes orthotopic allografts and patient derived xenografts. In‐addition, to understand the mechanism of entinostat action in aRMS and eRMS; RNAseq, ChIP‐exo, and CRISPR studies were carried out.</p><p><bold>Results</bold>: We find that entinostat most effectively silences Pax3:Foxo1. Entinostat delays tumor engraftment in aRMS after radiation treatment. In combination with the chemotherapy vincristine, entinostat has strong anti‐tumor activity in aRMS/eRMS orthotopic allografts and patient‐derived xenografts. Mechanistic interrogation by RNAseq, ChIP‐exo, and CRISPR studies suggest that HDAC3 inhibition is the primary mechanism of Pax3:Foxo1 downregulation in aRMS and cell‐autonomous cytoreduction in eRMS, but that the myogenic differentiation effect of chemotherapy‐entinostat therapy in eRMS is driven by crosstalk with the tumor microenvironment.</p><p><bold>Conclusions</bold>: These studies support the emerging clinical trial concepts for the use of entinostat with chemotherapy for aRMS and eRMS. It addresses the clinical need with preclinical evidence that suggests entinostat, may provide therapeutic benefit in RMS. We present both <italic>in vitro</italic> and <italic>in vivo</italic> evidence to not only document entinostat's therapeutic effect on RMS tumors, but also to understand the mechanism underlying its activity in both aRMS and eRMS.</p></sec><sec id="pbc26772-sec-0140"><label>O-004</label><title>Integrated Genetic and Epigenetic Analysis Defines Novel Molecular Subgroups in Hepatoblastoma</title><p><underline underline-style="single">E. Hiyama</underline><sup>1</sup>, S. Kurihara<sup>1</sup>, S. HIrano<sup>2</sup>, F. Irisuna<sup>2</sup>, Y. Ueda<sup>1</sup>, M. Kawashima<sup>1</sup></p><p><italic><sup>1</sup>Hiroshima University Hospital, Peditric Surgery, Hiroshima, Japan; <sup>2</sup>Hiroshima University, Natural Science Center for Basic Research and Development, Hiroshima, Japan</italic></p><p><bold>Background/Objectives</bold>: Hepatoblastoma (HB) is the most prevalent liver malignancies and its molecular pathogenesis is incompletely understood. HB incidence is significantly high in the children with extremely low‐birth weight and some HB patients diagnosed at old ages showed poor outcomes.</p><p><bold>Design/Methods</bold>: Here we describe an integrated molecular study in which we performed exome, transcriptome and, as well as array‐based copy number and methylation analyses in a total 130 HBL cases. Among them, we also performed whole‐genome sequence (WGS) and whole‐genome methylation (WGM) analysis in the 30 and 12 cases.</p><p><bold>Results</bold>: Exome and WGS analysis revealed that HB tumors have the few mutations. Younger patients showed the fewer somatic mutations but there are no difference of mutation rates between the patients with low‐birth weight and those with normal birth weight. The mutation signatures revealed two characteristic patterns. Most dominant alterations were <italic>CTNNB1</italic> exon 3 and other mutation of Wnt signal genes including <italic>AXIN1</italic> and <italic>FAP</italic> genes. However, RNA sequencing did not showed the activation of Wnt signaling genes. Some cases showed the mutations of <italic>ARID1A</italic>, <italic>KCNN3</italic>, and <italic>MLL2</italic>, but the number of these mutations were less than 10. Based on methylation patterns, HBL is clustered into four distinct subtypes named C1‐4. C1 showed the similar pattern of non‐cancerous liver tissues and C2 was highly correlated with 11p UPD. Interestingly, no cases with extreme low‐birth weight exhibited 11pUPD.C3 and C4 involved the cases diagnosed at older age. All C3 cases were alive but more than half of C4 cases showed poor outcomes.</p><p><bold>Conclusions</bold>: This integrated molecular analysis unmasked new correlations between DNA methylation including UPD, gene mutations, gene expression and copy number profiles, enabling the stratification of clinical risks for patients with HB. Molecular analysis provides new important clusters of the HB patients to be stratified in future clinical trials.</p></sec></sec><sec id="pbc26772-sec-0150"><title>Free Paper Session: Epidemiology ‐ I</title><sec id="pbc26772-sec-0160"><label>O-005</label><title>Maternal use of Hormonal Contraceptives and Risk of Childhood Leukaemia – A Nationwide Population‐Based Cohort Study</title><p><underline underline-style="single">M. Hargreave</underline><sup>1</sup>, L.S. Mørch<sup>1</sup>, J.F. Winther<sup>2</sup>, K. Schmiegelow<sup>3</sup>, S.K. Kjaer<sup>1</sup></p><p><italic><sup>1</sup>Danish Cancer Society, Virus‐ Lifestyle and Genes, Copenhagen, Denmark; <sup>2</sup>Danish Cancer Society, Childhood Cancer Survivorship Research Group‐ Survivorship Unit, Copenhagen, Denmark; <sup>3</sup>Copenhagen University hospital Rigshospitalet, Paediatric and Adolescent Medicine, Copenhagen‐ Denmark, Denmark</italic></p><p><bold>Background/Objectives</bold>: Following the discovery, that diethylstilboestrol (i.e. a synthetic oestrogen) can cause cancer in children exposed <italic>in utero</italic>, few case‐control studies have investigated the effect of maternal contraceptive use on the risk of cancer in children, and with inconsistent results. The aim of this study was to assess the association between maternal use of hormonal contraceptives and childhood leukaemia, using the unique Danish registries.</p><p><bold>Design/Methods</bold>: We followed a nationwide cohort of 1,185,157 live born children between 1996 and 2014 through individual linkage to Danish registries. Redeemed prescription data from the National Register of Medicinal Product Statistics provided information on maternal hormonal contraceptive use, categorized as: never before birth (reference), > 3 months prior to conception and < 3 months before conception to birth (that is, recent use). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) adjusted for potential confounders.</p><p><bold>Results</bold>: During 11,028,171 person‐years of observation (mean: 9.4 years), 598 children were diagnosed with leukaemia. An increased risk of leukaemia was found in children born to women with a recent use of any type of hormonal contraception (HR: 1.48; 95% CI: 1.10‐2.00) compared to children of never users. Specifically for non‐lymphatic leukaemia, the risk was more than doubled (HR: 2.41; 95% CI: 1.32‐4.38). The increase was mainly observed for recent use of combined products (progestin/oestrogen combined), both for any type of leukaemia (HR: 1.55; 95% CI: 1.14‐2.12) and for non‐lymphatic leukaemia (HR: 2.68; 95% CI: 1.47‐4.88) compared to never users.</p><p><bold>Conclusions</bold>: Maternal use of hormonal contraception up to or in early pregnancy may increase the risk of leukaemia in children.</p></sec><sec id="pbc26772-sec-0170"><label>O-006</label><title>Trends in Childhood Cancer Incidence and Survival in Japan and England</title><p><underline underline-style="single">K. Nakata</underline><sup>1,2,3</sup>, Y. Ito<sup>1</sup>, W. Magadi<sup>2</sup>, A. Bonaventure<sup>2</sup>, C. Stiller<sup>4</sup>, K. Katanoda<sup>5</sup>, T. Matsuda<sup>5</sup>, I. Miyashiro<sup>1</sup>, K. Pritchard‐Jones<sup>3</sup>, B. Rachet<sup>2</sup></p><p><italic><sup>1</sup>Osaka International Cancer Center, Cancer Control Center, Osaka, Japan; <sup>2</sup>London School of Hygiene & Tropical Medicine, Cancer Survival Group, London, United Kingdom; <sup>3</sup>UCL Great Ormond Street Institute of Child Health, Developmental Biology and Cancer Programme, London, United Kingdom; <sup>4</sup>Public Health England, National Cancer Registration and Analysis Service, Oxford, United Kingdom; <sup>5</sup>Center for Cancer Control & Information Services‐ National Cancer Center, Center for Cancer Registries, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: This study aimed to compare the time trends in cancer incidence and survival for children diagnosed in Japan and England, using population‐based cancer registry data.</p><p><bold>Design/Methods</bold>: The analysis was based on 5,192 children with cancer (age 0‐14) from 6 prefectural cancer registries in Japan and 21,295 children diagnosed in England, during 1993‐2010. Age‐standardised incidence rates (ASRs) were calculated using weights of the world standard population. Poisson regression models were used to evaluate changes in incidence rates over time. Overall 1‐year, 5‐year and 10‐year survival was estimated using the Kaplan‐Meier method.</p><p><bold>Results</bold>: Incidence of all childhood cancers combined has decreased in Japan throughout 1993‐2010 (ASR 1993‐1998: 127 per million person‐years vs 2005‐2010:116), which was mainly explained by a decrease in registration of infant neuroblastoma. Incidence for all cancers in England increased between 1993‐1998 and 1999‐2004, then plateaued (ASR 1993‐1998:129, 1999‐2004: 133, 2005‐2010:134). Incidence for Hodgkin lymphoma, renal tumours, and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumours, hepatic tumours, neuroblastoma, acute myeloid leukaemia (AML) was higher in Japan than in England.</p><p>For many cancers, 5‐year survival improved in both countries and the differences in survival between countries narrowed over time. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries. However, 5‐year survival remained less than 80% in both countries for AML, brain tumours, soft tissue sarcomas, malignant bone tumours, and neuroblastoma in children aged 1‐14 years.</p><p><bold>Conclusions</bold>: There were significant differences in incidence of several cancers between England and Japan, suggesting ethnic variation in susceptibility. The decrease in incidence in infant neuroblastoma in Japan coincided with cessation of the national screening programme. The great improvement in survival from CML in both countries coincided with the introduction of effective therapy (imatinib).</p></sec><sec id="pbc26772-sec-0180"><label>O-007</label><title>Parental Socioeconomic Factors Influencing Childhood Cancer Mortality in Finland: A Nationwide Register‐Based Study</title><p><underline underline-style="single">A. Tolkkinen</underline><sup>1</sup>, J. Pitkäniemi<sup>1,2</sup>, M. Taskinen<sup>3</sup>, L. Madanat‐Harjuoja<sup>1,4</sup>, M. Rantanen<sup>1</sup>, N. Malila<sup>1,5</sup></p><p><italic><sup>1</sup>Finnish Cancer Registry, Finnish Cancer Registry, Helsinki, Finland; <sup>2</sup>University of Helsinki, Department of Public Health, Helsinki, Finland; <sup>3</sup>Helsinki University Hospital, Division of Pediatric Hematology‐ Oncology and Stem Cell Transplantation, Helsinki, Finland; <sup>4</sup>Helsinki University Hospital, Department of Pediatric and Adolescent Medicine, Helsinki, Finland; <sup>5</sup>University of Tampere, School of Health Science, Tampere, Finland</italic></p><p><bold>Background/Objectives</bold>: Parental socioeconomic status has been suggested to have an influence on childhood cancer mortality even in high‐income countries. Our study investigated if parental socioeconomic factors influence childhood cancer mortality in Finland.</p><p><bold>Design/Methods</bold>: Using nationwide population‐based registries we identified 4,437 patients diagnosed with cancer under the age of 20 from 1990 to 2009. The outcome was death from primary cancer in 10 years follow‐up. Identification of parents and information on socioeconomic factors were retrieved from the central population registry and Statistics Finland. Poisson regression models were adjusted for follow‐up time, age at cancer diagnosis and diagnostic period.</p><p><bold>Results</bold>: Mortality was lower in the highest quartile of combined parental disposable income (HR 0.72, CI 95% 0.55‐0.93) compared to the lowest quartile. After adding parental education to the model, the result was still statistically significant. Compared to individuals with Finnish decent, mortality was higher if the patient (n=58, HR 2.18, CI 95 % 1.38‐3.44), the mother (n=113, HR 2.29, CI 95 % 1.66‐3.16) or the father (n=121, HR 2.04, CI 95 % 1.47‐2.82) was an immigrant and born aboard. Mortality was also higher if the maternal (n=115, HR 2.35, CI 95 % 1.71‐3.23) or paternal native language (n=119, HR 2.16, CI 95 % 1.57‐2.98) was other than Finnish or Swedish. The results for origin of birth and native language remained significant in the 5‐year follow‐up even after adjusting for parental income, employment status and education.</p><p><bold>Conclusions</bold>: In Finland, despite public health care and comprehensive social security, high parental income predicted lower mortality after childhood cancer compared to those with low parental income. Parental immigrant status and being born abroad were predictors of increased mortality. Underlying factors related to patient pathways should be explored to better understand and prevent these disparities in the future.</p></sec><sec id="pbc26772-sec-0190"><label>O-008</label><title>Pathways of Care for Adolescent and Young Adult Patients with Cancer Diagnosed in 2012 or 2013 in France</title><p><underline underline-style="single">E.</underline><underline underline-style="single">Desandes</underline><sup>1</sup>, L. Brugieres<sup>2</sup>, J. Clavel<sup>3</sup>, A. Monnereau<sup>4</sup>, B. Lacour<sup>1</sup></p><p><italic><sup>1</sup>CHRU Nancy, Registre National des Tumeurs Solides de l'Enfant, Nancy, France; <sup>2</sup>Institut Gustave Roussy, Département d'oncologie de l'enfant et de l'Adolescent, Villejuif, France; <sup>3</sup>Université Paris‐Sorbonne, Registre National des Cancers de l'Enfant‐ Inserm UMRS‐1153‐ CRESS équipe 7, Paris, France; <sup>4</sup>Faculté de Médecine de Purpan, Réseau français des registres de cancer‐FRANCIM, Toulouse, France</italic></p><p><bold>Background/Objectives</bold>: In France, as in other countries, there is a need for a population‐based view of access to care and modalities of treatment for adolescents and young adults (AYA) with cancer. The aim is to evaluate their pathway and quality of care in general population settings.</p><p><bold>Design/Methods</bold>: All AYA cases diagnosed with cancer in 2012‐2013, aged from 15 to 24 years, and living in 19 French administrative areas (covering rate:23%) were identified by the French cancer registries. Data on diagnosis and treatment delays, management with multidisciplinary decisional approach (MDT), and pathways of care were collected in medical records.</p><p><bold>Results</bold>: Overall, 412 adolescents and 581 young adults were included. Time to diagnosis was significantly longer for young adults than for adolescents (10 weeks [4‐23] vs 8 weeks [3‐21], P‐value =0.03), especially for soft‐tissue sarcomas (P=0.02). Decisions for treatment initiation were made within the context of MDT in 86% of adolescents and in 85% of young adults, and 23% of the MDT meetings for adolescents involved both pediatric and adult oncologists (vs. 10% for young adults). Most of AYA cases (67%) consulted general practitioner before referral to a specialist for investigation. The main institutions involved in the management of AYA with cancer were: University hospitals (56%), and private hospitals (26%). The main services were adult oncology units (84%), while 21% of adolescents and 10% of young adults with cancer were cared in dedicated AYA units. Overall, 39.5% of adolescents and 16.8% of young adults were included in clinical studies.</p><p><bold>Conclusions</bold>: Compared to the previous French study (period 2006‐07) [Desandes E et al. 2012], the organization of care for 15‐19‐year‐old adolescents with cancer shifted toward an increasing involvement of pediatricians (especially for 15‐17 years), an increasing management within the context of MDT and in specialized cancer health institutions, and an increasing participation in clinical studies.</p></sec></sec><sec id="pbc26772-sec-0200"><title>Free Paper Session: Supportive Care</title><sec id="pbc26772-sec-0210"><label>O-009</label><title>Meta‐Analytic Validation of the Picnicc Prediction Model for the Risk of Microbiologically Defined Infection in Febrile Neutropenic Episodes</title><p><underline underline-style="single">R. Phillips</underline><sup>1</sup>, L. Stewart<sup>1</sup>, C. PICNICC<sup>1</sup></p><p><italic><sup>1</sup>University of York, Centre for Reviews and Dissemination, York, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Risk stratified management of febrile neutropenia (FN), also known as “fever with neutropenia”, allows intensive management of high‐risk cases and early discharge of low‐risk cases. Validation of prediction rules are important, as geographical, temporal and chance variability may affect any derived rule, and calibration is advised. Validating across different data sources allows exploration of the possible reasons for differences and calibrations to be applied.</p><p><bold>Design/Methods</bold>: Using data derived from the “Predicting Infectious ComplicatioNs In Children with Cancer” (PICNICC) collaboration, we assessed the value of the PICNICC microbiologically defined infection (MDI) prediction rule in new datasets and combined study‐level data using different random‐effects meta‐analysis approaches, study‐level recalibration and bootstrapping to estimate variances. The multivariable risk prediction model has six components: Tumour type, temperature, clinically “severely unwell”, haemoglobin, white cell count and absolute monocyte count.</p><p><bold>Results</bold>: Seven data sets from six locations, reporting 27‐648 episodes of fever and neutropenia were included. The raw model over‐estimated the likelihood of MDI (Expected/Observed ratio 1.49, 95% CI 0.89 to 2.1) with only a moderate C‐statistic 0.59 (95% CI 0.41 to 0.79) compared with 0.72 (95% CI 0.71 to 0.76) in the derivation cohort. The analysis showed marked heterogeneity (I‐squared 47% to 56%). Different approaches to meta‐analysis led to similar estimates. After re‐calibration in the large, and assessed at a threshold of 10% to define ‘low risk’, the model had a pooled sensitivity of 89% (95% CI 72% to 97%) but pooled specificity of only 12% (95% CI 5% to 24%). No clear explanation for heterogeneity was found by assessing in‐patient status, continent, or case‐mix.</p><p><bold>Conclusions</bold>: This meta‐analysis of the PICNICC risk prediction model for microbiologically defined infection shows marked variation in validation across multiple data sets. This argues for local validation of any prediction rules before use.</p></sec><sec id="pbc26772-sec-0220"><label>O-010</label><title>Experience of Chemotherapy‐Induced Nausea and Vomiting in Children, an Undermanaged Symptom?</title><p><underline underline-style="single">S. Mouffak</underline><sup>1,2</sup>, A. Petit<sup>1</sup>, H. Boutroux<sup>1</sup>, M. Simonin<sup>1</sup>, K. Morand<sup>2</sup>, G. Leverger<sup>1</sup></p><p><italic><sup>1</sup>Trousseau Hospital ‐ APHP, Department of Pediatric Hematology and Oncology, PARIS, France; <sup>2</sup>Trousseau Hospital ‐ APHP, Department of Pharmacy, PARIS, France</italic></p><p><bold>Background/Objectives</bold>: Chemotherapy‐induced nausea and vomiting (CINV) are toxicities that impact children's quality of life and complicate cancer treatments. Imprecise international recommendations, difficulties in nausea detection in children and the low priority which is sometimes given to this symptom are risks of non‐optimal management of CINV. The purpose of this study was to assess children nausea and vomiting during their chemotherapy treatment.</p><p><bold>Design/Methods</bold>: We conducted a monocentric retrospective survey on children treated in a french paediatric cancers reference center. Patients were asked about their CINV experiences, in terms of frequency, severity and timing of the symptoms. When children could not answer, the questions were asked to their parents.</p><p><bold>Results</bold>: From July to October 2016, 48 children aged from 1 to 17 were surveyed. Twenty‐four children had received highly emetogenic chemotherapy, 21 had received moderately emetogenic chemotherapy, and 3 had received low emetogenic chemotherapy. In the overall population analysed, 83% of the patients indicated they had already experienced nausea and/or vomiting during chemotherapy treatments and 40% had experienced it from the first chemotherapy administration. Eight percent of children described anticipatory symptoms, 65% described acute CINV and 54% experienced delayed CINV. Patients receiving highly emetogenic chemotherapy were more exposed to these symptoms (p=0.02): in this population, 100% of children experienced nausea or vomiting during their treatment and 46% of them experienced vomiting systematically or frequently.</p><p><bold>Conclusions</bold>: This study showed that most children experienced CINV during their treatment. These symptoms occurred even if antiemetic prophylaxis were in accordance with local guidelines, but these guidelines were not updated, according to international guidelines. For 30 years, the emetogenic risk in adults with cancer has strongly decreased from 100% to 15%, thanks to therapeutic innovations and CINV management improvements. These improvements are required in paediatrics, and prospects of optimisation exist, starting by convincing and raising awareness among the medical community.</p></sec><sec id="pbc26772-sec-0230"><label>O-011</label><title>A Longitudinal Study of Pediatric Promis Symptom Clusters in Children Undergoing Chemotherapy</title><p>S. Jacobs<sup>1</sup>, J. Wang<sup>2</sup>, D. Dewalt<sup>3</sup>, E. Stern<sup>1</sup>, G. Heather<sup>4</sup>, <underline underline-style="single">P. HInds</underline><sup>5</sup></p><p><italic><sup>1</sup>Children's National Medical Center, Oncology, Washington, USA; <sup>2</sup>Children's National Medical Center, Division of Biostatistics and Study Methodology, Washington, USA; <sup>3</sup>University of North Carolina‐ Chapel HIll, Division of General Medicine and Clinical Epidemiology, Chapel HIll‐ NC, USA; <sup>4</sup>University of North Carolina‐ Chapel HIll, Sheps Center for Health Services Research, Chapel HIll‐ NC, USA; <sup>5</sup>Children's National Medical Center, Department of Nursing Research and Quality Outcomes, Washington, USA</italic></p><p><bold>Background/Objectives</bold>: Children in treatment for cancer experience multiple, troubling and interrelated symptoms. Analyzing the interrelatedness of symptoms and how that might change during treatment is an important focus in cancer symptom research. Applying advanced analytic approaches to this interrelatedness could identify clinically relevant patient profiles. The aims were to identify a) pediatric profiles with respect to fatigue, depression, anxiety and pain, b) changes in profile status throughout a chemotherapy cycle, c) if a baseline fatigue item score could significantly predict symptom profile.</p><p><bold>Design/Methods</bold>: In a longitudinal, single‐site, three data point design, children between 8 and 18 years completed the PROMIS Pediatric short form measures for fatigue, depression, anxiety and pain and a fatigue item from the Symptom Distress Scale. Latent class analysis (LCA) and latent transition analysis (LTA) were applied to the prospective symptom data</p><p><bold>Results</bold>: 96 children participated; 58.3% were between 13 and 18 years and 54.2% were male. The symptom mean scores remained relatively unchanged between the first two data points but significantly declined at the final data point (end of the course of chemotherapy). The LPA results indicated a 2‐profile model (‘Less severe symptoms, ‘Severe symptoms). The fatigue score did significantly predict to which profile a child was a member. The LTA findings indicated that only a small proportion of the sample changed profile groups across the three data points.</p><p><bold>Conclusions</bold>: Children experiencing troubling symptoms during cancer treatment are not a homogenous group. The four measured symptoms in this study represent at least two relatively stable profiles that can be identified with high accuracy early in a child's course of chemotherapy, and the transitions in the profile status were significantly predicted by a baseline single‐item fatigue measure.</p></sec><sec id="pbc26772-sec-0240"><label>O-012</label><title>Seizure in Children with Brain Tumour: A Retrospective Analysis and A Proposal for A Future Study</title><p><underline underline-style="single">C. Pilotto</underline><sup>1,2</sup>, J. Liu<sup>2</sup>, D.A. Walker<sup>2</sup>, W.P. Whitehouse<sup>3,4</sup></p><p><italic><sup>1</sup>University of Udine, Department of Medical and Biological Science, Udine, Italy; <sup>2</sup>University of Nottingham, Children's Brain Tumour Research Centre, Nottingham, United Kingdom; <sup>3</sup>University of Nottingham, School of Medicine, Nottingham, United Kingdom; <sup>4</sup>Nottingham Children's Hospital, Department of Paediatric Neurology, Nottingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: There is no consensus on the treatment and its withdrawal of brain tumour related epilepsies in children and young people. We describe the experience of epileptic seizures in children with brain tumours treated in a neuro‐oncology centre, the related risk factors, the seizure treatments and the withdrawal of antiepileptic drugs (AEDs).</p><p><bold>Design/Methods</bold>: Retrospective case note review of 120 newly diagnosed brain tumour patients referred between 01/2010 and 12/2014 to the regional paediatric neuro‐oncology service was carried out to determine patient, tumour, seizure characteristics, their treatment and outcomes</p><p><bold>Results</bold>: Data on 117/120 (98%) children and young people were analysed: 67 were male (57%), median age at tumour presentation was 8.1 years (IQR <sup>25°‐75°</sup>: 3.6‐12.7) with median follow up: 33 months (IQR <sup>25°‐75°:</sup> 24‐56). Anatomical distribution was posterior fossa 36%, cerebral hemisphere 28%, supratentorial midline 24%, spinal cord 5%, metastatic 7%. 35/117 (29%) experienced seizures. A significant risk factor for seizure occurrence was a cortical tumour location (OR: 7.1 IC 95% 2.9‐17.3). 24 months (IQR<sup>25°‐75°</sup>: 15‐48) was the median seizure follow up: 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF and off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. 34/35 (97%) were treated with AEDs. 12/34 (35%) patients withdraw AED. The median duration of AED before withdrawal was 11 months (IQR<sup>25°‐75°</sup> 5‐14 months), and the median follow up after withdrawal was 15 months (IQR<sup>25°‐75°</sup> 5‐34 months). 4/34 (12%) had seizure relapse, all after further acute events.</p><p><bold>Conclusions</bold>: We suggest that AEDs are withdrawn after a period of three months seizure freedom, in particular in children with only one acute symptomatic seizure, and an uncomplicated course, without on‐going epileptogenic complications. This time of withdrawal is proposed as a service evaluation target for future studies</p><p><bold>Acknowledgements</bold>: Prof Richard Grundy, Dr Sophie Wilne, EMCYPICS, and Children's Brain Tumour Research Centre (Nottingham)</p></sec></sec><sec id="pbc26772-sec-0250"><title>Free Paper Session: Brain Tumours ‐ I</title><sec id="pbc26772-sec-0260"><label>O-013</label><title>ACNS0334: Treatment of Young Children, with Supratentorial PNET (SPNET) and High Risk Medulloblastoma(HRMB) without or with High Dose Methotrexate(HDMTX). A Report from Children's Oncology Group</title><p><underline underline-style="single">C. Mazewski</underline><sup>1</sup>, G. Kang<sup>2</sup>, S. Kellie<sup>3</sup>, L. Hayes<sup>4</sup>, A. Reddy<sup>5</sup>, D. Shaw<sup>6</sup>, P. Burger<sup>7</sup>, A. Judkins<sup>8</sup>, J.R. Geyer<sup>9</sup>, A. Gajjar<sup>10</sup>, I. Pollack<sup>11</sup></p><p><italic><sup>1</sup>Emory University School of Medicine‐ Children's Healthcare of Atlanta, Department of Pediatrics, Alpharetta, USA; <sup>2</sup>St Judes Research Hospital, Biostatistics, Memphis‐ TN, USA; <sup>3</sup>University of Sydney‐Children's Hospital at Westmead, Paediatric and Child Health, Westmead, Australia; <sup>4</sup>Sarcred Heart Healthcare Systems, Radiology, Pennsacola‐ FLA, USA; <sup>5</sup>University of Alabama, Neurology, Birmingham‐ Ala, USA; <sup>6</sup>Seattle Children's Hospital, Radiology, Seattle‐ WA, USA; <sup>7</sup>John's Hopkins University, Pathology, Baltimore‐ MD, USA; <sup>8</sup>Children's Hospital of Los Angeles, Pathology, Los Angeles‐ CA, USA; <sup>9</sup>Seattle Children's Hospital, Hematology Oncology, Seattle‐ WA, USA; <sup>10</sup>St Judes Research Hospital, Oncology, Memphis‐ TN, USA; <sup>11</sup>Children's Hospital of Pittsburgh‐ University of Pittsburgh School of Medicine, Neurological Surgery, Pittsburgh‐ PA, USA</italic></p><p><bold>Background/Objectives</bold>: ACNS0334's primary objective was to determine if children <36 months old with HRMB and SPNET treated with intensive chemotherapy plus HDMTX results in higher complete response (CR) rates than the same regimen without methotrexate(w/oMtx).</p><p><bold>Design/Methods</bold>: Between 08/2007 and 05/2014, ACNS0334 enrolled 91 patients. Patients received 3 Induction Cycles (Cyclophosphamide/Etoposide/Vincristine/Cisplatin+/‐ HDMTX) followed by 3 Consolidation Cycles (Carboplatin/Thiotepa then autologous stem cell rescue(ASCR)). After completing consolidation, radiation(RT) was at treating physician's discretion.</p><p><bold>Results</bold>: Seventy‐seven patients were eligible after central pathology review, 59 were evaluable for response by central radiology.</p><p>After Induction 3/20 patients with HRMB treated w/oMTX achieved CR versus 7/19 treated with HDMTX. After Consolidation 6/20 without and 12/19 with HDMTX achieved CR(p=0.038).</p><p>For HRMB, not desmoplastic, not large cell, after Induction 1/11 achieved CR w/oMTX and 5/12 with HDMTX. After Consolidation 3/11 treated without and 7/12 with HDMTX achieved CR (p= 0.21).</p><p>For SPNET after Induction 4/9 without and 3/11 with HDMTX achieved CR and 7/9 without and 3/11 with HDMTX after Consolidation (p=0.07).</p><p>Estimated 2 and 5‐year Event Free Survival (EFS) for 46 eligible HRMB=68.2+/‐9.6% and 68.2+/‐14.5% for the HDMTX arm and 45.8+/‐9.7% and 45.8+/‐13.8% for the arm w/oMTX(p=0.17). Twenty‐six patients are in follow‐up (Median 4.6 years, range 2.5‐8.3 years).</p><p>Estimated 2 and 5‐year EFS rates for 31 eligible SPNET =29.2+/‐11% and 29.2+/‐17.4% with Methotrexate (N=16) and 40+/‐11.7% and 40+/‐17.9% for the arm w/oMTX(N=15) (p=0.44).Eleven patients are in follow‐up (Median 4.2 years, range1.2‐7.4 years).</p><p>Of 34 survivors, 24(71%) were never irradiated, 10 were irradiated (6 before relapse and 4 after relapse).</p><p><bold>Conclusions</bold>: Post‐consolidation CR rate and 5‐yr EFS were better for HRMB treated with HDMTX versus those treated with the same regimen w/oMTX. The 5‐year EFS for HRMB patients on ACNS0334 HDMTX arm is better than the EFS reported in the literature for CCG9921, COG 99703 and HeadStart.</p></sec><sec id="pbc26772-sec-0270"><label>O-014</label><title>ACNS1221: A Phase II Study for Non Metastatic Desmoplastic Medulloblastoma in Children < 4 Years of Age. A Report of the Children Oncology Group</title><p><underline underline-style="single">L. Lafay‐Cousin</underline><sup>1</sup>, E. Bouffet<sup>2</sup>, G. Robinson<sup>3</sup>, A. Onar<sup>4</sup>, C. Billups<sup>4</sup>, C. Hawkins<sup>5</sup>, C. Eberhart<sup>6</sup>, C. Horbinski<sup>7</sup>, D. Strother<sup>1</sup>, L. Heier<sup>8</sup>, M. Souweidane<sup>9</sup>, M. Fouladi<sup>10</sup>, A. Gajjar<sup>3</sup></p><p><italic><sup>1</sup>Alberta Children's Hospital, Pediatric Hematology Oncology and Bone Marrow Transplantation, Calgary, Canada; <sup>2</sup>Hospital for Sick Children, Pediatric brain tumor program, Toronto, Canada; <sup>3</sup>Saint Jude Children's Research Hospital, Neuro oncology program, Memphis, USA; <sup>4</sup>Saint Jude Children's Research Hospital, Biostatistics, Memphis, USA; <sup>5</sup>Hospital for Sick Children, Pediatric Laboratory Medecine, Toronto, Canada; <sup>6</sup>Sidney Kimmel Cancer Center, Neuro pathology, Baltimore, USA; <sup>7</sup>Ann and Robert H Lurie Children's Hospital of Chicago, Pathology, Chicago, USA; <sup>8</sup>Weill Medical College of Cornell University, Diagnostic Imaging, New York, USA; <sup>9</sup>Memorial Sloan Kettering Cancer Center, Neurological Surgery, New York, USA; <sup>10</sup>Cincinnati Children's Hospital Medical Center, Neuro‐Oncology Program, Cincinnati, USA</italic></p><p><bold>Background/Objectives</bold>: Nodular desmoplastic medulloblastoma and medulloblastoma with extensive nodularity (ND/MBEN) have been associated with a more favorable outcome in younger children. However, treatment‐related neurotoxicity remains a significant concern in this vulnerable group of patients.</p><p><bold>Design/Methods</bold>: We prospectively conducted a single‐arm multicenter trial of conventional chemotherapy for non‐metastatic ND/MBEN patients < 4 y old, based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate, aiming to achieve similar outcome with a reduced treatment‐related neurotoxicity. The design required 37 patients and targeted a 2y PFS ≥ 90%. Secondary objectives included feasibility of timely central pathology review, evaluation of molecular profile and neurocognitive outcome.</p><p><bold>Results</bold>: Between 12/2013 and 07/2016, 26 patients (16 males, 10 females) were enrolled. Nineteen patients had ND and 7 had MBEN histology. The median age at diagnosis was 19.7 months (7.1‐42.9). Four patients had residual disease at baseline. All cases were reviewed within 10 days by at least 2 of the 3 central neuropathologists. The study closed early for higher than expected relapse rate. At last follow‐up, 7 patients had relapsed (3 local, 2 distant and 2 combined) at a median time of 9.7 months from diagnosis(range, 9.5‐13.7). One patient died of disease. At the median follow‐up time of 1 year (range, 0.2‐1.9 years) the 1y PFS was 66.2 (SE 12.2%). ND histology (p=0.009) and older age (p=0.07) may be associated with worse PFS. None of the MBEN patients relapsed. A detailed molecular analysis utilizing DNA methylation arrays, next‐generation sequencing of tumor and matched germline is underway to characterize biologic heterogeneity that could predict for a differential response.</p><p><bold>Conclusions</bold>: The proposed modified regimen of chemotherapy without intraventricular methotrexate failed to achieve the desirable 2 y PFS of 90%, leading to premature closure of the study. The results of the molecular characterization of this ND/MBEN cohort may help uncover patients who may still benefit from this regimen.</p></sec><sec id="pbc26772-sec-0280"><label>O-015</label><title>Time, Pattern and Outcome of Medulloblastoma Relapse is Biology and Therapy‐Dependent</title><p><underline underline-style="single">R. Hill</underline><sup>1</sup>, S. Richardson<sup>1</sup>, J. Lindsey<sup>1</sup>, S. Crosier<sup>1</sup>, E. Schwalbe<sup>1</sup>, D. Hicks<sup>1</sup>, G. Rafiee<sup>1</sup>, A. Smith<sup>1</sup>, A. Joshi<sup>2</sup>, K. Robson<sup>3</sup>, S. Wharton<sup>4</sup>, T.S. Jacques<sup>5</sup>, S. Bailey<sup>1</sup>, S. Clifford<sup>1</sup></p><p><italic><sup>1</sup>Northern Institute for Cancer Research, Wolfson Childhood Cancer Research Centre, Newcastle upon Tyne, United Kingdom; <sup>2</sup>Great North Children's Hospital, Pathology Department, Newcastle upon Tyne, United Kingdom; <sup>3</sup>University of Nottingham, Children's Brain Tumour Research Centre, Nottingham, United Kingdom; <sup>4</sup>University of Sheffield, Sheffield Institute for Translational Neuroscience, Sheffield, United Kingdom; <sup>5</sup>UCL Institute of Child Health, Neural Development Unit, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma relapse occurs in 30‐40% of patients, is almost universally fatal, and accounts for ∼10% of childhood cancer deaths.</p><p><bold>Design/Methods</bold>: We undertook a comprehensive characterisation of the clinical features of medulloblastoma recurrence (e.g. time‐to‐relapse/pattern‐of‐relapse) in a cohort of 249 relapsed patients. We related these to clinico‐molecular features at diagnosis (e.g. high‐risk prognostic factors), with the aim of establishing whether disease characteristics at diagnosis are associated with the nature of recurrence and subsequent disease course.</p><p><bold>Results</bold>: Disease course following relapse was therapy‐dependent. Survival was rare (9/187 (5%)) in patients receiving standard‐upfront‐treatment (neurosurgery, craniospinal‐irradiation (CSI), chemotherapy) across all disease demographics. Notable survival rates were only observed following non‐CSI treatment at diagnosis (11/62 (18%) patients); all were <4 years at diagnosis, and overall survival in this cohort was associated with desmoplastic/nodular histology and CSI at relapse (p=0.0077 and p=0.00157; log‐rank).</p><p>In patients relapsing following upfront‐CSI (n=187), time‐to‐relapse and pattern‐of‐relapse were subgroup‐dependent. MB<sub>Group4</sub> patients had a longer time‐to‐relapse (2.0 years mean, 0.3‐8.9 years range; p=0.003 log‐rank), and MB<sub>Group3</sub> a shorter time (1.3 years, 0.2‐5.5 years; p=0.00019). Acquisition of metastatic/distant recurrence occurred at similar rates across all subgroups (50‐60% patients). However, final incidence of metastatic recurrences was subgroup‐dependent. MB<sub>Group4</sub> relapses were frequently metastatic (57/63, 90%; p=0.0272, Fisher's exact), whereas MB<sub>SHH</sub> were less frequently so (12/21, 57%; p=0.0017), reflecting the lower rate of metastasis at presentation in MB<sub>SHH.</sub>Distantly‐relapsed MB<sub>SHH</sub> patients were associated with leptomeningeal disease (p= 0.00012, Fisher's exact) and <italic>MYCN</italic> amplification at diagnosis (p= 0.0092), while MB<sub>Group3</sub> and MB<sub>Group4</sub> demonstrated nodular and diffuse distant relapses.</p><p><bold>Conclusions</bold>: Recurrence remains the most significant challenge in medulloblastoma, with cure only observed in a subset of radio‐naïve infants. In conventionally‐treated patients, subgroup predicts time‐to‐relapse and pattern‐of‐relapse, with clear potential to inform disease monitoring/management. Further work is essential to understand the biology/clinical behavior of recurrence, and its exploitation to improve therapies.</p></sec><sec id="pbc26772-sec-0290"><label>O-016</label><title>An International Expert Consensus Survey for A Treatment Versus Observation Strategy of Newly Diagnosed Patients with NF1 Associated Optic Pathway Glioma</title><p>D.A. Walker<sup>1</sup>, <underline underline-style="single">C. Pilotto</underline><sup>1,2</sup>, I. Beshlawi<sup>3</sup>, E. Opocher<sup>4</sup>, A.A. Aziz<sup>5</sup>, A.M. Sehested<sup>6</sup>, M.J. Fisher<sup>7</sup>, T. Jaspan<sup>8</sup>, I. Simmons<sup>9</sup>, R.E. Ferner<sup>10</sup>, J. Grill<sup>11</sup>, R. Deasy<sup>1</sup>, D. Hargrave<sup>12</sup>, P. Hernaiz Driever<sup>13</sup>, G. Evans<sup>14</sup>, J. Liu<sup>1</sup></p><p><italic><sup>1</sup>University of Nottingham, Children's Brain Tumour Research Centre, Nottingham, United Kingdom; <sup>2</sup>University of Udine, Department of Medical and Biological Science, Udine, Italy; <sup>3</sup>Nottingham University Hospital, NHS Trust, Nottingham, United Kingdom; <sup>4</sup>University of Padua, Department of Pediatrics, Padua, Italy; <sup>5</sup>Medical University of Vienna, Department of Pediatrics and Adolescent Medicine, Vienna, Austria; <sup>6</sup>Copenhagen University Hospital, Department of Pediatrics, Copenhagen, Denmark; <sup>7</sup>Children's Hospital of Philadelphia, Department of Pediatrics, Philadelphia‐ Pennsylvania, USA; <sup>8</sup>Nottingham University Hospitals NHS Trust, Department of Radiology, Nottingham, United Kingdom; <sup>9</sup>Leeds Teaching Hospitals NHS Trust, Departments of Ophthalmology and Paediatric Oncology, Leeds, United Kingdom; <sup>10</sup>Guy's and St. Thomas' NHS Foundation Trust, Neurofibromatosis Service‐ Department of Neurology, London, United Kingdom; <sup>11</sup>Institut de Cancérologie, Gustave Roussy, Villejuif, France; <sup>12</sup>Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom; <sup>13</sup>Charité‐Universitätsmedizin, Department of Pediatric Oncology and Hematology, Berlin, Germany; <sup>14</sup>St Mary's Hospital, Department of Genetic Medicine‐, Manchester, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Optic pathway glioma (OPG) develop in 15‐20% of children with neurofibromatosis type 1 (NF‐1), threatening vision loss but not survival. There is no consensus about the most appropriate strategy for selecting newly diagnosed patients with NF‐1 for treatment or observation.</p><p><bold>Design/Methods</bold>: 25 representative case scenarios, derived from a risk‐adapted matrix of newly diagnosed children with NF‐1 OPG, previously entered the SIOP LGG 2004 trial, were used for a strategy selection consensus survey. The respondents were 98 multi‐disciplinary specialists for the first survey (10 cases) and 46 for the second survey (15 cases) from an international multi‐professional expert group. Respondents selected cases for initial observation (O) initial treatment (T) or randomisation between the two (R), justifying their selection with free text comments. A qualitative analysis of the free text comments describing reasoning was carried out by two reviewers and a mediator, following the grounded theory approach, allocating reasons to 8 themes, developed inductively.</p><p><bold>Results</bold>: Greater than 70% agreement between survey respondents occurred for initial observation in 4/25 cases, initial treatment in 10/25 cases, less than 70% consensus occurred in 11/25 cases. The associated 808 free text comments justifying selection for O: 173; T: 426 and R: 209 were allocated by 2 reviewers to 8 themes (agreement; k: 0.762). Consensus selection for: observation was justified by risk of progression (39%) and visual function (33%); for treatment by visual function (39%); for randomization by visual function (31%), risk of progression (22%), site/dimension of tumour (15%) and age and gender (12%).</p><p><bold>Conclusions</bold>: This survey and its qualitative analysis identifies a new consensus of justified criteria for initial observation versus treatment, in 11/25 scenarios no consensus was reached. These criteria are proposed as eligibility criteria for future trials where a randomised trial of indications for initial management could be included.</p><p><italic>on behalf of the SIOPE NF‐1 OPG Nottingham, UK, Workshop (Participating centers: Berlin, Copenhagen, GOS, Hamburg, Leeds, Nottingham, Padua, Paris, Vienna)</italic></p></sec><sec id="pbc26772-sec-0300"><label>O-017</label><title>Comparison of Academic Achievement Scores After Proton and Photon Therapy in Children and Young Adults with Craniopharyngioma</title><p><underline underline-style="single">T. Merchant</underline><sup>1</sup>, D. Indelicato<sup>2</sup>, C.H. Hua<sup>1</sup>, S. Wu<sup>3</sup>, H. Conklin<sup>4</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Department of Radiation Oncology, Memphis, USA; <sup>2</sup>University of Florida Proton Therapy Institute, Department of Radiation Oncology, Jacksonville, USA; <sup>3</sup>St. Jude Children's Research Hospital, Department of Biostatistics, Memphis, USA; <sup>4</sup>St. Jude Children's Research Hospital, Department of Psychology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Patients with craniopharyngioma treated with radiation therapy risk deficits in cognitive function. Proton therapy reduces the volume and dose of normal tissue exposure compared to photon therapy. Cognitive testing results from two prospective trials were used to compare proton (NCT01419067) and photon (NCT00187226) cohorts.</p><p><bold>Design/Methods</bold>: Patients (age < 22 years) with craniopharyngioma were enrolled on prospective trials that included proton (2011‐2016) or photon (1998‐2010) therapy and serial cognitive testing. Proton therapy (54CGE) was administered using passive scattering methods targeting the post‐operative residual tumor and tumor bed surrounded by an anatomically‐constrained 5mm clinical target volume margin (CTV). Photon therapy (54Gy) was administered using conformal or intensity‐modulated methods targeting a 5‐10mm CTV. Tests of academic achievement (reading and math) were administered before and after treatment. Test scores were modeled with normal tissue dose variables to compare scores by modality.</p><p><bold>Results</bold>: Fifty‐two patients treated with proton therapy were compared to 70 treated with photon therapy. Whole brain dose (median, range) was lower for the proton cohort (7.63CGE, 0.25‐16.40CGE) compared to the photon cohort (17.35Gy, 11.00‐27.56Gy) (p < 0.0001). There was no difference comparing scores based on modality. When mean brain dose was included in the model, patients treated with photon therapy had a greater decline in reading and math scores. Rate of change (points/CGE or Gy/month) in reading scores was 0.001274 for proton and ‐0.1020 for photon (p = 0.0018). The rate of change in math scores was 0.000614 for proton and ‐0.08266 for photon (p = 0.0263). Score estimates based on median doses (baseline vs. 36 month) for reading and math were 103.08 vs. 103.13 and 100.98 vs. 101 for proton compared to 100.55 vs. 96.87 and 99.33 vs. 96.36 for photon.</p><p><bold>Conclusions</bold>: The results from a prospective trial of proton therapy for craniopharyngioma demonstrate preservation of academic achievement when compared to treatment using photons.</p></sec></sec><sec id="pbc26772-sec-0310"><title>Free Paper Session: All ‐ Clinical</title><sec id="pbc26772-sec-0320"><label>O-018</label><title>Delayed Intensification (DI) Enhances Continuous Complete Remission (CCR) Rates for Patients with B‐ALL when Combined with Intravenous Methotrexate: Childrens Oncology Group Study (COG) POG 9904/9905</title><p><underline underline-style="single">N. Winick</underline><sup>1</sup>, P. Martin<sup>2</sup>, M. Devidas<sup>3</sup>, M. Borowitz<sup>4</sup>, P. Bowman<sup>5</sup>, E. Larsen<sup>6</sup>, J. Pullen<sup>7</sup>, S. Hunger<sup>8</sup>, W. Carroll<sup>9</sup>, B. Camitta<sup>10</sup></p><p><italic><sup>1</sup>University of Texas Southwestern Medical Center, Pediatrics, Dallas, USA; <sup>2</sup>Duke University, Pediatrics, Durham, USA; <sup>3</sup>University of Florida, Biostatistics, Gainesville, USA; <sup>4</sup>Johns Hopkins University/Sidney Kimmel Cancer Center, Pathology, Baltimore, USA; <sup>5</sup>University of North Texas Health Science Center, Pediatrics, Ft Worth, USA; <sup>6</sup>Maine Children's Cancer Program, Pediatrics, Scarborough, USA; <sup>7</sup>University of Mississippi Medical Center, Pediatrics, Jackson, USA; <sup>8</sup>Childrens Hospital of Philadelphia, Pediatrics, Philadelphia, USA; <sup>9</sup>Laura and Isaac Perlmutter Cancer Center at New York University Langone, Pediatrics, New York, USA; <sup>10</sup>Childrens Hospital of Wisconsin, Pediatrics, Milwaukee, USA</italic></p><p><bold>Background/Objectives</bold>: Legacy POG 9904 and 9905 trials (2000‐05) assessed the impact of DI on outcome for low (LR), standard (SR) and a subset of NCI high risk (HR) pts, treated with therapy that included six courses of IV MTX (1 gm/m2/24 hrs).</p><p><bold>Design/Methods</bold>: NCISR patients received a dexamethasone‐based 3‐drug and NCIHR pts a prednisone‐based 4‐drug induction. Post‐induction, all NCISR pts except those with trisomy of chromosomes 4+10 and NCIHR pts who met refined age and WBC criteria (excluding those with t(9;22), t(4;11), or CNS3) were eligible to participate in the DI randomization. Consolidation included 6 courses of IV MTX with leucovorin rescue with randomization to +/‐ DI after the 3<sup>rd</sup> IV MTX course (week 16). DI included: weekly vincristine and daunomycin weeks 16‐18 with daily dexamethasone 6 mg/m2, PEG asparaginase week 16 and intrathecal MTX weeks 16, 20, 21, Cyclophosphamide week 20, subcutaneous Ara‐C daily x 4, weeks 20 and 21, and 6‐thioguanine weeks 21‐22. End induction minimal residual disease (MRD) was measured but not used to alter therapy.</p><p><bold>Results</bold>: Administration of DI improved 10‐year CCR from 75.5 +/‐ 2.5% (n=707) to 81.8 +/‐ 2.2% (n=689; p=0.0016), but did not have a significant effect on overall survival (OS): no DI 10‐year OS 90.9 +/‐ 1.7% versus 91.4 +/‐ 1.6% (p=0.2518) without DI. MRD was highly predictive of outcome with 10 yr CCRs of 87.7 + 2.2 and 82.1 + 2.5% among the MRD<0.01% patients with/without DI and 54.3 + 8 and 44 + 8% for the MRD≥0.01% patients with/without DI (p < 0.001).</p><p><bold>Conclusions</bold>: A delayed intensification phase enhances the CCR rate for a broad population of patients with B‐ALL including those with and without end induction MRD at < 0.01%, but does not impact OS. Expected EFS rates obtained in this study are lower than obtained with more contemporary trials.</p></sec><sec id="pbc26772-sec-0330"><label>O-019</label><title>Substitution with Cyclophosphamide and Etoposide does not Improve Outcome for Children and Young Adults with Very High Risk B‐Lymphoblastic Leukemia: Children's Oncology Group Study AALL1131</title><p><underline underline-style="single">M. Burke</underline><sup>1</sup>, W. Salzer<sup>2</sup>, S. Chen<sup>3</sup>, M. Devidas<sup>3</sup>, L. Gore<sup>4</sup>, J. Hilden<sup>4</sup>, E. Larsen<sup>5</sup>, E. Raetz<sup>6</sup>, N. Winick<sup>7</sup>, W. Carroll<sup>8</sup>, S. Hunger<sup>9</sup>, M. Loh<sup>10</sup></p><p><italic><sup>1</sup>Children's Hospital of Wisconsin, Pediatrics, Milwaukee, USA; <sup>2</sup>U.S. Army Medical Research and Materiel Command, Pediatrics, Fort Detrick, USA; <sup>3</sup>University of Florida, Biostatistics, Gainesville, USA; <sup>4</sup>Children's Hospital of Colorado, Pediatrics, Aurora, USA; <sup>5</sup>Maine Children's Cancer Program, Pediatrics, Scarborough, USA; <sup>6</sup>Primary Children's Hospital, Pediatrics, Salt lake City, USA; <sup>7</sup>UT Southwestern, Pediatrics, Dallas, USA; <sup>8</sup>New York University, Pediatrics, New York, USA; <sup>9</sup>Children's Hospital of Philadelphia, Pediatrics, Philadelphia, USA; <sup>10</sup>UCSF, Pediatrics, San Francisco, USA</italic></p><p><bold>Background/Objectives</bold>: With modern chemotherapy regimens, >90% of patients with pediatric acute lymphoblastic leukemia (ALL) are now cured. However, subsets of patients can be identified who remain at very high risk (VHR) of relapse with expected 4‐year DFS <80% and are appropriate candidates for more intensive therapeutic strategies designed to improve survival. AALL1131 aimed to determine, in a randomized fashion, if the substitution with cyclophosphamide + etoposide (CPM/ETOP) (Experimental Arm 1; Exp1) would improve the 4‐year DFS of children, adolescents, and young adults with VHR B‐ALL compared to a modified Berlin‐Frankfurt‐Münster regimen; (Control Arm; CA).</p><p><bold>Design/Methods</bold>: Patients 1‐30 years of age with newly diagnosed VHR B‐ALL were randomized post‐Induction in a 1:2 fashion to CPM/cytarabine/mercaptopurine (CA) or CPM (440mg/m<sup>2</sup> days 1‐5)/ETOP (100mg/m<sup>2</sup> days 1‐5) (Exp 1) during Part 2 of Consolidation (CONS) and Delayed Intensification (DI). Both arms included the same dose and schedule of PEG‐asparaginase on day 43 and vincristine days 43 and 50 of CONS and DI. Prospective interim monitoring rules for efficacy and futility were included where futility would be determined for a one‐sided p‐value ≥ 0.7664.</p><p><bold>Results</bold>: There were no significant differences in Grade 3/4 adverse events or delays in starting Interim Maintenance between the 2 arms (Table 1). Using a data cutoff date of 12/31/2016, 41 total events occurred between arms (CA: 10/228 vs. Exp1: 31/458) resulting in a log‐rank test statistic of ‐1.3904 (one‐sided p‐value = 0.9178). The study was stopped for futility as the interim monitoring boundary was crossed [Hazard Ratio 0.606 (95% CI: 0.297 ‐ 1.237)] (Figure 1) and the VHR arm of AALL1131 was closed February 2017.</p><p><bold>Conclusions</bold>: Substitution of therapy for VHR B‐ALL patients on COG AALL1131 randomized to CPM/ETOP during Part 2 of CONS and DI did not improve EFS.</p></sec><sec id="pbc26772-sec-0340"><label>O-020</label><title>Dasatinib Maintains Outstanding 5‐Year Survival Outcomes in Children with PH+ ALL, but does not Prevent CNS Relapses: Children's Oncology Group (COG) AALL0622 Trial</title><p><underline underline-style="single">W. Slayton</underline><sup>1</sup>, K. Schultz<sup>2</sup>, J. Kairalla<sup>3</sup>, D. Meenakshi<sup>4</sup>, M. Pulsipher<sup>5</sup>, L. Silverman<sup>6</sup>, M. Borowitz<sup>7</sup>, A. Carroll<sup>8</sup>, N. Heerema<sup>9</sup>, J. Gastier‐Foster<sup>10</sup>, S. Mizrahy<sup>11</sup>, B. Wood<sup>12</sup>, T. Merchant<sup>13</sup>, V. Brown<sup>14</sup>, E. Raetz<sup>15</sup>, N. Winick<sup>16</sup>, M. Loh<sup>17</sup>, W. Carroll<sup>18</sup>, S. Hunger<sup>19</sup></p><p><italic><sup>1</sup>University of Florida, Pediatrics, Gainesville‐ FL, USA; <sup>2</sup>BCs Children's Hospital, Pediatrics, Victoria‐ BC, Canada; <sup>3</sup>Children's Oncology Group Statistical Office, Department of Biostatistics, Gainesville‐ FL, USA; <sup>4</sup>Children's Oncology Group Statistical Office, Biostatistics, Gainesville‐ FL, USA; <sup>5</sup>University of California‐ Los Angeles, Pediatrics, Los Angeles‐ CA, USA; <sup>6</sup>Dana Farber Cancer Institute/Harvard, Pediatrics, Boston‐ MA, USA; <sup>7</sup>Johns Hpkins University School of Medicine, Hematopathology, Baltimore‐ MD, USA; <sup>8</sup>University of Alabama, Deparment of Pathology and Genetics, Birmingham‐AB, USA; <sup>9</sup>Ohio State University Wexner Medical Center, Pathology, Columbus‐ OH, USA; <sup>10</sup>Nationwide Children's Hospital, Pathology, Columbus‐ OH, USA; <sup>11</sup>University of Florida, Medicine, Gainesville‐ Fl, USA; <sup>12</sup>University of Washington, Pathology, Seattle‐ WA, USA; <sup>13</sup>St. Jude Research Hospital, Radiation Therapy, Memphis‐ TN, USA; <sup>14</sup>Children's Hospital Hershey, Pediatrics, Hershey‐ PA, USA; <sup>15</sup>University of Utah, Pediatrics, Salt Lake City‐ UT, USA; <sup>16</sup>University of Texas Southwestern Medical Center, Pediatrics, Dallas ‐ TX, USA; <sup>17</sup>University of California‐San Francisco, Pediatrics, San Francisco‐ CA, USA; <sup>18</sup>New York University, NYU Langone Cancer Center, New York‐ NY, USA; <sup>19</sup>University of Pennsylvania, Pediatrics, Philadelphia‐ PA, USA</italic></p><p><bold>Background/Objectives</bold>: Ph<sup>+</sup> ALL patients treated with intensive chemotherapy plus continuous imatinib had a 68% 5‐year event‐free survival (EFS) rate (COG AALL0031). Compared to imatinib, dasatinib has increased potency, better CNS penetration, and activity against imatinib‐resistant clones.</p><p><bold>Design/Methods</bold>: AALL0622 tested AALL0031 chemotherapy plus dasatinib 60 mg/m<sup>2</sup>/day in Ph<sup>+</sup> ALL subjects (1‐30 years). Cohort 1 subjects received dasatinib 2 weeks during each 3‐4 week block; Cohort 2 subjects received dasatinib continuously. Stem cell transplant (SCT) was recommended for subjects with a sibling donor and high‐risk (HR) subjects defined by minimal residual disease at end induction and consolidation. The remaining standard‐risk (SR) subjects were treated with chemotherapy plus dasatinib. While all AALL0031 subjects received cranial radiotherapy (CRT), only CNS3 cases on AALL0622 received CRT.</p><p><bold>Results</bold>: For 60 evaluable subjects, 5‐year EFS and overall survival (OS) rates were 60±7% and 86±5%. 5‐year EFS/OS rates were 61±7%/87±5% for SR subjects (n=48, 19% underwent SCT) and 67±19%/89±13% for HR subjects (n=9, 89% underwent SCT). AALL0622 subjects had a 5‐year cumulative incidence rate of isolated or combined CNS relapse of 10.6±4.1% vs 3.7±2.6% (p = 0.20) for those treated with continuous imatinib on AALL0031. No difference in outcome was seen between AALL0031 subjects receiving imatinib continuously and AALL0622 cohorts 1 and 2 (5‐yr DFS 68±7% for AALL0031 vs 60±7% on AALL0622, p=0.31; 5‐year OS 81±6% vs 86 ± 5%, p = 0.63). <italic>IKZF1</italic> deletion was present in 57% of tested AALL0622 subjects (25/44) and was associated with significantly inferior 5‐year EFS (52±10% vs 82.1±10.1%, p=0.04) and OS (80±8% vs 100%, p=0.04).</p><p><bold>Conclusions</bold>: There was a non‐significant trend toward increased rates of CNS relapse on AALL0622, but similar rates of 5‐year EFS/OS were obtained with intensive chemotherapy, imatinib and CRT (AALL0031) and intensive chemotherapy plus dasatinib without CRT (AALL0622). <italic>IKZF1</italic> deletions were associated with inferior EFS/OS.</p></sec><sec id="pbc26772-sec-0350"><label>O-021</label><title>Osteonecrosis (ON) is Associated with Improved Event Free Survival (EFS) in High‐Risk Acute Lymphoblastic Leukemia (HR‐ALL): Results of Children's Oncology Group (COG) Study AALL0232</title><p><underline underline-style="single">L.A. Mattano</underline><sup>1</sup>, M. Devidas<sup>2</sup>, S. Chen<sup>2</sup>, E. Raetz<sup>3</sup>, M. Loh<sup>4</sup>, N. Winick<sup>5</sup>, S.P. Hunger<sup>6</sup>, W.L. Carroll<sup>7</sup>, E. Larsen<sup>8</sup></p><p><italic><sup>1</sup>HARP Pharma Consulting, Pediatric Hematology/Oncology, Mystic‐ Connecticut, USA; <sup>2</sup>University of Florida, COG Data Center‐ Biostatistics, Gainesville‐ Florida, USA; <sup>3</sup>University of Utah Primary Children's Hospital, Pediatric Hematology/Oncology, Salt Lake City‐ Utah, USA; <sup>4</sup>UCSF Medical Center, Pediatric Hematology/Oncology, San Francisco‐ California, USA; <sup>5</sup>UT Southwestern/Simmons Cancer Center, Pediatric Hematology/Oncology, Dallas‐ Texas, USA; <sup>6</sup>Children's Hospital of Philadelphia, Pediatric Hematology/Oncology, Philadelphia‐ Pennsylvania, USA; <sup>7</sup>NYU Langone Cancer Center, Hassenfeld Children's Center, New York City‐ New York, USA; <sup>8</sup>Maine Children's Cancer Program, Pediatric Oncology, Scarborough‐ Maine, USA</italic></p><p><bold>Background/Objectives</bold>: ON is a well‐characterized ALL therapeutic toxicity attributed to glucocorticoids, asparaginase (ASNase), and methotrexate (MTX) that disproportionately affects adolescents. In CCG‐1961, alternate‐week dexamethasone (AWD; DEX) during double delayed intensification (DI) reduced ON vs continuous DEX (CD) with single DI in rapid early responders (RER) ≥10y.</p><p><bold>Design/Methods</bold>: HR‐ALL patients 1‐30y on AALL0232 (2004‐11) received COG augmented therapy with a 2x2 randomization to: (1) induction (IND) DEX (10 mg/M2 d1‐14) vs prednisone (PDN) (60 mg/M2 d1‐28), and (2) interim maintenance (IM) high‐dose MTX (HD‐MTX) vs escalating‐dose MTX/asparaginase (eMTX/ASNase). RER received single, and slow early responders (SER) double, IM/DI. Initially, all received monthly DEX maintenance (MTC) pulses, patients ≥13y received DI AWD, and patients ≤12y received DI CD. There were 2 ON‐related amendments: after 10/2006 all patients ≥10y received DI AWD; after 6/2008 all patients ≥10y were assigned to IND PDN, and all patients received DI AWD and MTC PDN pulses.</p><p><bold>Results</bold>: ON was confirmed in 315/2817 patients. Cumulative 5y incidence (CI) increased with age: 1‐9y 2.6%, 10‐12y 15.3% (AWD 11.7% vs CD 28.0%; P=0.0085), ≥13y 19.7%, ≥21y 31.6%. Among randomized RER patients ≥13y, ON CI differed by glucocorticoid (DEX 26.2% vs PDN 15.2%; P=0.0016) but not MTX assignment (HD‐MTX 19.9% vs eMTX/ASNase 21.4%; P=0.66). Among randomized SER patients ≥13y, CI was 22.0% with no difference by regimen. Five‐year EFS was significantly higher among randomized patients ≥10y with vs without ON (88.5% vs 72.9%; P<0.0001); this finding was present in different age ranges (≥10y, ≥13y, ≥16y) and RER/SER subsets within each, especially in the ≥13y RER (92.9% vs 80.6%; P=0.0046) and SER (74.8% vs 41.5%; P<0.0001) cohorts. Across groups ASNase allergy was significantly associated with reduced ON risk (≥10y: HR 0.43; P=0.0013).</p><p><bold>Conclusions</bold>: Patients who develop ON have significantly increased EFS, suggesting host differences that increase sensitivity to develop ON and render ALL cells more chemo‐responsive.</p></sec><sec id="pbc26772-sec-0360"><label>O-022</label><title>Outcome of B‐ALL Treated with A Risk‐Stratified and Response‐Adapted Protocol: Interim Analysis of A Single‐Institution Pilot Study for A Multicenter Collaborative Protocol from India</title><p><underline underline-style="single">G. Narula</underline><sup>1</sup>, B. Arora<sup>1</sup>, P. Subramanian<sup>2</sup>, P. Tembhare<sup>2</sup>, N. Patkar<sup>2</sup>, D. Shetty<sup>3</sup>, M. Prasad<sup>1</sup>, S. Gujral<sup>2</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Center, Medical Oncology Pediatric Division, Mumbai, India; <sup>2</sup>Tata Memorial Center, Hematopathology, Mumbai, India; <sup>3</sup>Tata Memorial Center, Cytogenetics, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Childhood ALL in developed countries has OS exceeding 95%, but remains challenging in developing countries. Since 2012, multiple centers in India have collaborated to devise a protocol for uniform management of ALL using comprehensive risk‐stratification and response‐based adaption. The standard arms of this protocol were piloted in our institution since 2013, and an interim analysis was done at 3‐year time‐point.</p><p><bold>Design/Methods</bold>: Prospectively maintained records of B‐ALL patients treated on a uniform strategy from Feb‐2013 to Dec‐2015 were analyzed. Risk‐stratification was done based on NCI criteria, further adapted by day‐8 prednisolone response (D‐8PR), and flowcytometric day‐35 bone‐marrow MRD (D35BM‐MRD). Data was analyzed by descriptive analytical tools and Kaplan‐Meier method on SPSS‐v24™.</p><p><bold>Results</bold>: Seven‐hundred and twenty‐six children with B‐ALL were registered in the study period. Thirteen were excluded due to ambiguous classification or protocol deviation. Median age was 5 yrs (0.5‐15) and median WBC‐10x10<sup>3</sup>/cmm (0.1‐543x10<sup>3</sup>/cmm). Bulky disease was seen in 253(35%), tumor lysis in 297(42%), CSF involvement in 34(5%), and Hypodiploidy in 100(14%). Cytogenetic abnormalities were trisomies in 257(36%), ETV6‐RUNX1 101(14%), t(1:19) 50(7%), BCR‐ABL 39(6%), MLL‐rearrangements 15(2%), with 215(34%) no abnormalities. Poor D‐8PR occurred in 98(14%). The initial risk‐stratification was Standard Risk (SR)‐219(31%), Intermediate (IR)‐267(37%), and High (HR)‐227(32%). Of 666 evaluable by D35BM‐MRD, 147(22%) were positive. Projected 3‐year OS was 90.4±1.4% with median follow‐up of 23 months (range, 1‐48), while EFS was 70.7±2.3%. 70% of mortality occurred in intensive phases of treatment, and 86% of all events in non‐SR arms. Three‐year OS for SR, IR and HR were 95.1±2%, 89.5±2.3% and 87.2±2.6% (p<0.01), while EFS was 86±3.2%, 63.6±4.7%, and 62.2±4.1% (p<0.001) respectively. D35BM‐MRD status predicted EFS‐68.2±4.8% in positive versus 76.7±2.5% in negative cases (p<0.001).</p><p><bold>Conclusions</bold>: A risk‐stratified response‐adapted protocol helped improve outcomes for childhood B‐ALL over historical results. D35BM‐MRD positivity predicted poorer EFS. Early mortality and relapse in non‐SR B‐ALL remain the biggest challenges.</p></sec><sec id="pbc26772-sec-0370"><label>O-023</label><title>Polymorphisms in the Thymidylate Synthetase (TYMS) Gene in Relation to Methotrexate‐Induced Oral Mucositis in Children with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">N. Oosterom</underline><sup>1</sup>, M. Berrevoets<sup>2</sup>, M. Den Hoed<sup>1</sup>, S. Pluijm<sup>1</sup>, R. Pieters<sup>1</sup>, R. De Jonge<sup>3</sup>, W. Tissing<sup>4</sup>, M. Van den Heuvel‐Eibrink<sup>1</sup>, S. Heil<sup>2</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Department of Pediatric Oncology, Utrecht, The Netherlands; <sup>2</sup>Erasmus Medical Center, Department of Clinical Chemistry, Rotterdam, The Netherlands; <sup>3</sup>VU Medical Center, Department of Clinical Chemistry, Amsterdam, The Netherlands; <sup>4</sup>Beatrix Children's Hospital‐ University of Groningen‐ University Medical Center Groningen, Department of Pediatric Oncology, Groningen, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Methotrexate (MTX) is a potent drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). MTX is cytotoxic as it impairs DNA and RNA synthesis by inhibiting the enzymes dihydrofolate reductase (<italic>DHFTR</italic>) and thymidylate synthase (<italic>TYMS</italic>). Twenty percent of patients with ALL receiving high‐dose MTX regimens develop MTX‐induced oral mucositis. The association between MTX‐induced toxicity and genetic variants within the Thymidylate Synthase <italic>(TYMS)</italic> gene has been studied, but results are contradictory and inconsistent. We studied the association between three previously described variants within the <italic>TYMS</italic> gene in relation to MTX‐induced oral mucositis in a prospective cohort of Dutch children with ALL.</p><p><bold>Design/Methods</bold>: We analyzed a 28‐base pair repeat (<italic>2R3R; rs34743033</italic>), a single nucleotide polymorphism present within the 28‐base pair repeat on the 3R allele (3R<italic>G>C; rs2853542</italic>) and a 6‐base pair deletion (<italic>TTAAAG; rs151264360)</italic> within the <italic>TYMS</italic> gene in germline DNA of 117 pediatric ALL patients treated with 5 gram m<sup>‐2</sup> MTX (DCOG ALL‐10 protocol). Clinically relevant oral mucositis was defined as grade ≥ 3 according to the National Cancer Institute Criteria. Data were analyzed for the individual <italic>rs3474303 (2R3R) and rs151264360 (6bp deletion)</italic> polymorphisms; <italic>rs2853542 (3RG>C)</italic> was combined with <italic>rs3474303 (2R3R)</italic> and analyzed according to predicted expression levels of TYMS: low expression (2R2R, 2R3RC, 3RC3RC) versus median expression (2R3RG, 3RC3RG) and high expression (3RG3RG).</p><p><bold>Results</bold>: <italic>rs3474303 (2R3R) and rs151264360 (6bp deletion)</italic> polymorphisms were not associated with the development of MTX‐induced oral mucositis (OR 2.49 [0.68‐9.20] and OR 0.79 [0.20‐3.10] respectively). Patients carrying the low expression <italic>TYMS</italic> genotype had a trend towards developing MTX‐induced oral mucositis, although not significantly (OR 2.42 [0.86 – 6.80], p‐value 0.09).</p><p><bold>Conclusions</bold>: We could not confirm the association between TYMS polymorphisms and MTX‐induced mucositis. However, the strong effect size suggests a possible role of the low expression genotype in MTX‐induced mucositis. This needs to be addressed in a meta‐analysis.</p></sec></sec><sec id="pbc26772-sec-0380"><title>Free Paper Session: Late Effects</title><sec id="pbc26772-sec-0390"><label>O-024</label><title>Dose Volume Parameters of the Radiation Dose Distribution in Cerebral Arteries are Highly Predictive of Long Term Risk of Stroke after Childhood Cancer Radiotherapy</title><p><underline underline-style="single">F. de Vathaire</underline><sup>1</sup>, C. El‐Fayech<sup>2</sup>, N. Haddy<sup>1</sup>, R. Sètchéou Allodji<sup>1</sup>, C. Veres<sup>1</sup>, D. Llanas<sup>1</sup>, A. Jackson<sup>1</sup>, S. Vincent<sup>1</sup>, C. Rubino<sup>1</sup>, H. Pacquement<sup>3</sup>, C. Teinturier<sup>4</sup>, B. Fresneau<sup>2</sup>, G. Vu‐Bezin<sup>1</sup>, I. Diallo<sup>1</sup></p><p><italic><sup>1</sup>Gustave Roussy, INSERM Unit 1018 ‐ Team Radiation and Cancer, Villejuif, France; <sup>2</sup>Gustave Roussy, Pediatry, Villejuif, France; <sup>3</sup>Institut Curie, Pediatry, Paris, France; <sup>4</sup>Hopital Kremlin Bicêtre, Paediatric Endocrinology, Le Kremlin Bicêtre, France</italic></p><p><bold>Background/Objectives</bold>: Stroke is one of the major potential long term iatrogenic risk of childhood cancer radiation therapy. Nevertheless, present knowledge is insufficient to predict the long‐term risk of stroke following radiation therapy as the dose‐response to fractionated high doses of radiation to the brain is not known.</p><p><bold>Design/Methods</bold>: We carried out an analysis in a cohort 7030 5‐years survivors of a solid childhood cancer treated in France before 2001, of whom 4150 treated by radiotherapy, and followed 20 years in average, by self‐questionnaire and cross‐linkage with French National Hospital and Medical Insurance Database (SNIIR‐AM). During the follow‐up, 139 patients developed a permanent stroke which could be validated. Each of them was matched to 8 controls of the same cohort on gender, age at childhood cancer and follow‐up duration. Radiation dose distribution in cerebral arteries was individually reconstructed for each case and controls treated by radiotherapy using medical records and anthropometric phantoms.</p><p><bold>Results</bold>: As compared to children not treated by radiation therapy, and when controlling for chemotherapy, children who received less than 1 Gy, in average, to the cerebral arteries had a 1.8 (95%CI: 0.80‐3.9) times higher risk of stroke, whereas those who received more than 20 Gy to cerebral arteries had a risk 26.0 (10.0‐67.8) times higher. These risk factors were higher for ischemic strokes than for haemorrhagic ones.</p><p>To take into account dose‐volume parameters allowed to improve risk predictions. High radiation doses strongly increased stroke risk. As an example, to received during childhood 30Gy or more to only 1 to 5% of the cerebral arteries volume increased the long term risk of stroke by 2.6 (1.3‐5.5).</p><p><bold>Conclusions</bold>: This study confirms that average radiation dose to the cerebral arteries is not the best parameter for predicting long term risk of stroke, and that classical dose‐volume parameters may be used for such predictions.</p></sec><sec id="pbc26772-sec-0400"><label>O-025</label><title>Long‐Term Efficacy of Thyroid‐Stimulating‐Hormone (TSH)‐Suppression during Radiotherapy (RT) for Medulloblastoma (MBL) and Hodgkin Lymphoma (HL)</title><p><underline underline-style="single">M. Massimino</underline><sup>1</sup>, L. Gandola<sup>2</sup>, M. Podda<sup>1</sup>, F. Spreafio<sup>1</sup>, V. Biassoni<sup>1</sup>, E. Pecori<sup>1</sup>, E. Schiavello<sup>1</sup>, A. Indini<sup>1</sup>, B. Diletto<sup>1</sup>, M. Casanova<sup>1</sup>, A. Ferrari<sup>1</sup>, R. Luksch<sup>1</sup>, C. Meazza<sup>1</sup>, N. Puma<sup>1</sup>, S. Chiaravalli<sup>1</sup>, E. Seregni<sup>1</sup>, L. Bergamaschi<sup>1</sup>, F. Pallotti<sup>1</sup>, C. Morosi<sup>1</sup>, M. Terenziani<sup>1</sup></p><p><italic><sup>1</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatrics, Milano, Italy; <sup>2</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Radiotherapy, Milano, Italy</italic></p><p><bold>Background/Objectives</bold>: Hypothyroidism is very frequent after neck/mediastinum RT, whose effects also depend on circulating TSH, a sensitive marker of thyroid damage. In 1998 we evaluated the protective effect of pharmacological TSH‐suppression during craniospinal‐RT for MBL and neck/mediastinum RT for HL, and relative preliminary results at medium 7/8 years were promising. Our aim is updating a definitive message to our community.</p><p><bold>Design/Methods</bold>: Children scheduled for craniospinal‐RT for MBL or RT for HL underwent thyroid ultrasound and FT3, FT4, TSH evaluation at beginning/end of RT. From 14 days before and up to the end of RT, patients received L‐thyroxine; every 3 days, TSH‐suppression was checked to ensure TSH <0.3 mM/ml. Blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was defined as TSH over normal range.</p><p><bold>Results</bold>: 25 MBL and 14 HL patients had a median follow‐up of 175/185 months of their thyroid status, respectively. At RT end we divided patients according to TSH either ˂0.3 mM/ml or ≥ 0.3 throughout their radiation treatment (representing the cohorts of TSH‐suppression or not, respectively). Though numerically small, the cohorts were well matched (gender/age/disease stage/chemotherapy courses/thyroid bed RT/duration of follow‐up). Hypothyroidism‐free survival rates were significantly different after doubling the follow‐up of the previous publications. In MBL group it was 62.5% for the TSH‐suppression cohort and 20% for the non TSH‐suppression cohort (P=0.02), respectively; for the HL group, 75% and 0% (P=0.0009), respectively. The appearance of colloidal cysts/solid nodules did not differ in the two groups.</p><p><bold>Conclusions</bold>: Thyroid dysfunction may develop from a few months to years after RT end. In children with lengthy anti‐neoplastic treatments, endocrine disorders have a negative effect on growth and development into adulthood. We showed how hypothyroidism can be possibly easily and cheaply prevented in the long‐term in two populations at great risk of late‐effects after RT.</p></sec><sec id="pbc26772-sec-0410"><label>O-026</label><title>Impact of Ovarian Transposition on Ovarian Function among Long‐Term Survivors of Childhood Hodgkin Lymphoma: A Report from the ST. Jude Lifetime Cohort Study</title><p><underline underline-style="single">I. Fernandez‐Pineda</underline><sup>1</sup>, A.M. Davidoff<sup>1</sup>, L. Lu<sup>2</sup>, B.N. Rao<sup>1</sup>, C.L. Wilson<sup>2</sup>, D.K. Srivastava<sup>3</sup>, J.L. Klosky<sup>4</sup>, M.L. Metzger<sup>5</sup>, M.J. Krasin<sup>6</sup>, K.K. Ness<sup>2</sup>, C.H. Pui<sup>5</sup>, L.L. Robison<sup>2</sup>, M.M. Hudson<sup>2</sup>, C.A. Sklar<sup>7</sup>, D.M. Green<sup>2</sup>, W. Chemaitilly<sup>8</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Department of Surgery, Memphis, USA; <sup>2</sup>St Jude Children's Research Hospital, Department of Epidemiology & Cancer Control, Memphis, USA; <sup>3</sup>St Jude Children's Research Hospital, Department of Biostatistics, Memphis, USA; <sup>4</sup>St Jude Children's Research Hospital, Department of Psychology, Memphis, USA; <sup>5</sup>St Jude Children's Research Hospital, Department of Oncology, Memphis, USA; <sup>6</sup>St Jude Children's Research Hospital, Department of Radiation Oncology, Memphis, USA; <sup>7</sup>Memorial Sloan Kettering Cancer Center, Department of Epidemiology & Endocrinology, New York, USA; <sup>8</sup>St Jude Children's Research Hospital, Department of Endocrinology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Data regarding the efficacy of ovarian transposition (OT) to preserve ovarian function among childhood cancer survivors are limited. We aimed to determine the effect of OT on ovarian function among long‐term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy.</p><p><bold>Design/Methods</bold>: Female participants in the St. Jude Lifetime Cohort Study (SJLIFE) (10+ years from diagnosis, age 18+ years) treated with pelvic radiotherapy for HL were clinically evaluated for premature menopause (PM). Multivariable logistic regression was used to study associations between demographic and treatment‐related risk factors as well as OT and PM. Survivors with a history of surgical menopause or bilateral oophorectomy before age 40 years were excluded.</p><p><bold>Results</bold>: Of 184 eligible females with HL, 158 (86%) were treated with pelvic radiotherapy. Of these, 84 (53%) participated in SJLIFE including 45 who underwent OT before pelvic radiotherapy. Median age was 16 years (range 4‐22) at HL diagnosis and 38 years (range 25‐60) at study. Pelvic radiotherapy > 1,500 cGy (HR = 5.54, 95% CI = 1.69 to 18.19; <italic>P=</italic> 0.005) and cumulative cyclophosphamide equivalent dose > 12,000 mg/m<sup>2</sup> (HR = 4.71, 95% CI =2.04 to 10.86; <italic>P</italic><.001) were associated with PM. There was no significant association between OT and occurrence of PM (HR = 1.21, 95% CI = 0.42 to 3.49; p = 0.720). Among women with PM, median age at menopause was not significantly different in patients with (25 years; range, 13‐38.5) or without (21.5 years; range, 14‐37) (<italic>P</italic>= 0.530) OT.</p><p><bold>Conclusions</bold>: OT did not seem to modify the risk of PM in this historic cohort of long‐term survivors of HL treated with gonadotoxic therapy. Further research in younger cohorts is needed given continued improvements in radiotherapy delivery techniques. Modern fertility preservation modalities such as mature oocyte cryopreservation should be offered to patients at risk whenever feasible.</p></sec><sec id="pbc26772-sec-0420"><label>O-027</label><title>Second and Subsequent Malignant Neoplasms after Cancer in Childhood in Finland: A Population‐Based Registry Study</title><p><underline underline-style="single">L. Madanat‐Harjuoja</underline><sup>1,2</sup>, J. Pitkäniemi<sup>2</sup>, M. Rantanen<sup>2</sup>, N. Malila<sup>2</sup>, P.M. Lähteenmäki<sup>3</sup>, K. Vettenranta<sup>4</sup></p><p><italic><sup>1</sup>HUCH Children's Hospital, Pediatric Oncology, Helsinki, Finland; <sup>2</sup>Finnish Cancer Registry, Childhood Cancer, Helsinki, Finland; <sup>3</sup>Turku University Hospital, Department of Pediatrics, Helsinki, Finland; <sup>4</sup>Children's Hospital and Helsinki University Central Hospitals, Division of pediatric hemato‐oncology and stem cell transplantation, Helsinki, Finland</italic></p><p><bold>Background/Objectives</bold>: Our aim was to evaluate the relative risk of second malignant neoplasms (SMNs) among survivors of childhood cancer (diagnosed under age 15) and investigate whether modern treatment regimens have resulted in reductions in the occurrence of second malignant neoplasms.</p><p><bold>Design/Methods</bold>: Childhood cancer patients and their second malignant neoplasms diagnosed between 1953 and 2007 were identified from the Finnish Cancer Registry. Risk of second malignancy was evaluated using standardized incidence ratios (SIRs). The effect of temporal characteristics including diagnostic era and length of follow‐up and disease related characteristics were assessed.</p><p><bold>Results</bold>: We observed 372 subsequent malignancies among 7696 survivors with 112,809 person‐years of follow up. The relative risk of developing a second malignancy was nearly five times higher than expected (SIR 4.83, 95% CI, 4.35‐5.34). SIRs were equal in both genders (p=0.9). The risk of SMNs stayed elevated in patients treated in the most modern eras with SIRs of 8.99 (95% CI 5.86‐13.8). SIRs were highest within one year after the primary cancer (SIR 11.2, 95% CI, 6.15‐18.4) and decreased linearly until reaching the population cancer risk after 50 years of follow‐up.</p><p><bold>Conclusions</bold>: Childhood cancer survivors are at elevated risk of SMNs. This elevated risk applies also to those diagnosed in the more recent eras and does not reach a plateau during follow‐up of up to 50 years. Patients should be encouraged to take part in cancer screening programs and avoid exposure to carcinogens such as tobacco and UV‐radiation.</p></sec><sec id="pbc26772-sec-0430"><label>O-028</label><title>Mental Healthcare use and Severe Psychiatric Diagnoses in Adult Survivors of Childhood Cancer: A Population‐Based Study Using Health Services Data</title><p><underline underline-style="single">S. Gupta</underline><sup>1</sup>, A. Nachman<sup>2</sup>, P. Kurdyak<sup>3</sup>, R. Sutradhar<sup>4</sup>, J. Pole<sup>5</sup>, P. Nathan<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Haematology/Oncology, Toronto, Canada; <sup>2</sup>University of Toronto, Institute of Medical Science, Toronto, Canada; <sup>3</sup>Institute for Clinical Evaluative Sciences, Mental Health & Addictions Research Program, Toronto, Canada; <sup>4</sup>Institute for Clinical Evaluative Sciences, Cancer Research Program, Toronto, Canada; <sup>5</sup>Pediatric Oncology Group of Ontario, POGO Research Unit, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Though physical late effects in childhood cancer survivors are well‐documented, risks for adverse mental health outcomes are less clear; existing evidence is contradictory. Health services data offer an objective method to measure population‐based mental health outcomes.</p><p><bold>Design/Methods</bold>: Using a provincial registry with detailed disease, treatment, and outcome data, we assembled a cohort of all five‐year childhood cancer survivors diagnosed <18 years and treated in an Ontario pediatric cancer Centre between 1987‐2008. Patients were linked to population‐based healthcare data capturing inpatient, outpatient, and emergency department (ED) visits. The primary outcome was the rate of mental healthcare visits (primary care, psychiatrist, ED or hospital). Secondary outcomes included time to a severe mental health event (ED visit, hospitalization, suicide) both overall and by psychiatric diagnostic categories. Outcomes were compared between survivors and matched controls using recurrent event and survival analyses, and predictors of adverse outcomes modeled.</p><p><bold>Results</bold>: When compared to 20,269 controls, 4,117 survivors had a significantly higher rate of mental health visits [47.1 vs. 36.1 visits/100 person‐years; adjusted relative rate (RR) 1.3, 95th% confidence interval (CI) 1.2‐1.5]. Higher rates were associated with female gender (RR 1.4, CI 1.1‐1.7; p=0.008) and adolescent age at diagnosis (RR 2.0, CI 1.3‐3.0; p=0.004). Cancer type, treatment intensity or treatments targeting the central nervous system were not significant predictors. The hazard of a severe mental health event did not differ between survivors and controls. Though rare in both groups, survivors were at increased risk of a severe event due to a psychotic disorder (HR 1.8, CI 1.1‐2.8; p<0.05).</p><p><bold>Conclusions</bold>: Childhood cancer survivors experience higher rates of mental health visits than the general population, but are no more likely to experience a severe mental health event. Their risk is not attributable to a specific diagnosis or aspect of treatment. An increased risk of severe psychotic disorders requires confirmation in other cohorts.</p></sec><sec id="pbc26772-sec-0440"><label>O-029</label><title>Role of Ace Inhibitors in Anthracycline‐Induced Cardiotoxicity: A Randomized Double Blind Placebo Controlled Trial</title><p><underline underline-style="single">V. Gupta</underline><sup>1</sup>, S.K. Singh<sup>1</sup>, V. Agrawal<sup>2</sup>, T.B. Singh<sup>3</sup></p><p><italic><sup>1</sup>Institute of Medical Sciences‐ Banaras Hindu University, Pediatrics, Varanasi, India; <sup>2</sup>Institute of Medical Sciences‐ Banaras Hindu University, Cardiology, Varanasi, India; <sup>3</sup>Institute of Medical Sciences‐ Banaras Hindu University, Biostatistics, Varanasi, India</italic></p><p><bold>Background/Objectives</bold>: Anthracyclines cause dose‐related cardiotoxicity in children. Several measures including drugs have been tried to reduce cardiac toxicity. Lack of randomized trials prompted this study to assess role of ACE inhibitor (enalapril) in anthracycline induced cardiotoxicity in children with hematological malignancies.</p><p><bold>Design/Methods</bold>: Randomized double blind placebo controlled trial was conducted in University teaching hospital over 26 months (Trial no. CTRI/2015/09/006174). 84 patients with leukemia (41) and lymphoma (43) were randomized to receive either enalapril [group A (44)] or placebo [group B (40)] for 6 months. Patients received anthracyclines (doxorubicin and/or daunorubicin) (cumulative dose >200 mg/m<sup>2</sup>) as per protocol. Cardiac biomarkers (cTnI, ProBNP, CKMB) and left ventricular ejection fraction (LVEF) were assessed at base line and after 6 months. Primary outcome was decrease in left ventricular ejection fraction (decrease ≥20% significant). Secondary outcomes were changes in cardiac biomarkers, development of heart failure, arrhythmias and side effects such as dizziness and hypotension.</p><p><bold>Results</bold>: Cardiac biomarkers increased at 6 months in all patients with more increase in group B. It was significant for pro BNP (49.60 ± 35.97 vs 98.60 ± 54.24, p value <0.001) and cTnI (0.01 ± 0.0007 vs 0.011 ± 0.0026, p value 0.035) and not significant for CKMB (1.08 ± 0.18 vs 1.21 ± 0.44, p value 0.079). 9.1% patients in group A showed increase in ProBNP level ≥100 pg/ml compared to 37.5% patients in Group B (p=0.001). LVEF decreased in both groups, more in group B (62.25 ± 5.49 vs 56.15 ± 4.79, p = 0.04). ≥20% decrease in LVEF was seen in 3 patients in group B and none in group A (p value 0.04). LVEF remained ≥50% in both groups at 6 months. No patient developed heart failure.</p><p><bold>Conclusions</bold>: Enalapril has a role in reducing acute cardiac toxicity after anthracycline administration. Further studies are needed to assess long term protection.</p></sec></sec><sec id="pbc26772-sec-0450"><title>Free Paper Session: Myeloid Leukemia and Transplant</title><sec id="pbc26772-sec-0460"><label>O-030</label><title>Characteristics and Outcome of Myeloid Sarcoma in Children at A Tertiary Care Centre from India: A Study of 126 Patients</title><p><underline underline-style="single">A. Kumar</underline><sup>1</sup>, A. Tyagi<sup>1</sup>, R. Pramanik<sup>1</sup>, A. Batra<sup>1</sup>, A. Chopra<sup>2</sup>, S. Bakhshi<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Department of Medical Oncology‐ 2nd Floor‐ BRA IRCH, New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences, Department of Lab Oncology‐ 4th Floor‐ BRA IRCH, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Myeloid sarcoma (MS) is a rare entity and it can precede or appear concomitantly with acute myeloid leukemia. Conventionally, it has been treated on lines of acute myeloid leukemia (AML). However, paucity of data in larger number of patients has led to difficulty in understanding its nature and management.</p><p><bold>Design/Methods</bold>: Present study was undertaken among children with MS presenting at a large tertiary care center in India from June, 2008 to Feb, 2016. All patients were treated on a uniform chemotherapy treatment protocol; radiotherapy was not used during the management.</p><p><bold>Results</bold>: Among 570 patients of AML (non–promyelocytic) attending our pediatric oncology clinic, 126 patients (22.1%) had MS at presentation. Median age was 6 years (0.3–18 years) and incidence was more common among males (M: F = 2.4:1). Cytogenetic parameters were available in 100 patients; good risk cytogenetics were found in 54% patients; this was significantly higher than non MS associated cohort (p=0.0001) wherein the good risk cytogenetics was observed in 28.2%of subjects. All 54 patients in good risk group of the MS cohort had t(8:21). At median follow‐up of 21 months, median event free survival was 19.4 months in MS group versus 11.1 months in non MS associated AML (p=0.003). Overall survival was 37.2 months versus 16.2 months in MS group versus non MS group, respectively (p=0.0009).</p><p><bold>Conclusions</bold>: MS are present in about one‐fifth of AML patients; this is distinctly more than the worldwide prevalence. The cohort with MS had a higher proportion of good risk cytogenetics with a striking association with t(8:21). Presently adopted AML like treatment strategy in such patients has resulted in favorable outcome in comparison to the non MS associated cohort.</p></sec><sec id="pbc26772-sec-0470"><label>O-031</label><title>Arsenic Trioxide and All‐Trans‐Retinoic Acid Based Trial May Eliminate the Need for Cytarabine In Pediatric Acute Promyelocytic Leukemia: Results from CCAPL2010 (NCT01191541)</title><p><underline underline-style="single">L. Zhang</underline><sup>1</sup>, Z. xiaofan<sup>1</sup>, Z. Yao Zou<sup>1</sup>, C. Yumei<sup>1</sup>, G. Ye<sup>1</sup>, Y. Wenyu<sup>1</sup>, C. xiaojuan<sup>1</sup>, W. shuchun<sup>1</sup>, L. xiaoming<sup>1</sup>, R. min<sup>1</sup>, Z. jiayuan<sup>1</sup>, L. tianfeng<sup>1</sup>, L. fang<sup>1</sup>, Q. benquan<sup>1</sup></p><p><italic><sup>1</sup>State Key Laboratory of Experimental Hematology‐ Institute of Hematology and Blo, Department of Pediatrics, tianjin, China</italic></p><p><bold>Background/Objectives</bold>: The objective of this study was to evaluate the efficacy and safety of using all‐trans‐retinoic acid (ATRA) and arsenic trioxide (ATO) to treat paediatric patients with newly diagnosed acute promyelocytic leaukemia (APL). Additionly, we assessed whether cytosine arabinoside (Ara‐C) could be omitted in ATO‐ and ATRA‐ based trials.</p><p><bold>Design/Methods</bold>: Patients were assigned to receive ATRA plus ATO for induction followed by idarubicin (IDA) and ATO. Then, patients were randomly assigned to receive 2 courses of daunorubicin (DNR, no Ara‐C group) or DNR+Ara‐C (Ara‐C group) followed by maintenance therapy for 1.5 years.</p><p><bold>Results</bold>: Between May 2010 and December 2016, 66 consecutive pediatric (≤14years old) patients who were genetically confirmed with a new diagnosis of APL were admitted in our hospital. Among 66 patients, 43 were male and 23 were female. All patients achieved complete remission (CR) except one who gave up treatment. During induction therapy, all toxicity events were reversed after appropriate management. No patient died at consolidation, and only one patient relapsed. In addition, there was no difference in outcomes between the two groups.</p><p>After a median follow‐up of 32 months, EFS was 97.0±3.0%, and OS was 100%. No factor impacted relapse or survival in our study. There was no difference in the median arsenic concentrations in plasma, urine, hair, and nail samples between patients in whom arsenic treatment had been ceased for more than 12 months and normal controls.</p><p><bold>Conclusions</bold>: The results of our study indicate that ATO is safe and effective in paediatric APL and that Ara‐C can be omitted, at least when using regimens similar to ours. Our analysis of arsenic levels in the plasma, urine, hair and nails of patients indicated that there was no significant accumulation of arsenic after ATO was discontinued for 12 months.</p></sec><sec id="pbc26772-sec-0480"><label>O-032</label><title>Efficacy and Safety of Nilotinib in Pediatric Patients with Philadelphia Chromosome–Positive (PH+) Chronic Myeloid Leukemia (CML): Results from A PHASE 2 Trial</title><p><underline underline-style="single">N. Hijiya</underline><sup>1</sup>, A. Maschan<sup>2</sup>, C. Rizzari<sup>3</sup>, H. Shimada<sup>4</sup>, C. Dufour<sup>5</sup>, H. Goto<sup>6</sup>, H.J. Kang<sup>7</sup>, T. Guinipero<sup>8</sup>, Z. Karakas<sup>9</sup>, F. Bautista<sup>10</sup>, A. Kheradpour<sup>11</sup>, S. Ducassou<sup>12</sup>, K.H. Yoo<sup>13</sup>, W. Mendes<sup>14</sup>, S. Quenet<sup>15</sup>, S. Hertle<sup>16</sup>, D. Sosothikul<sup>17</sup></p><p><italic><sup>1</sup>Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Hematology/Oncology, Chicago, USA; <sup>2</sup>Dmitrii Rogachev Federal Research Center for Pediatric Hematology‐ Oncology and Immunology, Pediatric Hematology‐ Oncology and Immunology, Moscow, Russia; <sup>3</sup>Pediatric Hematology Oncology Unit‐ University of Milano Bicocca‐ MBBM Foundation, Department of Pediatrics, ASST Monza, Italy; <sup>4</sup>Keio University School of Medicine, Department of Pediatrics, Shinjuku‐ku, Japan; <sup>5</sup>I.R.C.C.S. Istituto Giannina Gaslini, Department of General and Specialized Pediatrics Functional Department Hematology‐Oncology, Genova, Italy; <sup>6</sup>Kanagawa Children's Medical Center, Division of Hemato‐Oncology/Regenerative Medicine, Yokohama, Japan; <sup>7</sup>Seoul National University College of Medicine‐ Seoul National University Children's Hospital, Department of Pediatrics, Seoul, Republic of Korea; <sup>8</sup>Nationwide Children's Hospital, Division of Hematology/ Oncology/ Bone Marrow Transplantation, Columbus, USA; <sup>9</sup>Istanbul University‐ Istanbul Medical Faculty, Department of Pediatric Hematology and Oncology, Istanbul, Turkey; <sup>10</sup>Hospital Niño Jesus, Pediatric Oncology Service, Madrid, Spain; <sup>11</sup>Loma Linda University Cancer Center, Pediatric Hematology/Oncology, Loma Linda, USA; <sup>12</sup>Groupe Hospitalier Pellegrin ‐ Hôpital des Enfants, Pediatric Oncology and Hematology Unit, Bordeaux, France; <sup>13</sup>Samsung Medical Center‐ Sungkyunkwan University School of Medicine, Department of Pediatrics, Seoul, Republic of Korea; <sup>14</sup>Novartis Pharmaceuticals Corporation, Clinical Department, East Hanover, USA; <sup>15</sup>Novartis Pharma AG, Statistical Deartment, Basel, Switzerland; <sup>16</sup>Novartis Pharma AG, GDO Trial Management – Oncology, Basel, Switzerland; <sup>17</sup>Chulalongkorn Hospital, Div. of Hematology/Oncology Department of Pediatrics, Bangkok, Thailand</italic></p><p><bold>Background/Objectives</bold>: This ongoing phase 2 study is evaluating nilotinib in pediatric patients with CML.</p><p><bold>Design/Methods</bold>: Eligible patients (1‐<18y) had CML in chronic or accelerated phase (CP/AP) resistant/intolerant to imatinib/dasatinib, or newly‐diagnosed CML‐CP; no patients with CML‐AP enrolled. Patients were to receive oral nilotinib 230mg/m<sup>2</sup> BID (rounded to nearest 50mg) for 66 28‐day cycles; data from primary analysis (when all patients had completed 12 cycles or discontinued) are reported. Primary endpoint for resistant/intolerant cohort was major molecular response rate (MMR; <italic>BCR‐ABL1</italic> ≤0.1% on International Scale) at 6 cycles; coprimary endpoints for newly‐diagnosed cohort were MMR rate by 12 cycles and complete cytogenetic response (CCyR) rate at 12 cycles.</p><p><bold>Results</bold>: Fifty‐eight patients (resistant/intolerant, n=33; newly‐diagnosed, n=25) enrolled and received nilotinib (median age, 13y for both cohorts; median time on‐treatment, 16 and 15 months, respectively). Results in the resistant/intolerant cohort were: 13/33 patients had MMR at 6 cycles (39.4%; 95% CI, 22.9%‐57.9%); 6/13 had MMR at baseline. Median time to MMR was 2.8 (range, 0‐11.3) months among 19 patients in MMR by the data cutoff. Twenty‐seven patients (81.8%) had CCyR by 12 cycles; 14/27 had CCyR at baseline. One patient progressed to AP/blast crisis after 10.1 months on‐treatment. Results in newly‐diagnosed patients were: rates of MMR by 12 cycles and CCyR at 12 cycles were both 64.0% (16/25; 95% CI, 42.5%‐82.0%). Median time to response was 5.6 months for both MMR and CCyR among 17 and 21 patients with those responses, respectively, by the data cutoff. All patients had ≥1 AE; all‐grade AEs with incidences >30% overall were headache (46.6%), pyrexia (32.8%), and blood bilirubin increased (31.0%). Rates of serious AEs and AE‐related discontinuations (all‐grade) were 13.8% and 15.5%, respectively. No deaths were reported.</p><p><bold>Conclusions</bold>: Nilotinib 230mg/m<sup>2</sup> BID was efficacious in pediatric patients with newly‐diagnosed or resistant/intolerant CML‐CP, with an AE profile comparable to that in adults.</p></sec><sec id="pbc26772-sec-0490"><label>O-033</label><title>Prognostic Biomarkers for the Development of Respiratory Failure Post Allogeneic Hematopoietic Cell Transplantation</title><p>C.M. Rowan<sup>1</sup>, M.W. Geraci<sup>2</sup>, N. Swigonski<sup>1</sup>, <underline underline-style="single">S. Paczesny</underline><sup>1</sup></p><p><italic><sup>1</sup>Indiana University School of Medicine, Pediatrics, Indianapolis, USA; <sup>2</sup>Indiana University School of Medicine, Medicine, Indianapolis, USA</italic></p><p><bold>Background/Objectives</bold>: Currently, there is not a method for predicting respiratory failure in the allogeneic hematopoietic cell transplant (HCT) recipient. Biomarkers may be effective for risk recognition, understanding etiology, and serving as therapeutic targets. The study's aim was to identify prognostic biomarkers for the development of respiratory failure.</p><p><bold>Design/Methods</bold>: This is a single center analysis of an existing cohort from a clinico‐biologic repository. Plasma samples at days 7, 14, 21, and 30 post‐HCT were used to measure four proteins by ELISA: STimulation‐2 (ST2), the IL33 receptor, interleukin 6 (IL6), tumor necrosis factor receptor 1 (TNFR1) and osteopontin (OPN). Data is presented in medians and were compared using Wilcoxon rank sum test. ROC curves were also done for each protein.</p><p><bold>Results</bold>: A total of 122 adult and pediatric allogeneic HCT recipients were included with 24.6% (n=30) developing respiratory failure within 1 year post‐transplant. The median day to respiratory failure was 27.0. The medians of all four proteins were significantly higher in the group that developed respiratory failure at multiple time points: Day 7 ST2 [57.0 vs 24.9, p‐0.003], IL6 [100.0 vs 39.2] p=0.002, TNFR1 [4184.0 vs 2425.6 p=0.02]; Day 14 ST2 [58.5 vs 22.0, p‐0.003], IL6 [91.8 vs 32.5 p=0.001], TNFR15499.2 vs 3121.9 p=0.006], OPN [340.0 vs 277.8, p=0.04]; Day 21 ST2 [50.0 vs 25.0, p<0.0001], IL6 [62.8, 21.0, p=0.006], TNFR1 [5793.0 vs 3314.0 p=0.003], OPN [332.0 vs 220.0, p=0.003]; Day 30 ST2 [40.0 vs 20.0, p<0.0001], IL6 [53.0, 18.1, p=0.006], TNFR1 [5518.0 vs 3024.6 p=0.001], OPN [275.0 vs 185.0, p=0.02]. ROC curves indicate that these proteins allowed for good discrimination for the development of respiratory failure within 45 days of transplant (AUCs: ST2=0.83, TNFR1=0.78, OPN=0.78, and IL6=0.73).</p><p><bold>Conclusions</bold>: ST2, IL6, TNFR1, and OPN were all significantly elevated at multiple time points in those that develop respiratory failure post‐allogeneic HCT.</p></sec><sec id="pbc26772-sec-0500"><label>O-034</label><title>Hepatic Sinusoidal Obstruction Syndrome (SOS) in Children Undergoing Autologous Stem Cell Transplant (ASCT) Following High Dose Chemotherapy (HDCT) ‐ A Single Centre Experience from the UK</title><p><underline underline-style="single">N. Roy Moulik</underline><sup>1</sup>, L. Van Bruggen<sup>1</sup>, I. Johnson<sup>1</sup>, T. Petterson<sup>1</sup>, J. Mycroft<sup>1</sup>, S. Vaidya<sup>1</sup></p><p><italic><sup>1</sup>Royal Marsden Hospital, Paediatric Oncology, Greater London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Hepatic sinusoidal obstruction syndrome (SOS) or veno‐occlusive disease (VOD) is a serious complication of autologous stem cell transplant (ASCT) with historically high mortality rate. Defibrotide has shown proven benefit in its treatment and has a modest role in prevention.We report our experience with SOS in paediatric ASCT.</p><p><bold>Design/Methods</bold>: Case records of 82 consecutive patients undergoing ASCT following HDCT between 2010 and 2017 were reviewed, relevant data were retrieved and analysed using conventional statistics. Defibrotide was used for treatment of all cases of SOS. It was available for prophylaxis of SOS in patients receiving busulfan based conditioning until 2014 due to funding issues.</p><p><bold>Results</bold>: Fourteen of the 82 children (17%) were diagnosed with SOS. The incidence was significantly higher in those receiving busulfan based conditioning (13/42 vs.1/40) (p=0.008).The mean time to diagnosis of SOS was 19±5.6 days following stem cell rescue.Seven of 14 patients had bilirubin <34 micromoles/l and 3 had normal ultrasound. Coagulopathy was noted in 10 cases; 1 child developed multi‐organ involvement. Nine children had mild SOS. Five cases had moderate or severe SOS, of which 4 needed PICU support. Patients with SOS had significantly delayed platelet recovery, higher transfusion requirement and longer hospital stay. The unavailability of defibrotide prophylaxis for 17/42 patients receiving busulfan post‐2014 did not significantly increase the incidence of SOS (6 /17 vs. 7/25; p=0.74). No significant difference in clinical course or severity was observed in 7 children who developed SOS despite defibrotide prophylaxis when compared to the 6 without it. No SOS related mortality was seen in either group.</p><p><bold>Conclusions</bold>: Hepatic SOS was more commonly seen in children receiving busulfan conditioning. Changing practice of not using defibrotide prophylaxis did not seem to increase the incidence or severity of SOS. Overall outcome was excellent with supportive care and treatment with defibrotide.</p></sec><sec id="pbc26772-sec-0510"><label>O-035</label><title>Implementation of A Pediatric Early Warning System in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation in Latin America</title><p><underline underline-style="single">P. Vergara</underline><sup>1</sup>, S. Saez<sup>1</sup>, J. Palma<sup>1</sup>, D. Soberanis<sup>2</sup>, A. Agulnik<sup>3</sup></p><p><italic><sup>1</sup>Hospital Luis Calvo Mackenna, Unidad de Trasplante de Médula Osea, Santiago, Chile; <sup>2</sup>Unidad Nacional de Oncologia Pediatrica, Oncologia, Ciudad de Guatemala, Guatemala; <sup>3</sup>St. Jude Children's Research Hospital, Department of Global Pediatric Medicine, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Patients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk for clinical deterioration due to their immunosuppression and expected complications. Pediatric Early Warning Systems (PEWS) are nursing‐administered clinical acuity tools to aid with early identification of clinical deterioration in hospitalized patients. While these tools are commonly used in hospitals caring for HSCT patients in high‐resource settings, they have not previously been applied to HSCT patients hospitalized in Latin America. The objective of this study is to describe the implementation of PEWS in the HSCT Unit of Luis Calvo Mackenna Hospital (HLCM), a pediatric hospital in Santiago, Chile.</p><p><bold>Design/Methods</bold>: The PEWS used at Boston Children's Hospital, previously validated in HSCT patients, was modified at HLCM by a multidisciplinary team of physicians and nurses from the Oncology, BMT and Pediatric Intensive Care Unit (PICU) to adjust for practice variations between our hospitals. The modified PEWS was initially trialed as a one‐month pilot, and, after adjustments, implemented as a part of clinical practice in the unit. During this period, we analyzed compliance with PEWS documentation, error rates, abnormal (red) scores, and unplanned PICU transfers.</p><p><bold>Results</bold>: A total of 12 nurses, 12 nursing technicians, 3 staff physicians and 6 residents were trained in PEWS. Compliance with PEWS documentation was 89%, with an average of 37 PEWS calculated per day and 3.7% errors. The most common errors were interpretation of heart rate (38%) and oxygen use (36%). During 6 months of data collection, here were a total of 41 red PEWS among 8 patients, 3 of them required unplanned PICU transfer (37.5%).</p><p><bold>Conclusions</bold>: We describe the successful implementation of PEWS in a pediatric HSCT unit in Latin America with low error rates and appropriate identification of clinical deterioration. Sustainability of this program requires continuous reinforcement and monitoring to achieve 100% compliance.</p></sec></sec><sec id="pbc26772-sec-0520"><title>Free Paper Session: Solid Tumour Therapy</title><sec id="pbc26772-sec-0530"><label>O-036</label><title>Results from the UK Children's Cancer and Leukaemia Group Study of Extracranial Germ Cell Tumours in Children and Adolescents (GC III)</title><p><underline underline-style="single">S. Depani</underline><sup>1</sup>, J. Nicholson<sup>2</sup>, S. Stoneham<sup>3</sup>, M. Krailo<sup>4</sup>, C. Xia<sup>5</sup>, J. Hale<sup>6</sup></p><p><italic><sup>1</sup>University of Birmingham, Cancer Research UK Clinical Trials Unit‐ Institute of Cancer and Genomic Sciences, Birmingham, United Kingdom; <sup>2</sup>University Cambridge Hospitals NHS Trust, Paediatric Oncology and Haematology, Cambridge, United Kingdom; <sup>3</sup>University College London Hospitals NHS Trust, Children and Young Peoples Cancer Service, London, United Kingdom; <sup>4</sup>University of Southern California, Keck School of Medicine, Los Angeles‐ CA, USA; <sup>5</sup>Children's Oncology Group, Statistics and Data Center, Monrovia CA, USA; <sup>6</sup>Newcastle upon Tyne Hospitals NHS Foundation Trust, Paediatric and Adolescent Haematology and Oncology, Newcastle upon Tyne, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: For extracranial malignant germ cell tumours (MGCT) in the UK, the GCII study used carboplatin and demonstrated equivalent survival to cisplatin‐containing protocols. GCIII, a single arm observational study, used new risk stratification, replaced consolidation chemotherapy with standard number of cycles and introduced surveillance for all Stage 1 MGCTs with the aim of de‐escalating treatment where possible whilst maintaining excellent survival with the use of carboplatin.</p><p><bold>Design/Methods</bold>: Patients with a diagnosis of MGCT were stratified to three risk group ‐ low (LR), intermediate (IR), high (HR), using a combination of stage and prognostic factors. Patients with AFP >10,000U/L or Stage IV disease (except testis <5 and all germinomas) and Stage II‐IV thoracic were classified as HR. Stage I tumours (LR) were monitored and received chemotherapy only if disease progressed. IR patients received 4 cycles of JEB (etoposide 120mg/m<sup>2</sup> i.v d 1,2,3; bleomycin 15mg/m2 iv d3 and carboplatin i.v on d2); HR patients received 6 cycles. Carboplatin dose was calculated to give an AUC of 7.9ml/m2.min.</p><p><bold>Results</bold>: Eighty‐six patients with MGCT were treated on the study between 2005 ‐2009: 59% female, median age 5.7 years (0 – 17.5 years). Twenty‐five (29%) were LR, 23 (27%) IR and 38 (44%) HR. Seven LR patients (28%) had disease progression at a median of 3 months; all were cured with chemotherapy. Five year event‐free‐survival for IR/HR patients was 90.2% (95% CI, 79.4%‐95.5%) (IR 87%; HR 92%) and overall survival 94.9% (95%CI, 85.0%‐98.3%) (IR 96%; HR 95%). JEB was well tolerated with manageable toxicity. No patients developed significant oto‐ or nephrotoxicity. There was no discernible difference in carboplatin dose whether calculated by body surface‐area or creatinine clearance.</p><p><bold>Conclusions</bold>: JEB chemotherapy using this risk stratification resulted in excellent survival with manageable toxicity. Carboplatin should be evaluated against cisplatin for paediatric GCTs in a large randomised prospective study.</p></sec><sec id="pbc26772-sec-0540"><label>O-037</label><title>Treatment of Refractory Germ Cell Tumors in Children with Paclitaxel, Ifosfamide and Carboplatin: Results of the Children's Oncology Group AGCT0521 Study</title><p><underline underline-style="single">F. Pashankar</underline><sup>1</sup>, L. Frazier<sup>2</sup>, M. Krailo<sup>3</sup>, A. Pappo<sup>4</sup>, T. Olson<sup>5</sup>, C. Rodriguez‐Galindo<sup>6</sup></p><p><italic><sup>1</sup>Yale University School of Medicine, Pediatrics, New Haven, USA; <sup>2</sup>Dana Farber Cancer Cancer Institute and Boston Children's Hospital, Pediatrics, Boston, USA; <sup>3</sup>University of Southern California, Preventive Medicine, Los Angeles, USA; <sup>4</sup>Saint Jude Children's Research Hospital, Pediatrics, Memphis, USA; <sup>5</sup>Children's Healthcare of Atlanta, Pediatrics, Atlanta, USA; <sup>6</sup>Saint Jude Children‐s Research Hospital, Global Pediatric Medicine, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Currently there is no standard regimen for relapsed pediatric malignant germ cell tumors (MGCT). In adults, a salvage regimen commonly used is TIP (paclitaxel, ifosfamide, cisplatin) which is associated with overall survival of 50‐70%. Further doses of cisplatin in young children, however, can be associated with significant short and long term toxicities. Because carboplatin has been shown to be effective in pediatric GCT with less toxicity, the TIP regimen was modified by substituting carboplatin for cisplatin. The primary aim was to evaluate response after 2 cycles of paclitaxel, ifosfamide, and carboplatin (TIC) in children with relapse or refractory MGCT.</p><p><bold>Design/Methods</bold>: This Phase II study, conducted by the Children's Oncology Group between November 2007 and June 2011, included children < 21y with relapsed or chemotherapy‐resistant MGCT, who had previously received a regimen containing cisplatin. “TIC” consists of paclitaxel 135 mg/m2/day Day 1, ifosfamide 1800 mg/m2/dose Days 1‐5 and carboplatin AUC 6.5 Day 1. The endpoint of trial was response after 2 cycles.</p><p><bold>Results</bold>: 20 patients (12 male, median age 13.5 years) were enrolled. By RECIST criteria, 8 patients achieved a partial response (PR) during protocol therapy (response rate 40%), 10 patients had stable disease (SD) and 2 patients had progressive disease. Of the 8 patients with PR, all had elevated markers at enrollment (5 AFP, 2 B HCG, 1 both), and 6/8 patients (75%) had at least a 1 log reduction in tumor markers. Of the 10 patients with SD, 9 had elevated markers at enrollment (8 AFP, 1 BHCG), and 6/9 (67%) had at least 1 log decrease</p><p><bold>Conclusions</bold>: Evaluation after 2 cycles of TIC therapy indicates reasonable efficacy, particularly if one uses the metric of an appropriate AFP decline. Taxol‐based regimens, either with carboplatin, as in this regimen or cisplatin, as in adult regimens, should be considered for salvage therapy in children</p></sec><sec id="pbc26772-sec-0550"><label>O-038</label><title>Ovarian Yolk SAC Tumors: Does Age Matter?</title><p><underline underline-style="single">C. Faure Conter</underline><sup>1</sup>, C. Xia<sup>2</sup>, D. Gershenson<sup>3</sup>, J. Hurteau<sup>4</sup>, A. Covens<sup>5</sup>, F. Pashankar<sup>6</sup>, M. Krailo<sup>7</sup>, D. Billmire<sup>8</sup>, B. Fresneau<sup>9</sup>, C. Patte<sup>9</sup>, F. Shaikh<sup>10</sup>, S. Stoneham<sup>11</sup>, J. Nicholson<sup>12</sup>, M. Murray<sup>12</sup>, L. Frazier<sup>13</sup></p><p><italic><sup>1</sup>Centre Léon Bérard, paediatry, Lyon, France; <sup>2</sup>Children's Oncology Group, statistics, Monrovia, USA; <sup>3</sup>MD Anderson Cancer Center, oncology, Houston, USA; <sup>4</sup>North Shore University Health System, oncology, Evanston, USA; <sup>5</sup>Sunnybrook Health Sciences Center, oncology, Toronto, Canada; <sup>6</sup>Yale university, pediatry, New Haven, USA; <sup>7</sup>University of Southern California, statistics, Los Angeles, USA; <sup>8</sup>Riley Hospital for Children, surgery, Indianapolis, USA; <sup>9</sup>Gustave Roussy, pediatry, Villejuif, France; <sup>10</sup>Hospital for Sick Children, pediatry, Toronto, Canada; <sup>11</sup>Children's and Young Persons Cancer Services, pediatry, London, United Kingdom; <sup>12</sup>Cambridge University Hospitals NHS Foundation Trust, pediatry, Cambridge, United Kingdom; <sup>13</sup>Dana‐Farber/Boston Childrens Cancer and Blood Disorders Center, pediatry, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Whereas among pediatric oncologists, ovarian yolk sac tumor (O‐YST) is considered a chemo sensitive tumor, it is often cited as an adverse prognostic factor in adult women with ovarian germ cell tumors.</p><p><bold>Design/Methods</bold>: The MaGIC dataset included 6 pediatric clinical trials (United States, United Kingdom and France) and 2 adult gynecology clinical trials (United States). Any patient with an O‐YST that was ≥ FIGO Stage IC and treated with a platinum‐based chemotherapy was eligible. Age was modeled as a continuous and a categorical variable (children: 0‐10y; adolescents; 11‐17y and adults: ≥18y). In addition, analyses to establish the optimal cut‐point for age were conducted. Tumors were coded as pure YST (YST +/‐ teratoma), mixed YST (YST + other malignant germ cell component) or putative YST (‘mixed’ germ cell tumor + alpha‐fetoprotein (AFP) >1000 ng/ml). Histology, stage (II/III <italic>vs</italic>. IV), preoperative AFP levels (<1.000, 1.000‐10.000 or >10.000 ng/ml), and chemotherapeutic regimen (carboplatin <italic>vs</italic>. cisplatin) were analyzed as covariates.</p><p><bold>Results</bold>: Two hundred fifty one patients (median age: 13 y, range 0‐38) were identified (78 children, 139 adolescents and 34 adults). Histology was pure, mixed and putative in 129, 56 and 66 cases, respectively. Twenty six patients were Stage IV, similarly distributed in the 3 age‐groups. Median follow up was 5.8 years. The overall 5‐year EFS and OS was 91% (95% CI, 87%‐94%) and 96% (92%‐98%), respectively. Age did not affect risk of event or death, modeled either as a categorical or continuous variable. Analysis failed to identify an age cut‐point that affected risk. None of the other covariates investigated had a prognostic impact on EFS or OS.</p><p><bold>Conclusions</bold>: O‐YST have an excellent outcome across all age‐groups. Age has no apparent impact on the probability of event or death, allowing pediatric and gynecologic oncologist to enroll patients onto joint pediatric and adult trials.</p></sec><sec id="pbc26772-sec-0560"><label>O-039</label><title>Pulmonary Nodule Size Measurements in Children with Wilms Tumours: Do Radiologists Agree?</title><p>S. Shelmerdine<sup>1</sup>, <underline underline-style="single">J. Brok</underline><sup>2</sup>, S. Irtan<sup>3</sup>, K. Pritchard‐Jones<sup>2</sup>, O. Olsen<sup>1</sup></p><p><italic><sup>1</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, Clinical Radiology, London, United Kingdom; <sup>2</sup>University College Great Ormond Street Institute of Child Health‐ UCL‐ London‐ UK., Clinical Oncology, London, United Kingdom; <sup>3</sup>APHP Armand Trousseau Hospital, Paediatric Surgery, Paris, France</italic></p><p><bold>Background/Objectives</bold>: Children with pulmonary metastases from Wilms tumours are allocated treatment regimens based upon lung lesion(s) size and response to chemotherapy. In the upcoming SIOP‐protocol (UMBRELLA), chest CT will be used to measure lung lesions with thresholds of <3, 3‐5, and >5 mm determining treatment intensity. This study aims to measure inter‐ and intra‐observer variability in the radiological assessment of pulmonary nodule size.</p><p><bold>Design/Methods</bold>: CT thoraces from 15 patients at diagnosis enrolled in the multicentre 'Improving Population Outcomes of Renal Tumours of childhood' (IMPORT) study were assessed. Five radiologists (3 chest, 2 paediatric) from different centres (4 UK, 1 Netherlands) assessed nodule size on two occasions, 6 months apart. Readers were blinded to patient symptoms and original radiology reports. Modified Bland Altman graphs were created to measure inter and intra‐observer limits of agreement for the nodules detected by all readers.</p><p><bold>Results</bold>: 93 different nodules were seen by at least one reader on both of their individual assessments of the same scan 6 months apart. Only 14 nodules were seen by all readers at both assessments.</p><p>Of these, inter‐observer limits of agreement (in millimetres) for the 5 readers were ±2.0 and ±1.7 (antero‐posterior diameter), ±1.8 and ±2.0 (transverse diameter) and ±2.0 and ±1.9 (cranio‐caudal distance) at assessments 1 and 2, respectively. Intra‐observer mean differences in measurement and limits of agreement across the three dimensions were 0.1 ±1.5mm, 0.2 ±2.1mm, 0.3 ±1.7mm, 0.3± 2.4mm, and 0.1 ±2.5mm (readers 1‐5, respectively).</p><p>Applying UMBRELLA criteria, only seven patients (∼ 45%) would be allocated to the same treatment arm across all radiology assessments.</p><p><bold>Conclusions</bold>: The demonstrated intra‐ and inter‐observer variability of detection and measurement of pulmonary nodules on CT thorax has important implications for the diagnosis and risk stratified treatment of metastatic disease.</p></sec><sec id="pbc26772-sec-0570"><label>O-040</label><title>Clinicopathological Study on the Sensitivity and Specificity of Indocyanine Green Fluorescent Imaging Test in the Pulmonary Metastases Resections of Hepatoblastoma</title><p><underline underline-style="single">M. Yoshida</underline><sup>1</sup>, M. Tanaka<sup>1</sup>, N. Kitagawa<sup>2</sup>, M. Shinkai<sup>2</sup>, H. Goto<sup>3</sup>, Y. Tanaka<sup>1</sup></p><p><italic><sup>1</sup>Kanagawa Children's Medical Center, Pathology, Yokohama, Japan; <sup>2</sup>Kanagawa Children's Medical Center, Surgery, Yokohama, Japan; <sup>3</sup>Kanagawa Children's Medical Center, Hemato‐oncology & Regenerative medicine, Yokohama, Japan</italic></p><p><bold>Background/Objectives</bold>: Pulmonary metastasis resection of hepatoblastoma using indocyanine green fluorescent imaging (ICG) is effective for lesions that cannot be detected by CT or are nonpalpable during operations. However, the detailed evaluation of the sensitivity and specificity of ICG tests was insufficient.</p><p><bold>Design/Methods</bold>: The subjects were 378 specimens submitted to the pathology department as pulmonary metastatic lesions of hepatoblastoma that were resected using ICG imaging tests in Kanagawa Children's Medical Center from January 2013 to March 2017. In total, there were 61 operations for 16 cases. By collating operation records and pathological reports, we studied the sensitivity and specificity of the ICG tests.</p><p><bold>Results</bold>: Among 378 specimens, 4 specimens were false‐negative (ICG‐negative and tumor‐positive), and the sensitivity of the ICG tests was 0.98. There were also 112 false‐positive specimens (ICG‐positive and tumor‐negative) with a specificity of 0.018 and a positive predictive value of 0.70. All the false‐negative specimens were resected from the same case. In false‐positive specimens, as far as operation records could confirm, the ICG‐positive regions were generally smaller than 2 mm in diameter. Even if the ICG‐positive regions were relatively wide, the ICG uptake patterns were weak, heterogeneous, and poorly marginated. Microscopically, false‐positive specimens often contained necrosis, fibrosis, granuloma, infiltrates of inflammatory cells, hemorrhage, thrombus, and/or unspecified mesenchymal tissue, which sometimes suggests the presence of preceding metastatic lesions.</p><p><bold>Conclusions</bold>: Our study demonstrated that ICG tests had high sensitivity but occasionally yielded false‐negative specimens. The specificity was low, but false‐positive specimens showed relatively uniform ICG uptake patterns by which the absence of viable tumors was predictable. These findings suggested high ICG test reliability as a technique to detect pulmonary metastases when considering high sensitivity to be more important. Closer communication between surgeons and pathologists about the ICG uptake patterns of the specimens might improve the usefulness of these tests.</p></sec><sec id="pbc26772-sec-0580"><label>O-041</label><title>Intensive Multi‐Modality Therapy for Extra‐Ocular Retinoblastoma (RB): A Children's Oncology Group (COG) Trial (ARET0321)</title><p><underline underline-style="single">I.J. Dunkel</underline><sup>1</sup>, M.D. Krailo<sup>2</sup>, G.L. Chantada<sup>3</sup>, A. Banerjee<sup>4</sup>, S. Abouelnaga<sup>5</sup>, J. Buchsbaum<sup>6</sup>, T.E. Merchant<sup>7</sup>, M. Granger<sup>8</sup>, R.F. Jubran<sup>9</sup>, M. Kellick<sup>10</sup>, J. Weinstein<sup>11</sup>, D.H. Abramson<sup>12</sup>, C. Rodriguez‐Galindo<sup>13</sup>, M.M. Chintagumpala<sup>14</sup></p><p><italic><sup>1</sup>Memorial Sloan Kettering Cancer Center, Pediatrics, New York, USA; <sup>2</sup>Children's Oncology Group, Biostatistics, Arcadia, USA; <sup>3</sup>Hospital JP Garrahan, Hemato‐oncologia, Buenos Aires, Argentina; <sup>4</sup>UCSF, Pediatrics, San Francisco, USA; <sup>5</sup>Children's Cancer Hospital Foundation 57357, Pediatric oncology, Cairo, Egypt; <sup>6</sup>National Cancer Institute, Radiation oncology, Rockville, USA; <sup>7</sup>St. Jude Children's Research Hospital, Radiation oncology, Memphis, USA; <sup>8</sup>Cook Children's Medical Center, Pediatrics, Fort Worth, USA; <sup>9</sup>Children's Hospital Los Angeles, Pediatrics, Los Angeles, USA; <sup>10</sup>Memorial Sloan Kettering Cancer Center, Pharmacy, New York, USA; <sup>11</sup>Lurie Children's Hospital, Pediatrics, Chicago, USA; <sup>12</sup>Memorial Sloan Kettering Cancer Center, Ophthalmology, New York, USA; <sup>13</sup>St. Jude Children's Research Hospital, Pediatrics, Memphis, USA; <sup>14</sup>Texas Children's Cancer Center, Pediatrics, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Metastatic RB is associated with a poor prognosis. COG opened this prospective, multi‐institutional, international trial to study whether intensified systemic chemotherapy with or without radiation therapy (RT) would improve outcomes in this population.</p><p><bold>Design/Methods</bold>: Patients with regional extra‐ocular RB (stage 2 or 3) received 4 cycles of chemotherapy (vincristine 0.05 mg/kg/day, cisplatin 3.5 mg/kg/day, cyclophosphamide 65 mg/kg x 2 days, etoposide 4 mg/kg x 2 days) followed by involved‐field RT (4,500 cGy). Two strata of patients with metastatic RB [stage 4a: no central nervous system (CNS) involvement; and stage 4b: CNS metastases/trilateral RB)] also received 4 cycles of chemotherapy. Patients with ≥ partial response then received 1 cycle of high‐dose carboplatin (Calvert formula with AUC=7/day, maximum 16.7 mg/kg/day) on days ‐8 to ‐6, thiotepa (10 mg/kg/day), & etoposide (8.3 mg/kg/day) on days ‐5 to ‐3 with autologous hematopoietic stem cell rescue on day 0. Patients with metastatic RB who achieved an inadequate response to chemotherapy received RT.</p><p><bold>Results</bold>: Sixty subjects (20 in each stratum) were enrolled; 57 eligible were included in the analyses (data current to 6‐30‐16). Toxicity was significant as expected and included 2 therapy related deaths. Event‐free survival (EFS) at 36 months was 87.7% (90% CI 65.4 to 96.0%) for subjects with stage 2 or 3 disease, 79.3% (90% CI 54.2 to 91.6%) for subjects with stage 4a disease and 8.0% (90% CI 1.0 to 25.1%) for subjects with stage 4b/trilateral disease. The observed results significantly improved the EFS in each stratum compared with historical results used for planning the study.</p><p><bold>Conclusions</bold>: Intensive multi‐modality therapy is highly effective for patients with regional extra‐ocular RB and metastatic RB not involving the CNS. More effective therapy is required for patients with CNS RB.</p></sec></sec><sec id="pbc26772-sec-0590"><title>Free Paper Session: Brain Tumours ‐ II</title><sec id="pbc26772-sec-0600"><label>O-042</label><title>Proteogenomic Approach Discriminates Pediatric and Adult Pilocytic Astrocytoma as Distinct Biological Entities</title><p>D. Picard<sup>1,2,3</sup>, J. Felsberg<sup>3</sup>, M. Langini<sup>4,5</sup>, D. Pauck<sup>1,2,3</sup>, V. Marquardt<sup>1,2,3</sup>, F. Meyer<sup>1,2,3</sup>, A. Stefanski<sup>4,5</sup>, K. Stühler<sup>4,5</sup>, A. Borkhardt<sup>2</sup>, G. Reifenberger<sup>3</sup>, C. Faria<sup>6,7</sup>, <underline underline-style="single">M. Remke</underline><sup>1,2,3</sup></p><p><italic><sup>1</sup>German Cancer Consortium DKTK and German Cancer Research Center DKFZ, Department of Pediatric Neuro‐Oncogenomics, Düsseldorf, Germany; <sup>2</sup>Hematology‐ and Clinical Immunology‐ Medical Faculty‐ University Hospital Düsseldorf, Department of Pediatric Oncology, Dusseldorf, Germany; <sup>3</sup>Heinrich Heine University Düsseldorf‐ Medical Faculty, Department of Neuropathology, Düsseldorf, Germany; <sup>4</sup>BMFZ‐ Heinrich‐Heine‐University Düsseldorf, Molecular Proteomics Laboratory, Dusseldorf, Germany; <sup>5</sup>University Hospital Düsseldorf‐ Heinrich‐Heine‐University Düsseldorf, Institute for Molecular Medicine, Düsseldorf, Germany; <sup>6</sup>Instituto de Medicina Molecular‐ da Universidade de Lisboa, Faculdade de Medicina, Lisbon, Portugal; <sup>7</sup>Hospital de Santa Maria‐ Centro Hospitalar Lisboa Norte, Department of Neurosurgery, Lisbon, Portugal</italic></p><p><bold>Background/Objectives</bold>: Pilocytic astrocytoma (PA) comprise the most common primary brain tumor in childhood. Genome‐wide profiling and next‐generation sequencing studies point towards a single‐pathway disease with oncogenic activation of MAPK signaling, typically driven by BRAF alterations. Incompletely resected tumors recur frequently despite radiation and/or chemotherapy. Less favorable therapeutic responses are observed in adults compared their pediatric counterparts. Thus, we utilized a proteogenomic approach to reveal the biological heterogeneity of PA across all age‐groups to identify novel therapeutic targets.</p><p><bold>Design/Methods</bold>: Our proteogenomic approach encompasses RNA sequencing (RNAseq) and LC/MS‐based proteomic profiling in pediatric (n=55) and adult patients (n=24) with PA. Unsupervised hierarchical clustering (HCL) analyses were applied to determine the biological heterogeneity of the disease. Integrative genomics combined with downstream pathway analysis were used to identify specific pathway activation in biological subgroups. Lastly, we performed high‐throughput drug screening encompassing conventional chemotherapeutics and targeted therapeutics (n=211) currently evaluated in phase III and IV clinical trials to validate novel molecular targets in PA primary culture models (n=8).</p><p><bold>Results</bold>: Pediatric and adult PA segregate into two main subgroups identified by unsupervised HCL using RNAseq and proteomic profiling (p=0.001). Adult tumors form a single entity, while we observed additional heterogeneity in pediatric tumors segregating into two subgroups (p=0.01). Initial analyses show that adult PA display an over‐representation of factors involved in translation initiation and ciliogenesis according to GeneSet Enrichment Analysis, whereas pediatric PA show a significant enrichment of pathways involved in glycolysis, signal transmission and AKT signaling.</p><p><bold>Conclusions</bold>: In all, our proteogenomic approach reveals clear biological heterogeneity in pediatric and adult PA. Ongoing drug screening experiments are used to determine therapeutics with preferential activity against pediatric and adult PA cultures. These biological insights may improve biological stratification and reveal novel therapeutic targets specifically useful for non‐resectable tumors with high risk of progressive disease.</p></sec><sec id="pbc26772-sec-0610"><label>O-043</label><title>Genomic Landscape of the First 100 Tumors Registered in the Biological Medicine for Diffuse Intrinsic Pontine Glioma (BIOMEDE) Trial</title><p><underline underline-style="single">J. Grill</underline><sup>1</sup>, M.A. Debily<sup>2</sup>, D. Castel<sup>1</sup>, E. Barret<sup>3</sup>, S. Picot<sup>3</sup>, A. Plessier<sup>3</sup>, L. Le Dret<sup>3</sup>, K. Nysom<sup>4</sup>, S. Huybrechts<sup>5</sup>, C. Dufour<sup>1</sup>, P. Capolino<sup>6</sup>, M.C. Le Deley<sup>7</sup>, S. Puget<sup>8</sup>, P. Varlet<sup>9</sup>, G. Vassal<sup>6</sup></p><p><italic><sup>1</sup>Institut Gustave Roussy, Pediatric and Adolescent Oncology & CNRS UMR 8203, Paris, France; <sup>2</sup>Gustave Roussy & Université d'Evry Val d'Essone, CNRS UMR 8203, Villejuif, France; <sup>3</sup>Institut Gustave Roussy, CNRS UMR 8203, Paris, France; <sup>4</sup>Rigshospitalet, Pediatric and Adlescent Medicine, Copenhagen, Denmark; <sup>5</sup>Hôpital de la Reine Fabiola, Oncologie Pédiatrique, Bruxelles, Belgium; <sup>6</sup>Gustave Roussy, Clinical Research Direction, Villejuif, France; <sup>7</sup>Gustave Roussy & Centre Oscar Lambret, Biostatistiques, Villejuif, France; <sup>8</sup>Hôpital necker Enfants Malades, Neurochirurgie, Paris, France; <sup>9</sup>Hôpital Sainte‐Anne, Neuropathologie, Paris, France</italic></p><p><bold>Background/Objectives</bold>: DIPG genomics has been so far mostly done on autopsy samples and in restrospective studies. In the frame of the BIOMEDE randomized trial of three targeted therapies (erlotinib, everolimus, dasatinib) based on three biomarkers identification (EGFR, PTEN, PDGFRA), a systematic whole exome and RNA sequencing of stereotactic biopsies performed at diagnosis was implemented to inform the results of the trial and define additional targets that could be used to guide therapy at relapse.</p><p><bold>Design/Methods</bold>: The results of the first 100 patients from France, Danemark and Belgium are presented. Seventy‐five percents of the samples could be profiled for DNA & RNA, no frozen material was available for 6% of the tumors and only one sample was not contributive.</p><p><bold>Results</bold>: All tumor samples but one included in the study on the basis of histology showed a loss of H3‐K27 trimethylation. With respect to histone H3‐K27M mutation, 75% of the samples were mutated in the <italic>H3F3A</italic> gene, 17% in the <italic>HIST1H3B</italic> gene and 8% were wild‐type. Structural copy number aberrations were only found in <italic>TP53</italic> mutated samples. Gain of chromosome 1q and whole chromosome 2 were more frequent in the <italic>HIST1H3B</italic>‐K27M mutated samples. Translocations were rarely identified and none was recurrent. <italic>ACVR1</italic> mutations were almost exclusively found in <italic>HIST1H3B‐</italic>K27M mutated samples but two in histone H3 wt samples and one in a <italic>H3F3A‐</italic>K27M mutated sample. 75% of <italic>H3F3A</italic>‐K27M DIPG had either a <italic>TP53</italic> or a <italic>PPM1D</italic> mutation while no of the <italic>HIST1H3B‐</italic>K27M DIPG had a mutation in the TP53 pathway. Recetors Tyrosine‐Kinase mutations or amplifications were only found in <italic>H3F3A</italic>‐K27M DIPG.</p><p><bold>Conclusions</bold>: This study refines the description of the differences in the subtypes of DIPG and may support specific treatment adaptations with respect to potential biomarkers. (Supports: INCa PHRC and Imagine for Margo).</p></sec><sec id="pbc26772-sec-0620"><label>O-044</label><title>The Clinical and Molecular Landscape of Infantile Medulloblastoma</title><p><underline underline-style="single">G. Robinson</underline><sup>1</sup>, V. Rudneva<sup>2</sup>, I. Buchhalter<sup>3</sup>, D. Bowers<sup>4</sup>, A. Bendel<sup>5</sup>, P. Fisher<sup>6</sup>, J. Crawford<sup>7</sup>, T. Hassall<sup>8</sup>, C. Billups<sup>9</sup>, A. Onar<sup>9</sup>, V. Ramamswamy<sup>10</sup>, M. Taylor<sup>11</sup>, T. Merchant<sup>12</sup>, M. Kool<sup>13</sup>, B. Orr<sup>14</sup>, D. Ellison<sup>14</sup>, S. Pfister<sup>13</sup>, A. Gajjar<sup>1</sup>, P. Northcott<sup>2</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Oncology, Memphis, USA; <sup>2</sup>St. Jude Children's Research Hospital, Developmental Neurobiology, Memphis, USA; <sup>3</sup>German Cancer Research Center DKFZ, Applied Bioinformatics, Heidelberg, Germany; <sup>4</sup>University of Southwestern Medical Center at Dallas, Pediatric Hematology and Oncology, Dallas, USA; <sup>5</sup>Children's Hospitals and Clinics of Minnesota, Pediatric Hematology and Oncology, Minneapolis, USA; <sup>6</sup>Stanford University, Neurology, Palo Alto, USA; <sup>7</sup>UC San Diego ‐ Rady Children's Hospital, Neurosciences, San Diego, USA; <sup>8</sup>Lady Cilento Children's Hospital, Paediatric Oncology, Brisbane, Australia; <sup>9</sup>St. Jude Children's Research Hospital, Biostatistics, Memphis, USA; <sup>10</sup>The Hospital for Sick Children, Haematology and Oncology, Toronto, Canada; <sup>11</sup>The Hospital for Sick Children, Neurosurgery, Toronto, Canada; <sup>12</sup>St. Jude Children's Research Hospital, Radiation Oncology, Memphis, USA; <sup>13</sup>German Cancer Research Center DKFZ, Pediatric Neurooncology, Heidelberg, Germany; <sup>14</sup>St. Jude Children's Research Hospital, Pathology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Survival of children ≤ 5 years‐old (called “infants”) with medulloblastoma (MB) is vastly inferior to that of older children with MB. The difference is principally due to radiation‐sparing therapy, however, radiation is not a requisite for survival in all. Therefore it is imperative to understand which infants benefit and which fail current approaches. Herein we comprehensively describe the molecular landscape of the infantile medulloblastoma (iMB) and show that differences in molecular makeup translate to major differences in outcome.</p><p><bold>Design/Methods</bold>: We amassed a discovery cohort of 165 and a validation cohort of 73 iMB. All were analyzed on 450K DNA methylation arrays and sequenced against matched normal. The discovery cohort came from a pooled international series and the validation from the SJYC07 clinical trial (NCT00602667).</p><p><bold>Results</bold>: iMB divides into three subgroups; SHH, G3, G4. No WNT MB was observed. Distribution between the 2 cohorts were similar – Discovery ‐ 31% SHH‐MB, 44% G3 and 25% G4: Validation ‐ 56% SHH‐MB, 30% G3 and 14% G4. The most frequent mutations in SHH‐MB are <italic>PTCH1</italic> (51% ‐discovery cohort; 29% validation), <italic>SUFU</italic> (14% and 16%), <italic>KMT2D</italic> (12% and 27%). <italic>MYCN</italic> amplification (6% and 2%) and <italic>TP53</italic> mutations (5% and 2%) are rare. Non‐SHH‐MB displayed relatively few recurrent mutations but exhibited multiple large copy number aberrations. In the validation cohort, four‐year progression free survival (PFS) of SHH‐MB is superior to non‐SHH‐MB (54%±9 vs 10%±10 p value <0.0001). Histology and metastatic disease within subgroups were not prognostic for PFS. Ongoing analysis is occurring to determine if any molecular heterogeneity within subgroups is prognostic.</p><p><bold>Conclusions</bold>: Infant SHH‐MB benefits more from radiation‐sparing therapy than non‐SHH‐MB. Future clinical trials need to prospectively divide into SHH‐MB and non‐SHH‐MB. The therapeutic goals need to shift towards optimizing the current chemotherapeutic backbone for SHH‐MB, while a paradigm shift in therapy for infant non‐SHH‐MB is necessary.</p></sec><sec id="pbc26772-sec-0630"><label>O-045</label><title>Who is Who? Ex‐CNS‐PNETS and New Entities: Clinical Consequences of Confined Diagnostic Groups</title><p><underline underline-style="single">K. von Hoff</underline><sup>1</sup>, C. Haberler<sup>2</sup>, G. Robinson<sup>3</sup>, D. Sumerauer<sup>4</sup>, J. Cho<sup>5</sup>, M. Mynarek<sup>1</sup>, P. Hauser<sup>6</sup>, M. Lastowska<sup>7</sup>, A. Korshunov<sup>8</sup>, T. Jacques<sup>9</sup>, F. Giangaspero<sup>10,11</sup>, C. Hawkins<sup>12</sup>, D. Figarella‐Branger<sup>13</sup>, P. Burger<sup>14</sup>, M. Gessi<sup>15</sup>, B. Orr<sup>16</sup>, D. Sturm<sup>17,18</sup>, S.M. Pfister<sup>17,18</sup>, T. Pietsch<sup>15</sup>, M. Kool<sup>17</sup></p><p><italic><sup>1</sup>University Medical Center Hamburg‐Eppendorf, Pediatric Hematology and Oncology, Hamburg, Germany; <sup>2</sup>Medical University of Vienna, Institute of Neurology, Vienna, Austria; <sup>3</sup>St Jude Children's Research Hospital, Department of Oncology, Memphis, USA; <sup>4</sup>University Hospital Motol, Department of Pediatric Hematology and Oncology, Prague, Czech Republic; <sup>5</sup>Yonsei Cancer Center‐ Yonsei University College of Medicine, Dept. of Radiation Oncology, Seoul, Republic of Korea; <sup>6</sup>Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary; <sup>7</sup>Children's Memorial Health Institute, Department of Pathology, Warsaw, Poland; <sup>8</sup>German Cancer Research Center DKFZ, Division of Clinical Cooperation Unit Neuropathology, Heidelberg, Germany; <sup>9</sup>University College London, Institute of Child Health, London, United Kingdom; <sup>10</sup>Sapienza University of Rome, Department of Radiological‐ Oncological and Anatomopathological Sciences, Rome, Italy; <sup>11</sup>IRCCS, Neuromed Institute, Pozzilli IS, Italy; <sup>12</sup>The Hospital for Sick Children, Division of Pathology, Toronto, Canada; <sup>13</sup>La Timone Hospital‐ Aix Marseille University, Department of Pathology and Neuropathology, Marseille, France; <sup>14</sup>Johns Hopkins University, Department of Pathology, Baltimore, USA; <sup>15</sup>University of Bonn, Department of Neuropathology, Bonn, Germany; <sup>16</sup>St Jude Children's Research Hospital, Department of Pathology, Memphis, USA; <sup>17</sup>German Cancer Research Center DKFZ, Division of Pediatric Neurooncology, Heidelberg, Germany; <sup>18</sup>University Hospital, Department of Pediatric Hematology and Oncology, Heidelberg, Germany</italic></p><p><bold>Background/Objectives</bold>: The diagnosis “CNS primitive neuroectodermal tumor” (CNS‐PNET) was removed from the updated 2016 WHO classification of CNS tumors. In a cohort of patients with a previous diagnosis of CNS‐PNET, new entities with recurrent genetic alterations were delineated, which were then also identified in patients with previous other diagnoses (Sturm,2016). Utility of current treatment paradigms in confined diagnostic groups is not known.</p><p><bold>Design/Methods</bold>: Through an international collaboration, additional tumor samples of patients with a previous diagnosis of CNS‐PNET were re‐evaluated by DNA methylation profiling and blinded neuropathological panel review. Clinical data to the newly re‐evaluated cases and to previously published cases, irrespective of historic diagnosis, were pooled and analyzed.</p><p><bold>Results</bold>: The given numbers represent preliminary data of the ongoing project. DNA methylation profile classified 173 newly re‐evaluated tumors with historic CNS‐PNET diagnosis as: other defined non CNS‐embryonal‐tumor entity (60%, n=104), ETMR (21%, n=37), CNS‐NB‐FOXR2 (9%, n=16), CNS‐HGNET‐BCOR (3%, n=5), CNS‐HGNET‐MN1 (4%, n=6), and CNS‐EFT‐CIC (3%, n=5). Blinded neuropathology panel diagnosis fully overlapped with methylation result for 18 correspondingly analyzed ETMR, and a group of embryonal tumors displaying varying degrees of neuronal and ganglionic differentiation corresponded to 12 CNS‐NB‐FOXR2. In the combined data set, historic diagnosis other than CNS‐PNET was uncommon in CNS‐NB‐FOXR2 (1 of 59, 2%), but was common in CNS‐HGNET‐BCOR (28 of 48, 58%), CNS‐HGNET‐MN1 (34 of 51, 67%, mostly diagnosed as astroblastoma, or ependymoma), and CNS‐EFT‐CIC (5 of 22, 23%). Five‐year PFS and OS was 60% and 95%, respectively, for 31 patients with CNS‐NB‐FOXR2, 0% and 40% for 16 patients with CNS‐HGNET‐BCOR, 27% and 94% for 21 patients with CNS‐HGNET‐MN1, and 50% and 51% for 11 patients with CNS‐EFT‐CIC methylation profile.</p><p><bold>Conclusions</bold>: Consensus on diagnostic criteria and treatment strategy is needed. International collaboration will aim for prospective molecular and clinical data collection to inform the development of specific trials e.g. for controlled de‐escalation of treatment for CNS‐NB‐FOXR2.</p></sec><sec id="pbc26772-sec-0640"><label>O-046</label><title>Molecular Subgrouping of Pineal Tumors Reveals Distinct Classes Correlated with Clinical Parameters and Genetic Alterations</title><p><underline underline-style="single">E. Pfaff</underline><sup>1,2</sup>, M. Snuderl<sup>3,4,5</sup>, M.A. Karajannis<sup>6</sup>, L. Chavez<sup>1</sup>, S.M. Pfister<sup>1,2</sup>, D.T.W. Jones<sup>1</sup></p><p><italic><sup>1</sup>German Cancer Research Center DKFZ, Pediatric Neurooncology, Heidelberg, Germany; <sup>2</sup>Heidelberg University Hospital, Department of Pediatric Oncology‐ Hematology & Immunology, Heidelberg, Germany; <sup>3</sup>NYU Langone Medical Center, Division of Neuropathology, New York, USA; <sup>4</sup>NYU Langone Medical Center, Department of Neurology, New York, USA; <sup>5</sup>NYU Langone Medical Center, Laura and Isaac Perlmutter Cancer Center, New York, USA; <sup>6</sup>Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, USA</italic></p><p><bold>Background/Objectives</bold>: Tumors of the pineal region comprise several different entities with distinct clinical and histopathological features.</p><p>Pineocytoma (PC, WHO grade I), pineal parenchymal tumors of intermediate differentiation (PPTID) and papillary tumors of the pineal region (PTPR) (WHO grade II‐III), predominantly affect adults and are associated with a favorable prognosis.</p><p>Pineoblastoma (PB) is a highly aggressive tumor (WHO grade IV) in the family of primitive embryonal tumors/PNET occurring in infants, children and adolescents. Especially for infants and patients with metastatic disease, the outcome is poor despite aggressive multimodal treatment, and no therapeutically actionable molecular targets have been identified to date. Whereas most PB arise sporadically, cancer predisposition syndromes including <italic>DICER1</italic> or <italic>RB1</italic> germline mutations are associated with PB, the latter in the context of trilateral retinoblastoma (PB‐RB).</p><p>We investigated the biological relationships between clinico‐pathological entities of pineal tumors based on DNA methylation and copy number analysis.</p><p><bold>Design/Methods</bold>: We performed genome‐wide DNA methylation profiling in 230 pineal tumors and normal pineal tissue controls, including copy‐number analysis.</p><p><bold>Results</bold>: Unsupervised clustering revealed clear separation of the known entities (PC, PTPR, PPTID and PB‐RB). Within these groups, distinct subgroups could be distinguished, including the previously hypothesized PTPR‐A and PTPR‐B groups. Interestingly, the tumors initially diagnosed as either PB or pineal PNET formed a number of biologically discrete subgroups, which are now being further characterized. One group harbored recurrent alterations of <italic>DROSHA</italic>, an endoribonuclease involved in miRNA processing upstream of <italic>DICER1</italic>, implicating a central role of altered miRNA biogenesis in the development of PB.</p><p><bold>Conclusions</bold>: Using methylation profiling, we identified biologically distinct subgroups of pineal tumors, including novel sub‐clusters. Our findings provide a foundation for further molecular and functional characterization, including the role of miRNA processing defects in oncogenesis.</p></sec><sec id="pbc26772-sec-0650"><label>O-047</label><title>Improved Survival and Decreasing Neurocognitive Function Over Time in Posterior Fossa Ependymoma</title><p><underline underline-style="single">M. Zapotocky</underline><sup>1</sup>, J. Adamski<sup>1</sup>, A. Lassaletta<sup>1</sup>, P. Dirks<sup>1</sup>, S. Laughlin<sup>1</sup>, C. Hawkins<sup>1</sup>, N. Laperriere<sup>2</sup>, U. Tabori<sup>1</sup>, U. Bartels<sup>1</sup>, D. Mabbott<sup>1</sup>, E. Bouffet<sup>1</sup>, V. Ramaswamy<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Pediatrics/ Division of Hematology/Oncology, Toronto, Canada; <sup>2</sup>Princess Margaret Hospital, Radiation Oncology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Intracranial ependymoma is third most frequent pediatric brain tumor comprising of distinct biological entities arising in posterior fossa (PF) or supratentorial (ST) region. We aimed to identify predictors of survival and neurocognitive outcome in a large consecutive cohort over three decades.</p><p><bold>Design/Methods</bold>: Data on demographics, treatment, survival and neurocognitive functioning were collected in 102 consecutive patients with intracranial ependymoma diagnosed at SickKids from 1985‐2014.</p><p><bold>Results</bold>: No significant difference between survival of PF and ST ependymoma was observed (PF 5‐year PFS 47.8% (95%CI, 37.2‐61.5%), PF 5‐year OS 71.5% (95%CI, 61.3‐83.4%); ST 5‐year PFS 56.6% (95%CI, 40.6‐79%), ST 5‐year OS 76.9% (95%CI, 62.2‐95.1%)). Independent predictors of favourable outcome in PF ependymoma include gross total resection (GTR) (p=0.037) and upfront radiotherapy (p<0.0001). Analysis of consecutive 10 year epochs revealed a significant improvement in PFS and OS over time (2005‐2014 compared to 1985‐1994 and 1995‐2004). This pertains to the rate of GTR increased from 35% to 77% and use of upfront radiation increased from 65% to 96% over observed period in PF ependymoma. None of observed variables were prognostic in ST ependymoma. The proportion of patients with recurrent ependymoma who can be salvaged with re‐irradiation increases 5‐year PFS post‐recurrence from 0% to 28% (p<0.0001). Complete resection at recurrence is a strong favourable predictor of survival (p=0.005). Upfront radiation in primary diagnosis or re‐irradiation at recurrence significantly influences neurocognitive outcome, especially in very young children.</p><p><bold>Conclusions</bold>: Data from our large homogeneously treated cohort clearly indicate improved survival of posterior fossa ependymoma over time, related to more aggressive surgery and upfront radiation. However for the first time in a large consecutive cohort, we show that this approach results in reduced neurocognitive outcomes over time. Our data suggests that all children with posterior fossa ependymoma should receive upfront radiation and be concomitantly prioritized for early neuropsychological testing and intervention.</p></sec></sec><sec id="pbc26772-sec-0660"><title>Free Paper Session: Leukemia ‐ Biology</title><sec id="pbc26772-sec-0670"><label>O-048</label><title>Integrated Genetic and Epigenetic Analysis in Pediatric T‐Cell Acute Lymphoblastic Leukemia (T‐ALL)</title><p><underline underline-style="single">S. Kimura</underline><sup>1,2</sup>, M. Seki<sup>1</sup>, T. Kawai<sup>3</sup>, K. Yoshida<sup>4</sup>, T. Isobe<sup>1</sup>, H. Ueno<sup>4</sup>, H. Suzuki<sup>4</sup>, K. Oki<sup>5</sup>, T. Imamura<sup>6</sup>, N. Kiyokawa<sup>5</sup>, M. Kobayashi<sup>2</sup>, K. Koh<sup>7</sup>, A. Manabe<sup>8</sup>, A. Ohara<sup>9</sup>, M. Sanada<sup>10</sup>, Y. Hayashi<sup>11</sup>, K. Hata<sup>3</sup>, S. Miyano<sup>12</sup>, S. Ogawa<sup>4</sup>, J. Takita<sup>1</sup></p><p><italic><sup>1</sup>Tokyo Univesity, Pediatrics, Tokyo, Japan; <sup>2</sup>Hiroshima University Graduate School of Biomedical Sciences, Pediatrics, Hiroshima, Japan; <sup>3</sup>National Center for Child Health and Development, Maternal‐Fetal Biology, Tokyo, Japan; <sup>4</sup>Graduate School of Medicine‐ Kyoto University, Pathology and Tumor Biology, Kyoto, Japan; <sup>5</sup>National Center for Child Health and Development, Pediatric Hematology and Oncology, Tokyo, Japan; <sup>6</sup>Kyoto Prefectural University of Medicine‐ Graduate School of Medical Science, Pediatrics, Kyoto, Japan; <sup>7</sup>Saitama Children's Medical Center, Hematology/Oncology, Saitama, Japan; <sup>8</sup>St. Luke's International Hospital, Pediatrics, Tokyo, Japan; <sup>9</sup>Toho University, Pediatrics, Tokyo, Japan; <sup>10</sup>National Hospital Organization Nagoya Medical Center, Clinical Research Center, Nagoya, Japan; <sup>11</sup>Gunma Children's Medical Center, Hematology/Oncology, Shibukawa, Japan; <sup>12</sup>Institute of Medical Science‐ The University of Tokyo, Laboratory of DNA Information Analysis‐ Human Genome Center, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: Pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematologic‐cancer. Although genetic basis of pediatric T‐ALL has been well characterized, no comprehensive study has yet explored the epigenetic profiles and their potential contribution to clinicopathological features of T‐ALL.</p><p><bold>Design/Methods</bold>: To describe epigenetic landscape of T‐ALL, we conducted methylation array analysis using Illumina HumanMethylationEPIC array, whole transcriptome sequencing (WTS), and targeted‐capture sequencing for 158 ALL‐related genes in a cohort of 49 cases with T‐ALL. Following analyses were performed using R (v3.3.0).</p><p><bold>Results</bold>: After normalization, 2975 probes were selected to identify the most variable methylated probes, when a standard deviation of the beta‐values across the samples was above 0.35. Unsupervised consensus clustering using selected 2975 probes clearly identified 3 distinct sample clusters. Combined analyses with expression and fusion data from WTS revealed that these 3 clusters were characterized by TAL1 fusions/high‐expression (M1 cluster; low‐methylation), high TLX1/TLX3 expression (M2 cluster; high‐methylation), and PU.1 fusions/high expression (M3 cluster; intermediate‐methylation), respectively. Although the number of frequently affected genes (>15%) was relatively low in M3 cluster, <italic>PTEN</italic> and <italic>USP7</italic> abnormalities were particularly enriched in M1 cluster and <italic>PHF6</italic>, <italic>DNM2</italic>, and <italic>EZH2</italic> mutations were frequently observed in M2 cluster. Furthermore, it should be noted that, patients in M3 cluster displayed adverse prognosis, whereas patients in M2 cluster showed excellent clinical outcome (Log‐Rank p = 0.02).</p><p><bold>Conclusions</bold>: Based on the DNA methylation profiles, pediatric T‐ALL is clustered into 3 distinct subtypes, which exhibited remarkable correlation with fusion gene status, gene expression patterns, genetic signatures, and clinical outcomes. Although our cohort in the current study is very limited, our results suggested that the biological phenotype of T‐ALL is mediated by both genetic and epigenetic regulations. Therefore, explorations for aberrant DNA methylation along with genetic alterations might be helpful for development a new therapeutic strategy for T‐ALL.</p></sec><sec id="pbc26772-sec-0680"><label>O-049</label><title>Genomic Breakpoint and Fusion Transcript Analysis of KMT2A Rearrangement in Infant Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">E. Guest</underline><sup>1</sup>, B. Yoo<sup>2</sup>, M. Farooqi<sup>2</sup>, N. Miller<sup>2</sup>, J. Johnston<sup>2</sup>, R. Kostadinov<sup>3</sup>, E. Farrow<sup>2</sup>, S. Kelley<sup>4</sup>, M. Gibson<sup>2</sup>, P. Brown<sup>4</sup></p><p><italic><sup>1</sup>Children's Mercy Hospital, Hematology/Oncology/Bone Marrow Transplantation, Kansas City, USA; <sup>2</sup>Children's Mercy Hospital, Center for Pediatric Genomic Medicine, Kansas City, USA; <sup>3</sup>Johns Hopkins University School of Medicine, Biostatistics, Baltimore, USA; <sup>4</sup>Johns Hopkins University School of Medicine, Pediatric Oncology, Baltimore, USA</italic></p><p><bold>Background/Objectives</bold>: Rearrangement of <italic>KMT2A</italic> (KMT2A‐R) is a high risk, recurrent molecular driver of acute lymphoblastic leukemia (ALL) among infants less than 1 year of age. We sought to determine if variation in the genomic breakpoints of <italic>KMT2A</italic> and its partner genes correlates with risk of treatment failure for infants with ALL.</p><p><bold>Design/Methods</bold>: We performed whole genome sequencing (WGS) to an average depth of 30x, and mRNA sequencing on 47 blood and marrow samples from 32 infants with KMT2A‐R ALL. The infants were enrolled on the Children's Oncology Group trial AALL0631. Cases with the partner genes <italic>AF4</italic> (n=19)or <italic>ENL</italic> (n=13) were selected for study. Twenty‐one infants had experienced treatment failure, and 13 had paired relapse samples. Alignment of sequencing data was done using BWA. Translocation detection (WGS) was done using Manta, and fusion transcript detection (RNAseq) was performed using FusionCatcher.</p><p><bold>Results</bold>: Whole genome sequencing detected the <italic>KMT2A</italic> translocation in 100% of samples and the precise nucleotide breakpoint in 82% of samples. The location of <italic>KMT2A</italic> breakage was within introns 8, 9, or 10, or exons 10 or 11 in all cases. In contrast, the breakpoint locations within <italic>AF4</italic> and <italic>ENL</italic> were more variable. Relapses were observed in both <italic>AF4</italic> and <italic>ENL</italic> groups and the breakpoints were unchanged in paired samples at relapse.</p><p>Known fusion transcripts were detected in 76% of samples and were biologically consistent with identified DNA breakpoints. Exon skipping and alternative splice sites were observed. The reciprocal fusion transcript was frequently detected for <italic>AF4</italic>, but never detected for <italic>ENL</italic>. Fusion of <italic>KMT2A</italic>‐exon‐9 was dominant, detected in 17 cases with relapse and only 3 without relapse.</p><p><bold>Conclusions</bold>: The breakpoints of <italic>KMT2A</italic> in infant ALL are conserved within a narrow genomic window, in contrast to the breakpoints of partner genes <italic>AF4</italic> and <italic>ENL</italic>. Fusion of <italic>KMT2A</italic>‐exon‐9 is common among cases with relapse.</p></sec><sec id="pbc26772-sec-0690"><label>O-050</label><title>Identification by RT‐PCR Multiplex of Key Partners of KMT2A in Pediatric Patients with Acute Myeloid Leukemia</title><p><underline underline-style="single">I. Cezar</underline><sup>1</sup>, F. Andrade<sup>1</sup>, M. Pombo‐de‐Oliveira<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional do Cancer, Paediatric Haematology‐Oncology Program, RIO DE JANEIRO, Brazil</italic></p><p><bold>Background/Objectives</bold>: Pediatric acute myeloid leukemia (p‐AML) is a phenotypic and genetically heterogeneous disease. The identification of gene fusion allows the definition of molecular subtypes in p‐AML, with an important role in the prognosis and follow‐up of the treatment response. In early‐age AML the majority of genomic abnormality is characterized by <italic>KMT2A</italic> rearrangements (<italic>KMT2A</italic>‐r) identified by FISH <italic>MLL</italic> break apart. The <italic>KMT2A</italic> partners gene defines the prognosis outcome. In this context, we standardized the multiplex RT‐PCR (mRT‐PCR) technique to identify the most frequent partners [<italic>MLLT1</italic>, <italic>MLLT3</italic>, <italic>MLLT4</italic>, <italic>MLLT10</italic>, <italic>AFF1</italic> and partial tandem duplication (PTD)] of the <italic>KMT2A</italic> gene.</p><p><bold>Design/Methods</bold>: It was analyzed 241 cases of <italic>de novo</italic> p‐AML, for the identification of<italic>KMT2A</italic>‐r through the mRT‐PCR identifying all partners studied in the same PCR reaction. In order to standardized the method described by Burmeister <italic>et al</italic>, 2014 some modification was necessary, as reagent changes were performed, including tests of Taq DNA Polymerase and changes in cycles program. Sanger sequencing was performed to confirm the results.</p><p><bold>Results</bold>: Two hundred and forty‐one AML cases were included in the study and about 22% were infants (52 cases); The most frequent morphological subtype was myelomonocytic (FAB‐M4) (36,1%). Thirty‐three cases with KMT2A‐r were identified by mRT‐PCR. Partners were identified in the following frequencies: 5/33(15.2%) with KMT2A‐MLLT1 fusion, 12/33(36.4%) positive for <italic>KMT2A‐MLLT3</italic>, 3/33(9.1%) with <italic>KMT2A‐MLLT4</italic> fusion, 8/33 (24.2%) were identified with <italic>KMT2A ‐MLLT10</italic>, 2/33(6.1%) were positive for <italic>KMT2A‐AFF1</italic> and 3/33 (9.1%) presented <italic>KMT2A</italic>‐PTD.</p><p><bold>Conclusions</bold>: The proposed technique was successfully standardized in our laboratory and it is possible reliable in the identification of <italic>KMT2A</italic> with the partner gene and with less cost compared with FISH.</p></sec><sec id="pbc26772-sec-0700"><label>O-051</label><title>Identification of Genetic Aberrations Predisposing to Familial Burkitt Lymphoma Using Whole Genome Sequencing</title><p>R. Van Paemel<sup>1</sup>, C. Derpoorter<sup>1</sup>, R. Demuynck<sup>1</sup>, E. Terras<sup>1</sup>, B. De Wilde<sup>1</sup>, T. Lammens<sup>1</sup>, <underline underline-style="single">G. Laureys</underline><sup>1</sup></p><p><italic><sup>1</sup>Ghent University Hospital, Department of Pediatric Hematology‐Oncology and Stem Cell Transplantation, Ghent, Belgium</italic></p><p><bold>Background/Objectives</bold>: Burkitt lymphoma (BL) is a rare pediatric tumor characterized by the translocation of <italic>MYC</italic> on chromosome 8 to one of the immunoglobulin loci. Since exposure time to carcinogenics is shorter in children, genetic factors are assumed to be more important in tumor development. At our department, 2 related children were diagnosed with BL, strongly suggesting a predisposing factor.</p><p><bold>Design/Methods</bold>: Whole genome sequencing was performed on constitutional material from both patients, parents and grandparents (n=10). Variant calling using genome analysis toolkit (GATK) was followed by prioritization filtering with GEMINI (Paila et al., 2013).</p><p><bold>Results</bold>: At first, data reduction was done through selecting rare variants (< 1% in 1000G_EUR) shared by the patients and the related parents and absent in spousal controls. Three deleterious variants were identified including 1 in <italic>USP28</italic> (rs45570432) and 2 in <italic>MAP2K3</italic> (rs56067280 and rs55796947). Data reduction based on inheritance modeling revealed a compound heterozygous variation in <italic>C4orf33</italic>. In addition, 13 mutations followed a <italic>de novo</italic> model of which, based on the probability of mendelian error, the non‐coding mutations in <italic>USP32</italic> and <italic>DRD3</italic> seem most plausible. In a third approach, using a published cancer gene panel (Zhang et al., 2015), 14 non‐coding variants were found segregating in the family.</p><p><bold>Conclusions</bold>: Collectively, these data show that multiple candidate BL predisposing variants can be found in the family under investigation. It is becoming more apparent that non‐coding variants play a major role in the development of cancer through up‐ or downregulating expression, altering splice‐sites and gene silencing. The identified variants, however, need functional validation and further examination in large populations and other families. Importantly, this approach can be expanded to other pediatric cancer entities to improve our understanding of tumorigenesis, to enable genetic counseling and to contribute to novel diagnostic applications and therapeutic options.</p><p>* TL and GL are shared senior authors</p></sec></sec><sec id="pbc26772-sec-0710"><title>Free Paper Session: Neuroblastoma ‐ Clinical</title><sec id="pbc26772-sec-0720"><label>O-052</label><title>Neuroblastoma Stage 4S: Regression Rate and Patients at Risk</title><p><underline underline-style="single">M. Tas</underline><sup>1</sup>, M. Nagtegaal<sup>2</sup>, K. Kraal<sup>1</sup>, G. Tytgat<sup>1,2</sup>, N. Abeling<sup>3</sup>, S. Pluijm<sup>1,4</sup>, M. Zwaan<sup>4</sup>, J. Molenaar<sup>5</sup>, M. van Noesel<sup>1</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Pediatric Oncology, Utrecht, The Netherlands; <sup>2</sup>Emma Children's Hospital/Academic Medical Center, Pediatric Oncology, Amsterdam, The Netherlands; <sup>3</sup>Academic Medical Center, Laboratory for Genetic Metabolic Diseases, Amsterdam, The Netherlands; <sup>4</sup>Erasmus MC‐Sophia Children's Hospital, Pediatric Oncology, Rotterdam, The Netherlands; <sup>5</sup>Princess Máxima Center for Pediatric Oncology, Translational Research, Utrecht, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma stage 4S/MS is a low risk tumor with an overall survival of 65‐92%. The natural course consists of initial growth of multifocal disease followed by regression. However, the precise clinical course of the initial growth and regressive phase is poorly described. We performed a retrospective cohort study to describe the clinical course, to identify patients at risk of an adverse outcome and to compare regression rate between treated and untreated patients.</p><p><bold>Design/Methods</bold>: Charts of all patients diagnosed with neuroblastoma stage 4S/MS between 1972 and 2012 in two Dutch oncology centers were evaluated for therapy, response, outcome and for clinical, metabolic and radiological regression of tumor and liver metastases. Patients with high risk criteria were excluded.</p><p><bold>Results</bold>: We identified 31 patients. The 5 year overall survival was 84% (median follow up 193.5 months, range 40‐468). Treatment was given to 55% of the patients. In the first 3 weeks after diagnosis 4 patients died of rapid liver growth and compression. Neonates were at highest risk of dying: 4/7 (58%) neonates died, while none of the older patients died. During the regressive phase, the primary tumor completely regressed in 69% of the patients after a median of 13 months (range 6‐73); liver size normalized in 91% after a median of 2 months (range 0‐131), and architecture normalized in 52% after a median of 14.5 months (range 5‐131). No differences in regression rate were seen between the treated and untreated patients. Late progression to stage 4 was observed in 3 patients, all had persistent elevated catecholamines. Two of three are currently in complete remission.</p><p><bold>Conclusions</bold>: Neonates are at risk of dying of rapid liver growth. Patients with persistent elevated catecholamines are at risk of progression to stage 4. Radiological regression of primary tumor and liver architecture is slow and takes over 12 months.</p></sec><sec id="pbc26772-sec-0730"><label>O-053</label><title>I‐131‐Meta‐Iodobenzylguanidine (MIBG) Therapy Improves Survival in High‐Risk Neuroblastoma Patients with MIBG Positive Residual Metastatic Disease</title><p><underline underline-style="single">T. Simon</underline><sup>1</sup>, M. Schmidt<sup>2</sup>, B. Decarolis<sup>1</sup>, A. Eggert<sup>3</sup>, F. Berthold<sup>1</sup>, B. Hero<sup>1</sup></p><p><italic><sup>1</sup>University of Cologne, Pediatric Oncology and Hematology, Cologne, Germany; <sup>2</sup>University of Cologne, Nuclear Medicine, Cologne, Germany; <sup>3</sup>Charite Univeristy Hospital, Pediatric Oncology and Hematology, Berlin, Germany</italic></p><p><bold>Background/Objectives</bold>: Randomized trials on mIBG therapy in the first‐line treatment of high‐risk neuroblastoma are not available. Therefore, we analyzed the national neuroblastoma data base on the impact of I‐131‐meta‐iodobenzylguanidine (mIBG) therapy, local radiotherapy, and single agent ch14.18 immunotherapy in the first‐line therapy of high‐risk neuroblastoma.</p><p><bold>Design/Methods</bold>: Patients of two consecutive national neuroblastoma trials were included if they met all key criteria: (1) stage 4 neuroblastoma, (2) age at diagnosis >18 months, (3) N5/N6 induction chemotherapy, (4) diagnosis between 1997 and 2014. mIBG therapy prior to the myeloablative chemotherapy was scheduled for non‐progressing mIBG positive lesions. Local radiotherapy 36‐40 Gy was delivered to unresectable mIBG positive residual at the primary site. Single agent ch14.18 immunotherapy was stratified according to open trials.</p><p><bold>Results</bold>: A total of 264 patients were included. The median observation time was 8.9 years. The presence of mIBG positive metastases at the end of induction chemotherapy was associated with inferior EFS (5yEFS 29.0+/‐4.5% vs 41.3+/‐4.1%, p=0.049). It had no impact on OS (5yOS 49.7+/‐5.1% vs 51.2+/‐4.2%, p=0.655). Among 108 patients with residual MIBG positive metastatic disease the EFS was similar between patients who underwent mIBG therapy (5yEFS 31.8+/‐6.3%) and patients who did not (5yEFS 25.2+/‐6.4%, p=0.238). The OS was better after mIBG therapy (61.2+/‐6.6%) compared to no mIBG therapy (5yEFS 37.7+/‐7.2%, p=0.038). Multivariable analysis of all 264 patients including the variables MYCN, mIBG therapy, local radiotherapy, and immunotherapy with ch14.18 revealed an independent impact of MYCN amplification (p=0.034, hr 1.445) and ch14.18 treatment (p<0.001, hr 0.455) on EFS, and MYCN amplification (p=0.001, hr 1.894) and ch14.18 treatment (p=0.001, hr 0.475) on OS.</p><p><bold>Conclusions</bold>: mIBG therapy can improve the outcome of high‐risk neuroblastoma patients with incomplete metastatic response to induction chemotherapy. These results warrant a prospective multicenter trial on mIBG therapy. In addition, this analysis confirmed the long term effect of immunotherapy with ch14.18.</p></sec><sec id="pbc26772-sec-0740"><label>O-054</label><title>Thrombocytopenia in MIBG‐Treated Patients May be Prevented by the Concomitant Administration of a Selective Serotonin Reuptake Inhibitor</title><p><underline underline-style="single">T. Blom</underline><sup>1</sup>, M. Hansen<sup>2</sup>, A. Van Kuilenburg<sup>3</sup>, E. Van der Schoot<sup>4</sup>, L. Tytgat<sup>5</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Research, Utrecht, The Netherlands; <sup>2</sup>Sanquin Research, Hematopoiesis, Amsterdam, The Netherlands; <sup>3</sup>Academisch Medisch Centrum, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; <sup>4</sup>Sanquin Research, Experimental Immunohematology, Amsterdam, The Netherlands; <sup>5</sup>Princess Máxima Center for Pediatric Oncology, Pediatric oncology, Utrecht, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Thrombocytopenia is the major toxicity of metaiodobenzylguanidine (MIBG)‐therapy. Whether this is caused by the whole‐body‐absorbed radiation dose or by other mechanisms is not clear. We previously showed that MIBG is transported via the serotonin transporter (SERT) in platelets and via the NET in neuroblastoma. We tested if selective serotonin reuptake inhibitors (SSRIs) inhibit MIBG accumulation in platelets, with no effect on MIBG accumulation in neuroblastoma in a mouse model.</p><p><bold>Design/Methods</bold>: The uptake of [<sup>125</sup>I]MIBG and [<sup>3</sup>H]serotonin in isolated human platelets was inhibited by a panel of SSRIs. MIBG uptake in platelets (presumably via SERT) was compared to uptake in SK‐N‐SH neuroblastoma cells (via NET). The IC<sub>50</sub> (i.e. the inhibitor concentration that reduces the uptake by 50%) and the selectivity (IC<sub>50</sub> ratio of MIBG uptake in neuroblastoma cells over that in platelets) were calculated. MIBG tumor accumulation with and without SSRI's and NET inhibitors was studied in neuroblastoma xenografts. SSRI containing plasma of nude mice was used to test the inhibitory potency on MIBG uptake in human platelets (<italic>ex vivo</italic>).</p><p><bold>Results</bold>: Inhibition of serotonin and MIBG uptake in platelets appeared comparable for the SSRIs suggesting that both substrates share the same transport system. SSRIs were 40‐100 times more potent in inhibiting platelet MIBG uptake than in neuroblastoma cells. Imipramine, a classical tricyclic antidepressant, showed no selectivity and inhibited the MIBG platelet and MIBG neuroblastoma uptake to the same extent. MIBG accumulation in neuroblastoma xenografts was not significantly affected by SSRI administration, but was 60% diminished in mice treated with desipramine (NET inhibitor). SSRI drug levels in the murine circulation highly exceeded those required for effective inhibition of platelet MIBG uptake.</p><p><bold>Conclusions</bold>: SSRIs are effective in reducing MIBG uptake in platelets while leaving the tumor loading unaffected. Administration of SSRIs may prevent MIBG related thrombocytopenia if similar mechanisms are involved in megakaryocytes.</p></sec><sec id="pbc26772-sec-0750"><label>O-055</label><title>Feasibility and Toxicity of Busulfan and Melphalan Conditioning Regimen in the Context of the German Induction Chemotherapy</title><p><underline underline-style="single">B. Hero</underline><sup>1</sup>, T. Simon<sup>1</sup>, H. Lode<sup>2</sup>, A. Eggert<sup>3</sup>, F. Berthold<sup>1</sup></p><p><italic><sup>1</sup>University of Cologne, Pediatric Oncology and Hematology, Cologne, Germany; <sup>2</sup>University Medicine Greifswald, Pediatric Hematology and Oncology, Greifswald, Germany; <sup>3</sup>Charité ‐ Universitätsmedizin Berlin, Pediatric Oncology and Hematology, Berlin, Germany</italic></p><p><bold>Background/Objectives</bold>: High‐dose chemotherapy with autologous stem‐cell rescue is considered standard in the treatment of high risk neuroblastoma patients. A randomized trial recently showed improved outcome with a regimen using busulfan and melphalan (Ladenstein et al., Lancet Oncol, 2017). Per protocol, high‐dose chemotherapy in trials of the German neuroblastoma group (GPOH) consisted of melphalan, etoposide, and carboplatin (MEC). However, in patients with contra‐indications (e.g. ototoxicity), busulfan and melphalan was recommended as an alternative. Here, we evaluated the feasibility and toxicity of busulfan and melphalan in patients treated with the GPOH induction treatment using long‐time infusion of cisplatin, etoposide, and ifosfamid.</p><p><bold>Design/Methods</bold>: Data of high risk neuroblastoma patients registered in the German neuroblastoma trials NB97 and NB2004‐HR and receiving high‐dose chemotherapy with autologous stem‐cell rescue in first line treatment were analyzed.</p><p><bold>Results</bold>: High‐dose chemotherapy with melphalan, etoposide, and carboplatin (MEC) was given to 459 patients, while 79 patients received busulfan and melphalan (Bu‐Mel). mIBG therapy was applied to 135 patients receiving MEC and to nine patients receiving Bu‐Mel in median 17 resp. 19 days prior to high dose chemotherapy. Hematologic recovery was not different between groups (median leukocyte take in both cohorts: 11 days, platelet take: 17 (MEC) vs. 18 days (Bu‐Mel, n.s.)).</p><p>Detailed toxicity data were available in 371 patients (MEC: n=322; Bu‐Mel: n=49) revealing no significant difference in toxicity grade 3 or 4 for fever, infection, stomatitis, or liver enzymes. Veno‐occlusive disease (VOD) was reported in 4.8% after MEC, but in 21.5% after Bu‐Mel.</p><p>Sixteen out of 459 patients (3.5%) receiving MEC and three out of 79 (3.8%) receiving Bu‐Mel died from high dose chemotherapy related complications (n.s.) including VOD in six patients (MEC: n=4; Bu‐Mel: n=2).</p><p><bold>Conclusions</bold>: High‐dose chemotherapy with busulfan and melphalan was feasible after the GPOH induction treatment. As expected, VOD was observed more often, but otherwise, the toxicity was comparable.</p></sec></sec><sec id="pbc26772-sec-0760"><title>Free Paper Session: Bone Tumours ‐ Nollenburg Prize</title><sec id="pbc26772-sec-0770"><label>O-056</label><title>Pathological Fractures and Prognosis of High‐Grade Osteosarcoma of the Extremities in Adoloscents and Young Adults. An Analysis of 1,299 Cooperative Osteosarcoma Study Group (COSS) Patients</title><p><underline underline-style="single">L. Kelley</underline><sup>1</sup>, M. Schlegel<sup>1</sup>, S. Hecker‐Nolting<sup>2</sup>, C. Rössig<sup>3</sup>, P. Reichardt<sup>4</sup>, L. Kager<sup>5</sup>, T. Kühne<sup>6</sup>, G. Gosheger<sup>7</sup>, R. Windhager<sup>8</sup>, K. Specht<sup>9</sup>, M. Kevric<sup>2</sup>, H. Rechl<sup>10</sup>, P.U. Tunn<sup>11</sup>, D. Baumhoer<sup>12</sup>, M. Werner<sup>11</sup>, T. von Kalle<sup>13</sup>, M. Nathrath<sup>14</sup>, S. Burdach<sup>1</sup>, S. Bielack<sup>2</sup>, I. von Luettichau<sup>1</sup></p><p><italic><sup>1</sup>Klinikum Rechts der Isar‐ Technische Universität München‐ CCCM Munich ‐ Comprehensive Cancer Center‐ and German Translational Cancer Research Consortium DKTK, Department of Paediatrics, München, Germany; <sup>2</sup>Klinikum Stuttgart ‐ Olgahospital, Paediatrics 5 – Oncology‐ Hematology‐ Immunology, Stuttgart, Germany; <sup>3</sup>Klinik für Kinder‐ und Jugendmedizin‐ Universitätsklinikum Münster, Pediatric Hematology and Oncology, Münster, Germany; <sup>4</sup>Onkologisches Zentrum Berlin‐Buch, Klinik für Interdisziplinäre Onkologie, Berlin, Germany; <sup>5</sup>St. Anna Kinderspital, Department for Hematology and Oncology, Vienna, Austria; <sup>6</sup>Universitäts‐Kinderspital beider Basel, Pediatric Oncology and Hematology, Basel, Switzerland; <sup>7</sup>Universitätsklinikum Münster, Klinik für Allgemeine Orthopädie und Tumororthopädie, Münster, Germany; <sup>8</sup>Allgemeines Krankenhaus der Stadt Wien, Universitätsklinik für Orthopädie der Medizinischen Universität Wien, Vienna, Austria; <sup>9</sup>Klinikum rechts der Isar ‐ Technische Universität München, Institut für Allgemeine Pathologie und Pathologische Anatomie, Munich, Germany; <sup>10</sup>Klinikum Rechts der Isar, Klinik und Poliklinik für Orthopädie und Sportorthopädie, München, Germany; <sup>11</sup>HELIOS Klinikum Berlin‐Buch, Zentrum für Orthopädie und Unfallchirurgie ‐ Department Tumororthopädie, Berlin, Germany; <sup>12</sup>Universitätsspital Basel, Institut für Pathologie ‐ Knochentumor‐Referenzzentrum, Basel, Switzerland; <sup>13</sup>Klinikum Stuttgart ‐ Olgahospital, Radiologisches Institut, Stuttgart, Germany; <sup>14</sup>Klinikum Kassel, Pediatric Hematology and Oncology, Kassel, Germany</italic></p><p><bold>Background/Objectives</bold>: The objective of this study was to investigate the age group of Adolescents and Young Adults (AYAs) regarding correlations between pathological fractures (PFs) and prognosis of patients with primary central high‐grade osteosarcoma of the extremities.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed 1,299 patients ages 15 to 29 with localized or metastatic primary central high‐grade osteosarcoma of the extremities, treated between 1980 and 2010 and registered into the COSS‐database. Intended treatment included pre‐ and postoperative chemotherapy and surgery. Univariate survival analysis was performed with Kaplan‐Meier‐Analysis and compared with Log‐Rank‐Test. Multivariate survival analysis was conducted with Cox's proportional hazards model.</p><p><bold>Results</bold>: Out of 1,299 patients, 97 (7.5%) had documented PFs. Presence of PF correlated with younger age (P=0.040), tumor site (P<0.001), localization within the affected bone (P<0.001), histological subtype (P<0.001) and relative tumor size (P=0.001), but not with sex, body mass index, primary metastases, type of operation, local surgical remission or response to chemotherapy. In univariate survival analysis, 5‐year overall survival (OAS) of patients with and without PF was 61% vs. 71%, respectively (P=0.025), 5‐year event‐free survival (EFS) was 53% vs. 59% (P=0.158) and 5‐year local recurrence‐free survival (LRFS) was 60% vs. 69% (P=0.049). In multivariate Cox analysis, PF resulted as an independent prognostic factor for overall survival (P=0.028) with a hazard ratio of 1.539 (95%CI: 1.048–2.260) and 5‐year LRFS (P=0.023; HR=1.556, 95%CI:1.062–2.278); however, it did not result as an independent prognostic factor for EFS (P=0.646; HR=1.090, 95%CI: 0.755–1.572).</p><p><bold>Conclusions</bold>: We observed the presence of PF to correlate with inferior OAS and LRFS, with PF remaining as an independent prognostic factor in multivariable analysis. Our survival analyses suggest that local recurrence might be more common in patients with PF. Therefore further analysis is needed to exclude other influencing factors. However, the presence of PF does not seem to influence the type of operation performed.</p></sec><sec id="pbc26772-sec-0780"><label>O-057</label><title>Development of a Standardized System for Measuring Value‐Based Healthcare in Osteosarcoma at Children's Cancer Hospital Egypt</title><p>R. Soliman<sup>1</sup>, <underline underline-style="single">M. Zamzam</underline><sup>2</sup>, W. Eweida<sup>3</sup>, S. Abouelnaga<sup>4</sup></p><p><italic><sup>1</sup>Children's Cancer Hospital ‐ 57357 Egypt, Health Economics and Outcomes, Cairo, Egypt; <sup>2</sup>Children's Cancer Hospital ‐ 57357 Egypt, Pediatric Oncology, Cairo, Egypt; <sup>3</sup>Children's Cancer Hospital ‐ 57357 Egypt, Chief Operating Office, Cairo, Egypt; <sup>4</sup>Children's Cancer Hospital Egypt, Chief Executive Office, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Value‐based healthcare is crucial for medical conditions that have failed to improve outcomes such as Osteosarcoma. Aim of work was to develop a standardized system to measure the value of health care delivered to Osteosarcoma patients, through developing a uniform set of health outcomes for Osteosarcoma and using a consistent approach to measure the costs of care delivery.</p><p><bold>Design/Methods</bold>: The Porter's Outcomes Measurement Hierarchy was used to define the domains of health outcomes for Osteosarcoma. Time‐driven activity‐based costing (TDABC) method was used to determine the total costs of care delivered to Osteosarcoma patients throughout their journey of cure.</p><p><bold>Results</bold>: A standardized health outcomes reporting system was developed for Osteosarcoma based on the outcomes that mattered most to the patients. The degree of health was measured by the remission status as defined by EURAMOS‐1 protocol criteria, response to neo‐adjuvant treatment was defined as poor or good response pathologically, functional outcome was defined using the MSTS system, and return to normal activities was measured by the AMPS tool. Process of recovery was measured by evaluating the adverse events using CTCAE v.4.0, determining the delay in care cycles, reporting any medical or medication errors, and assessing the time to recovery. Sustainability of health was defined by measuring the quality of life using PedsQL questionnaire, palliative care at end‐of‐life using POS survey, and measuring the long‐term sequelae of treatment. Process mapping was done for Osteosarcoma care cycles, which included a total of twenty‐five process maps to cover all the activities of care delivery. The costs were calculated based on the TDABC method for each process map.</p><p><bold>Conclusions</bold>: Developing a standardized system for measuring Osteosarcoma outcomes and the total costs for care is fundamental to improving the value of health care delivered to Osteosarcoma patients and for value‐based decision‐making.</p></sec><sec id="pbc26772-sec-0790"><label>O-058</label><title>Outcomes and Prognostic Variables in Relapsed Primitive Neuroectodermal Tumors (PNET) Treated with a Hybrid Salvage Chemotherapy Regimen</title><p><underline underline-style="single">K. Vijaysekharan</underline><sup>1</sup>, S. Ramanathan<sup>1</sup>, M. Prasad<sup>1</sup>, T. Vora<sup>1</sup>, G. Chinnaswamy<sup>1</sup>, A. Gulia<sup>2</sup>, A. Janu<sup>3</sup>, B. Rekhi<sup>4</sup>, M. Ramadwar<sup>4</sup>, N. Khanna<sup>5</sup>, S. Laskar<sup>5</sup>, N. Purandare<sup>6</sup>, A. Puri<sup>2</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Medical Oncology ‐ Pediatric, Mumbai, India; <sup>2</sup>Tata Memorial Hospital, Surgical oncology ‐ Bone and Soft Tissue Tumor, Mumbai, India; <sup>3</sup>Tata Memorial Hospital, Radiodiagnosis, Mumbai, India; <sup>4</sup>Tata Memorial Hospital, Pathology, Mumbai, India; <sup>5</sup>Tata Memorial Hospital, Radiation Oncology, Mumbai, India; <sup>6</sup>Tata Memorial Hospital, Nuclear Medicine, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Survival in relapsed PNET continues to be suboptimal (5 year survival:10‐20%). Considering that 30% patients with initially non‐metastatic PNET and a larger proportion of primary metastatic disease relapse, factors that determine outcome of relapsed patients needs clarity. This is an analysis of patients with relapsed PNET treated on a hybrid salvage regimen consisting of Topotecan/cyclophosphamide and Irinotecan/Temozolomide.</p><p><bold>Design/Methods</bold>: Retrospective analysis of patients with relapsed PNET treated with curative intent from Jan’ 2012 to Dec’2016. All patients received a total of 12 cycles of chemotherapy and local therapy (surgery/radiotherapy after initial 4 cycles). A subset of patients also received oral metronomic maintenance therapy for 12 months.</p><p><bold>Results</bold>: The salvage regimen was employed in a total of 53/108 relapsed patients with the rest having opted for palliation upfront. The median age of the treated patients is 19 years(4‐40); male:female‐2.7:1. The median time to first relapse was 18.8 months from end of primary treatment. While 41/53 patients(77%)completed the salvage therapy, 6 patients(11.3%) progressed and 6(11.3%) abandoned treatment. The median follow up of the study cohort is 23.6 months. Of the analyzable cohort(n=47),18(47%)had a second relapse. At time of last follow up, 17 patients had died (including one due to toxicity) and 30 patients were alive (22 with no active disease and 8 with disease). The 4 year‐EFS and OS is 29.7% and 43% respectively for the entire cohort. While older patients (>17 years) had a better EFS (p=0.013), time to first relapse, site of primary disease, metastatic status at primary diagnosis, type of relapse (local vs metastatic), and gender had no impact on outcome.</p><p><bold>Conclusions</bold>: Salvage chemotherapy in relapsed PNET have been shown to have encouraging results in early phase and retrospective studies. This reasonably well tolerated regimen produced promising results in a tumor with otherwise poor outcome.</p></sec><sec id="pbc26772-sec-0800"><label>O-059</label><title>Treatment of Localized Ewing Sarcomas of the Rib: Euro‐EWING99 Analysis of French Patients</title><p><underline underline-style="single">A. Claren</underline><sup>1</sup>, J. Doyen<sup>1</sup>, M. Eric<sup>2</sup>, A. Jouin<sup>3</sup>, S. Bolle<sup>4</sup>, A. Laprie<sup>5</sup>, N. Corradini<sup>6</sup>, C. Vérité<sup>7</sup>, P.Y. Bondiau<sup>1</sup>, P. Marec‐Bérard<sup>6</sup>, M.C. Le Deley<sup>8</sup>, N. Gaspar<sup>9</sup>, L. Claude<sup>10</sup></p><p><italic><sup>1</sup>Centre Antoine Lacassagne, Radiotherapy, Nice, France; <sup>2</sup>Hôpital Necker, Chirurgie orthopédique et traumatologique pédiatrique, Paris, France; <sup>3</sup>Centre Oscar Lambret, Radiotherapy, Lille, France; <sup>4</sup>Gustave Roussy, Radiotherapy, Villejuif, France; <sup>5</sup>Institut Universitaire du Cancer de Toulouse, Radiotherapy, Toulouse, France; <sup>6</sup>Institut d'hématologie et d'Oncologie Pédiatrique Centre Léon Bérard, Pediatry, Lyon, France; <sup>7</sup>CHU de Bordeaux, Radiotherapy, Bordeaux, France; <sup>8</sup>Centre Oscar Lambret, Public health, Lille, France; <sup>9</sup>Gustave Roussy, Pediatry, Villejuif, France; <sup>10</sup>Centre Léon Bérard, Radiotherapy, Lyon, France</italic></p><p><bold>Background/Objectives</bold>: Primary Ewing sarcoma (ES) of the rib represents the most frequent thoracic tumor in children and young adults, but specific data published remain scarce. The main objectives of this study were to evaluate survivals according to local treatment and to define precisely prognostic factors of these tumors.</p><p><bold>Design/Methods</bold>: French patients included in Euro‐EWING99 study (EE99) for localized ES of the rib, with or without pleural effusion, were eligible. Data were collected from the prospective EE99 database. In addition, a systematic retrospective review of all patient records was performed, to obtain more precise clinical, radiological or therapeutic data, which were not included in the EE99 database.</p><p><bold>Results</bold>: Eighty‐two patients, median age 13.6 years, were treated between 12/1999 and 04/2013. Median follow‐up was 8.4 years. Fifty‐one percent had initial pleural effusion. Local treatment included surgery in 81/82 patients, mostly after induction chemotherapy. Sixty patients (73%) were irradiated: 28% on the tumor bed, 13% on the hemithorax (HRT), and 32% on both. Five‐year disease free survival (DFS) and overall survival (OS) were 69% and 71% respectively. Twenty‐six patients (31%) relapsed, with a median time of 19 months after diagnosis. Pleural effusion and incomplete surgical resection (R1 or R2) have proven to be independent prognostic factors for DFS and OS. In case of initial pleural effusion, documented or not, OS was 27% without HRT versus 68% after HRT (p=0.01). Delivering radiation on the tumor bed increased significantly the OS only in case of poor histological response.</p><p><bold>Conclusions</bold>: Pleural effusion at diagnosis and incomplete resection are two independent risk factors for survival in localized ES of the rib. Hemithoracic irradiation increases significantly overall survival in case of pleural effusion, proven or not. The impact of the boost on tumor bed according to the histological response and quality of surgery should be confirmed on more patients.</p></sec></sec><sec id="pbc26772-sec-0810"><title>Free Paper Session: PODC</title><sec id="pbc26772-sec-0820"><label>O-060</label><title>Developing a Clinical Diagnostic Algorithm for Pediatric Burkitt Lymphoma in Malawi</title><p><underline underline-style="single">K. Westmoreland</underline><sup>1,2</sup>, N. Montgomery<sup>3</sup>, T. van der Gronde<sup>4</sup>, S. Itimu<sup>4</sup>, A. Salima<sup>4</sup>, T. Tomoka<sup>5,6</sup>, B. Dhungel<sup>5</sup>, C. Kampani<sup>5</sup>, M. Sanders<sup>7</sup>, D. Dittmer<sup>7</sup>, G. Fedoriw<sup>8</sup>, G. Satish<sup>4,9,10</sup></p><p><italic><sup>1</sup>UNC Project‐Malawi, Pediatric Hematology Oncology, Lilongwe, Malawi; <sup>2</sup>University of North Carolina, Pediatric Hematology Oncology, Chapel Hill, USA; <sup>3</sup>University of North Carolina, Pathology, Chapel Hill, USA; <sup>4</sup>UNC Project‐Malawi, Oncology, Lilongwe, Malawi; <sup>5</sup>UNC Project‐Malawi, Pathology, Lilongwe, Malawi; <sup>6</sup>University of Malawi School of Medicine, Pathology, Lilongwe, Malawi; <sup>7</sup>University of North Carolina, Microbiology and Immunology, Chapel Hill, USA; <sup>8</sup>University of North Carolina, Pathology, Chapell Hill, USA; <sup>9</sup>University of North Carolina, Oncology and Infectious Disease, Chapel Hill, USA; <sup>10</sup>University of Malawi School of Medicine, Oncology, Lilongwe, Malawi</italic></p><p><bold>Background/Objectives</bold>: Burkitt lymphoma (BL) is the commonest pediatric cancer in sub‐Saharan Africa (SSA). Tissue‐based molecular confirmation of pediatric BL is standard in resource‐rich settings, but is often impossible in SSA settings due to limited pathology, absent molecular diagnostic tools, and difficulty obtaining diagnostic tissue particularly from visceral sites.</p><p><bold>Design/Methods</bold>: We prospectively enrolled pediatric patients <18 years of age with possible lymphoma at Kamuzu Central Hospital in Lilongwe. Based on hematopathologist review of diagnostic specimens in the United States, cases were categorized as gold standard BL, possible but not confirmed BL, and non‐BL. Gold standard BL was defined histologically based on classic morphology and immunophenotype (CD20+, CD10+, BCL2‐, TdT‐, Ki‐67 >90%). Plasma Epstein‐Barr virus load (EBV‐VL) was measured at baseline by quantitative polymerase chain reaction. Gold standard BL was compared to non‐BL using a t‐test.</p><p><bold>Results</bold>: We identified 17 gold standard BL cases and 23 non‐BL cases for analysis. Fifty‐seven cases of possible BL were excluded, most due to cytologic specimen only prohibiting detailed immunophenotyping. Median age of BL cases was 11.7 years (IQR 7.8‐14.2) and non‐BL was 12.3 years (IQR 10.0‐14.3, p=0.66). Median lactate dehydrogenase (LDH) level at diagnosis was 642 IU/L (IQR 418‐1465) for BL and 295 IU/L (IQR 254‐410, p=0.053) for non‐BL. Median plasma EBV‐VL at diagnosis was 6.5 log<sub>10</sub>copies/mL (IQR 4.9‐7.1) for BL and 4.7 log<sub>10</sub>copies/mL (IQR 2.8‐5.5, p=0.039) for non‐BL. The positive predictive value of LDH >1.25x the upper limit of normal (ULN) and EBV‐VL >3.0 for BL was 71% (10/14 cases). The negative predictive value of LDH < 1.25x ULN or EBV‐VL <3.0 was 92% (12/13 cases).</p><p><bold>Conclusions</bold>: LDH and EBV‐VL are implementable diagnostic tools that can assist with confirming pediatric BL in SSA. Ongoing work includes developing and validating a clinical diagnostic algorithm for molecularly confirmed pediatric BL in a larger cohort of Malawian children.</p></sec><sec id="pbc26772-sec-0830"><label>O-061</label><title>Clinical Profile and Outcome of Intermediate and High Risk Classical Hodgkin Lymphoma Treated in a Tertiary Care Cancer Centre</title><p><underline underline-style="single">B. Cheriyalinkal Parambil</underline><sup>1</sup>, G. Narula<sup>1</sup>, M. Prasad<sup>1</sup>, B. Arora<sup>1</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Pediatric Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Classical Hodgkin lymphoma(cHL) has excellent 5‐year OS, though long term survival declines after 5 years due to relapse and late effects of therapy. Recent strategies seek to limit anthracyclines, alkylating agents, bleomycin and radiation therapy. We studied clinical profile and outcome of children with advanced cHL on this strategy.</p><p><bold>Design/Methods</bold>: Children(<15years) with cHL from February 2013 to December 2016 were retrospectively analyzed. Staging was by Positron emission computerized tomography(PET‐CT) in all. Bulky sites(X) at baseline received involved field radiation(IFRT) post‐chemotherapy. IAX,IBX,IIAX,IIE,IIIA were Intermediate‐risk(IR) and IIBX,IIBE,IIIX,IIIE,IIIB,IV High risk(HR). Patients received 2 cycles OEPA(vincristine,etoposide,prednisolone, doxorubicin) followed by early PET‐CT. Complete metabolic responses(CMR) received 2 cycles COPDac(cyclophosphamide,vincristine,prednisolone,dacarbazine) for IR,4 for HR. Partial Responses(PR) were re‐evaluated after 2 or 4 cycles COPDac. Refractory at end treatment or progressive disease at any time were considered for salvage options.</p><p><bold>Results</bold>: Hundred and seventeen children(IR‐12, HR‐105) were eligible. Median age was 9 years,M:F‐4.5:1,B‐symptoms‐70.6%,Bulky disease‐86%. Median LDH was 273IU/L(range,24‐986), and median B2‐microglobulin‐2.68mg/l(range,1.58‐8.58). Sixty‐four(55.3%) had Hemoglobin<10.5 g/dl,and 78(66.4%) serum albumin10.5g/dl.</p><p><bold>Conclusions</bold>: Primary chemotherapy based on OEPA+COPDac with IFRT in advanced cHL has good 3‐year OS and EFS with manageable toxicities,but long‐term effects needs further follow‐up. Intensifying primary chemotherapy in advanced cHL attains better disease control,while avoiding therapies with known late toxicities.</p></sec><sec id="pbc26772-sec-0840"><label>O-062</label><title>Improvement in Compliance of Patients with Non‐Metastatic Retinoblastoma with Low‐Cost Prospective Database and Patient Tracking System: A Study from Tertiary Care Centre in India</title><p><underline underline-style="single">A. Batra</underline><sup>1</sup>, D. Dhawan<sup>1</sup>, R. Paul<sup>1</sup>, M. Kumari<sup>1</sup>, S. Bakhshi<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Medical Oncology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Poor compliance has been reported in retinoblastoma (RB) from resource constraint settings. Prospective database and patient tracking system (PDPTS) may improve compliance and hence treatment outcomes in RB.</p><p><bold>Design/Methods</bold>: PDPTS was introduced in January 2008 at our centre, wherein patients were contacted telephonically on missing their outpatient visit and were encouraged to complete the treatment; and contact information was updated at each visit. We compared compliance of patients with non‐metastatic RB treated prior to and after PDPTS. ‘Adequate therapy’ and ‘Effective therapy’ defined compliance during treatment period (Stage 0: 4 cycles chemotherapy and 1 EUA; Stage 1: Enucleation; Stage 2: Enucleation and 4 cycles chemotherapy; Stage 3: Enucleation, 4 cycles chemotherapy and radiation) and follow‐up (1 year follow‐up or recurrence, in addition to adequate therapy), respectively.</p><p><bold>Results</bold>: Two hundred fourteen and 298 patients with RB were treated during June 2003 to December 2007 (phase 1) and January 2008 to December 2014 (phase 2), respectively. Median age (36 months) and sex distribution (male: female‐2:1) were similar in both phases. Patients with stage III RB had lowest compliance. Proportion of patients receiving adequate (All stages: 63% vs 77%, p=0.001; Stage 0: 30% vs 100%, p=0.001; Stage 1: 78% vs 90%, p=0.002; Stage 2: 58% vs 75%, p=0.39; Stage 3: 26% vs 47%, p=0.03) and effective therapies (All stages: 62% vs 75%, p=0.001; Stage 0: 26% vs 100%, p<0.001; Stage 1: 78% vs 90%, p=0.002; Stage 2: 50% vs 62%, p=0.58; Stage 3: 24% vs 42%, p=0.06) was significantly higher in phase 2. Annual cost was 7USD per patient and 350 USD per extra effectively treated patient.</p><p><bold>Conclusions</bold>: PDPTS has significantly improved compliance in patients with RB with minimal added cost. Improvement was seen even in stage III disease with lowest compliance.</p></sec><sec id="pbc26772-sec-0850"><label>O-063</label><title>Impact of a Patient Navigator Program on Pediatric Cancer Outcomes in a Low Resource Setting</title><p>F. Alvi<sup>1</sup>, J. Mafwimbo<sup>2</sup>, N. Masalu<sup>2</sup>, <underline underline-style="single">K. Schroeder</underline><sup>3,4</sup></p><p><italic><sup>1</sup>Washington University, School of Medicine, St. Louis, USA; <sup>2</sup>Bugando Medical Centre, Oncology, Mwanza, Tanzania; <sup>3</sup>Duke University, Pediatric Hematology/ Oncology, Durham, USA; <sup>4</sup>Duke University, Global Health, Durham, USA</italic></p><p><bold>Background/Objectives</bold>: Oncology patient navigation programs have been successfully implemented at hospitals throughout the U.S., enhancing the quality of care through financial guidance, treatment coordination, and psychosocial support. In low resource settings, the barriers to receiving cancer care are increased and a patient navigator in this setting has the potential to significantly impact outcomes. However, there is limited research on the efficacy of such programs in these settings. At Bugando Medical Centre (BMC) in Mwanza, Tanzania, a patient navigation program was established to identify potential pediatric oncology patients, then assist patients and their families throughout the diagnosis and treatment process, with the goals of reducing time to oncology evaluation and diagnosis, and ultimately improving survival outcomes.</p><p><bold>Design/Methods</bold>: A retrospective analysis of hospital records was conducted of all pediatric oncology patients seen at BMC from 2010‐2016, separated by presentation date before or after establishment of navigation program. Collected data includes demographics, diagnosis, time from presentation to oncology evaluation and diagnosis, treatment completion and 1 year survival outcomes.</p><p><bold>Results</bold>: A total of 238 patient files were reviewed, with 169 pre‐ and 69 post‐ program initiation. Patient groups did not differ by age or gender (p=0.329 and 0.744), or diagnosis distribution. After establishing a patient navigator program, the average time to oncology evaluation decreased from 49.7 to 16.6 days (p=0.015), and time to diagnosis decreased from 49.1 to 23.6 days (p=0.07). Treatment abandonment decreased from 50% to 38% (p<0.001) and 1 year survival increased from 27% to 53% (p<0.001).</p><p><bold>Conclusions</bold>: In pediatric cancer, early diagnosis is critical to the initiation of chemotherapy and improving outcomes. This study has shown that a patient navigation program has the potential to significantly impact patient outcomes, and should be included in comprehensive pediatric cancer care programs.</p></sec><sec id="pbc26772-sec-0860"><label>O-064</label><title>Cost Effectiveness of Implementing a Pediatric Early Warning System (PEWS) At a Pediatric Oncology Hospital in a Low‐Middle Income Country</title><p><underline underline-style="single">A. Agulnik</underline><sup>1</sup>, F. Antillon‐Klussmann<sup>2</sup>, D.J. Soberanis Vasquez<sup>2</sup>, R.H. Arango<sup>2</sup>, E. Moran<sup>2</sup>, V. Lopez<sup>2</sup>, C. Rodriguez‐Galindo<sup>1</sup>, N. Bhakta<sup>1</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Department of Global Pediatric Medicine, Memphis, USA; <sup>2</sup>Unidad Nacional de Oncología Pediátrica, Hematology/Oncology, Guatemala, Guatemala</italic></p><p><bold>Background/Objectives</bold>: Hospitalized pediatric oncology patients are at high risk for clinical decline and mortality, particularly in low‐ and middle‐income countries. Pediatric Early Warning Systems (PEWS) are nursing‐administered clinical assessment tools that aid with early identification of deterioration. In 2014, a multidisciplinary team implemented a modified PEWS at Unidad Nacional de Oncología Pediátrica (UNOP), a pediatric oncology hospital in Guatemala. Published data demonstrated this intervention reduced clinical deterioration events and PICU utilization. In this study, we investigate the cost and cost‐effectiveness of PEWS implementation at UNOP.</p><p><bold>Design/Methods</bold>: The variable costs of running and maintaining the PICU and floor wards at UNOP were calculated for 2013 (pre‐implementation) and 2015 (post‐implementation) using hospital administrative data. PEWS implementation costs were based on study expenditures in 2014. The number of PICU inpatient‐days averted due to reduced unplanned PICU transfers (clinical deterioration events) post‐implementation was calculated after adjusting for changes in total hospital inpatient‐days. Hospital savings per inpatient‐day due to reduced variable cost expenditures from unplanned PICU transfers were calculated. All costs were adjusted for inflation and standardized using 2013 international dollars (I$).</p><p><bold>Results</bold>: There were 457 fewer PICU inpatient‐days due to unplanned transfers after PEWS implementation in 2015 compared to 2013. The difference in variable costs of an unplanned PICU transfer was I$597.36 per day (PICU minus ward). The total cost of implementing PEWS at UNOP was I$20,706.08, representing a cost I$10.08 per hospital inpatient‐day. Through reductions in variable PICU costs such as supportive care measures, UNOP was able to save a net I$122.77 per inpatient admission (I$252,176.31 annual net savings) as a result of PEWS implementation.</p><p><bold>Conclusions</bold>: Implementation of PEWS at UNOP, a pediatric oncology hospital located in a low‐middle income country, resulted in net cost‐savings. This work demonstrates that hospital investment in a PEWS program can both improve the quality pediatric cancer care and reduce hospital costs.</p></sec><sec id="pbc26772-sec-0870"><label>O-065</label><title>Participatory Action Research in Lilongwe, Malawi: Identification of Five Pediatric Palliative Care Interventions That Address Total Pain for Pediatric Oncology Patients and Their Families</title><p><underline underline-style="single">M. Butia Mutai</underline><sup>1,2</sup>, I. Mtete Kumwenda<sup>1,2</sup>, M. Chasela<sup>1,2</sup>, A. Mpasa<sup>1,2</sup>, S. Wachepa<sup>1,2</sup>, P. Ward<sup>1</sup>, P. Musiwa<sup>1</sup>, P. Wasswa<sup>1</sup>, P. Mehta<sup>3</sup>, N.K. El‐Mallawany<sup>3</sup>, P. Kazembe<sup>1</sup>, D. Mahoney<sup>4</sup>, J. Casas<sup>3,5</sup></p><p><italic><sup>1</sup>Kamuzu Central Hospital, Pediatric Oncology, Lilongwe, Malawi; <sup>2</sup>Baylor College of Medicine Children's Foundation Malawi, Pediatric Oncology, Lilongwe, Malawi; <sup>3</sup>Baylor College of Medicine, Texas Children's Cancer and Hematology Centers, Houston, USA; <sup>4</sup>Baylor College of Medicine, Texas Children's Hospital Pediatric Palliative Care, Houston, USA; <sup>5</sup>Baylor College of Medicine, Texas Children's Hospital Section of Palliative Care, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: The World Health Organization defines effective pediatric palliative care (PPC) as the total care of a child's body, mind and spirit involving interdisciplinary support to the entire family using community resources. While assessment and management of children's pain remains a global priority, the International Children's Palliative Care Network has also identified creation of interventions and models of care for PPC as a top global research priority. Additional literature demonstrates that participatory action research (PAR) results in sustainable health care delivery models. A program that maximizes community involvement to establish interventions and models of care for PPC and treatment of total pain in Malawi is needed.</p><p><bold>Design/Methods</bold>: Qualitative data obtained through semi‐structured interviews were collected and analyzed to identify methods to address patients’ total pain. Participants included bereaved parents of children with incurable hematologic/oncologic diagnoses (n=5) and medical providers from a tertiary care public hospital oncology unit (n=5). Two independent reviewers conducted thematic data analyses.</p><p><bold>Results</bold>: Five interventions to mitigate total pain were identified. All participants described parents’ “abandonment from their spiritual community” and expressed urgent need for spiritual support. All participants cited need for financial support for food security. Supportive home visits and enhanced community education to minimize stigma were universally suggested. All parents recommended support groups to address emotional/psychological distress. Four medical providers advocated for play therapy to address patients’ stress and pain, and all providers cited the need for ongoing psychosocial support training.</p><p><bold>Conclusions</bold>: Using PAR to promote community involvement in the creation of a PPC program to treat total pain in Malawi is feasible and enlightened areas of focus. Financial support, spiritual support, play therapy, home visits, and parental support groups were identified as the most immediate needs and will guide next steps in developing a novel PPC program in this population.</p></sec></sec><sec id="pbc26772-sec-0880"><title>Free Paper Session: Neuroblastoma ‐ Biology</title><sec id="pbc26772-sec-0890"><label>O-066</label><title>Mutations in CIC, DMD and PHOX2B Activate the RAS‐MAPK Pathway in Neuroblastoma and Activation of this Pathway Causes Tumor Progression</title><p><underline underline-style="single">T.F. Eleveld</underline><sup>1,2</sup>, L. Schild<sup>1</sup>, J. Koster<sup>2</sup>, D.A. Zwijnenburg<sup>2</sup>, L. Alles<sup>1</sup>, M.E. Ebus<sup>1</sup>, R. Volckmann<sup>2</sup>, G.A. Tijtgat<sup>3</sup>, P. van Sluis<sup>2</sup>, H.N. Caron<sup>3</sup>, R. Versteeg<sup>2</sup>, J.J. Molenaar<sup>1</sup></p><p><italic><sup>1</sup>Department of Translational Research, Princess Maxima Centre for Childhood Oncology, Utrecht, the Netherlands; <sup>2</sup>Department of Oncogenomics, AMC Amsterdam, Amsterdam, the Netherlands; <sup>3</sup>Department of Pediatric Oncology, Emma Children′s Hospital, AMC Amsterdam, Amsterdam, the Netherlands</italic></p><p><bold>Background/Objectives</bold>: We recently showed that mutations affecting the RAS‐MAPK pathway occur frequently in neuroblastoma relapse tumors. We hypothesized that activation of this pathway is associated with poor prognosis and tumor progression. Hence the objectives were to detect the activation state of the RAS‐MAPK pathway in tumors, correlate this to prognosis and find mutations that can serve as biomarkers for pathway activation.</p><p><bold>Design/Methods</bold>: We generated a gene signature that can identify the activation state of the RAS‐MAPK pathway in cell lines and tumors. These data were correlated to Whole Genome Sequencing data to identify novel mutations that activate this pathway. Candidate mutations were induced in cell lines using gene editing and characterized both in vitro and in vivo.</p><p><bold>Results</bold>: In primary neuroblastoma tumors activation of the RAS‐MAPK pathway correlates with poor survival and is associated with mutations in ALK and other known RAS‐MAPK genes. From integrative analysis we identify mutations in PHOX2B, CIC and DMD that activate the RAS‐MAPK pathway in vitro and we show that activation of this pathway causes tumor progression in vivo.</p><p><bold>Conclusion</bold>: We identify novel biomarkers of RAS‐MAPK activation and reinforce this pathway as a promising target in neuroblastoma. Further research should determine whether the identified mutations also function as biomarkers for sensitivity to MEK inhibition.</p></sec><sec id="pbc26772-sec-0900"><label>O-067</label><title>Primary Site of Origin Predicts Differential Genomics in Thoracic Versus Adrenal Neuroblastoma</title><p><underline underline-style="single">B. Truong</underline><sup>1</sup>, D. Oldridge<sup>2</sup>, D. Russ<sup>2</sup>, Z. Vaksman<sup>2</sup>, S. Diskin<sup>2</sup>, Y. Mosse<sup>2</sup>, S. DuBois<sup>3</sup>, J. Maris<sup>2</sup>, K. Matthay<sup>1</sup></p><p><italic><sup>1</sup>University of California‐ San Francisco, Pediatrics, San Francisco, USA; <sup>2</sup>University of Pennsylvania School of Medicine, Pediatrics, Philadelphia, USA; <sup>3</sup>Harvard Medical School, Dana‐Farber / Boston Children's Cancer and Blood Disorders Center, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is the second most common extracranial malignancy of childhood, and has long been recognized as a biologically and clinically heterogeneous disease. Based on recent studies demonstrating a significant relationship between the primary tumor site, prognosis, and tumor biological features, we hypothesized that thoracic and adrenal neuroblastoma represent different disease subsets with different genomic features.</p><p><bold>Design/Methods</bold>: We utilized the TARGET dataset to evaluate the genetic profiles of adrenal (N=646) versus thoracic (N=118) primary tumors. We also evaluated for association of common germline variation with primary site in a separate European‐American cohort of adrenal (N=707) or thoracic (N=320) primary tumors. Appropriate platforms were employed to evaluate differences in copy number alterations, mutations, RNA expression, pathway enrichment, and common germline variation between primary sites. Binary variable associations were evaluated by Fisher‐exact test. Prior evidence of <italic>in vitro</italic> transforming capability were applied to call high‐likelihood driver mutations in <italic>ALK</italic> prior to association testing.</p><p><bold>Results</bold>: We observed higher rates of <italic>MYCN</italic> amplification, chromosome 1q gain, and chromosome 11q deletion among adrenal tumors, which were highly predictive of functional signatures observed in RNA data. Adrenal neuroblastomas were less likely to harbor <italic>ALK</italic> driver mutations than thoracic cases among all cases (OR 0.53, 95% CI 0.29‐0.97) and among cases without <italic>MYCN</italic> amplification (OR 0.35, 95% CI 0.18‐0.65). Common germline SNPs in <italic>BARD1</italic> (previously associated with high‐risk neuroblastoma) were found to be strongly associated with predisposition for origin at adrenal, rather than thoracic, sites.</p><p><bold>Conclusions</bold>: Genomic features differ between adrenal and thoracic neuroblastoma. Most unfavorable somatic features (<italic>MYCN</italic> amplification and segmental chromosomal aberrations) were more common among adrenal tumors, though <italic>ALK</italic> driver mutations were more common among thoracic tumors. The presence of specific germline variants increase the likelihood of adrenal over thoracic site of origin, reinforcing the differences between these two subgroups of this disease.</p></sec><sec id="pbc26772-sec-0910"><label>O-068</label><title>Liquid Biopsies of Patients with HIGH‐RISK Neuroblastoma Disclose Exosomal miRNA Modulation after the Induction Therapy</title><p><underline underline-style="single">M. Morini</underline><sup>1</sup>, D. Cangelosi<sup>1</sup>, D. Segalerba<sup>1</sup>, R. Luksch<sup>2</sup>, A. Castellano<sup>3</sup>, D. Fruci<sup>3</sup>, J. Font de Mora<sup>4</sup>, V. Castel<sup>5</sup>, A. Canete<sup>5</sup>, Y. Yanez<sup>5</sup>, S. Burchill<sup>6</sup>, V.F. Viprey<sup>6</sup>, A. Garaventa<sup>7</sup>, A.R. Sementa<sup>8</sup>, M.V. Corrias<sup>9</sup>, A. Pezzolo<sup>9</sup>, B. Carlini<sup>9</sup>, G. Schleiermacher<sup>10</sup>, A. Eggert<sup>11</sup>, L. Varesio<sup>1</sup></p><p><italic><sup>1</sup>G. Gaslini Children's Hospital, Laboratory of Molecular Biology, Genoa, Italy; <sup>2</sup>Istituto Nazionale Tumori, Pediatric Oncology, Milan, Italy; <sup>3</sup>Bambino Gesù Children's Hospital, Paediatric Haematology/Oncology, Rome, Italy; <sup>4</sup>Instituto de Investigación Sanitaria La Fe, Laboratory of Cellular and Molecular Biology, Valencia, Spain; <sup>5</sup>Hospital Universitario y Politécnico La Fe, Pediatric Oncology, Valencia, Spain; <sup>6</sup>Leeds Institute of Cancer and Pathology, Children's Cancer Research Group, Leeds, United Kingdom; <sup>7</sup>G. Gaslini Children's Hospital, Pediatric Oncology, Genoa, Italy; <sup>8</sup>G. Gaslini Children's Hospital, Pathology, Genoa, Italy; <sup>9</sup>G. Gaslini Children's Hospital, Laboratory of Oncology, Genoa, Italy; <sup>10</sup>Curie Institute, Pediatric Oncology, Paris, France; <sup>11</sup>Charité Universitätsmedizin, Pediatric Oncology and Hematology, Berlin, Germany</italic></p><p><bold>Background/Objectives</bold>: The response of patients with High‐risk (HR) neuroblastoma (NB) to the front line induction chemotherapy is crucial to determine the subsequent treatment. The absence of early molecular markers predictive of sensitivity/resistance to treatment led us to the study of exosomes, small vesicles considered the bioprint of tumor cells in liquid biopsies. We investigated whether exosomal miRNA (exo‐miRs) can be early biomarkers of the response to the induction‐chemotherapy.</p><p><bold>Design/Methods</bold>: We collected exosomes from plasma samples of 50 patients with HR‐NB before and after the induction chemotherapy. Exo‐miR expression was evaluated with RTqPCR on a 381 target panel. Data analyses included feature selection and pathway analysis.</p><p><bold>Results</bold>: The expression of 20 exo‐miRs was significantly modulated in response to chemotherapy, providing the first evidence that exo‐miRs may serve as biomarkers of the chemotherapic response. Cluster analysis distinguished two groups of patients, effectively dividing very good partial responders and minor responders. The correlation of the two groups with other clinical and biological features is under investigation. Pathway analysis determined whether chemotherapy influenced the expression of miRNAs known to be involved in sensitivity/resistance to drugs commonly employed in the induction‐chemotherapy. The analysis revealed that 42% of the 20 differentially expressed exo‐miRs were associated with sensitivity/resistance to drug response. Mapping the results to individual patients, we identified distinct groups of subjects potentially unresponsive/resistant to the induction drugs. The exo‐miR profile in the middle phase of the induction therapy is under investigation to find miRNAs predictors of the response, which may allow a timely change in the induction protocol for those unresponsive patients.</p><p><bold>Conclusions</bold>: We demonstrated that exo‐miR can represent biomarkers of the response to induction‐chemotherapy and potential indicators of sensitivity/resistance to specific drugs for patients with HR‐NB. These results pave the way to a broad application of exo‐miRs in liquid biopsies applied to neuroblastoma targeted treatment.</p></sec><sec id="pbc26772-sec-0920"><label>O-069</label><title>Circulating Tumor DNA for Disease Monitoring in Neuroblastoma</title><p><underline underline-style="single">L. van Zogchel</underline><sup>1,2</sup>, E. van Wezel<sup>2</sup>, J. van Wijk<sup>2</sup>, W.C. Bruins<sup>2,3</sup>, L. Zappeij‐Kannegieter<sup>2</sup>, T.J. Slager<sup>3</sup>, I. Verly<sup>3</sup>, M.M. van Noesel<sup>1</sup>, H.N. Caron<sup>3</sup>, C.E. van der Schoot<sup>2</sup>, G.A.M. Tytgat<sup>1,3</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Pediatric Oncology, Utrecht, The Netherlands; <sup>2</sup>Sanquin Research‐ Amsterdam‐ The Netherlands and Landsteiner Laboratory of the AMC‐ University of Amsterdam, Department of Experimental Immunohematology, Amsterdam, The Netherlands; <sup>3</sup>Emma Childrens Hospital‐ Academical Medical Center, Department of Pediatric Oncology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Circulating tumor DNA (ctDNA) has been used for disease monitoring in several types of cancer. The aim of our study was to investigate whether ctDNA can be used for response monitoring in neuroblastoma.</p><p><bold>Design/Methods</bold>: 162 plasma samples from 63 patients were analyzed for detection of hypermethylated RASSF1A DNA. DNA was isolated and total cell free DNA (cfDNA) was determined by qPCR for albumin and the amount of ctDNA was determined by qPCR for methylated RASSF1A after bisulfite conversion. Detection of ctDNA was compared with clinic‐biological patient characteristics, such as BM and PB MRD (qPCR), MIBG scans and urinary catecholamines.</p><p><bold>Results</bold>: In 17/26 (65%) diagnostic samples ctDNA was detected, including 4/10 (40%) patients with Iocalized disease. During induction chemotherapy (stage 4 patients only) in 15/45 samples ctDNA was detected (33%). At (suspected) relapse in 11 out of 18 samples ctDNA was detected (61%). The amount of cfDNA was significantly higher in patients with neuroblastoma at time of diagnosis and relapse compared to healthy controls, with the highest amount in patients with stage 4. There was significant correlation between ctDNA and PB or BM MRD, when tumor levels were high or no tumor was detected. Discrepancies were observed in 20 samples and were studied in detail. The discrepancies indicated either low tumor burden (ctDNA‐/MRD+) or tumor (and metastases) without or with minimal BM involvement (ctDNA+/MRD‐).</p><p><bold>Conclusions</bold>: Hypermethylated RASSF1A can be used for monitoring of ctDNA in patients with neuroblastoma and highly correlates with the disease status at diagnosis. Our data indicate that there is a poorer correlation when tumor load is very low, with both samples with ctDNA+/MRD‐ and ctDNA‐/MRD+. It is likely that ctDNA can originate from both primary tumor and metastases and may be of special interest for disease monitoring in patients relapsing in other organs than the BM.</p></sec><sec id="pbc26772-sec-0930"><label>O-070</label><title>Efficacy of ANTI‐GD2 Antibody CH14.18/CHO and PD1/PD‐L1 Checkpoint Blockade in Neuroblastoma</title><p><underline underline-style="single">H. Lode</underline><sup>1</sup>, M. Zumpe<sup>1</sup>, M. Jüttner<sup>1</sup>, S. Troschke‐Meurer<sup>1</sup>, H. Loibner<sup>2</sup>, N. Siebert<sup>1</sup></p><p><italic><sup>1</sup>University Medicine Greifswald, Pediatric Hematology and Oncology, Greifswald, Germany; <sup>2</sup>Apeiron Biologics, Apeiron Biologics, Vienna, Austria</italic></p><p><bold>Background/Objectives</bold>: Anti‐GD<sub>2</sub> antibody (Ab) ch14.18/CHO is effective for treatment of high‐risk neuroblastoma (NB) patients and was approved by EMA with and without IL2 co‐medication. The mechanism of action is induction of GD<sub>2</sub>‐specific Ab‐dependent cellular cytotoxicity (ADCC). Programmed death‐1 (PD‐1) is an inhibitory receptor expressed by activated T‐ and NK‐cells, and cancer cells express PD‐1 ligand (PD‐L1). Here, we report for the first time effect and mechanism of PD‐1/PD‐L1 blockade in the context of ch14.18/CHO therapy in preclinical models.</p><p><bold>Design/Methods</bold>: Expression of PD‐L1 and PD‐1 on NB cells and leukocytes was analyzed by RT‐PCR and flow cytometry in the presence of ch14.18/CHO with and without IL‐2. Mechanism of PD‐L1 induction was analyzed with anti‐CD11b Ab. The effect of PD‐1/PD‐L1 blockade on ch14.18/CHO‐mediated anti‐NB immune response was evaluated using anti‐PD‐1 Ab both in vitro (Nivolumab) and in the syngeneic GD<sub>2</sub><sup>+</sup>/PD‐L1<sup>+</sup> NB mouse model (anti‐mouse PD‐1). Mice (n=10) were treated with ch14.18/CHO (5x300 μg, i.p.) in combination with anti‐PD‐1 (8x250 μg, i.p.), and compared to controls.</p><p><bold>Results</bold>: Culture of LAN‐1 NB cells with leukocytes (E/T 10:1), sub‐therapeutic ch14.18/CHO concentrations (10 ng/ml), without and with IL2 (100 IU/ml) induced a 2 and 3 fold upregulation of PD‐L1, respectively, and inhibited GD<sub>2</sub> specific ADCC. Co‐incubation with anti‐CD11b abrogated this PD‐L1 upregulation and increased ADCC. Importantly, blockade with Nivolumab reversed the PD‐L1‐dependent inhibition of ADCC. Finally, mice treated with ch14.18/CHO in combination with PD‐1 blockade showed strongest reduction of tumor growth, longest survival rate as well as the highest level of NB cell lysis mediated by serum and leukocytes of treated mice compared to controls.</p><p><bold>Conclusions</bold>: Ch14.18/CHO and IL2 upregulate the inhibitory checkpoint PD‐1/PD‐L1 and combination of ch14.18/CHO with PD‐1/PD‐L1 blockade results in synergistic treatment effects in preclinical models. This suggests clinical evaluation of ch14.18/CHO in combination with PD‐1/PD‐L1 checkpoint inhibition.</p></sec><sec id="pbc26772-sec-0940"><label>O-071</label><title>Targeted Combination Strategies to Improve the Clinical Implementation of Venetoclax for Neuroblastoma Treatment</title><p><underline underline-style="single">E. Dolman</underline><sup>1</sup>, L.T. Bate‐Eya<sup>1</sup>, T.E. Eleveld<sup>1</sup>, N.A. Schubert<sup>1</sup>, B. Koopmans<sup>1</sup>, L.A. Alles<sup>1</sup>, L. Schild<sup>1</sup>, D. Lelieveld<sup>2</sup>, D.A. Egan<sup>2</sup>, M. Kerstjens<sup>3</sup>, R.W. Stam<sup>1</sup>, J. Koster<sup>4</sup>, H.N. Caron<sup>5</sup>, J.J. Molenaar<sup>1</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Translational Research, Utrecht, The Netherlands; <sup>2</sup>University Medical Center Utrecht, Cell Biology, Utrecht, The Netherlands; <sup>3</sup>Erasmus MC‐ Sophia Children's Hospital, Pediatric Oncology and Hematology, Rotterdam, The Netherlands; <sup>4</sup>Amsterdam Medical Center‐ University of Amsterdam, Oncogenomics, Amsterdam, The Netherlands; <sup>5</sup>Emma Children's Hospital‐ Amsterdam Medical Center‐ University of Amsterdam, Pediatric Oncology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: The anti‐apoptotic protein B cell lymphoma/leukaemia 2 (BCL‐2) is highly expressed in the majority of all neuroblastoma. In previous preclinical studies, we have shown that treatment of BCL‐2‐dependent neuroblastoma with BCL‐2 inhibitors leads to programmed cell death. These results have contributed to the initiation of a phase I trial to study the safety and pharmacokinetics of venetoclax in children with relapsed or refractory neuroblastoma. The current study focused on the identification and validation of targeted combination strategies to prevent or overcome neuroblastoma resistance to venetoclax.</p><p><bold>Design/Methods</bold>: Targeted drugs for combination treatment with venetoclax were identified by compound‐wide screens with >200 compounds using normal neuroblastoma cell lines and neuroblastoma cell lines made resistant to venetoclax. Top hits were subsequently tested more extensively <italic>in vitro</italic> and <italic>in vivo</italic> to validate the screening results.</p><p><bold>Results</bold>: High‐throughput drug screens identified MDM2 inhibitor idasanutlin as one of the strongest re‐sensitizers for venetoclax in venetoclax‐resistant BCL‐2‐dependent neuroblastoma cells with wild‐type p53 cellular tumor antigen. Subsequent <italic>in vitro</italic> validation showed that idasanutlin caused cyclin dependent kinase inhibitor 1 (p21)‐mediated growth arrest in non‐resistant neuroblastoma cells, while inducing a BCL‐2‐associated X protein (BAX)‐mediated apoptotic response in venetoclax‐resistant neuroblastoma cells in the presence of venetoclax. <italic>In vivo</italic> combination of venetoclax with idasanultin resulted in a remarkably improved anticancer effect compared to single agent therapy, with almost complete regression of BCL‐2‐dependent neuroblastoma xenografts. Combination screens additionally revealed that inhibitors of mitogen‐activated protein kinase kinase (MEK), anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs) synergize with venetoclax, depending on the genomic background of the neuroblastoma tumors.</p><p><bold>Conclusions</bold>: Our findings indicate that the clinical use of venetoclax for the treatment of children with BCL‐2‐dependent neuroblastoma tumors can be improved by combination therapy with targeted inhibitors. Optimal targeted combination strategies depend on the presence of additional genomic events driving neuroblastoma tumors.</p></sec></sec><sec id="pbc26772-sec-0950"><title>Free Paper Session: Renal Tumours</title><sec id="pbc26772-sec-0960"><label>O-072</label><title>Impact OF 1Q Status on Outcomes of Stage IV Favorable Histology Wilms Tumor (FHWT) Patients Treated on the Children's Oncology Group (COG) Study AREN0533</title><p><underline underline-style="single">E. Mullen</underline><sup>1</sup>, E. Perlman<sup>2</sup>, Y.Y. Chi<sup>3</sup>, D. Dix<sup>4</sup>, G. Eric<sup>5</sup>, J. Gastier‐Foster<sup>6</sup>, G. Khanna<sup>7</sup>, P. Ehrlich<sup>8</sup>, J. Geller<sup>9</sup>, J. Kalapurakal<sup>10</sup>, C. Fernandez<sup>11</sup>, J. Dome<sup>12</sup></p><p><italic><sup>1</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Pediatric Oncology, Boston, USA; <sup>2</sup>Ann & Robert H. Lurie Children's Hospital of Chicago, Pathology, Chicago, USA; <sup>3</sup>University of Florida, Biostatistics, Gainsville, USA; <sup>4</sup>University of British Columbia, Hematology and Oncology, Vancouver, Canada; <sup>5</sup>University of Tennessee College of Medicine, Pediatric Oncology, Chattanooga, USA; <sup>6</sup>Nationwide Children's Hospital and The Ohio State University Medical Center, Biopathology Center, Columbus, USA; <sup>7</sup>Washington University School of Medicine, Pediatric Radiology, Saint Louis, USA; <sup>8</sup>University of Michigan, Pediatric Surgery, Ann Arbor, USA; <sup>9</sup>Cincinnati Children's Hospital, Pediatric Oncology, Cincinnati, USA; <sup>10</sup>Northwestern University, Radiation Oncology, Chicago, USA; <sup>11</sup>IWK Health Centre and Dalhousie University, Pediatric Hematology and Oncology, Halifax, Canada; <sup>12</sup>Children's National Health System, Pediatric Hematology and Oncology, Washington‐ DC, USA</italic></p><p><bold>Background/Objectives</bold>: 1q gain has been found to be a negative prognostic marker in multiple retrospective European and North American studies. Following 6 weeks of vincristine/dactinomycin/doxorubicin (DD4A), protocol AREN0533 stratified Stage IV FHWT patients to intensified five drug therapy with addition of cyclophosphamide/etoposide (regimen M) for slow incomplete response (SIR) of pulmonary metastasis, extrapulmonary metastasis (EPM), and/or gain of combined LOH 1p and 16q. DD4A was continued and pulmonary radiation withheld for those with rapid complete response (RCR). We analyzed the impact of 1q status in this novel treatment algorithm.</p><p><bold>Design/Methods</bold>: 1q status was successfully analyzed in 248 evaluable patients by multiplex ligation‐dependent probe amplification. Event free survival (EFS) and overall survival (OS) were summarized at year 4 and compared using the log‐rank test.</p><p><bold>Results</bold>: 30% (75/248) had gain of 1q. Overall, those with 1q gain (N= 75) had an EFS of 75% (95% CI: 62%, 87%) and OS: 91% (95% CI: 84%, 99%); those without 1q gain (N= 173) had an EFS of 89% (95% CI: 83%, 94%) and OS of 96% (95% CI: 92%, 99%). Patients with SIR and 1q gain (42/116=36%) had an EFS of 86%, compared to 92% with SR without 1q gain (p=0.15); OS was 93% and 96% (p=0.45). Patients with RCR and 1q gain (21/96=22%) had worse outcome than those with RCR without 1q gain (EFS 57% vs 86%, p=0.0013; OS 89% vs 97%, p=0.16<italic>)</italic>. Relapse in RCR with 1q gain was predominantly (9/11) pulmonary. For patients with EPM (n=36), 33% (N=12) had 1q gain (EFS 67%) and 67% (N=24) had no 1q gain (EFS 88%) [p=0.15].</p><p><bold>Conclusions</bold>: 1q gain was associated with inferior EFS for RCR Stage IV FHWT patients with isolated pulmonary metastasis; these patients are not appropriate candidates for radiation omission. Regimen M may mitigate adverse impact of 1q gain in other stage IV risk categories.</p></sec><sec id="pbc26772-sec-0970"><label>O-073</label><title>Effect of Chemotherapy Dosage on Outcome of Patients with Stage II‐IV Diffuse Anaplastic Wilms Tumor: Results from the Children's Oncology Group AREN0321 Study</title><p><underline underline-style="single">N. Daw</underline><sup>1</sup>, Y.Y. Chi<sup>2</sup>, Y. Kim<sup>2</sup>, J.A. Kalapurakal<sup>3</sup>, F. Hoffer<sup>4</sup>, J. Geller<sup>5</sup>, E. Perlman<sup>6</sup>, P. Ehrlich<sup>7</sup>, K. Gow<sup>8</sup>, E. Mullen<sup>9</sup>, A. Warwick<sup>10</sup>, P. Grundy<sup>11</sup>, E.J. Gratias<sup>12</sup>, D. Ward<sup>13</sup>, J.R. Anderson<sup>14</sup>, A.D.C. Paulino<sup>15</sup>, Z. Tochner<sup>16</sup>, R. Venkatramani<sup>17</sup>, C. Fernandez<sup>18</sup>, J. Dome<sup>19</sup></p><p><italic><sup>1</sup>The University of Texas MD Anderson Cancer Center, Division of Pediatrics, Houston, USA; <sup>2</sup>University of Florida, Statistics, Gainsville, USA; <sup>3</sup>Ann and Robert H Lurie Children's Hospital of Chicago, Radiation Oncology, Chicago, USA; <sup>4</sup>Quality Assurance Review Ctr, Diagnostic Imaging, Lincoln, USA; <sup>5</sup>Cincinnati Children's Hospital Medical Center, Hematology/Oncology, Cincinnati, USA; <sup>6</sup>Ann and Robert H Lurie Children's Hospital of Chicago, Pathology, Chicago, USA; <sup>7</sup>C S Mott Children's Hospital, Surgery, Ann Arbor, USA; <sup>8</sup>Seattle Children's Hospital, Surgery, Seattle, USA; <sup>9</sup>Dana‐Farber/Harvard Cancer Center, Hematology/Oncology, Boston, USA; <sup>10</sup>Walter Reed National Military Medical Center, Hematology/Oncology, Bethesda, USA; <sup>11</sup>University of Alberta Hospital, Hematology/Oncology, Edmonton, Canada; <sup>12</sup>eviCore Healthcare, Hematology/Oncology, Bluffton, USA; <sup>13</sup>Saint Jude Children's Research Hospital, Pharmaceutical Services, Memphis, USA; <sup>14</sup>Merck Research Laboratories, Oncology, North Wales, USA; <sup>15</sup>The University of Texas MD Anderson Cancer Center, Radiation Oncology, Houston, USA; <sup>16</sup>University of Pennsylvania‐ Perelman School of Medicine, Radiation Oncology, Philadelphia, USA; <sup>17</sup>Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center, Hematology/Oncology, Houston, USA; <sup>18</sup>IWK Health Centre, Pediatrics and Bioethics, Halifax, Canada; <sup>19</sup>Children's National Medical Center, Center for Cancer and Blood Disorders, Washington, USA</italic></p><p><bold>Background/Objectives</bold>: In National Wilms Tumor Study‐5, 4‐year relapse‐free survival for patients with stages II‐IV diffuse anaplastic Wilms tumor (DAWT) treated with vincristine, doxorubicin, cyclophosphamide, and etoposide, plus radiotherapy (XRT) (Regimen I) was 58% (95% CI, 48‐68%). AREN0321 evaluated a more intensive regimen containing carboplatin in addition to adjusted doses of chemotherapy used in Regimen I (Regimen UH‐1). Dosages of chemotherapy were reduced mid‐study due to non‐hematologic toxicity that exceeded predefined stopping rules. We analyzed the effect of this dose reduction on event‐free survival (EFS), overall survival (OS) and toxicity.</p><p><bold>Design/Methods</bold>: Patients with stages II‐IV DAWT without measurable disease received Regimen UH‐1. Patients with stage IV measurable disease had the option to receive vincristine in combination with irinotecan (VI) in an upfront window; those with partial response had VI incorporated into Regimen UH‐1 (Regimen UH‐2). Cumulative doses of doxorubicin, cyclophosphamide and etoposide were reduced by 20‐40% in “revised” Regimens UH1/UH2 due to non‐hematologic toxicity.</p><p><bold>Results</bold>: Of 66 eligible patients, 23 were treated with UH‐1, 32 with revised UH‐1, and 5 each with UH‐2 and revised UH‐2. Four‐year EFS for all patients was 75% (95% CI, 62‐87%); OS was 76% (95% CI, 64‐88%). Four‐year EFS for stage II, III and IV disease were 86% (95% CI, 66‐100%), 85% (95% CI, 69‐100%) and 54% (95% CI, 30‐78%), respectively. The EFS for patients treated with UH‐1/UH‐2 was 85% (95% CI, 71‐99%) compared to 68% (95% CI, 49‐88%) for patients treated with revised UH‐1/UH‐2 (p=0.12). There was one grade 5 toxicity attributed to treatment on UH‐1/UH‐2 and two on revised UH‐1/UH‐2. The number of grade 3‐4 non‐hematologic toxicities per patient was 3.9 for UH‐1/UH‐2 and 3.1 for revised UH‐1/UH‐2.</p><p><bold>Conclusions</bold>: For patients with stage II‐IV DAWT, Regimens UH‐1/UH‐2 showed a trend toward superior EFS compared to Revised UH‐1/UH‐2, with comparable rates of grade 3‐5 toxicity.</p></sec><sec id="pbc26772-sec-0980"><label>O-074</label><title>Epidemiology of Patients with Wilms Tumour Registered in Successive UK‐Trials through 38 Years</title><p><underline underline-style="single">K. Nakata</underline><sup>1,2</sup>, S. Tugnait<sup>1</sup>, M.P. Falcone<sup>1</sup>, N. Galea<sup>3</sup>, F. Ceroni<sup>1,4</sup>, R. Al‐Saadi<sup>1</sup>, M. Chagtai<sup>1</sup>, R. Williams<sup>1</sup>, W. Mifsud<sup>1</sup>, J. Brok<sup>1,5</sup>, C. Stiller<sup>6</sup>, V. Moroz<sup>7</sup>, A. Kelsey<sup>8</sup>, G. Vujanic<sup>9</sup>, K. Pritchard‐Jones<sup>1</sup></p><p><italic><sup>1</sup>UCL Great Ormond Street Institute of Child Health, Developmental Biology and Cancer Programme, London, United Kingdom; <sup>2</sup>Cancer Control Center‐ Osaka International Cancer Center, Department of Cancer Strategy, Osaka, Japan; <sup>3</sup>Mater Dei Hospital, Paediatric and Adolescent Cancer Unit, Msida, Malta; <sup>4</sup>Watford General Hospital, Paediatric Department, Watford, United Kingdom; <sup>5</sup>Rigshospitalet, Dept. of Paediatric Oncology and Haematology, Copenhagen, Denmark; <sup>6</sup>Public Health England, National Cancer Registration and Analysis Service, Oxford, United Kingdom; <sup>7</sup>Institute of Cancer and Genomic Sciences‐ University of Birmingham, Cancer Research UK Clinical Trials Unit, Birmingham, United Kingdom; <sup>8</sup>Royal Manchester Children's Hospital, Department of Paediatric Histopathology, Manchester, United Kingdom; <sup>9</sup>University Hospital of Wales, Department of Cellular Pathology, Cardiff, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Since 1979, 2,510 patients with Wilms tumour (WT) have been registered in five consecutive UK clinical trials (UKW1‐3, SIOP‐2001, and IMPORT). We reviewed all trial data with focus on congenital abnormalities (CA) and laterality.</p><p><bold>Design/Methods</bold>: We categorised patients with WT into five mutually exclusive groups; WT and aniridia with/without urogenital malformations (WA), urogenital/renal malformations including Denys‐Drash syndrome (UM), hemi‐hypertrophy including Beckwith‐Wiedemann syndrome (HH), other congenital abnormalities (other‐CA), and without CA (non‐CA). We compared distribution of sex, age at diagnosis, stage, histology and 5‐year overall survival (OS) of each group to those of non‐CA. Bilateral vs unilateral tumours were compared for similar outcomes.</p><p><bold>Results</bold>: Numbers and proportions in each group were: WA (n=24, 1%); UM (n=79, 3%); HH (n=65, 3%); other‐CA (n=116, 5%); non‐CA (n=2,226, 88%). Bilateral (n=181, 7%); unilateral (n=2,309, 92%).</p><p>Patients in WA, UM and other‐CA groups had younger median age of diagnosis and higher proportion of bilateral disease compared to non‐CA (20m, 21m and 30m vs 39m, and 33%, 19%, 17% vs 6%, respectively). HH patients showed no significant difference compared to non‐CA group (41m and 11%). UM had male predominance (M/F ratio 1.72 vs 0.88 in non‐CA). There were no significant differences in 5‐year OS for each group compared to non‐CA [83% (WA), 88% (UM), 91% (HH), 87% (other‐CA), vs 88% (non‐CA)].</p><p>Compared to unilateral disease, the bilateral group had female excess (M/F ratio 0.62 vs 0.93), younger age at diagnosis (24m vs 39m) and poorer 5‐year OS (82% vs 89%, p=0.003) that had improved to 90% for cases diagnosed since 2002.</p><p><bold>Conclusions</bold>: About one in nine patients with WT had congenital abnormalities. These patients are diagnosed at earlier age, have more frequent bilateral tumours but 5‐year survival rate seems very similar. Compared to unilateral, bilateral WT were younger and had poorer survival.</p></sec><sec id="pbc26772-sec-0990"><label>O-075</label><title>Prognostic Value of Age in Patients with Wilms Tumour Treated According to International Society of Paediatric Oncology (SIOP) 93‐01 and SIOP 2001 Protocols</title><p><underline underline-style="single">J. Hol</underline><sup>1</sup>, M. Lopez<sup>2</sup>, M. Van Grotel<sup>1</sup>, K. Pritchard‐Jones<sup>3</sup>, B. De Camargo<sup>4</sup>, T. Acha<sup>5</sup>, H. Van Tinteren<sup>2</sup>, C. Bergeron<sup>6</sup>, N. Graf<sup>7</sup>, M. Van den Heuvel‐Eibrink<sup>1</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Paediatric Oncology, Paediatric Oncology, Utrecht, The Netherlands; <sup>2</sup>Netherlands Cancer Institute, Biostatistics, Amsterdam, The Netherlands; <sup>3</sup>UCL Great Ormond Street Institute of Child Health, Paediatric Oncology, London, United Kingdom; <sup>4</sup>Instituto Nacional de Cancer INCA, Paediatric Haematology‐Oncology Program, Rio de Janeiro, Brazil; <sup>5</sup>Hospital Materno‐Infantil Carlos Haya, Paediatric Oncology, Málaga, Spain; <sup>6</sup>Institut d'Hematologie et d'Oncologie Pédiatrique‐ Centre Léon Bérard, Paediatric Oncology, Lyon, France; <sup>7</sup>Saarland University Medical Center, Paediatric Oncology and Haematology, Homburg, Germany</italic></p><p><bold>Background/Objectives</bold>: Age has been suggested to be a prognostic factor for recurrence and mortality in patients with Wilms tumour (WT). In this study, we assess the prognostic value of age and cutoffs for risk stratification in paediatric patients with unilateral WT treated according to recent International Society of Paediatric Oncology(SIOP) protocols.</p><p><bold>Design/Methods</bold>: Patients (6 months‐18 years) with stage I‐IV WT were derived from the SIOP93‐01 and SIOP2001 database. Only patients who received preoperative chemotherapy were included. The prognostic value of age at diagnosis, per year/categorized, for 5‐year event‐free survival (EFS) and overall survival (OS) was assessed using the Kaplan Meier method, log‐rank test and multivariable Cox regression models. Martingale residual plots were used to assess the functional form of age. The multivariable analysis was adjusted for gender, biopsy (yes/no), pathological stage, histological classification and tumour volume at surgery.</p><p><bold>Results</bold>: 5386/7880 patients met the inclusion criteria; stage I: 46%, stage II: 23%, stage III: 17%, stage IV: 15%. Median age at diagnosis was 3.4 years (interquartile range, IQR: 2.0–5.1) and median follow‐up was 6.3 years (IQR: 3.0‐8.6). Estimated 5‐year EFS and OS were 84% (95%CI 83.3‐85.3) and 93% (95%CI 91.9‐93.4), respectively. Assessment of martingale residual plots suggested a linear trend for age in both EFS and OS. Significant differences in EFS and OS were found between ages <2, 2‐4, 4‐10 and ≥10 (log‐rank p<0.0001). In multivariable analyses, increasing age was associated with poorer EFS (linear trend p<0.0001). OS was lower in patients ≥4 years compared to patients <2 years (HR=1.32, 95%CI 1.13‐2.57). No linear trend was found. Higher stage, histological risk group and volume were associated with poorer OS and EFS in univariable and multivariable analyses.</p><p><bold>Conclusions</bold>: Survival worsens with increasing age in patients with WT. However, our results do not seem to justify the use of age cutoffs for risk stratification in pretreated patients.</p></sec><sec id="pbc26772-sec-1000"><label>O-076</label><title>Mode of Presentation of Renal Tumours of Childhood: First Analysis of Data from the Prospective “IMPORT” Study in the UK and Republic of Ireland</title><p><underline underline-style="single">K. Pritchard‐Jones</underline><sup>1</sup>, J. Brok<sup>1</sup></p><p><italic><sup>1</sup>University College London, UCL Great Ormond Street Institute of Child Health, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: The Improving Population Outcomes for Renal Tumours of childhood (IMPORT) study collects data on the mode of presentation to facilitate international benchmarking of Wilms tumour (WT) survival rates in relation to patient/tumour demographics and different models of primary care.</p><p><bold>Design/Methods</bold>: Data were extracted from case report forms submitted by all 20 UK and Republic of Ireland principal treatment centres for childhood cancer. All cases had central pathology review. The registration form had 4 categories of mode of tumour presentation: route1:routine child health examination; route2:congenital abnormality screening; route3:non‐specific symptoms; route4:tumour‐specific symptoms.</p><p><bold>Results</bold>: 331 patients were registered with WT from Q4/2012‐Q4/2016. Diagnosis was through routes 1&2 in twenty (6 %) patients, route 3 in 53 (16%) and route 4 in 258 (78%). Median age at diagnosis of WT was 1.8y, 3.3y & 3.6y, respectively. Stage distribution was:</p><p>Routes 1&2:stage I:11 (55%), II:1 (5%), III:2 (10%), IV:1 (5%), V:5 (25%)</p><p>Route 3:stage I:19 (36%), II:9 (17%), III:7 (13%), IV:13 (24%), V:5 (9%)</p><p>Route 4:stage I:96 (37%), II:36 (14%), III:53 (21%), IV:52 (20%), V:19 (7%)</p><p>There was no difference in the proportion with high risk histology (15%; 13%; 10.5%) versus low+intermediate risk (85%; 87%; 89.5%) by routes 1+2; 3; 4, respectively. Median tumour volume at diagnosis was 623ml for 306 patients with 3D measurements; 59ml for routes 1&2; 522ml for route 3; 665ml for route 4.</p><p><bold>Conclusions</bold>: Majority of patients presented with tumour‐specific symptoms. Patients diagnosed by screening or child health checks were younger, with less metastatic disease. Stage III disease was more frequent in children presenting with tumour‐specific symptoms who also had the highest median tumour volume. This ongoing data collection on mode of presentation is now being extended across Europe and will allow benchmarking, including tumour size and stage at diagnosis, to offer evidence regarding need for paediatric expertise in the primary care of symptomatic children</p></sec><sec id="pbc26772-sec-1010"><label>O-077</label><title>Long‐Term Renal Function in Children with Wilms Tumour and Constitutional WT1 Mutation</title><p>M.P. Falcone<sup>1,2</sup>, J. Brok<sup>1</sup>, W. Mifsud<sup>1</sup>, R. Williams<sup>1</sup>, K. Nakata<sup>1</sup>, S. Tugnait<sup>1</sup>, R. Al‐Saadi<sup>1</sup>, L. Side<sup>3</sup>, J. Anderson<sup>1</sup>, T. Chowdhury<sup>1</sup>, C. Duncan<sup>1</sup>, D. Böckenhauer<sup>4</sup>, <underline underline-style="single">K. Pritchard‐Jones</underline><sup>1</sup></p><p><italic><sup>1</sup>UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom; <sup>2</sup>Paediatric Residency Program, University of Foggia, Foggia, Italy; <sup>3</sup>Dept. of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; <sup>4</sup>Dept. of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Wilms Tumour (WT) survivors, especially patients with associated syndromes or genitourinary anomalies due to constitutional <italic>WT1</italic> mutation, have increased risk of end‐stage renal disease. We described the long‐term renal function in children with WT and <italic>WT1</italic> mutation to guide their challenging oncological management.</p><p><bold>Design/Methods</bold>: Retrospective analysis of patients with WT and <italic>WT1</italic> mutation treated 1993‐2016 at Great Ormond Street Hospital,UK, reviewing genotype, phenotype, tumour histology, laterality, treatment and renal outcome.</p><p><bold>Results</bold>: We identified 23 patients with <italic>WT1</italic> mutation; deletion (4), missense (2), nonsense (7), frameshift (6), splice site (4). Males 61%, bilateral disease 48%, median age at diagnosis 14m (4‐74m). Three (13%) patients had WT‐aniridia, 10(43%) genitourinary malformation, 10(43%) no phenotypic anomalies.</p><p>Two patients underwent bilateral nephrectomy, 9 unilateral nephrectomy, 5 bilateral/unilateral nephron‐sparing‐surgery (NSS), 7 unilateral nephrectomy with contralateral NSS. Histological subtype for 32 tumours/22 patients (10 bilateral) showed 13 mixed, 14 stromal, 2 regressive, 1 blastemal, 2 only intralobar‐nephrogenic rest. Twenty‐three tumours had associated nephrogenic rests (17 intralobar) and none had anaplasia.</p><p>At median 6y duration follow‐up, all patients were alive, 3 in remission after relapse. Six patients (26%) required long‐term dialysis; 4 due to chronic kidney disease 2 due to bilateral nephrectomy (one upfront, one relapse). Of these, 4 had renal transplants and 2 are listed. Two patients developed chronic kidney disease stage≥3 (e‐GFR <60ml/min/1.73m<sup>2</sup>), 15 retained normal e‐GFR, but 11 had increased albuminuria (9 on ACE‐inhibitors). Four patients (3 frameshift; 1 <italic>WT1</italic> deletion) had normal kidney parameters (follow‐up 11, 8, 1.5, 0.5 years).</p><p><bold>Conclusions</bold>: Despite the known high frequency of chronic kidney disease in patients with WT and constitutional <italic>WT1</italic> mutation, 2/3 patients had sustained normal e‐GFR. This should guide oncology management regarding the balanced decision about NSS without compromising oncological risk. Larger international studies are needed to further refine the prediction of <italic>WT1</italic> genotype for longevity of renal function.</p></sec></sec><sec id="pbc26772-sec-1020"><title>Free Paper Session: Supportive Care and Palliative Care</title><sec id="pbc26772-sec-1030"><label>O-078</label><title>Safety Profile of High‐Dose Thiotepa with Autologous Stem Cells Rescue in Children and Adolescents Treated for a Solid Tumor: A Single‐Institution Report on 465 Courses</title><p>C. Pasqualini<sup>1</sup>, C. Dufour<sup>1</sup>, I. Hezam<sup>2</sup>, Y. Oubouzar<sup>1</sup>, G. Goma<sup>3</sup>, V. Lapierre<sup>4</sup>, <underline underline-style="single">D. Valteau‐Couanet</underline><sup>1</sup></p><p><italic><sup>1</sup>Gustave Roussy, Children and Adolescent Oncology Unit, Villejuif, France; <sup>2</sup>Gustave Roussy, Clinical Research Operations Department, Villejuif, France; <sup>3</sup>Gustave Roussy, Biostatistic and Epidemiology Unit, Villejuif, France; <sup>4</sup>Gustave Roussy, Cell Therapy Unit, Villejuif, France</italic></p><p><bold>Background/Objectives</bold>: Reported data on high‐dose Thiotepa (HD‐Thio) followed by autologous stem cell rescue (ASCR) in pediatric settings are very few. We aim to define the safety profile of HD‐Thio with ASCR in a large pediatric cohort of solid tumors.</p><p><bold>Design/Methods</bold>: We analysed data prospectively recorded from patients with a solid tumor treated with HD‐Thio followed by ASCR from 1986 to January 2016 in the Children and Adolescents Oncology Unit at Gustave Roussy. No sinusoidal obstruction syndrome (SOS) prophylaxis was performed. Toxicity is reported according to CTCAE v4.0.</p><p><bold>Results</bold>: HD‐Thio was administered to 354 patients, as a tandem HD‐chemotherapy (HDC) in 111 patients. The median age at diagnosis was 6.4 years (0.2‐24.1). The most represented diseases were medulloblastoma (n=114), osteosarcoma (n=63), neuroblastoma (n=49), Ewing sarcoma (n=26) and rhabdomyosarcoma (n=20). HD‐Thio was delivered at relapse for 135/355 patients (38%). In total, 465 courses were performed, at the dose of 600, 720, 900 mg/m<sup>2</sup> for 165, 84 and 216 patients, respectively. The most common toxicity was digestive, as grade ≥ 3 mucositis and diarrhoea in 102 (22%) and 50 (11%) patients, respectively. Neurological toxicity grade ≥ 3 was reported in 42 patients (9%). Three patients experienced SOS, mild for 2 of them. The median days to neutrophils and platelets recovery was 8 days (2‐37 and 0‐377, respectively), and the median duration of hospitalisation was 22 days (14‐70). A toxic mortality rate of 2% (n=7) was observed, directly related to HD‐Thio in 1 patient (SOS). Toxicity profile was not different between single and tandem HD‐Thio and between relapse and first‐line treatment.</p><p><bold>Conclusions</bold>: HD‐Thio with ASCR is globally well tolerated in children and adolescents with solid tumors, even as a tandem HDC and in heavily pre‐treated patients. Prophylaxis for SOS is not mandatory. Digestive and neurological toxicities need a careful supportive care management.</p></sec><sec id="pbc26772-sec-1040"><label>O-079</label><title>Guideline for the Infusion Duration of Anthracycline Chemotherapy Agents in Children with Cancer</title><p><underline underline-style="single">E.A.H. Loeffen</underline><sup>1</sup>, E.C. Van Dalen<sup>2</sup>, R.L. Mulder<sup>2</sup>, L.C.M. Kremer<sup>2</sup>, M.D. Van de Wetering<sup>2</sup>, W.J.E. Tissing<sup>1</sup>, O.B.O.T. Anthracycline Cardiotoxicity Working Group<sup>1</sup></p><p><italic><sup>1</sup>Beatrix Children's Hospital‐ University Medical Center Groningen‐ University of Groningen, Department of Pediatric Oncology/Hematology, Groningen, The Netherlands; <sup>2</sup>Emma Children's Hospital‐ Academic Medical Center, Department of Pediatric Oncology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: One of the established side effects of anthracycline chemotherapy agents, which are used in various pediatric oncology treatment protocols, is short‐ and long‐term cardiotoxicity. A proposed strategy to minimise this cardiotoxicity is to lengthen the infusion duration. We aimed to develop recommendations for the infusion duration of anthracycline chemotherapy agents in children with cancer.</p><p><bold>Design/Methods</bold>: Using an existing Cochrane sytematic review as starting point, first a top‐up search was performed. A national, multidisciplinary panel (16 persons) was formed, representing all relevant fields and including patient representatives. With use of the established GRADE system for evidence appraisal and their more recent Evidence to Decision framework, the panel formulated evidence summaries and recommendations.</p><p><bold>Results</bold>: 7 studies (4 adult, 3 pediatric) were included, with a low to very low quality of evidence. Regarding outcomes, overall survival, clinical heart failure, progression free survival and subclinical heart failure were unanimously categorized as critical for decision‐making. The panel agreed on a weak recommendation against a push infusion of anthracycline chemotherapy. A recommendation defining a more precise infusion time period was currently not possible. Research recommendations were formulated, calling for large randomized trials and pharmacokinetic studies.</p><p><bold>Conclusions</bold>: In this guideline we provide recommendations regarding infusion duration of anthracycline chemotherapy in children with cancer. Given the evidence shortage of high‐quality studies that address this question, further research is needed.</p></sec><sec id="pbc26772-sec-1050"><label>O-080</label><title>Anesthetic Management of Superselective Ophtalmic Arterial Chemotherapy for Retinoblastoma in Children</title><p>L. Martynov<sup>1</sup>, <underline underline-style="single">N. Matinyan</underline><sup>1</sup>, A. Sotnikov<sup>1</sup>, I. Letyagin<sup>1</sup>, N. Milaschenko<sup>1</sup>, Y. Buidenok<sup>1</sup>, T. Ushakova<sup>2</sup>, I. Trofimov<sup>3</sup>, V. Polyakov<sup>2</sup></p><p><italic><sup>1</sup>Pediatric Oncology and Hematology Institute‐ Blokhin Russian Oncological Research Center, Anesthesiology, Moscow, Russia; <sup>2</sup>Pediatric Oncology and Hematology Institute‐ Blokhin Russian Oncological Research Center, Oncology department, Moscow, Russia; <sup>3</sup>Pediatric Oncology and Hematology Institute‐ Blokhin Russian Oncological Research Center, Endovascular surgery department, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Superselective ophthalmic artery chemotherapy (SOAC) with melphalan has significantly reduced the need of enucleation in patients with retinoblastoma. Life‐threatening complication of the SOAC procedure, which is expressed in hemodynamic instability and bronchospasm (presumably due to oculo‐cardiac reflex), significantly limits the wider implementation of this technique in children. Our experience of SOAC and life‐threatening adverse cardio‐respiratory reactions we have observed are described.</p><p><bold>Design/Methods</bold>: Between February 2011 and February 2017 in Pediatric Oncology and Hematology Institute 229 SOAC procedures were performed under general anesthesia, patients aged 17 +/‐ 5.1 months. After a. carotis interna catheterization continuous iv infusion of Epinephrine 0.05 – 0.1 mcg/kg/min was started. If the signs of oculo‐cardiac reflex were observed, bolus of Epinephrine 0.5 mcg/kg was administered.</p><p><bold>Results</bold>: There were no deaths or major complications. Oculo‐cardiac reflex was triggered during 74 procedures (32%). All reactions occurred during second or subsequent procedures and were characterized by hypoxia, reduced lung compliance (bronchospasm) followed by a subsequent deterioration in the oxygen saturation(Sp02) to 70%. Ventilation with 100% oxygen was initiated. Adverse reactions were successfully treated during 5‐10 min in all patients with Epinephrine (0.5 mcg/kg bolus). One procedure was interrupted due to prolonged hemodynamic instability. 10 patients required prolonged vasopressor support in early postoperative period. In 3 cases children had an acute ishemic stroke, which was confirmed by MRI.</p><p><bold>Conclusions</bold>: Adverse cardio‐respiratory reactions are commonly observed in SOAC for retinoblastoma. We believe that the adverse clinical signs represent an autonomic reflex response and all patients should be considered at‐risk. Reactions occur only during second or subsequent procedures and can be life‐threatening. Anesthesiologists must be vigilant for adverse reactions and deal with them quickly and effectively. However, further investigations are needed to improve the understanding of the manifestations, management, and clinical significance of the described oculo‐cardiac reflex.</p></sec><sec id="pbc26772-sec-1060"><label>O-081</label><title>Fertility Preservation After Ovarian Transposition in Pediatric, Adolescent and Young Adult Female Cancer Patient</title><p><underline underline-style="single">J.</underline><underline underline-style="single">VALDUGA</underline><sup>1</sup>, L. CLAUDE<sup>2</sup>, C. ROUSSET‐JABLONSKI<sup>2</sup>, V. BERNIER‐CHASTAGNER<sup>3</sup>, A. LUC<sup>4</sup>, P. CHASTAGNER<sup>1</sup>, P. MAREC‐BERARD<sup>5</sup></p><p><italic><sup>1</sup>Centre Hospitalier Universitaire de Nancy‐Brabois, Oncologie et hématologie pédiatrique, Nancy, France; <sup>2</sup>Centre Léon BERARD, Radiothérapie, Lyon, France; <sup>3</sup>Institut de Cancérologie de Lorraine, Radiothérapie, Nancy, France; <sup>4</sup>Centre Hospitalier Universitaire de Nancy‐Brabois, Plateforme d'Aide à la Recherche Clinique PARC, Nancy, France; <sup>5</sup>Institut d'Hématologie et Oncologie Pédiatrique Européen IHOPe, Oncologie et hématologie pédiatrique, Lyon, France</italic></p><p><bold>Background/Objectives</bold>: With increasing survival rates, preserve fertility of young patients treated for cancer is essential. Ovarian transposition (OT) can preserve the ovarian function from radiotherapy‐related damage in pubertal women. However, little data are available about the possibilities of pregnancy after OT, especially when performed in pre or peri‐pubertal period.</p><p><bold>Design/Methods</bold>: A retrospective analysis of women who underwent an OT before the age of 26 yrs between 1990 and 2015 was perfomed. Data on puberty, menstruations, pregnancies and ovarian reserve were collected.</p><p><bold>Results</bold>: An OT was performed in 32 patients before a pelvic or craniospinal irradiation, associated to chemotherapy in 28 cases. Mean age at the time of the analysis was 24.4 yrs. Median follow‐up was 7.1 yrs. The mean age at the time of the OT was 15.6 years (95% CI = [14.0‐17.2]) and 9 were prepurbetal. Only 3 patients underwent a second procedure in order to replace the transposed ovary(ies) in their original position. The incidence of amenorrhea after the end of treatment was 47%. All prepubertal patients at the time of the OT had a spontaneous menarche. Among 10 patients who have attempted, 6 obtained a pregnancy, 2 of them after an OT performed in the peri‐pubertal period and after pelvic irradiation > 20 Gy for 3. The rate of spontaneous abortion was 33%. Endocrine function was preserved in 82% of the 13 nulligeste evaluated patients but the ovarian reserve was altered in two thirds of the cases.</p><p><bold>Conclusions</bold>: These results show that OT during cancer treatment is possible and safe in young females including prepubertal, to preserve ovarian function even in younger patients. Pregnancies can occur spontaneously, even without resorting to detransposition. Further studies are needed to evaluate fertility after OT performed in pre‐pubertal period, in order to elaborate recommendations concerning the indications of this technique.</p></sec><sec id="pbc26772-sec-1070"><label>O-082</label><title>Pain in Pediatric Cancer Patients Receiving Chemotherapy in an Outpatient Setting</title><p><underline underline-style="single">E. Michiels</underline><sup>1</sup>, F. Van Loon<sup>1</sup>, J. Van Amstel<sup>1</sup>, G. Elmont<sup>1</sup>, M. Zwaan<sup>1</sup></p><p><italic><sup>1</sup>ErasmusMC/Sophia Children's Hospital, Pediatric Oncology, Rotterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer patients currently spend more time at home. Only a few studies have studied pain in children receiving chemotherapy in outpatient clinics.Therefore, the objective of this study was to explore if children experience pain when receiving chemotherapy at the outpatient clinic, the severity of the pain and its effect on quality of life (QoL).</p><p><bold>Design/Methods</bold>: In this longitudinal observational study, children visiting the outpatient clinic received 4 pain questionnaires, covering the last day before and the first 3 days following the outpatient chemotherapy administration. Children were asked to complete at least 3 times the set of 4 questionnaires. Minimum time between 2 sets of questionnaires was one week. The validated Brief Pain Inventory, Dutch Version was used. For children aged 0‐4 years (for which parents completed the questionnaire) and 9‐18 years the numeric rating scale was used to measure pain intensity. Children aged 4‐9 years used the Faces Pain Scale‐Revised. Demographic data, use of pain medication and effect of the pain on QoL were documented.</p><p><bold>Results</bold>: Seventy‐five participants completed 1,028 questionnaires. Diagnoses included ALL (52%), lymphoma (16%), brain tumor (20%) and other malignancies (12%). In 40.3% of the questionnaires pain was reported by 82.6% of the children. Clinically significant pain, defined as a score of > 4 on ‘average’ pain or a score > 7 on ‘worst’ pain, was noticed in 45 patients (60.0%) and in 21.0% of the questionnaires. Twenty‐one percent of children experienced pain at least 50% of the measurements. In 32.4% of the questionnaires in which clinically significant pain was reported, no analgesic medication was used. The higher the pain scores, the more pronounced its effect on QoL.</p><p><bold>Conclusions</bold>: Pain is still very prevalent in children being treated in an outpatient setting, and the effect on their QoL is significant. Pain treatment is still suboptimal.</p></sec><sec id="pbc26772-sec-1080"><label>O-083</label><title>Predictors of Specialized Pediatric Palliative Care Involvement and Impact on Patterns of End‐of‐Life Care in Children with Cancer: A Population‐Based Study</title><p><underline underline-style="single">S. Gupta</underline><sup>1</sup>, S. Rinku<sup>2</sup>, R. Adam<sup>3</sup>, K. Nelson<sup>3</sup>, Y. Liu<sup>2</sup>, C. Vadeboncouer<sup>4</sup>, S. Zelcer<sup>5</sup>, A. Kassam<sup>6</sup>, J. Pole<sup>7</sup>, C. Earle<sup>8</sup>, J. Wolfe<sup>9</sup>, K. Widger<sup>3</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Haematology/Oncology, Toronto, Canada; <sup>2</sup>Institute for Clinical Evaluative Sciences, Cancer Research Program, Toronto, Canada; <sup>3</sup>The Hospital for Sick Children, Paediatric Advanced Care Team, Toronto, Canada; <sup>4</sup>Children's Hospital of Eastern Ontario, Pediatric Palliative Care Outreach Team, Ottawa, Canada; <sup>5</sup>London Health Sciences Centre, Paediatric Haematology/Oncology, London, Canada; <sup>6</sup>Southlake Regional Health Centre, Paediatric Oncology, Newmarket, Canada; <sup>7</sup>Pediatric Oncology Group of Ontario, POGO Research Unit, Toronto, Canada; <sup>8</sup>Ontario Institute for Cancer Research, Health Services Research Program, Toronto, Canada; <sup>9</sup>Dana‐Farber Cancer Institute, Pediatric Palliative Care, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Children with cancer are at risk of receiving high‐intensity (HI) end‐of‐life (EOL) care with associated high symptom burden. The impact of palliative care (PC) delivered by generalists or of specialized pediatric palliative care (SPPC) on EOL care patterns is unknown, with previous studies limited by small sample sizes or low response rates.</p><p><bold>Design/Methods</bold>: We assembled a retrospective cohort of all Ontario children with cancer who died between 2000‐2012 and who received care through a pediatric institution with a SPPC team and a clinical PC database. Patients were linked to population‐based healthcare data capturing inpatient, outpatient, and emergency visits. Clinical PC databases identified patients receiving SPPC. Remaining patients were categorized as having received either general PC (GPC) or no PC depending on the presence of PC‐associated physician billing or inpatient codes. We determined predictors of SPPC involvement, and whether either SPPC or GPC was associated with HI‐EOL outcomes: ICU admission <30 days from death, mechanical ventilation <14 days from death, or in hospital death. Sensitivity analyses excluded treatment‐related mortality (TRM) cases.</p><p><bold>Results</bold>: 572 patients met inclusion criteria. Children less likely to receive SPPC services included those with hematologic cancers [odds ratio (OR) 0.33, 95<sup>th</sup> confidence interval (CI) 0.30‐0.37; p<0.001)], lowest income quintile (OR 0.44, 95CI 0.23‐0.81; p=0.009), and increased distance from treatment centers (OR 0.46, 95CI 0.40‐0.52; p<0.0001). In multivariate analysis, SPPC was associated with a 3‐fold decrease in the odds of an EOL ICU admission (OR 0.32, 95CI 0.18‐0.57), while GPC had no impact. Similar associations were seen with all other HI‐EOL indicators. Excluding TRM had little impact.</p><p><bold>Conclusions</bold>: SPPC, but not GPC, is associated with lower intensity care at EOL. Access to SPPC remains uneven. Without randomized trials, these results provide the strongest evidence to date supporting the creation of SPPC teams, and can be used to support advocacy and policy efforts.</p></sec></sec><sec id="pbc26772-sec-1090"><title>Free Paper Session: Soft Tissue Sarcomas</title><sec id="pbc26772-sec-1100"><label>O-084</label><title>Revisiting Risk Stratification in Patients with Localized Rhabdomyosarcoma (RMS): A Report from the European Paediatric Soft Tissue Sarcoma Study Group (EPSSG)</title><p><underline underline-style="single">G. Bisogno</underline><sup>1</sup>, M. Jenney<sup>2</sup>, S. Gallego<sup>3</sup>, C. Bergeron<sup>4</sup>, J.H. Merks<sup>5</sup>, C. Julia<sup>6</sup>, A. Ferrari<sup>7</sup>, Z. Angelica<sup>8</sup>, H. Martelli<sup>9</sup>, A. Kelsey<sup>10</sup>, H. Glosli<sup>11</sup>, V. Minard Colin<sup>12</sup>, M. Ben‐Arush<sup>13</sup>, I. Zanetti<sup>14</sup>, G.L. De Salvo<sup>15</sup></p><p><italic><sup>1</sup>University of Padua, Department of Pediatrics, Padova, Italy; <sup>2</sup>Children's Hospital for Wales Heath Park, Department of Pediatric Oncology, Cardiff, United Kingdom; <sup>3</sup>Hospital Universitari Vall d'Hebron, Department of Pediatric Oncology, Barcelona, Spain; <sup>4</sup>Centre Léon Bérard, Institut d'hématologie et d'Oncologie Pédiatrique, Lyon, France; <sup>5</sup>Emma Children's Hospital‐Academic Medical Center, Department of Pediatric Oncology, Amsterdam, The Netherlands; <sup>6</sup>Royal Marsden Hospital, Department of Paediatric Oncology, London, United Kingdom; <sup>7</sup>Istituto Nazionale dei Tumori, Pediatric Oncology Unit, Milano, Italy; <sup>8</sup>Istituto Fondazione Città della Speranza, Solid Tumor Laboratory, Padova, Italy; <sup>9</sup>Hôpital Bicêtre, Chirurgie Pédiatrique, Paris, France; <sup>10</sup>Royal Manchester Children's Hospital, Department of Pediatric Histopathology, Manchester, United Kingdom; <sup>11</sup>Rikshospitalet, Department of paediatric haematology and oncology, Oslo, Norway; <sup>12</sup>Institut Gustave Roussy, Departement d'Oncologie de l'Enfant et l'Adolescent, Villejuif, France; <sup>13</sup>Ruth Rappaport Children's Hospital, Pediatric Hematology Oncology and Bone Marrow Transplantation Division, Haifa, Israel; <sup>14</sup>Azienda Ospedaliera di Padova, Department of Woman's and Child's Health, Padova, Italy; <sup>15</sup>Istituto Oncologico Veneto, UOS Sperimentazioni Cliniche‐ Biostatistica e Nucleo Ricerca Clinica, Padova, Italy</italic></p><p><bold>Background/Objectives</bold>: In the stratification system of the recently closed RMS2005 protocol, 6 factors were used to define the risk group of children with localized RMS and assign treatment: histology, IRS Group, nodal involvement, patients age, tumor site and size. We re‐evaluated the value of this stratification, adding FOXO1 fusion status, in preparation of the next EpSSG protocol.</p><p><bold>Design/Methods</bold>: A total of 991 patients enrolled from 10/2005 to 6/2013 with >3 yrs follow up were included in the analysis. The initial step was a validation of the current system, examining its accuracy to discriminate groups of patients with different prognosis. This was followed by a multivariable analysis in order to select independent prognostic variables. Finally the role of PAX3/PAX7‐FOXO1 fusion status was evaluated in a cohort of 660 patients with the available data.</p><p><bold>Results</bold>: 3‐yrs EFS was 94.3, 75.8, 66.8 and 52.8 for low, standard, high and very high risk groups, respectively and all risk factors within the stratification system had prognostic value within the univariate analysis. On multivariable analysis IRS group and tumor site were identified as independent risk factors. An interaction between tumor size (>5cm) and patient age (>10yrs) emerged discriminating patients with worst prognosis When fusion status was included in the model a better risk determination was evident.</p><p><bold>Conclusions</bold>: the current stratification system has demonstrated good discrimination and calibration in a new cohort of patients. It will be adopted in the next EpSSG protocol with the inclusion of FOXO1 status instead of histology.
<table-wrap id="nlm-table-wrap-1" xml:lang="en" orientation="portrait" position="anchor"><table frame="hsides" rules="groups"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><thead><tr style="border-bottom:solid 1px #000000"><th align="left" rowspan="1" colspan="1">Variable</th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1">HR (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>(HR) p‐value</italic></th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1"><bold>IRS</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>I</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">1</td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>II</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">1.8 (0.8;4.0)</td><td align="left" rowspan="1" colspan="1"><italic>0.1758</italic></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>III</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">2.9 (1.4;6.0)</td><td align="left" rowspan="1" colspan="1"><italic>0.0043</italic></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Site</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Fav</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">1</td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Unfav</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">1.7 (1.2;2.4)</td><td align="left" rowspan="1" colspan="1"><italic>0.0018</italic></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Size</bold> (cm)</td><td align="left" rowspan="1" colspan="1"><bold>Age</bold> (yrs)</td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold><=5</bold></td><td align="left" rowspan="1" colspan="1"><bold><10</bold></td><td align="left" rowspan="1" colspan="1">1</td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold><=5</bold></td><td align="left" rowspan="1" colspan="1"><bold>>=10</bold></td><td align="left" rowspan="1" colspan="1">0.7 (0.4;1.2)</td><td align="left" rowspan="1" colspan="1"><italic>0.2161</italic></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>>5</bold></td><td align="left" rowspan="1" colspan="1"><bold><10</bold></td><td align="left" rowspan="1" colspan="1">0.8 (0.4;1.2)</td><td align="left" rowspan="1" colspan="1"><italic>0.3237</italic></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>>5</bold></td><td align="left" rowspan="1" colspan="1"><bold>>=10</bold></td><td align="left" rowspan="1" colspan="1">1.6 (1.1;2.3)</td><td align="left" rowspan="1" colspan="1"><italic>0.0111</italic></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Fusion status</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Negative</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">1</td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Positive</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">1.4 (1.0;1.9)</td><td align="left" rowspan="1" colspan="1"><italic>0.0310</italic></td></tr></tbody></table><permissions><copyright-holder>John Wiley & Sons, Ltd.</copyright-holder><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions></table-wrap></p></sec><sec id="pbc26772-sec-1110"><label>O-085</label><title>Does Early Detection with off‐Therapy Surveillance Imaging Improve Survival in Pediatric Rhabdomyosarcoma Patients? The European Experience</title><p><underline underline-style="single">B. Vaarwerk</underline><sup>1</sup>, C. Mallebranche<sup>2</sup>, M. Adams<sup>3</sup>, M.C. Affinita<sup>4</sup>, M. Jenney<sup>3</sup>, G. Bisogno<sup>4</sup>, K. McHugh<sup>5</sup>, R.R. van Rijn<sup>6</sup>, D. Orbach<sup>2</sup>, J.H.M. Merks<sup>1</sup></p><p><italic><sup>1</sup>Emma Children's Hospital ‐ Academic Medical Centre, Pediatric Oncology, Amsterdam, The Netherlands; <sup>2</sup>Institut Curie, Department of Pediatric adolescent young adult Oncology, Paris, France; <sup>3</sup>Children's Hospital for Wales, Department of Pediatric Oncology, Cardiff, United Kingdom; <sup>4</sup>Padova University, Pediatric Hematology and Oncology Division, Padova, Italy; <sup>5</sup>Great Ormond Street Hospital for Children, Department of Radiology, London, United Kingdom; <sup>6</sup>Emma Children's Hospital ‐ Academic Medical Centre, Pediatric Radiology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: After completion of treatment patients with localized rhabdomyosarcoma (RMS) are subject to intensive radiologic tumor surveillance, however the clinical significance of surveillance is unclear. We retrospectively analyzed the value of off‐therapy surveillance, by comparing survival of patients in whom relapse was detected by routine imaging to patients in whom relapse was first suspected by symptoms.</p><p><bold>Design/Methods</bold>: We studied patients with relapsed RMS, after completion of treatment for localized RMS, treated in large pediatric oncology hospitals in France, the Netherlands, United Kingdom and Italy and enrolled in the SIOP‐MMT‐95 (1995‐2004), ICG‐RMS96 (1996‐2004) or E<italic>p</italic>SSG‐RMS‐2005 (2005‐2013) studies. Survival time after relapse was compared by log‐rank test between patients in whom relapse was detected by routine imaging (imaging group) and patients in whom relapse was first suspected by clinical symptoms (symptoms group).</p><p><bold>Results</bold>: Preliminary data of 139 patients with relapsed RMS (treated in France and the Netherlands) revealed 52 patients (37.4%) in the imaging group and 86 patients (61.9%) in the symptoms group (1 patient missing). Median follow‐up time after relapse was 7.3 years for survivors (n=66); 5‐year post‐relapse survival [95% CI] was 45.2% [30.5‐59.9%] for patients in the imaging group and 50.1% [39.1‐61.1%] for patients in the symptoms group (p=0.93).</p><p><bold>Conclusions</bold>: Although systematic routine imaging is standard of care after treatment for RMS, these analyses indicate that the majority of patients with relapsed RMS are detected because of clinical symptoms. Furthermore, no survival advantage was observed for patients in whom relapse was detected before the emergence of clinical symptoms. These preliminary results show that the value off‐therapy surveillance is controversial, particularly since repeated imaging also entails potential harm (psychological impact, risk of anesthesia). Final results, including data of patients from the United Kingdom and Italy, will be presented.</p></sec><sec id="pbc26772-sec-1120"><label>O-086</label><title>Outcome of Patients with Group I Embryonal Rhabdomyosarcoma in the EPSSG RMS 2005 Study</title><p><underline underline-style="single">C. Bergeron</underline><sup>1</sup>, M. Jenney<sup>2</sup>, S. Gallego<sup>3</sup>, J.H.M. Merks<sup>4</sup>, H. Glosli<sup>5</sup>, A. Ferrari<sup>6</sup>, D. Ranchère ‐Vince<sup>7</sup>, T. Rogers<sup>8</sup>, V. Minard‐Colin<sup>9</sup>, J. Chisholm<sup>10</sup>, D.S. Gian Luca<sup>11</sup>, B. Gianni<sup>12</sup></p><p><italic><sup>1</sup>Centre Léon Bérard, Institut d'hématologie et d'Oncologie Pédiatrique, Lyon, France; <sup>2</sup>Children's Hospital for Wales, Department of haematology and oncology, Cardiff, United Kingdom; <sup>3</sup>Hospital Universitari Vall d'Hebron‐, Department of Pediatric Oncology‐, Barcelona‐, Spain; <sup>4</sup>Emma Children's Hospital–Academic Medical Center‐ University of Amsterdam‐, Department of Pediatric Oncology, Amsterdam, The Netherlands; <sup>5</sup>Oslo University Hospital, Department for Pediatric and Adolescent Medicine, Oslo, Norway; <sup>6</sup>Fondazione IRCCS Istituto Nazionale Tumori, Pediatric Oncology Unit, Milano, Italy; <sup>7</sup>Centre Léon Bérard, Bio‐pathology department, Lyon, France; <sup>8</sup>University Hospitals Bristol NHS Foundation Trust, Department of Paediatric Surgery, Bristol, United Kingdom; <sup>9</sup>Institut Gustave Roussy, Département d'Oncologie de l'Enfant et l'Adolescent, Villejuif, France; <sup>10</sup>Royal Marsden NHS Foundation Trust, Children and Young People's Unit, London, United Kingdom; <sup>11</sup>Istituto Oncologico Veneto IRCCS, Clinical Trials and Biostatistics Unit, Padova, Italy; <sup>12</sup>University of Padova, Pediatric Oncology Division, Padova, Italy</italic></p><p><bold>Background/Objectives</bold>: To evaluate the reduction of the burden of treatment in patients enrolled in the EpSSG RMS 2005 protocol after initial microscopic complete surgery for embryonal rhabdomyosarcoma (ERMS).</p><p><bold>Design/Methods</bold>: All patients with ERMS with initial microscopic complete resection (group I), lymp‐node (LN) negative, were prospectively enrolled in low‐risk group A (age <10 years and tumour size < 5 cm) or in standard‐risk group B (age > 10 year or tumour size >5 cm). Regional LN were investigated with imaging without systematic surgical sampling. Group A patients received 8 courses of vincristin and actinomycin‐D (VA) for 22 weeks while group B received 4 courses of ifosfamide, vincristin and actinomycine‐D (IVA) plus 5 VA for a total of 25 weeks. No radiotherapy was planned. OS and EFS were calculated using the Kaplan‐Meier method.</p><p><bold>Results</bold>: From December 2005 to April 2015, 149 patients (139 males) were enrolled in the study, 59 (39%) in group A and 90 (61%) in group B. Tumour location was 134 genito‐urinary non bladder‐prostate (129 para‐testicular, 3 uterus, 1 vagina, 1 vulva), 7 extremities, 3 bladder‐prostate, 1 head&neck, 1 orbit and 3 others. After pathological review, one case of nodular fasciitis was excluded from the analysis. Median follow‐up was 44 months. Eight of the 9 relapses occurred in group B patients and 7 were older than 10 years and had paratesticular tumour. Three died of the disease. The 3 yrs EFS and OS were 91% (95% CI 83.9‐95.1) and 97% ( 95% CI91.1‐99), respectively 95.3% and 100% for group A, and 88.2% and 95.2% for group B.</p><p><bold>Conclusions</bold>: Low‐risk ERMS patient treated without alkylating agents and radiotherapy have excellent survivals. The place of systematic RPLND and/or modern imaging to evaluate regional nodal involvement in patients > 10 years with paratesticular ERMS requires further discussion.</p></sec><sec id="pbc26772-sec-1130"><label>O-087</label><title>Malignant Peripheral Nerve Sheet Tumors (MPNST) in Children and Adolescents: Report of the European Pediatric Soft Tissue Sarcoma Group (EPSSG) NRSTS‐2005 Study</title><p><underline underline-style="single">M. van Noesel</underline><sup>1</sup>, D. Orbach<sup>2</sup>, B. Brennan<sup>3</sup>, G.L. de Salvo<sup>4</sup>, I. Zanetti<sup>5</sup>, N. Francotte<sup>6</sup>, R. Alaggio<sup>7</sup>, A. Kelsey<sup>8</sup>, G. Bisogno<sup>9</sup>, M. Casanova<sup>10</sup>, A. Ferrari<sup>10</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Dept of Solid tumors, Utrecht, The Netherlands; <sup>2</sup>Institut Curie, Pediatric Adolescent Young Adult Department, Paris, France; <sup>3</sup>Royal Manchester Children's Hospital, Pediatric Oncology, Manchester, United Kingdom; <sup>4</sup>EpSSG Data Centre Istituto Oncologico Veneto IRCCS, Data Centre, Padova, Italy; <sup>5</sup>EpSSG Data Centre Istituto Oncologico Veneto IRCCS, EpSSG Data Centre, Padova, Italy; <sup>6</sup>CHC‐Clinique Esperance, Department of Pediatrics, Montegnée, Belgium; <sup>7</sup>Padova University, Pathology Department, Padova, Italy; <sup>8</sup>Royal Manchester Children's Hospital, Department of Pathology, Manchester, United Kingdom; <sup>9</sup>Padova University, Pediatric Hematology and Oncology Division, Padova, Italy; <sup>10</sup>Fondazione IRCCS Istituto Nazionale Tumori, Pediatric Oncology, Milan, Italy</italic></p><p><bold>Background/Objectives</bold>: MPNST are the third most frequent pediatric soft tissue sarcoma. In 50% MPNST is associated with Neurofibromatosis type 1. Retrospective studies showed poor outcome and poor response to conventional chemotherapy. Here, we present the results for patients with localized MPNST enrolled in the prospective EpSSG NRSTS‐2005 study with a risk adapted strategy.</p><p><bold>Design/Methods</bold>: A cohort of 59 localized MPNST patients from 8 European countries were treated in 3 treatment groups: 1. Surgical group (R0 ≤5 cm; R0 >5cm and R1/N0) (n=14). 2. Radiotherapy group (R0 >5cm G2 and R1/N0 G2‐G3 ≤5cm and R1/N0 G2 >5cm) (n=4) with 50.4 Gy for R0 tumors and 54.0 Gy for R1 tumors. 3. Perioperative chemotherapy group (R0‐1/N0 G3 >5cm; n=8) and (R2 + N1; n=33). Chemotherapy: 6 courses ifosfamide 3 g/m²/day, 3 days + doxorubicin 37.5 mg/m²/day, 2 days.</p><p><bold>Results</bold>: Post‐surgical staging of all tumors: 24% R0 resection ; 20% R1 resection, 56% R2 resection. In 28/33 evaluable neo‐adjuvant patients, chemotherapy response was complete (CR) in 6.9%; partial (PR) in 10.3%; minor (MR) in 31.0%; no progression in 34.5%. Total response to chemotherapy (CR + PR + MR) is 47.2%. The 3‐yrs EFS for the surgical group was 100%; radiation group 67%; Perioperative group <40%. Outcome of 55/59 evaluable patients with a median follow‐up of 39.5 months: 27 alive in 1st CR, 9 alive with disease and 19 died. The 3‐yrs EFS was 56.1 (95%CI 41.0‐68.7) and 3‐yrs OS 66.5 (95%CI 50.9‐78.2). NF1 was diagnosed in 47% of patients.</p><p><bold>Conclusions</bold>: Outcome of pediatric MPNST patients is poor and the results of this prospective, interational treatment protocols is comparable or slightly better to historic, retrospective studies. Novel treatment strategies are necessary to improve outcome in MPNST.</p></sec><sec id="pbc26772-sec-1140"><label>O-088</label><title>Intraperitoneal Radioimmunotherapy for Desmoplastic Small Round Cell Tumor: Results of a PHASE I Study (Clinicaltrials.Gov Identifier NCT01099644)</title><p><underline underline-style="single">S. Modak</underline><sup>1</sup>, M.P. LaQuaglia<sup>1</sup>, N. Pandit‐Taskar<sup>2</sup>, P. Zanzonico<sup>3</sup>, T. Heaton<sup>1</sup>, J. Lewis<sup>2</sup>, N.K. Cheung<sup>1</sup>, J. Carrasquillo<sup>2</sup></p><p><italic><sup>1</sup>Memorial Sloan Kettering Cancer Center, Pediatrics, New York, USA; <sup>2</sup>Memorial Sloan Kettering Cancer Center, Radiology, New York, USA; <sup>3</sup>Memorial Sloan Kettering Cancer Center, Medical Physics, New York, USA</italic></p><p><bold>Background/Objectives</bold>: Desmoplastic small round cell tumor (DSRCT), a rare sarcoma of adolescents and young adults, has a long‐term survival of <20% despite aggressive multimodality therapy, warranting a search for novel treatments. The murine monoclonal IgG1 antibody 8H9 recognizes cell surface antigen 4Ig‐B7H3 and binds to 96% of DSRCTs with restricted normal tissue reactivity. DSRCT recurrences often present as multifocal peritoneal implants. We hypothesized that intraperitoneal (IP) radioimmunotherapy (RIT) by virtue of prolonged residence time and slow transfer to the circulation, may selectively target IP DSRCT.</p><p><bold>Design/Methods</bold>: We conducted a phase I study of radioiodinated 8H9 to evaluate toxicity, pharmacokinetics, biodistribution and efficacy. Cohorts of 3‐6 patients were treated with escalated doses of IP <sup>131</sup>I‐8H9. A prior dose of 2mCi <sup>124</sup>I‐8H9 IP was used to acquire PET images and biodistribution data. Toxicity was monitored clinically and biochemically. Pharmacokinetics was studied using serial blood draws.</p><p><bold>Results</bold>: Thirty‐seven DSRCT patients were treated at doses of 30‐90mCi/m<sup>2</sup>. Maximum tolerated dose was not reached; there were no dose‐limiting toxicities. Adverse events (n=1 each) were transient: grade 3 transaminitis, neutropenia, and thrombocytopenia. Blood and peritoneal half‐times were 32.5h and 14.6h respectively. Mean projected absorbed doses to blood, kidney, liver, lung and spleen were 0.7,1.72,1.92,0.64 and 1.03 rad/mCi <sup>131</sup>I‐8H9 respectively (n=12 patients analyzed). Dehalogenation was insignificant: >80% blood <sup>131</sup>I remained protein‐bound 66h post‐RIT. Recommended phase II dose was 80mCi/m<sup>2</sup>. Progression‐free survival (PFS) for patients undergoing gross total resection followed by RIT and whole‐abdominal radiotherapy was 17.9±3 months. 11/20 patients survive PF at a median of 29 months post‐RIT. In contrast patients with gross residual disease pre‐RIT (n=13) had PFS of 3.3±1.4 months. Overall survival was also better for the former (p<0.05).</p><p><bold>Conclusions</bold>: <sup>124</sup>I‐8H9‐directed radioimmuno‐PET successfully determined biodistribution, whole‐body and organ exposure. <sup>131</sup>I‐8H9 IP RIT had a satisfactory safety profile and activity against micro‐metastatic DSRCT. A phase II trial will commence shortly.</p></sec><sec id="pbc26772-sec-1150"><label>O-089</label><title>Genomic Index in Pediatric Synovial Sarcoma (Synobio Study), Final Results the European Pediatric Soft Tissue Sarcoma Group (EPSSG) Experience</title><p><underline underline-style="single">D. Orbach</underline><sup>1</sup>, V. Mosseri<sup>2</sup>, D. Pissaloux<sup>3</sup>, B. Brennan<sup>4</sup>, A. Ferrari<sup>5</sup>, F. Chibon<sup>6</sup>, G. Bisogno<sup>7</sup>, G.L. De Salvo<sup>8</sup>, C. Chakiba<sup>6</sup>, N. Corradini<sup>9</sup>, V. Minard‐Colin<sup>10</sup>, A. Kelsey<sup>11</sup>, D. Ranchère‐Vince<sup>3</sup></p><p><italic><sup>1</sup>Institut Curie, Pediatric adolescents young adults department, Paris, France; <sup>2</sup>Institut Curie, Department of Biostatistics, Paris, France; <sup>3</sup>Institut d'Hematologie et d'Oncologie Pediatrique‐ Centre Léon Bérard, Pathology department, Lyon, France; <sup>4</sup>Royal Manchester Children's Hospital, Paediatric Oncology, Manchester, United Kingdom; <sup>5</sup>Fondazione IRCCS Istituto Nazionale Tumori, Pediatric Oncology Unit, Milan, Italy; <sup>6</sup>Institut Bergonié, Département de Biopathologie, Bordeaux, France; <sup>7</sup>Padova University, Pediatric Hematology and Oncology Division, Padova, Italy; <sup>8</sup>IRCCS Istituto Oncologico Veneto, Clinical Trials and Biostatistics Unit, Padova, Italy; <sup>9</sup>Institut d'Hematologie et d'Oncologie Pediatrique‐ Centre Léon Bérard, Pediatric oncology, Lyon, France; <sup>10</sup>Gustave Roussy, Département de Cancérologie de l'Enfant et de l'Adolescent, Villejuif, France; <sup>11</sup>Royal Manchester Children's Hospital, Department of Diagnostic Paediatric Histopathology, Manchester, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: A genomic index (GI) tool using array comparative genomic hybridization (aCGH) on tumor cells correlates with genomic instability and has recently been developed. GI has emerged as independent prognostic factor associated with the risk of metastatic relapse in adult synovial sarcoma (SS). The aim is to assess the role of GI in pediatric patients with SS.</p><p><bold>Design/Methods</bold>: All pediatric/adolescent/young adults’ (<25 years) with localized SS (central pathological review or specific fusion transcript (SYT‐SSX)) prospectively included in the European EpSSG‐NRSTS‐05 protocol (EUDRACT2005‐001139‐31) with a contributive aCGH were selected. Definition of GI was A<sup>2</sup>/C, where A is the total number of alterations (segmental gains and losses) and C is the number of involved chromosomes on aCGH results. GI<sub>1</sub> group corresponds to cases with no alterations (flat profile, GI=0) and GI<sub>2</sub> group cases with many alterations (complex CGH profile; GI≥1).</p><p><bold>Results</bold>: Samples were available from 62 patients. The median age of the cohort was 13 years (range: 4‐24). The commonest primary site was extremities (69%). Patients received either surgery only (23%), adjuvant therapy (16%) or perioperative therapy with surgery and radiotherapy (61%). In summary, 54.8% were GI<sub>1</sub> group, and 45.2% GI<sub>2</sub>. After a median follow up of 60 months (range: 0.1‐112), 10 tumor events occurred and 5 patients died. Respectively for GI<sub>1</sub> vs. GI<sub>2</sub> groups, 5‐year event free survival (EFS) rates were 93.8±4.2% vs. 66.4±9.8% (P<0.007) and 5Y‐Metastatic Free Survival (MFS) 93.8±4.2% vs. 74.1±9.1% (P<0.05). In multivariate analysis, GI status as adjusted for IRS‐group, site and tumor size remains independent prognostic for EFS with a relative risk (RR) of 6.3[1.3‐31.3] (p<0.015) and RR for MFS is 4.7 [0.9‐25.2] (p=0.051).</p><p><bold>Conclusions</bold>: GI may explain aggressive behavior of some pediatric SS. Although tumor events were rare, high GI selected patients with a poorer outcome that may require therapy intensification in future protocols.</p><p><italic>Founding sources: “Enfant‐et‐santé/SFCE” “Info‐sarcome” “La‐ligue‐contre‐le‐cancer”</italic></p></sec></sec><sec id="pbc26772-sec-1160"><title>Free Paper Session: Immunotherapy</title><sec id="pbc26772-sec-1170"><label>O-090</label><title>Encouraging Responses and Survival for Patients with Replication Repair Deficiency and Hypermutant Cancers to Immune Checkpoint Inhibition. A Report from the International bMMRD Consortium</title><p><underline underline-style="single">P. Angelini</underline><sup>1</sup>, M. Sabel<sup>2</sup>, V. Larouche<sup>3</sup>, E. Opocher<sup>4</sup>, S. Lindhorst<sup>5</sup>, D. Ziegler<sup>6</sup>, B. George<sup>7</sup>, M. Oren<sup>8</sup>, P. Tomboc<sup>9</sup>, D. Samuel<sup>10</sup>, M. Osborn<sup>11</sup>, A. Bronsema<sup>12</sup>, K. Cole<sup>13</sup>, D. Stearns<sup>14</sup>, S. Chiaravalli<sup>15</sup>, G. Mason<sup>16</sup>, G. Thomas<sup>17</sup>, M. Vanan<sup>18</sup>, E. Bouffet<sup>19</sup>, U. Tabori<sup>19</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Haematology/Oncology, Toronto, Canada; <sup>2</sup>University of Goteborg, Paediatric Haematology and Oncology, Goteborg, Sweden; <sup>3</sup>Centre Mere‐Enfant Soleil du CHU du Quebec, Paediatric Haematology and Oncology, Sainte‐Foy Quebec, Canada; <sup>4</sup>University of Padua, Paediatric Haematology and Oncology, Padua, Italy; <sup>5</sup>Medical University of South Carolina, Neuro‐Oncology, Charleston, USA; <sup>6</sup>University of New South Wales, Paediatric haematology and Oncology, Sidney, Australia; <sup>7</sup>Medical College of Winsconsin, Haematology and Oncology, Milwaukee, USA; <sup>8</sup>Sheba medical Centre, Paediatric Haematology and Oncology, Sheba, Israel; <sup>9</sup>West Virginia University, Paediatric Haematology and Oncology, Morgantown, USA; <sup>10</sup>Valley Children Health Care, Paediatric Haematology and Oncology, Madera, USA; <sup>11</sup>Women's and Children's Hospital, Department of Clinical Haematology/Oncology, North Adelaide, Australia; <sup>12</sup>University Medical Center Hamburg‐Eppendorf, Department of Pediatric Hematology and Oncology, Hamburg, Germany; <sup>13</sup>Children's Hospital of Philadelphia, Research Institute, Philadelphia, USA; <sup>14</sup>University Hospital Clevelan Medical Centre, Pediatrics‐Hematology and Oncology, Cleveland, USA; <sup>15</sup>National Cancer Institute, Paediatric Oncology, Milan, Italy; <sup>16</sup>Children's Hospital Pittsburgh, Haematology adn Oncology, Pittsburgh, USA; <sup>17</sup>Oregon Health and Science University, Paediatric Haematology adn Oncology, Portland, USA; <sup>18</sup>Children's Hospital Research Institute of Manitoba, Paediatric Haematology and Oncology, Winnipeg, Canada; <sup>19</sup>The Hospital for Sick Children, Neuro‐Oncology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Biallelic mismatch repair disease (bMMRD) is the most aggressive cancer predisposition syndrome in which patients succumb to multiple hypermutated cancers during childhood. Since hypermutated cancers have responded to immune checkpoint inhibitors (ICI), we treated patients with recurrent hypermutant cancers with ICI to assess toxicity, tumour response and survival.</p><p><bold>Design/Methods</bold>: As a part of the international bMMRD consortium collaboration, bMMRD patients with recurrent/progressive cancers received nivolumab or pembrolizumab. Clinical data was prospectively collected. Tumour mutation analysis and neo‐antigen formation analysis were performed.</p><p><bold>Results</bold>: Twenty patients (11 males, median age at starting ICI 11.9 years) with 25 cancers received ICI. All tumors were hypermutant (>10mut/MB) and 12 were ultra‐hypermutant (>100mut/MB). Nine patients developed acute “flare” symptoms following the first ICI administration. These included 8 patients with brain tumors and heavy burden of disease and one bone metastasis from colon cancer. All these patients required steroid use and 6 died within a few days or weeks after this first administration. Only 2 patients developed autoimmune phenomena related to ICI. Of patients with evidence of disease, objective responses were observed in 5/11 brain tumors and 4/4 metastatic extra‐cranial tumours. One year survival is 62+/‐13% for the whole cohort and 52+/‐12% for gliomas. All 5 patients with extra‐CNS solid tumors are alive and in continuous response. At a median of 7.2 (3‐19) months, 12 patients are still alive and on therapy.</p><p><bold>Conclusions</bold>: This is the first cohort of prospectively followed patients with bMMRD and hypermutant cancers treated with ICI. The encouraging initial responses and prolonged survival in this cohort warrants a prospective genetic based study of ICI in children. The role of “flare reactions” following initiation of treatment needs to be further investigated.</p></sec><sec id="pbc26772-sec-1180"><label>O-091</label><title>Preclinical Efficacy and Safety Profile of CD19CAR+ T Cells Engineered with Sleeping Beauty Gene Transfer for the Treatment of Acute Lymphoblastic Leukemia</title><p>C.F. Magnani<sup>1</sup>, C. Cappuzzello<sup>1</sup>, F. Benedicenti<sup>2</sup>, S. Tettamanti<sup>1</sup>, E. Montini<sup>2</sup>, G. Gaipa<sup>1</sup>, B. Andrea<sup>1</sup>, <underline underline-style="single">E. Biagi</underline><sup>1</sup></p><p><italic><sup>1</sup>Research Center "M. Tettamanti", Pediatric Oncology, Monza MB, Italy; <sup>2</sup>San Raffaele Telethon Institute for Gene Therapy HSR‐TIGET, Safety of Gene Therapy and Insertional Mutagenesis Research Unit, Milan, Italy</italic></p><p><bold>Background/Objectives</bold>: Adoptive transfer of autologous CD19‐specific chimeric antigen receptor (CAR)T cells engineered by viral vectors demonstrated unexpected positive results, achieving durable responseS in relapsed and refractory patients affected by B‐lineage leukemias. We recently established a platform for non‐viral gene manipulation of Cytokine‐Induced Killer (CIK) cells, in compliance with Good Manufacturing Practices (GMP). In this study, we evaluated the feasibility and reproducibility of a GMP‐compliant protocol, and the preclinical efficacy and safety of SB modified CARCIK‐CD19 cells.</p><p><bold>Design/Methods</bold>: With an improved SB transposon platform, we genetically modified CIK cells to express the CAR specific for acute lymphoblastic leukemia CD19+ blasts and evaluated their preclinical efficacy and safety in vitro and in vivo.</p><p><bold>Results</bold>: Large scale manufacturing process was verified starting from 45 ml of peripheral blood or, alternatively, 30‐60X10^6 PBMC isolated from Buffy Coats, reaching stable expression of CD19CAR (62.425%±6.399). Modified cells displayed a specific and effective cytotoxicity, IL‐2 and IFN‐gamma production and proliferation towards primary tumors. We manufactured three lots in an academic Cell Factory, authorized by Agenzia Italiana del Farmaco. The median expression of CD3+CD19CAR + cells was 46.90% (range 31.27% – 65.45%). CARCIK‐CD19 cells showed a dose‐dependent antitumor response and persisted in a xenograft mouse model of common BCP‐ALL, bearing the feature of a Ph‐like gene rearrangement (PAX5/AUTS2), and in a survival model with Daudi‐cell lymphoma. CARCIK‐CD19 cells induced complete eradication of disseminated tumor. Infusion of CARCIK‐CD19 cells proved to be safe and well tolerated. The infused cells persisted in time in the hematopoietic and post‐injection perfused organs. Highly polyclonal distribution of Integration Sites in CARCIKCD19 cell product was demonstrated.</p><p><bold>Conclusions</bold>: CARCIK‐CD19 may offer a valid and sustainable alternative to patient‐derived viral approach for patients with r/r B cell malignancies after HSCT. This study provides the proof‐of‐concept for designing phase I/II study for relapsing and refractory ALL post Hematopoietic Stem Cell Transplantation.</p></sec><sec id="pbc26772-sec-1190"><label>O-092</label><title>BAFF Receptor (BAFF‐R) Car‐Redirected T Cells as a Novel Tool to Treat High Risk B‐Cell Acute Lymphoblastic Leukemia (B‐ALL)</title><p><underline underline-style="single">N. Turazzi</underline><sup>1</sup>, G. Fazio<sup>1</sup>, V. Rossi<sup>1</sup>, A. Rolink<sup>2</sup>, G. Cazzaniga<sup>1</sup>, A. Biondi<sup>1</sup>, C.F. Magnani<sup>1</sup>, E. Biagi<sup>1</sup></p><p><italic><sup>1</sup>M. Tettamanti Reserach Center‐ University of Milano Bicocca S.Gerardo Hospital/Fondazione MBBM, Department of Pediatrics, Monza, Italy; <sup>2</sup>University of Basel, Department of Biomedicine, Basel, Switzerland</italic></p><p><bold>Background/Objectives</bold>: B‐cell Acute Lymphoblastic Leukemia (B‐ALL) is the most common malignancy in children (80%). CD19‐targeting approaches paved the way for the treatment of relapsed/refractory ALL. However, the emergence of CD19‐negative relapses in 10‐30% of treated patients has been reported. Receptor of B‐cell Activating Factor (BAFF‐R) is fundamental for B‐cell maturation and survival with an expression restricted to mature B cells while not on B‐cell precursors and plasmablasts. Recent studies reported the over‐expression of BAFF‐R in B‐cell malignancies, including B‐ALL. Moreover, leukemic cells express both BAFF and BAFF‐R suggesting an autocrine signaling loop. BAFF is also expressed in leukemic niche supporting proliferation and survival of B‐ALL blasts.</p><p>In this study, we aimed to develop a chimeric antigen receptor (CAR)‐mediated approach targeting BAFF‐R molecule.</p><p><bold>Design/Methods</bold>: To target BAFF‐R molecule, we developed anti‐BAFFR.CARs that differ for the inversion of the VH and VL and the length of the spacer domain. Cytokine‐induced Killer (CIK) cells, an heterogeneous population enriched in highly cytotoxic CD3+CD56+ cells, were engineered with an improved <italic>Sleeping Beauty</italic> platform and used as effector population.</p><p><bold>Results</bold>: We showed that BAFF‐R expression in B‐ALL primary samples is maintained at relapse. Anti‐BAFFR.CARs were stably expressed and the shortest VHVL.CAR exerted the highest anti‐leukemic activity (average 60%) and cytokine release (8.9±2% of IFN‐γ and 16.4±5.5% of IL‐2 producing cells) towards NALM‐6<italic>in vitro</italic>. Importantly, we detected specific lysis of primary B‐ALL blasts (65.6±4.5%). Combining the INVsh.CAR with CD19.CAR, we detected a superior anti‐tumor activity towards NALM‐6 and primary blasts (78.1±6.9% and 72.2±2.9% of lysis respectively) compared to single population <italic>per se</italic>. Furthermore, we demonstrated the ability of the INVsh.CAR to lysate blasts collected from CD19‐negative relapse.</p><p><bold>Conclusions</bold>: Taken together, these findings make this receptor a safe and attractive target for a second line immunotherapy in case of CD19‐negative relapse or for a double targeted approach.</p></sec><sec id="pbc26772-sec-1200"><label>O-093</label><title>Specific Targeting of Acute Myeloid Leukemia by the use of Engineered CIK (Cytokine‐Induced Killer) Cells Expressing the Anti‐CD33 Chimeric Antigen Receptor (CAR)</title><p>M.C. Rotiroti<sup>1</sup>, S. Arcangeli<sup>1</sup>, C.F. Magnani<sup>1</sup>, C. Cappuzzello<sup>1</sup>, A. Biondi<sup>1</sup>, S. Tettamanti<sup>1</sup>, <underline underline-style="single">E. Biagi</underline><sup>1</sup></p><p><italic><sup>1</sup>Research Center “M. Tettamanti”, Pediatric Clinic, Monza MB, Italy</italic></p><p><bold>Background/Objectives</bold>: Acute Myeloid Leukemia (AML) is still associated with a dismal prognosis.</p><p>Immunotherapy employing T cells redirected with Chimeric Antigen Receptors (CARs) could represent a valid alternative to current strategies.</p><p>CD33 is broadly expressed on AML blasts, representing a suitable antigen to be targeted with CAR‐T cells.</p><p>The aim of the study is to preclinically evaluate efficacy and safety profiles of CD33.CAR redirected Cytokine Induced Killer (CIK) cells alone and in combination with standard chemotherapeutic agents.</p><p><bold>Design/Methods</bold>: We generated CD33.CAR‐expressing CIK cells through the non viral Sleeping‐Beauty transposon system, starting from healthy mononuclear cells and primary AML samples.</p><p>The <italic>in vitro</italic> anti‐AML activity of CD33.CAR‐CIK cells has been assessed by cytotoxicity, proliferation and cytokine production assays upon challenge with AML samples.</p><p>The <italic>in vivo</italic> efficacy of CD33.CAR CIK cells is evaluated in NSG mice transplanted with MA9‐NRas AML cells and primary samples. Moreover we investigate the potential benefit of combining CD33.CAR CIK cells with standard AML induction therapy.</p><p><bold>Results</bold>: CD33.CAR‐CIK cells resulted in a potent anti‐leukemic activity, in terms of specific killing, proliferation and cytokine production. We observed that the already established “5+3” induction protocol significantly reduced the leukemic burden from around 20% to 0.1% in the bone marrow of MA9‐NRas cell grafted mice. Since the disease was not totally eradicated, we are currently investigating the efficacy of the CD33.CAR‐CIK cells on chemotherapy resistant/residual AML cells. Preliminary data have shown a survival advantage when adding CD33.CAR‐CIK cells on the top of chemotherapy.</p><p><bold>Conclusions</bold>: Having demonstrated the <italic>in vitro</italic> anti‐leukemic activity of SB‐modified CD33.CAR‐CIK cells, we aim to further evaluate their efficacy <italic>in vivo</italic> against chemotherapy resistant/residual AML cells to corroborate our initial observations. Envisaging a safer clinical translation, transient CAR expression, by CD33.CAR mRNA, is under investigation, to limit the potential long‐term off‐target effect on normal hematopoietic stem/myeloid progenitor cells.</p></sec><sec id="pbc26772-sec-1210"><label>O-094</label><title>Precision Targeting of Acute Myeloid Leukaemia Using Costimulatory‐Only Chimeric Antigen Receptors Provides Efficacy without Toxicity</title><p><underline underline-style="single">J. Fisher</underline><sup>1</sup>, P. Abramowski<sup>1</sup>, N.D. Wisidagamage Don<sup>1</sup>, J. Anderson<sup>1</sup></p><p><italic><sup>1</sup>UCL Institute of Child Health, Cancer section, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: On‐target off‐tumour toxicity constrains the development of immunotherapies targeting highly expressed tumour antigens, producing challenging and sometimes fatal toxicity. The strength of CD3ζ‐containing chimeric antigen receptors expressed in αβT cells is also a limitation as it offers no escape to antigen‐expressing healthy cells. Vδ2+ γδT cells differentiate between healthy and transformed cells in an MHC‐independent manner determined by differing expression of phosphoantigen on stressed versus healthy cells. Their native TCR is therefore not redundant in the tumour context and need not be replaced with an artificial construct. We sought to determine the efficacy and safety of Vδ2+ γδT cells expressing ”co‐stimulation only” CARs in a pre‐clinical model.</p><p><bold>Design/Methods</bold>: To demonstrate the lack of on‐target off‐tumour toxicity, anti‐CD33 “co‐stimulation only” CARs expressed in Vδ2+ γδT cells were compared to a conventional second generation anti‐CD33 CAR (CD33‐28ζ). Cytotoxicity against CD33+ AML cell lines, healthy myeloid cells and myeloid progenitors was assessed. Phenotype was assessed by flow cytometry and secondary expansion potential was determined by co‐culture with irradiated target cells. Mechanistic information was obtained using cell‐free systems to determine cytokine production and signalling profiles by PhosFlow following stimulus of CD3, CAR or both.</p><p><bold>Results</bold>: γδT cells expressing a “costimulation‐only” CAR retain anti‐tumour cytotoxicity but show no activity against healthy cells which do not engage the γδTCR. Clinically useful numbers of cells can be generated from a 100ml blood draw. Precise control of cytokine production and activatory signalling is achievable with selective stimulus of CAR and/or TCR. “Costimulation‐only” CAR expressing γδT cells have a phenotype favourable for adoptive transfer with significantly lower exhaustion marker expression than cells expressing a conventional CD3ζ‐CD28 CAR, and are capable of mounting a secondary expansion following antigen re‐challenge.</p><p><bold>Conclusions</bold>: This approach offers a means of safely recapitulating immunotherapy against tumour antigens previously rejected on grounds of on‐target off‐tumour toxicity.</p></sec><sec id="pbc26772-sec-1220"><label>O-095</label><title>Resistance Mechanisms of Rhabdomyosarcomas to Rhabdomyosarcoma‐Directed Chimeric T Cells</title><p><underline underline-style="single">K. Simon‐Keller</underline><sup>1</sup>, A. Seils<sup>1</sup>, P.D.A. Marx<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Mannheim, Institute of Pathology, Mannheim, Germany</italic></p><p><bold>Background / Objectives: Background</bold>: Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy of childhood and adolescence. Outcome of children with advanced RMS is still poor. Immunotherapies may offer new perspectives for high‐risk patients.</p><p><bold>Design / Methods: Objective</bold>: To reveal tumor cell‐intrinsic resistance mechanisms of RMS cell lines, RMS redirected cytotoxic T cells expressing a chimeric antigen receptor (CAR) with specificity for the fetal acetylcholine receptor (fAChR), which is an almost RMS‐specific, tumor associated antigen, were used. Futhermore sensitivity of RMS tumor cells against Cytokine induced killer cells (CIK) and NK cells were tested.</p><p><bold>Methods</bold>: RMS‐directed chimeric T‐cells (cTCs) were generated by retroviral transduction of peripheral blood lymphocytes with fAChR specific CAR. CIK and NK cells were enriched by cultivation. Killing efficiency of the named immune cells and survival of RMS cells were determined by apoptosis tests after co‐culture. RMS were checked for expression of anti‐apoptotic genes and immunosuppressive as well as co‐stimulatory receptors using FACS, Western Blot and qRT‐PCR.</p><p><bold>Results</bold>: fAChR specific chimeric T‐cells showed RMS tumor cell lysis <italic>in vitro</italic> and <italic>in vivo</italic>, but were less efficient. RMS cells were resistant to IFNγ, TNFα, FAS‐L and TRAIL. Molecular features associated with resistance of RMS to cTCs are (a) lack of essential costimulators for tumour ‐ T cell interaction and expression of inhibitory molecules like B7H1 and B7H3; (b) over‐expression of <italic>inhibitor of apoptosis (IAP)</italic> family members in RMS cells and tissue. Inhibition of IAPs through siRNA or pharmacological substances improved killing efficiency by chimeric T cells <italic>in vitro</italic> and <italic>in vivo</italic>. The mentioned resistance mechanisms were ‘spontaneously’ circumvented by CIK and NK cells to which RMS cells were highly sensitive.</p><p><bold>Conclusions</bold>: Blockade of anti‐apoptotic mechanisms and use NK and CIK cell‐mediated therapeutic strategies as well as RMS‐specific chimeric T cells should be evaluated as therapeutic strategy in RMS.</p></sec></sec><sec id="pbc26772-sec-1230"><title>Free Paper Session: PPO ‐ I</title><sec id="pbc26772-sec-1240"><label>O-096</label><title>Interventions to Support Parents Whose Child is Being Treated for Cancer: Lessons Learned from Research on Existing Programs</title><p><underline underline-style="single">S. Sultan</underline><sup>1</sup>, D. Ogez<sup>1</sup>, K. Peloquin<sup>2</sup>, R. Ribeiro<sup>2</sup>, D. Curnier<sup>1</sup>, V. Marcil<sup>1</sup>, D. Sinnett<sup>1</sup></p><p><italic><sup>1</sup>CHU Sainte‐Justine, Hematology‐Oncology, Montreal, Canada; <sup>2</sup>Université de Montréal, Psychology, Montréal, Canada</italic></p><p><bold>Background/Objectives</bold>: Parents of children treated for cancer are vulnerable to a variety of issues including heightened distress and lack of control. Distress during treatment has been identified as a risk factor for future distress and for increased difficulties for the family and the child in the long run. To help parents during treatments, manualized interventions have been developed and applied with this population.This presentation will identify, review and criticize existing manualized intervention. We concentrate on program development processes and criteria of quality of psychological treatments to identify previous achievements as well as avenues for future improvements.</p><p><bold>Design/Methods</bold>: A systematic search was run in databases (electronic and manual) to identify existing programs corresponding to inclusion criteria. The ORBIT framework was used to evaluate and compare program development processes. Criteria from the APA task force on psychological treatments were used to evaluate the consistency or coherence of programs.</p><p><bold>Results</bold>: Ten manualized interventions (24 reports) were identified and coded. Some programs yielded clinical effects (e.g. Bright Ideas, SCCIP). An in‐depth analysis revealed that lack of clinical signal may be due to a variety of factors. A subset of programs (N=4) lack precise concept definition, explicit model of change and defined target. Social validity and acceptability was seldom documented prior efficacy testing. Importantly, dosage or treatment intensity was never systematically studied.</p><p><bold>Conclusions</bold>: Fine methodological design is necessary for program testing but is not sufficient for appropriate program development. Systematic psychosocial interventions to help parents should build on one another and therefore explicitly refer to sound models of change. Models of change should also translate more clearly in the format, tools, and interaction style of programs. Future programs should also address underserved populations (e.g. fathers) and optimize contact rates (e.g. e‐health initiatives).</p></sec><sec id="pbc26772-sec-1250"><label>O-097</label><title>Child Versus Parent Perceptions of Parenting In Childhood Cancer Surivivors and Healthy Peers</title><p><underline underline-style="single">S. Schepers</underline><sup>1</sup>, A. Long<sup>1</sup>, K. Russell<sup>1</sup>, S. Phipps<sup>1</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Psychology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: A pediatric cancer diagnosis is a challenging event that may have an impact on how children and parents perceive parent‐child relationships. The aims of this study were to (a) examine possible differences in child and parent perceptions of parenting between childhood cancer survivors and healthy peers, and (b) determine the concordance between child and parent perceptions of parenting.</p><p><bold>Design/Methods</bold>: Participants were children aged 8‐21 years (N=206 children with a history of cancer, N=119 healthy peers), and one of their parents. All patients were ≥ 3 years from diagnosis (<italic>M</italic>=7.06, <italic>SD</italic>=4.25). Both children (Parental Bonding Instrument (PBI)) and parents (Parenting Relationship Questionnaire (PRQ)) reported on their perceptions of parenting. Two separate MANCOVA's (PBI and PRQ) were conducted to determine possible differences between the cancer and the comparison group, while controlling for child age/gender, and parent SES/gender. Concordance between the PBI scales of parental care and overprotection and the PRQ scales of involvement, attachment, communication, parenting confidence, and relational frustration was assessed with Pearson correlation coefficients.</p><p><bold>Results</bold>: Survivors of childhood cancer (<italic>p=</italic>.868) and their parents (<italic>p=</italic>.202) did not differ in their perceptions of parenting compared to healthy peers. The magnitude of effect between parent‐child dyads was not significantly different for childhood cancer survivors and healthy peers. The child's report of a caring parent‐child relationship was positively and significantly associated with parent‐reported involvement, attachment, communication, and parenting confidence (<italic>r’</italic>s ranged from .20 to .30), and negatively associated with relational frustration (<italic>r=</italic>‐.36). Children that perceived their parents as overprotective had parents that reported significantly more relational frustration (<italic>r=</italic>.24).</p><p><bold>Conclusions</bold>: A history of childhood cancer does not appear to influence parenting behavior, as perceived by both children and parents. However, children who experienced their parents to be overprotective had more frustrations in the parent‐child relationship, which might warrant future interventions.</p></sec><sec id="pbc26772-sec-1260"><label>O-098</label><title>Parental Functioning after Induction Treatment of Their Child with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">L.M.H. Steur</underline><sup>1</sup>, N. Rensen<sup>1</sup>, M.A. Grootenhuis<sup>2,3</sup>, N.K.A. van Eijkelenburg<sup>2</sup>, I.M. van der Sluis<sup>2,4</sup>, D.W.M.W. te Loo<sup>5</sup>, C. van den Bos<sup>6</sup>, W.J.E. Tissing<sup>7</sup>, G.J.L. Kaspers<sup>1,2,8</sup>, R.R.L. Litsenburg<sup>1,2</sup></p><p><italic><sup>1</sup>VU University medical center, Department of pediatric oncology/hematology, Amsterdam, The Netherlands; <sup>2</sup>Princess Máxima Center for pediatric oncology, Utrecht, The Netherlands; <sup>3</sup>Emma Children's Hospital Academic Medical Center, Psychosocial department, Amsterdam, The Netherlands; <sup>4</sup>Sophia Children's Hospital Erasmus Medical Center, Department of pediatric oncology, Rotterdam, The Netherlands; <sup>5</sup>Amalia Children's Hospital Radboud University Medical Center, Department of pediatric oncology, Nijmegen, The Netherlands; <sup>6</sup>Emma Children's Hospital Academic Medical Center, Department of pediatric oncology, Amsterdam, The Netherlands; <sup>7</sup>Beatrix Children's Hospital University Medical Center Groningen, Department of pediatric oncology, Groningen, The Netherlands; <sup>8</sup>Dutch Childhood Oncology Group, The Hague, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Parental and child quality of life (QoL) are bidirectionally related. To improve QoL of families, parental functioning should also be addressed. This study aims to describe parental QoL, sleep and distress and to investigate predictors of parental QoL in childhood ALL.</p><p><bold>Design/Methods</bold>: Parents of children aged 2‐18 years, treated according to the Dutch Childhood Oncology Group ALL‐11 treatment protocol, were included (expected final sample size n=105).</p><p>Parental functioning (QoL, sleep and distress) was assessed shortly after end of induction treatment with questionnaires (Short Form‐12, Medical Outcome Study Sleep Scale, Distress Thermometer). Scores were compared to healthy norms. QoL‐ and sleep scores 1 and 2 standard deviation (SD) different from the norm reflected clinical relevance. A distress score of 4 or higher indicated clinical distress. Predictors for parental QoL were selected with backward regression analyses.</p><p><bold>Results</bold>: Ninety parents (mean age 38.4±6.0 years, 77.8% mothers) of 90 children (mean age 7.0±4.4 years, 43.3% girls), were included (response rate 66%).</p><p>Parents reported significantly lower mental QoL, more overall sleep problems, and more distress (P<0.001). Physical QoL was not different from norms. Clinically relevant lower mental QoL was found in 45.6% (SD<‐1) and 18.9% (SD<‐2) of the parents and clinically relevant sleep problems in 52.2% (SD>1) and 24.4% (SD>2), compared to 15.9% and 2.3% in healthy norms, respectively. Clinical distress was present in 74.7% of the parents compared to 41.2% in the norm. Lower child age, higher parental age, more parental sleep problems and more parental distress predicted lower mental QoL (explained variance 53%). Male child gender and more child sleep problems predicted lower physical QoL (explained variance 10%).</p><p><bold>Conclusions</bold>: Parents of children with ALL are at risk for a lower QoL and impaired psychosocial functioning. Aiming to improve functioning of the whole family, interventions targeting parents at risk are warranted.</p><p><bold>Acknowledgements</bold>: Grant sponsor: Dutch Cancer Society.</p></sec><sec id="pbc26772-sec-1270"><label>O-099</label><title>Improvements in Psychological Adjustment in Siblings and Parents of Children with Cancer after Participation in A Sibling Group Intervention: A Randomized Control Trial</title><p><underline underline-style="single">B. Maru</underline><sup>1</sup>, E. Atenafu<sup>2</sup>, F. Schulte<sup>3</sup>, P. Nathan<sup>4</sup>, K. Hancock<sup>5</sup></p><p><italic><sup>1</sup>Hospital for Sick Children, Psychology, Toronto, Canada; <sup>2</sup>University Health Network, Biostatistics, Toronto, Canada; <sup>3</sup>Alberta Children's Hospital, Psychology, Calgary, Canada; <sup>4</sup>Hospital for Sick Children, Haematology/Oncology, Toronto, Canada; <sup>5</sup>Hospital for Sick Children, Pscyhology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer diagnosis and treatment can affect psychological adjustment in parents and healthy siblings. Systematic, rigorous assessment of interventions targeting the psychosocial needs of these siblings are rare. Our objective was to assess the effects of a manualized group intervention, Siblings Coping Together (SCT), on siblings’ and parents’ adjustment and to explore factors related to intervention effect.</p><p><bold>Design/Methods</bold>: We conducted blocked randomized controlled trial <bold>(</bold>RCT) with two arms, the experimental arm (EG) and an attention control group (CG). 75 healthy siblings (average age 11 years, range 7‐18) of children with cancer who were >3 months from diagnosis participated. Both groups had eight weekly two‐hour sessions. <bold>EG</bold> followed SCT's educational, social, and therapeutic problem‐solving plan through games and crafts; <bold>CG</bold> consisted of games and crafts only. Siblings self‐reported on symptoms of depression and anxiety; parent self‐reported on symptoms of anxiety, at baseline, after intervention ended, and 3 months later. Multivariable analyses with a mixed effects model were used to examine the intervention effect over time, controlling for covariates (e.g. gender, on/off ill child's treatment).</p><p><bold>Results</bold>: A significant group by gender interaction with the total depression scores indicated female siblings in the EG reported significantly lower scores than girls in the CG across times (p < 0.05, h<sup>2</sup> =0.071). This was also the case for the subscales of ineffectiveness (p < 0.01, h<sup>2</sup> =0.096) and anhedonia (p <0.05, h<sup>2</sup> =0.064). A significant difference on group by gender interaction was also found for total anxiety scores for parents (p =‐0.002, h<sup>2</sup> =0.159), with parents of females in the EG reporting lower scores than equivalent parents in the CG.</p><p><bold>Conclusions</bold>: A group intervention for siblings of children with cancer can result in improvements in psychological adjustment for both siblings and parents, particularly if the sibling is female. This research was funded by the Canadian C17 Network.</p></sec><sec id="pbc26772-sec-1280"><label>O-100</label><title>Changes in Quality of Life in Siblings of Children with Cancer after Group Intervention Participation: A Randomized Control Trial</title><p><underline underline-style="single">M. Barrera</underline><sup>1</sup>, E. Atenafu<sup>2</sup>, P. Nathan<sup>3</sup>, F. Schulte<sup>4</sup>, K. Hancock<sup>1</sup></p><p><italic><sup>1</sup>Hospital for Sick Children, Psychology, Toronto, Canada; <sup>2</sup>University Health Network, Biostatistics, Toronto, Canada; <sup>3</sup>Hospital for Sick Children, Heamatology/Oncology, Toronto, Canada; <sup>4</sup>Alberta Children's Hospital, Psychology, Calgary, Canada</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer diagnosis and treatment can result in reduced quality of life (QOL) in healthy siblings. Interventions targeting sibling QOL and the rigorous examination of these interventions are lacking. Our objective was to assess the efficacy of a manualized group intervention (EG), Siblings Coping Together (SCT), on siblings’ quality of life compared to an Attention Control Group (CG), and to identify factors related to the intervention effect.</p><p><bold>Design/Methods</bold>: We conducted a randomized controlled trial <bold>(</bold>RCT) with two arms: EG and CG. 75 healthy siblings (average age 11 years, range 7‐18) of children with cancer who were >3 months from diagnosis participated. <bold>EG</bold> followed SCT's educational, social, and therapeutic problem‐solving plan through games and crafts; <bold>CG</bold> consisted of games and crafts only. Self‐ and proxy reported Pediatric Quality of Life Questionnaires (PedsQL) were completed at baseline, end of intervention, and 3 months later. Total and subscales scores were generated. Multivariable analyses with a mixed effects model were used to examine the intervention effect over time, controlling for covariates (e.g., gender).</p><p><bold>Results</bold>: Improvements in PedsQL proxy scores (total and subscales) were noted over time in both groups (p < 0.001, h<sup>2</sup> =0.134 and h<sup>2</sup> =0.133. respectively). Siblings in the EG reported significantly better school PedsQL scores overall than siblings in the CG (M = 79.51 vs 73.74; p < 0.03, effect size=5.76). A significant group by gender interaction in the proxy school PedsQL scores indicated that compared to the EG, girls in the CG were rated with worse scores (p < 0.003, h<sup>2</sup> =0.126).</p><p><bold>Conclusions</bold>: Participating in groups with other siblings of children with cancer can result in improved overall QOL. However, participating in specific group intervention to address siblings’ needs can improve school QOL, particularly in females. Challenges to this research need to be addressed. This research was funded by Canadian C17 Network.</p></sec><sec id="pbc26772-sec-1290"><label>O-101</label><title>Development and Validation of Age Stratified Paediatric Oncology Distress Thermometer</title><p><underline underline-style="single">L. Edwards</underline><sup>1</sup></p><p><italic><sup>1</sup>The Royal Marsden NHS Foundation Trust, Paediatric Psychological Support, Sutton, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: The aim of this project is to complete the development and validation of a brief psychosocial and memory distress thermometer (DT) to be used with paediatric/young adult cancer patients</p><p><bold>Design/Methods</bold>: Pre‐pilot/Development of the tool</p><p>Age‐appropriate versions of the screening tool were developed: under five, 5‐7, 8‐12, 13‐17 and 18plus . along with an accompanying parent proxy version.</p><p>Pilot</p><p>A pilot study was carried out with 45 patients and their parents to test acceptability and usability of the tool. Amendments were made to the tools according to the feedback.</p><p>Validation</p><p>The cross sectional questionnaire project was conducted in 7 collaborating paediatric oncology centres with 549 participants ( child patient and parent proxy) to validate the DT against the Strengths and Difficulties Questionnaire (SDQ), the Hospital Anxiety and Depression scale (HADS) for psychological distress, Health Utilities Index (HUI2) for memory and learning validation and Paediatric quality of life scale (Pedsql)</p><p><bold>Results</bold>: Using a cut‐off of 4, sensitivity against SDQ for all age groups under 18 was 75.8 (range 65.7–84.2), 18plus against HADS was 75.8 (65.7–84.2). The specificity was 53.3 (range 47.8–58.7) against the SDQ for the 18 plus specificity against the HADS was 47.1 (34.8–59.6). The sensitivity against the HUI2 for all age groups was 89.0 (79.5–95.1), sensitivity was 70.3 (65.9–74.4).</p><p><bold>Conclusions</bold>: The DT is valid and acceptable for use as a rapid screening instrument for paediatric cancer patients in the UK. The results indicate that it can be used to monitor change in psychological distress and memory problems over time, but we recommend further work to determine how and when to use the tool clinically.</p><p>The screening tool research project was approved by the Royal Marsden Research and Development committee and Surrey Borders Ethics Committee (MREC).</p></sec></sec><sec id="pbc26772-sec-1300"><title>Free Paper Session: PPO ‐ II</title><sec id="pbc26772-sec-1310"><label>O-102</label><title>Establishing a Paediatric Oncofertility Program: Uptake of Procedures and Acceptance of Fertility Decisions in Families at A Tertiary Centre</title><p><underline underline-style="single">Y. Jayasinghe</underline><sup>1</sup>, M. Kemertzis<sup>1</sup>, L. Orme<sup>2</sup>, M. Zacharin<sup>3</sup>, M. Peate<sup>4</sup>, C. Ho<sup>5</sup>, D. Gook<sup>6</sup>, K. Stern<sup>6</sup>, H. Bourne<sup>6</sup>, G. Clarke<sup>7</sup>, Y. Heloury<sup>8</sup>, M. Sullivan<sup>2</sup>, S. Jayasuriya<sup>9</sup>, H. Clark<sup>9</sup>, F. Agresta<sup>10</sup>, P. Downie<sup>2</sup>, L. Super<sup>2</sup>, L. Gillam<sup>11</sup></p><p><italic><sup>1</sup>Royal Children's Hospital, Gynaecology, Melbourne, Australia; <sup>2</sup>Royal Children's Hospital, Children's Cancer Centre, Melbourne, Australia; <sup>3</sup>Royal Children's Hospital, Endocrinology, Melbourne, Australia; <sup>4</sup>University of Melbourne, Obstetrics & Gynaecology, Melbourne, Australia; <sup>5</sup>National University Hospital, Endocrinology, Singapore, Singapore; <sup>6</sup>Royal Womens Hospital, Reproductive Services, Melbourne, Australia; <sup>7</sup>Royal Childrens Hospital, Andrology, Melbourne, Australia; <sup>8</sup>Royal Children's Hospital, Surgery, Melbourne, Australia; <sup>9</sup>Monash University, Medicine, Melbourne, Australia; <sup>10</sup>Melbourne IVF, Clinical Research, Melbourne, Australia; <sup>11</sup>Royal Children's Hospital, Clinical Ethics Service, Melbourne, Australia</italic></p><p><bold>Background/Objectives</bold>: There is little published data regarding fertility preservation in the paediatric population, including data on families feelings of regret or acceptance of their fertility decision. We aim to describe uptake of fertility preservation procedures at The Royal Childrens Hospital Melbourne since 1987, and their impact on decision regret in families.</p><p><bold>Design/Methods</bold>: Bidirectional cohort study. In August 2013, we introduced a formalised oncofertility service under three levels of governance (as a novel technology, with research and clinical ethics governance). Oncofertility data was recorded in a fertility preservation database. Families completed a validated decision regret scale regarding the fertility decision with scores ≥ 30 representing high regret.</p><p><bold>Results</bold>: Three hundred and ten patients underwent fertility preservation procedures at a mean age of 13.9 years (range 0.1‐23 years), 55% were male, 32% pre‐pubertal. Most procedures (65%) occurred between 2013‐2016. These included ovarian tissue preservation [28% (n=88)] with follicle density of 0.3‐134/mm2, (where 4 patients had mature oocytes within the tissue); testicular tissue preservation [28% (n=88)] (where 8 had mature sperm within the tissue); sperm cryopreservation [39% (n=121)]; oocyte collection [0.9%(n=3)], GnRH analogues alone [1.9% (n=6)]. Invasive procedures were done for moderate to high risk of infertility. Minor complications occurred in 3%, with no delays to cancer treatment. One hundred and thirty eight participants (108 parents, 30 patients) completed a decisional regret survey. Most (82.5%) reported low regret (mean score 13.7, SD 18.8; range 0‐95). Having a fertility preservation procedure was an independent predictor of low regret on (p<0.0001, OR=0.11, CI= 0.03 ‐ 0.37). Expectation of a positive fertility outcome within the next generation was high.</p><p><bold>Conclusions</bold>: Paediatric fertility preservation procedures are safe, and associated with low regret in families. Demand is steadily increasing. It is important to provide accurate and transparent and realistic information support to families prior to diagnosis and throughout survivorship.</p></sec><sec id="pbc26772-sec-1320"><label>O-103</label><title>Genetics‐Related Beliefs, and Information and Service Needs, of Childhood Cancer Survivors and Their Parents</title><p><underline underline-style="single">C. Wakefield</underline><sup>1,2</sup>, E. Doolan<sup>1,2</sup>, C. Signorelli<sup>1,2</sup>, K. Tucker<sup>3</sup>, A. Patenaude<sup>4</sup>, J. Vetsch<sup>1,2</sup>, R. Cohn<sup>1,2</sup></p><p><italic><sup>1</sup>University of NSW, School of Women's and Children's Health, Sydney, Australia; <sup>2</sup>Kids Cancer Centre, Sydney Children's Hospital, Sydney, Australia; <sup>3</sup>Prince of Wales Hospital, Hereditary Cancer Clinic, Sydney, Australia; <sup>4</sup>Dana‐Farber Cancer Institute, Department of Psychosocial Oncology and Palliative Care, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Despite increasing recognition of the potential role of genetics risk assessment in childhood cancer survivorship, the genetics‐related needs of survivors and their families are understudied. This mixed‐methods study assessed survivors’ and parents’ beliefs about what caused the cancer (causal attributions), their genetics‐related service use, future service needs and their unmet genetics‐related information needs.</p><p><bold>Design/Methods</bold>: 596 participants (384 survivors; 211 parents of survivors) completed questionnaires and optional interviews. We used multiple logistic regression to determine clinical/demographic associations with perceived importance of access to a geneticist and with unmet information needs.</p><p><bold>Results</bold>: 36/49 survivors offered cancer‐related genetic testing chose to undergo testing. Of those not offered genetic testing (n=547, 92% of total sample), 16% of survivors and parents endorsed genetics (‘it runs in the family’) as a cause of the cancer. Most participants (survivors=80%, parents=82%) indicated it was ‘important’/’very important’ to receive genetics‐related information in survivorship care, and 28% of survivors and 35% of parents indicated that it was important to have access to a genetics specialist. 47% of survivors and 51% of parents indicated they had an unmet need for genetic information related to their cancer. In survivors, greater fear of cancer recurrence (p=.03) and longer time since diagnosis (p=.01) was associated with greater likelihood of indicating access to a genetic counsellor/geneticist was important. Participants who believed the cancer was genetic and those with greater fear of recurrence were more likely to have unmet genetics‐related information needs (p≤.03). Survivors satisfied with their follow‐up care were less likely to indicate they had unmet genetics‐related information needs than those who were unsatisfied (p≤.04).</p><p><bold>Conclusions</bold>: Our findings suggest that survivors and their parents have needs for genetics‐related services and information, which are largely unmet. Meeting such needs using innovative models of care may improve satisfaction with survivorship care.</p></sec><sec id="pbc26772-sec-1330"><label>O-104</label><title>Impact of Chronic Pulmonary Deficits and Cardiac Abnormalities on Neurocognitive Function in Long‐Term Survivors of Childhood Hodgkin Lymphoma</title><p><underline underline-style="single">Y.T. Cheung</underline><sup>1</sup>, N.D. Sabin<sup>2</sup>, D.A. Mulrooney<sup>3</sup>, K.K. Ness<sup>1</sup>, M.J. Krasin<sup>4</sup>, T.M. Brinkman<sup>1</sup>, P. Banerjee<sup>1</sup>, D. Srivastava<sup>5</sup>, L.L. Robison<sup>1</sup>, M.M. Hudson<sup>3</sup>, K.R. Krull<sup>1</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Epidemiology and Cancer Control, Memphis, USA; <sup>2</sup>St. Jude Children's Research Hospital, Diagnostic Imaging, Memphis, USA; <sup>3</sup>St. Jude Children's Research Hospital, Oncology, Memphis, USA; <sup>4</sup>St. Jude Children's Research Hospital, Radiation Oncology, Memphis, USA; <sup>5</sup>St. Jude Children's Research Hospital, Biostatistics, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: To compare neurocognitive function in long‐term survivors of Hodgkin lymphoma (HL) to community controls and examine associations with pulmonary deficits and cardiac abnormalities.</p><p><bold>Design/Methods</bold>: 158 HL survivors treated with thoracic radiation (mean[SD] age 37.7[7.8] years, 23.4[8.1] years post‐diagnosis) and 164 age‐ and sex‐matched controls completed neuropsychological testing. Age‐adjusted Z‐scores (μ=0, σ=1.0) were compared between groups. Systematic grading of pulmonary deficits (obstructive, restrictive, diffusion deficits) and cardiac abnormalities (structural, functional defects, arrhythmias) was conducted and analyzed as predictors of neurocognitive function using generalized linear modeling, adjusting for age. Analyses were stratified to examine the effect of smoking on neurocognitive function in survivors with/without morbidity.</p><p><bold>Results</bold>: Survivors performed poorer than controls on short‐ (mean[SD] Z‐scores: ‐0.24[1.0] <italic>v</italic> 0.13[1.0]; <italic>P</italic>=0.008) and long‐delay recall (‐0.29[1.1] <italic>v</italic> 0.05[1.1]; <italic>P</italic>=0.02), sustained attention (‐0.60[3.1] <italic>v</italic> 0.24[0.8]; <italic>P</italic>=0.005) and visual‐motor processing speed (0.14[1.0] <italic>v</italic> 0.39[1.0]; <italic>P</italic>=0.05). Moderate to disabling pulmonary deficits (32%) and cardiac abnormalities (22%) were present in survivors. Survivors with pulmonary deficits performed worse than survivors without any morbidity, on sustained attention (‐1.47[3.5] <italic>v</italic> ‐0.09[2.2]; <italic>P</italic>=0.009), visual processing speed (‐0.28[1.0] <italic>v</italic> 0.46[1.0]; <italic>P</italic>=0.003) and visual‐motor processing speed (‐0.23[0.8] <italic>v</italic> 0.30[1.0]; <italic>P</italic>=0.005). Cardiac abnormalities were not associated with neurocognitive function. In survivors without pulmonary deficits, current smokers were more impaired than non‐current smokers (<italic>P's</italic><0.05) but in survivors with pulmonary deficits, smoking did not contribute to worse performance.</p><p><bold>Conclusions</bold>: Roughly 20 years post‐treatment, survivors of HL have worse neurocognitive outcomes than controls. Pulmonary deficits and smoking were associated with worse outcomes. Future work should evaluate the impact of pulmonary insufficiency on neurocognitive outcomes. HL survivors should be educated on the neurocognitive effects of smoking.</p></sec><sec id="pbc26772-sec-1340"><label>O-105</label><title>The use of Murine Models of Chemosensitivity to Anticancer Agents in Childhood Cancer Clinical Care: Survivor, Parent and Community Acceptability and Willingness‐to‐Pay</title><p><underline underline-style="single">C. Wakefield</underline><sup>1,2</sup>, V. Quinn<sup>1,2</sup>, E. Doolan<sup>1,2</sup>, J. Fardell<sup>1,2</sup>, K. Tucker<sup>3</sup>, A. Patenaude<sup>4</sup>, K. Marshall<sup>1,2</sup>, R. Lock<sup>1,5</sup>, C. Signorelli<sup>1,2</sup>, G. Georgiou<sup>1,2</sup>, R. Cohn<sup>1,2</sup></p><p><italic><sup>1</sup>University of NSW, School of Women's and Children's Health, Sydney, Australia; <sup>2</sup>Kids Cancer Centre, Sydney Children's Hospital, Sydney, Australia; <sup>3</sup>Prince of Wales Hospital, Department of Medical Oncology, Sydney, Australia; <sup>4</sup>Dana‐Farber Cancer Institute, Department of Psychosocial Oncology and Palliative Care, Boston, USA; <sup>5</sup>Children's Cancer Institute, Lowy Cancer Research Centre, Sydney, Australia</italic></p><p><bold>Background/Objectives</bold>: Using patient‐derived xenografts (PDXs) to assess chemosensitivity to anti‐cancer agents in real‐time may improve child cancer care, potentially enabling individualized clinical decision‐making. However, it is unknown whether this application of a new methodology to clinical practice will meet with wider community acceptance. Our two‐stage study with 491 participants investigated the acceptability of PDXs in those affected by childhood cancer and the community.</p><p><bold>Design/Methods</bold>: Stage 1 identified the most commonly perceived advantages/disadvantages of PDXs in 24 individuals affected by childhood cancer (16 survivors, 8 parents). In Stage 2, we interviewed 68 individuals (26 survivors, 42 parents of survivors), and surveyed 399 matched community members (213 young adults, 186 parents) on the issues highlighted in Stage 1. We computed regressions to identify factors influencing willingness‐to‐use, willingness‐to‐pay, acceptable wait‐times for results, and acceptable number of mice used.</p><p><bold>Results</bold>: PDXs were highly acceptable: 90% of those affected by cancer leaned toward using PDXs (community participants: 65%). Survivors and survivors’ parents were more willing to use PDXs [t(465)=2.39, p=.02], and were willing to pay more [t(65.47)=5.49, p<.001], wait longer [t(69.61)=2.94, p=.004], and sacrifice more mice (t(31.90), p=.003) than community participants. Willingness‐to‐use remained high in survivors/survivors’ parents after considering PDX disadvantages [t(66)=0.15, p=.88]. Community participants had higher willingness‐to‐use, would pay more, and use more mice when considering their child rather than themselves. Better understanding predicted higher willingness‐to‐use, and increased willingness‐to‐wait. Harm to animals was the least endorsed disadvantage.</p><p><bold>Conclusions</bold>: Although clinical efficacy of PDXs is not yet established, consent rates will likely be high when PDXs are used in clinical practice, especially when the patient is a child. Willingness‐to‐pay and maximum acceptable number of mice aligned well with planned usage, although maximum acceptable wait‐times were lower than is likely to be clinically achievable.</p></sec><sec id="pbc26772-sec-1350"><label>O-106</label><title>Social Outcomes among Adolescent Long‐Term Survivors of Wilms Tumor: A Report from the Childhood Cancer Survivor Study</title><p><underline underline-style="single">R. Foster</underline><sup>1,2</sup>, R. Hayashi<sup>2</sup>, M. Wang<sup>3</sup>, W. Liu<sup>3</sup>, C. Mohrmann<sup>2</sup>, R. Howell<sup>4</sup>, S. Smith<sup>4</sup>, T. Gibson<sup>5</sup>, D.K. Srivastava<sup>3</sup>, D. Green<sup>5</sup>, K. Oeffinger<sup>6</sup>, W. Leisenring<sup>7</sup>, L. Robison<sup>5</sup>, G. Armstrong<sup>5</sup>, K. Krull<sup>5</sup>, K. Hardy<sup>8,9</sup></p><p><italic><sup>1</sup>St. Louis Children's Hospital, Department of Psychology, St. Louis MO, USA; <sup>2</sup>Washington University School of Medicine, Department of Pediatrics, St. Louis MO, USA; <sup>3</sup>St. Jude Children's Research Hospital, Department of Biostatistics, Memphis TN, USA; <sup>4</sup>University of Texas MD Anderson Cancer Center, Department of Radiation Physics, Houston TX, USA; <sup>5</sup>St. Jude Children's Research Hospital, Department of Epidemiology and Cancer Control, Memphis TN, USA; <sup>6</sup>Memorial Sloan Kettering Cancer Center, Departments of Pediatrics and Internal Medicine, New York NY, USA; <sup>7</sup>Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle‐ WA, USA; <sup>8</sup>Children's National Health System, Neuropsychology Division, Washington DC, USA; <sup>9</sup>George Washington University School of Medicine, Departments of Psychiatry & Behavioral Sciences and Pediatrics, Washington DC, USA</italic></p><p><bold>Background/Objectives</bold>: The study aims were to identify social problems among adolescent long‐term survivors of Wilms tumor (WT) and determine whether treatment exposures, chronic health conditions, or psychological concerns relate to peer interaction frequency and quality.</p><p><bold>Design/Methods</bold>: Parent‐reports from the Childhood Cancer Survivor Study (CCSS) were analyzed for 666 survivors of WT diagnosed between 1970‐1999 (Median[range] age at diagnosis=2.59[0.01‐11.18] years; time since diagnosis=12.56[5.62‐17.44] years; age at survey=15.42[12.00‐17.97] years) and 698 siblings of survivors from the overall CCSS cohort (15.49[12.01‐18.00] years). Survivors were compared to siblings on frequency and quality of parent‐reported peer interactions on the Behavior Problem Inventory (BPI) adjusting for race and household income. Survivors’ treatment exposures, chronic medical conditions (CTCAE v4.03), and psychological outcomes from the BPI were examined via multinomial logistic regression adjusting for sex, race, household income, and age at diagnosis to calculate adjusted Relative Risk (aRR) and 95% confidence intervals (CI).</p><p><bold>Results</bold>: Compared to siblings, fewer survivors were reported to have zero or one friend (10.10% vs. 7.21%, <italic>p</italic>=0.04); however, survivors were rated as having greater difficulties getting along with friends (<italic>p</italic><0.0001). Survivors with anxiety/depression (aRR=5.27, 95% CI 2.34‐11.90), headstrong behavior (aRR=3.74, CI 1.80‐7.74), attention problems (aRR=3.28, CI 1.56‐6.91), or social withdrawal (aRR=8.35, CI 3.91‐17.85) had fewer friends compared to survivors without these problems. Survivors with antisocial behavior (aRR=0.31, CI 0.14‐0.67), anxiety/depression (aRR=0.41, CI 0.20‐0.83), headstrong behavior (aRR=0.36, CI 0.20‐0.67), attention problems (aRR=0.44, CI 0.25‐0.80), or social withdrawal (aRR=0.12, CI 0.05‐0.30) were described as having greater difficulty getting along with friends compared to survivors without problems. Treatment exposures (e.g., chemotherapy, radiation) and endocrine and cardiovascular problems did not impact number of friends, time spent with friends, or ability to get along with friends.</p><p><bold>Conclusions</bold>: Despite multiple friendships, relationship quality for adolescent survivors of WT appears worse than for siblings. Adolescent survivors require support to develop socialization skills enhancing relationship quality.</p></sec><sec id="pbc26772-sec-1360"><label>O-107</label><title>Sleep Problems After Induction Therapy in Children with Acute Lymphoblastic Leukemia and their Association with Quality of Life and Fatigue</title><p><underline underline-style="single">L.M.H. Steur</underline><sup>1</sup>, M.A. Grootenhuis<sup>2,3</sup>, N.K.A. van Eijkelenburg<sup>2</sup>, I.M. van der Sluis<sup>2,4</sup>, D.W.M.W. te Loo<sup>5</sup>, C. van den Bos<sup>6</sup>, W.J.E. Tissing<sup>7</sup>, G.J.L. Kaspers<sup>1,2,8</sup>, R.R.L. Litsenburg<sup>1,2</sup></p><p><italic><sup>1</sup>VU University Medical Center, Department of pediatric oncology/hematology, Amsterdam, The Netherlands; <sup>2</sup>Princess Máxima Center for pediatric oncology, Utrecht, The Netherlands; <sup>3</sup>Emma Children's Hospital Academic Medical Center, Psychosocial department, Amsterdam, The Netherlands; <sup>4</sup>Sophia Children's Hospital Erasmus Medical Center, Department of pediatric oncology, Rotterdam, The Netherlands; <sup>5</sup>Amalia Children's Hospital Radboud University Medical Center, Department of pediatric oncology, Nijmegen, The Netherlands; <sup>6</sup>Emma Children's Hospital Academic Medical Center, Department of pediatric oncology, Amsterdam, The Netherlands; <sup>7</sup>Beatrix Children's Hospital University Medical Center Groningen, Department of pediatric oncology, Groningen, The Netherlands; <sup>8</sup>Dutch Childhood Oncology Group, The Hague, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Sleep may be a predictor of quality of life (QoL) and fatigue in children with acute lymphoblastic leukemia (ALL). This study aims to investigate the extent of sleep problems and their relation to QoL and fatigue in children during treatment for ALL.</p><p><bold>Design/Methods</bold>: Patients aged 2‐18 years, treated according to the Dutch Childhood Oncology Group ALL‐11 treatment protocol, were included (expected final sample size n=105).</p><p>Sleep, QoL and fatigue were assessed shortly after end of induction treatment with parent‐proxy questionnaires (Children Sleep Habits Questionnaire and Pediatric Quality of Life Inventory Generic and Multidimensional Fatigue Scale). Additionally, sleep was objectively measured using actigraphy. Z‐scores were calculated for total sleep questionnaire scores using healthy norms. Scores exceeding Z‐scores of 1 and 2 reflected clinically relevance. Actigraphy outcomes (sleep duration, sleep efficiency and wake after sleep onset (WASO)) were compared to norms. Regression models were constructed for the associations between sleep and QoL and fatigue.</p><p><bold>Results</bold>: Ninty‐nine children (mean age 6.9±4.5 years, 40.8% girls) were included (response rate 66%). Questionnaires were assessed in 98 children and actigraphy data were available in 56 children.</p><p>Clinically relevant sleep problems were found in 36.8% (Z‐score>1) and 14.9% (Z‐score>2) of the patients, compared to 15.9% and 2.3% in healthy norms, respectively.</p><p>Patients had a longer sleep duration (508.3 versus 412.1 minutes (p<0.001)), a lower sleep efficiency (76.0% versus 78.2% (p=0.03)) and more WASO (134.4 versus 87.0 minutes (p<0.001)).</p><p>Adjusted for pre‐existing sleep problems and gender, sleep problems were significantly associated with lower physical‐ (B:‐7.25(95%CI:‐11.19;‐3.30)) and psychosocial QoL (B:‐3.98(95%CI:‐7.31;‐0.66)) and more general‐ (B:‐6.55(95%CI:‐10.74;‐2.36)), sleep/rest‐ (B:‐8.77(95%CI:‐12.06;‐5.48)) and cognitive fatigue (B:‐4.55(95%CI:‐7.90;‐1.20)).</p><p><bold>Conclusions</bold>: Clinically relevant sleep problems are common during treatment for ALL and were negatively associated with QoL and fatigue. Intervention studies aiming to improve sleep are needed to improve QoL and fatigue in children with ALL.</p><p><bold>Acknowledgements</bold>: Grant sponsor: Dutch Cancer Society.</p></sec></sec><sec id="pbc26772-sec-1370"><title>Free Paper Session: Podc Supportive Care</title><sec id="pbc26772-sec-1380"><label>O-108</label><title>Sofosbuvir‐Based Therapy for Chronic Hepatitis C Infection in Children with Malignancies</title><p>S. Jayabose<sup>1</sup>, A. Palaniappan<sup>1</sup>, N. Iyer<sup>1</sup>, <underline underline-style="single">K. Viswanathan</underline><sup>1</sup>, A. Annamalai<sup>1</sup></p><p><italic><sup>1</sup>Meenakshi Mission Hospital & Research Center, Pediatric Hematology‐Oncology, Madurai, India</italic></p><p><bold>Background/Objectives</bold>: In adults with chronic hepatitis C virus (HCV) infection, their outcomes have dramatically improved with directly acting antiviral agents (DAA) like sofosbuvir. But there are no data or guidelines on the use of DAA in children under 12 years of age. The objective of our study is to analyze the efficacy and safety of sofosbuvir‐based therapy in children with malignancies and genoype‐1 HCV infection, refractory to peg‐Interferon alfa 2b (pegIFNa2b) plus ribavirin.</p><p><bold>Design/Methods</bold>: Our cohort includes 13 children with cancer and genotype 1 HCV infection who had failed standard treatment with pegIFNa2b plus ribavirin (twelve of them off all chemotherapy) treated in 2015. All patients received triple drug combination: fixed dose sofosbuvir‐400 mg P.O. once daily; weekly pegIFNa2b, 1.5 to 2.0 μg/kg, by s/c inj; and ribavirin P.O.,15 mg/kg/day in 2 doses, for 12 weeks. HCV titers were followed at 12 and 24 weeks from start of treatment.</p><p><bold>Results</bold>: Thirteen children with chronic HCV infection, all with genotype 1, were treated: Male,6; female, 7; median age, 9.5 years (range 7 to 21). Underlying malignancies were B ALL, 9; T‐ALL, 1; Burkitt Lymphoma, 1; AML,1; Hodgkin Lymphoma, 1.. Viral load at diagnosis ranged from 0.1 to 10 million IU/ml. Sustained virologic response ([SVR] defined as negative HCV RNA at 12 weeks after completion of treatment) was achieved in 10 of 11 patients evaluable for SVR; one patient died within 3 months due to progressive malignancy; and one was lost to follow‐up after 12 weeks. Median follow‐up: 14 months (range, 3‐21). One patient had oral aphthous ulcers, requiring interruption of peg‐Interferon alone for 2 weeks. No patient had grade 3 or 4 neutropenia or significant elevation of AST and ALT on therapy.</p><p><bold>Conclusions</bold>: Sofosbuvir containing triple drug therapy is an effective and safe treatment for genotype‐1 HCV infection in children with malignancies.</p></sec><sec id="pbc26772-sec-1390"><label>O-109</label><title>Infectious Complications in HIV‐Infected and HIV‐Uninfected Children Treated for B‐Cell Non‐Hodgkins Lymphomas (NHL)</title><p><underline underline-style="single">G. Naidu</underline><sup>1</sup>, A. Izu<sup>2</sup>, R. Wainwright<sup>1</sup>, S. Poyiadjis<sup>1</sup>, D. MacKinnon<sup>1</sup>, B. Rowe<sup>1</sup>, S.A. Madhi<sup>3</sup></p><p><italic><sup>1</sup>University of the Witwatersrand and Chris Hani Baragwanath Academic Hospital, Paediatrics, Johannesburg, South Africa; <sup>2</sup>Medical Research Council‐, Meningeal and Respiratory Pathogens Research Unit‐ University of the Witwatersrand, Johannesburg, South Africa; <sup>3</sup>Medical Research Council‐ Department of Science/ National Research Foundation: Vaccine Preventable Diseases‐ Faculty of Health Science‐ National Institute for Communicable Diseases‐ a Division of National Health Laboratory Service‐ Sandringham‐, Meningeal and Respiratory Pathogens Research Unit‐ University of the Witwatersrand, Johannesburg, South Africa</italic></p><p><bold>Background/Objectives</bold>: INTRODUCTION: Treatment of cancer in HIV‐infected children is challenging as therapy compromises an already immune‐suppressed state.</p><p>AIM OF THE STUDY: To establish the infectious complications in HIV‐infected and HIV‐uninfected children treated for NHL with the BFM‐NHL protocol.</p><p><bold>Design/Methods</bold>: METHOD: Hospital records for children with NHL (2000 to 2009) were reviewed. Age, HIV status (CD4+ count and HIV viral load if HIV‐infected), cancer stage, sex and anthropometry were recorded. The temperature, duration of fever, white cell count, neutrophil, lymphocyte and monocyte counts, blood culture and clinical syndromes were recorded for each septic episode.</p><p><bold>Results</bold>: 58 children had NHL (51.7% HIV‐infected, 80.7% males, and median age 89.5 months). The microbiologically‐confirmed septic episodes (100 child years) among HIV‐infected children was 122.5 and for HIV‐uninfected children was 48.2 (p<0.001). The incidence of Gram‐positive bacteraemia was (121 vs. 35; p<0.001), Gram‐negative bacteraemia (101 vs. 31; p<0.001), pneumonia (75 vs. 12; p<0.001), tuberculosis (25 vs. 2; p<0.001), and invasive fungal infections (28 vs 7; p=0.001) in the HIV‐infected compared with the HIV‐uninfected cohort. The mean maximum temperature was higher in the HIV‐infected (p=0.022). HIV‐infected children had a longer duration of neutropenia (p<0.001) and lymphopenia (p<0.001) than HIV‐uninfected children. Ten (33.3%) of the HIV‐infected cohort died because of sepsis (p=0.0006), 60% had Stage 4 disease, 80% had a CD4+ < 15%, and 70% had a HIV‐viral load > 200 000 RNA copies/ml. Multiple pathogens were isolated from children who died including multi‐drug resistant bacteria, and 90% had pneumonia.</p><p><bold>Conclusions</bold>: ARVs have reduced the mortality and morbidity of HIV‐infected patients; but lymphomas remain a major issue. The use of chemotherapy in HIV‐infected patients results in further immune‐depletion and an increased rate of infections. As children with HIV survive longer due to better antiretroviral and supportive therapies, HIV‐related malignancies may become an increasingly common problem.</p></sec><sec id="pbc26772-sec-1400"><label>O-110</label><title>Clinical Impact of Isolating Respiratory Viruses in Children with Febrile Neutropenia</title><p><underline underline-style="single">P. Jain</underline><sup>1</sup>, V. Gunasekaran<sup>1</sup>, V. Dinand<sup>1</sup>, N. Radhakrishnan<sup>1</sup>, A. Sachdeva<sup>1</sup></p><p><italic><sup>1</sup>Sir Ganga Ram Hospital‐ Delhi, Pediatric Hematology Oncology and BMT unit, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Febrile respiratory illness (FRI) is common in immunocompromised children receiving treatment for malignancy. Data on viral respiratory pathogens as a cause of febrile neutropenia is limited. Etiologic significance of respiratory virus detection, its impact on hospital stay and antibiotic use was evaluated.</p><p><bold>Design/Methods</bold>: Immunocompromised children (≤18years of age) receiving treatment at a pediatric oncology unit, presenting with FRI, were prospectively analysed from September2015–February2017. Children were evaluated clinically and respiratory secretions were obtained for detection of 16 viruses and 6 bacteria by real‐time polymerase chain reaction.</p><p><bold>Results</bold>: A total of 85 episodes were evaluated from 53 eligible children out of 182 being treated. Male:female ratio was 2.2:1, median age 3.16 years. Cough (92.9%) was the most common respiratory symptom associated with tachypnoea in 32.9%. Atleast one respiratory pathogen was identified in 70 (82.3%) samples and 17 (20%) of them tested positive for dual respiratory pathogens. Rhino‐virus(24.4%) was the most common isolate followed by Parainfluenza‐virus (18.7%) and Respiratory‐Syncytial‐virus (17.4%). Others being Coronavirus (7.3%), Bocavirus (7%), Influenzavirus (4.7%), respiratory bacteria (4.7%) and Adenovirus (1.2%). Febrile neutropenia (FN) was present in 61.6% of the total FRI episodes. Viral respiratory pathogen was the only identifiable etiology of febrile neutropenic episode in 47.3%. Culture positive sepsis (20.7%) or other underlying cause was detected in 11.3% while cause of FN could not be identified in 20.7%. Duration of hospitalisation was significantly shorter in those with solely respiratory pathogen as an etiology for FN compared to those with sepsis (P<0.001). These children could be managed with lesser number of antibiotics compared to those where no cause of FN was established (P=0.02) and had no mortality compared to children with co‐existent sepsis (33.3%) or other underlying cause (13.3%).</p><p><bold>Conclusions</bold>: Respiratory viruses are common in FRI during febrile neutropenia. Isolation of respiratory virus can minimize antibiotics use and hospital stay.</p></sec><sec id="pbc26772-sec-1410"><label>O-111</label><title>Is it Safe to Administer High‐Dose Methotrexate (HD‐MTX) without Monitoring Mtx Levels? Experience with 100 Cycles</title><p>K. Vaishnavi<sup>1</sup>, <underline underline-style="single">D. Bansal</underline><sup>1</sup>, A. Trehan<sup>1</sup>, R. Jain<sup>1</sup>, S. Attri<sup>2</sup></p><p><italic><sup>1</sup>Postgraduate Institute of Medical Education and Research, Pediatric Hematology‐Oncology unit‐ Dept. of Pediatrics‐ Advanced Pediatrics Centre, Chandigarh, India; <sup>2</sup>Postgraduate Institute of Medical Education and Research, Biochemistry‐ Dept. of Pediatrics‐ Advanced Pediatrics Centre, Chandigarh, India</italic></p><p><bold>Background/Objectives</bold>: Access to MTX‐levels is often lacking in developing countries. To evaluate if HD‐MTX can be administered safely with extended hydration/leucovorin rescue, with monitoring of serum‐creatinine and urinary‐pH.</p><p><bold>Design/Methods</bold>: In the prospective study, 3 and 5 gm/m<sup>2</sup> of MTX (24‐hour infusion) was administered to patients with B and T‐cell ALL/NHL, respectively. Six doses of leucovorin (15 mg/m<sup>2</sup>/dose), instead of recommended 3 (if the levels were to be optimally reduced) at the standard timing (42‐hours from start of HD‐MTX) were administered. Hydration was continued for 72‐hours, instead of recommended 30‐hours. If serum creatinine exceeded 1.25 times the baseline, the volume of hydration was increased. Urinary‐pH was measured at three time points. The study was approved by institution's ethics committee (NK/1938/MD/2692‐93). Informed consent was obtained.</p><p><bold>Results</bold>: Study included 100‐cycles of HD‐MTX in 53 patients: B‐lineage ALL: 51, T‐lineage ALL: 28, T‐NHL: 18 and relapsed‐ALL: 3. The mean age was 6.8±3.2 years (range: 1‐13). Patients were underweight in 15 (15%) cycles. Patients in 23 (23%) cycles had a rise in creatinine to >1.25 times the baseline. Augmentation of alkalinization was not indicated, as urinary‐pH was optimal (≥7) in all. Toxicities (NCI‐CTCAE‐v4.0) included, mucositis (32%), diarrhea (10%) and febrile neutropenia (9%). The mean serum‐creatinine at 0/24/48 hours of HD‐MTX was 0.324±0.105, 0.330±0.114 and 0.342±0.128, respectively (p=0.537). Grade 1/2/3/4 rise in creatinine was observed in 26/16/1/0 cycles, respectively. Toxicities at 12‐14 days were neutropenia (64%), thrombocytopenia (37%) and anemia (62%). Mucositis was increased with co‐administration of voriconazole (p=0.005). A single mortality was observed from seasonal, dengue‐shock‐syndrome.</p><p><bold>Conclusions</bold>: Administration of HD‐MTX without measuring MTX‐levels, with extended hydration, additional doses of leucovorin and monitoring of serum creatinine is feasible with manageable toxicities. The study could be replicated in additional centers for generating evidence, for suggesting guidelines for administration of HD‐MTX in numerous centers in developing countries that lack access to MTX‐levels</p></sec><sec id="pbc26772-sec-1420"><label>O-112</label><title>Degree of Organ Dysfunction is the Major Risk Factor for Mortality in Pediatric Cancer Patients Admitted to Pediatric Intensive Care Unit</title><p><underline underline-style="single">H. Abdel Rahman Sayed</underline><sup>1</sup>, S. Abdel Hamid<sup>2</sup>, H. El Gebaly<sup>3</sup>, S. Hassan<sup>4</sup>, N. Hassan<sup>5</sup></p><p><italic><sup>1</sup>National Cancer Institute‐ Cairo University‐ Egypt, Pediatric Oncology, Guizah, Egypt; <sup>2</sup>National Cancer Institute‐ Cairo University‐ Egypt, Pediatric Oncology, Cairo, Egypt; <sup>3</sup>Cairo University, Pediatric, Cairo, Egypt; <sup>4</sup>Nasser Institute, Pediatric Oncology, Cairo, Egypt; <sup>5</sup>National Cancer Institute‐ Cairo UIniversity, Medical biostatisics, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Improvement of survival in pediatric cancers has been linked to more aggressive treatment regimens, increasing life‐threatening complications that may require Pediatric Intensive Care Units (PICU) admission. Nearly 40% of pediatric cancer patients may require intensive care services, accounting for approximately 3% of all PICU admissions.The aim of the current study was to evaluate predictors of outcome among pediatric cancer patients treated at the PICU, National Cancer Institute (NCI), Cairo University, and its co‐relation to patient's risk factors.</p><p><bold>Design/Methods</bold>: A retrospective study including 217 patients, for whom 267 PICU admissions was recorded during the period between July 2013 to June 2014. Data analysis included patients’ demographics. Patients were assessed according to Pediatric Risk of Mortality III (PRISM), as well as Pediatric Organ Logistic Dysfunction (PELOD) on their 1st day of PICU admission. Moreover, survival was correlated to other risk factors including age, diagnosis, disease status, sepsis, the use of mechanical ventilation, and need for inotropes.</p><p><bold>Results</bold>: Patients age ranged from 6 months to 18 years (median 6 years), with evident male predominance. Sixty percent of the patients had hematological malignancies. Average length of stay was 8 days [SD± 6.6], ranging from 1 to 38 days.</p><p>Risk factors associated with worse outcome included high PRISM and PLEOD score; p‐value 0.003, and <0.001 respectively. Survival outcome was worse in patients who were mechanically ventilated, and/or on inotropic support, with a p‐value of <0.001.</p><p><bold>Conclusions</bold>: high PRISM III as well as PELOD scoring ‐rather than type of malignancy and disease status‐ is the main predictor of outcome in PICU among pediatric cancer patients. Early recognition of signs of organ failure, and referral to PICU may shorten the ICU length of stay with its morbid complication that can worsen the outcome.</p></sec><sec id="pbc26772-sec-1430"><label>O-113</label><title>Early Deaths in Pediatric Acute Leukemia; A Major Challenge in Developing Countries</title><p><underline underline-style="single">H. Hafez</underline><sup>1,2</sup>, R. Soliaman<sup>1</sup>, D. Bilal<sup>3</sup>, L. Shalaby<sup>1,2</sup></p><p><italic><sup>1</sup>National Cancer Institute ‐ Cairo University, pediatric hematology/oncology, Cairo, Egypt; <sup>2</sup>Children Cancer Hospital Egypt CCHE 57357, pediatric hematology/oncology, Cairo, Egypt; <sup>3</sup>National Cancer Institute ‐ Cairo University, Biostatistics, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Despite a steady improvement in supportive care over the last 30 years, treatment related toxicity remains a major challenge in childhood acute leukemia therapy, especially in middle income countries. The aim of the study is to describe the incidence and risk factors associated with early deaths (first 42 days of treatment) among children with acute leukemia</p><p><bold>Design/Methods</bold>: This is a retrospective study included newly diagnosed patients with acute leukemia who presented to the National Cancer Institute, Cairo University between Jan. 2011 to Dec. 2013. Patients’ data were collected and analyzed for the total and early death rates and proposed causes of death.</p><p><bold>Results</bold>: The study included 370 patients, 253 with acute lymphoblastic leukemia (ALL), 100 with acute myeloid leukemia (AML) and 17 with mixed phenotypic acute leukemia. The total death rate among the whole group was 40.5% (n=150) and induction death rate was 19.2% (n=71). Patients with AML had higher total and induction death rates as they were 58% and 25% respectively, compared to 33.6% and 17.4% in ALL. Most of the early deaths were attributed to infection 64.7% and cerebrovascular accidents 18.3%. Early deaths were significantly higher in patients below 2 years old (p. = 0.008), and in those with poor response to therapy (p. = 0.001). Using enhanced supportive care measures with available intensive care unit during 2013 had significantly reduced the overall and induction mortality rates (27.8% and 13.8% respectively in 2013 versus 45% and 20.3% in 2011 and 49% and 25% in 2012)</p><p><bold>Conclusions</bold>: Induction deaths in pediatric acute leukemia remain a major challenge in developing countries and constitute an increasing fraction of all deaths. Accordingly, using well equipped centers with better supportive care guidelines is essential to improve the survival in this group of patients</p></sec></sec><sec id="pbc26772-sec-1440"><title>Free Paper Session: Epidemiology ‐ II</title><sec id="pbc26772-sec-1450"><label>O-114</label><title>Pilot Study Identifies CSF Metabolomic Biomarkers for Symptoms of Cognitive Impairment during Treatment for Pediatric Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">A.L. Brown</underline><sup>1</sup>, K.P. Raghubar<sup>2</sup>, O.A. Taylor<sup>1</sup>, I.M. Moore<sup>3</sup>, C.C. Rodgers<sup>4</sup>, M.C. Hooke<sup>5</sup>, W. Pan<sup>4</sup>, M.J. Hockenberry<sup>4</sup>, M.E. Scheurer<sup>1</sup>, P.J. Lupo<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Department of Pediatrics – Oncology, Houston‐ TX, USA; <sup>2</sup>Baylor College of Medicine, Department of Pediatrics – Psychology, Houston‐ TX, USA; <sup>3</sup>University of Arizona, College of Nursing, Tucson‐ AZ, USA; <sup>4</sup>Duke University, School of Nursing, Durham‐ NC, USA; <sup>5</sup>University of Minnesota, School of Nursing, Minneapolis‐ MN, USA</italic></p><p><bold>Background/Objectives</bold>: While survival rates for pediatric acute lymphoblastic leukemia (pALL) exceed 90%, many patients experience treatment‐related cognitive impairment. Because prognostic markers of cognitive impairment are lacking, the purpose of this pilot study was to identify cerebrospinal fluid (CSF) biomarkers for symptoms of cognitive impairment during pALL chemotherapy.</p><p><bold>Design/Methods</bold>: CSF samples were collected at 5‐months post‐induction on 96 patients. Untargeted metabolomics detected 314 metabolites by gas chromatography (GC)‐mass spectrometry (MS) and liquid chromatography (LC)/MS/MS. Caregiver‐perceived cognitive function was evaluated during the first month of treatment and 12‐months post‐induction using a 13‐item scale (pedsFACIT‐PCF). Mann‐Whitney U test and logistic regression were used to compare metabolite values between: 1) cases whose ratings declined from the normal range (T‐score≥50) during the first month of treatment to the mild‐moderate difficulty range (T‐score<50), and 2) controls with ratings in the normal range at 12‐months post‐induction. A false discovery rate (FDR) p‐value accounted for multiple comparisons.</p><p><bold>Results</bold>: In this cohort diagnosed 2012‐2014, 24% of patients displayed symptoms of mild‐moderate cognitive impairment at 12‐months post‐induction. Significant alterations (FDR<0.05) were observed in six metabolites, including tyrosine (3‐(4‐hydroxyphenyl)lactate, Fold Change [FC]=0.69, p=1.7e‐4), glutamate (5‐hydroxyindoleacetate, FC=0.67, p=3.6e‐4), and histidine (3‐methylhistidine, FC=2.29, p=3.8e‐4) metabolites. These associations remained after adjusting for age, sex, race, and treatment intensity. Notably, four of the six metabolites identified by this study are involved in dopamine neurotransmitter metabolism. Compared to patient and treatment factors alone (area under curve [AUC]=0.71), CSF biomarkers significantly (p=0.01) improved the ability to distinguish patients with symptoms of cognitive impairment from those with normal cognitive function (AUC=0.89 for 5‐hydroxyindoleacetate and tyrosine).</p><p><bold>Conclusions</bold>: We identified novel CSF biomarkers for caregiver‐perceived symptoms of treatment‐related cognitive impairment among patients treated for pALL. These findings may translate to clinical improvements in the management of cognitive outcomes by introducing the opportunity to deliver targeted interventions to high‐risk patients prior to irreversible cognitive impairment.</p></sec><sec id="pbc26772-sec-1460"><label>O-115</label><title>TED: A French National Registry for Childhood Cancers and Congenital Abnormalities Associations</title><p><underline underline-style="single">C.</underline><underline underline-style="single">Fouquet</underline><sup>1</sup>, M. Semeraro<sup>2</sup>, F. Bourdeaut<sup>3</sup>, H. Cave<sup>4</sup>, L. Galmiche‐Rolland<sup>5</sup>, Y. Perel<sup>6</sup>, L. Brugières<sup>7</sup>, A. Jeanne<sup>8</sup>, S. Sarnacki<sup>1</sup></p><p><italic><sup>1</sup>Hôpital Necker Enfants‐Malades, Service de chirurgie viscérale pédiatrique, Paris, France; <sup>2</sup>Imagine, Centre d'Investigation Clinique, Paris, France; <sup>3</sup>Institut Curie, Laboratoire de Recherche Translationnelle en Oncologie Pédiatrique, Paris, France; <sup>4</sup>Hôpital Robert Debré, Département de Génétique, Paris, France; <sup>5</sup>Hôpital Necker Enfants‐Malades, Service Anatomie Pathologique, Paris, France; <sup>6</sup>Hôpital Pellegrin, Unité d'onco‐hématologie pédiatrique, Bordeaux, France; <sup>7</sup>Institut Gustave Roussy, Département de cancérologie de l'enfant et de l'adolescent, Villejuif, France; <sup>8</sup>Imagine, Embryologie et Génétiques des malformations congénitales, Paris, France</italic></p><p><bold>Background/Objectives</bold>: Most of the cancers arising in early childhood result from the embryonic layers and represent, unlike the adults tumors, developmental and implementation accidents of various tissues more than accidents bound to ageing or tissue turnover.</p><p><bold>Design/Methods</bold>: Launched in June 2013, the <italic>TED (Tumeur Et Developpement)</italic> study is a national, prospective and retrospective registration of cases combining a paediatric cancer and congenital abnormalities. A data extraction has been performed and the clinical characteristics of these patients are here depicted.</p><p><bold>Results</bold>: From 2013 to March 2017, 628 patients have been enrolled in the <italic>TED</italic> database by 27 French medical centres. The number of cases was slightly higher for boys (<italic>sex ratio</italic> 1.12) and the most frequent tumors were leukaemias (17%), brain tumors (16%) and nephroblastomas (15%), which were different from that that described by the National Registry of Childhood Cancers. Data concerning both developmental abnormalities and tumors were available for 532 patients. Among them, about 177 predisposition syndromes (33%) have been recorded. Despite the evidence of the already known associations, (type 1 neurofibromatosis and optic glioma, Beckwith‐Wiedemann syndrome and nephroblastoma, Down syndrome and leukaemia, gonosome abnormalities and malignant germinal tumors), new interesting associations were found highlighting common embryonic origin (ie neuroblastoma and depigmentation phenotype), somatic mosaicisms (ie bladder rhabdomyosarcoma and hypospadias) and early cancer diagnoses compared to median age of paediatric cancer occurrence (4.3 <italic>vs</italic> 5 years old). Only 44.5 % of the patients recorded in the database benefited from a genetic counselling.</p><p><bold>Conclusions</bold>: TED is one of the most important and exhaustive study reporting associations of birth defects with paediatric cancers. It represents a key collection for describing new mechanisms and genetic pathways involved in tumorigenesis and malformations. Further efforts are actually deployed to better identify the clinical and genetic clusters.</p></sec><sec id="pbc26772-sec-1470"><label>O-116</label><title>Narrowing Childhood Cancer Survival GAP in Brazil: Analisys of 6126 Patients by A Hospital Based Cancer Registry in 25 Years’ History of a Single Institution</title><p><underline underline-style="single">M. Cypriano</underline><sup>1</sup>, A. Pires<sup>1</sup>, M. Silva<sup>1</sup>, E. Caran<sup>1</sup>, M.L. Lee<sup>1</sup>, A.V. Sousa<sup>1</sup>, N. Silva<sup>1</sup>, A. Cappellano<sup>1</sup>, F. Luisi<sup>1</sup>, C. Macedo<sup>1</sup>, C. Bassioli<sup>1</sup>, S. Petrilli<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Oncology Institute/GRAACC/Unifesp, Pediatric Oncology, Sao Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Approximately 80% of children and adolescents diagnosed with cancer live in countries with limited resources were the chances of cure are much lower than the 80% reported in developed countries. Data from 2004 São Paulo‐Brazil population‐based cancer registry revealed a 5‐years survival (OS) rate of only 41% for children 0‐14 years of age. <bold>Objective</bold>: to evaluate the characteristics and 5 years OS of pediatric patients in a single institution.</p><p><bold>Design/Methods</bold>: In 2010, we established an institutional cancer registry that is fully organized and mature enough to provide reliable data of our patient population. The data for survival estimates were extracted from patients’ charts and by active search of public records. We excluded from the survival analysis patients who received only one treatment modality and then returned to the service of origin.</p><p><bold>Results</bold>: Of 6126 patients registered from 1991 to 2015, 56% were boys. Age distribution at diagnosis was as follows: 0‐9 years of age 58%, 10‐19 years old 37%, over 19 years 5%. The most common cancer type was brain tumors (18%), leukemia (17%) and bone tumors (13%). There was a noticeable shift in the patients’ profile reflecting institutional growth: in the first decade, malignancies amenable to outpatient treatment were more common, whereas in the second decade we registered a marked increase of high complexity cases such as brain tumors. The 5‐years OS for patients < 19yrs was 71%. Survival has reached international standards for Hodgkin's lymphoma (95%), Wilms tumor (87%) and B‐lineage ALL (80%).</p><p><bold>Conclusions</bold>: The organization of a registry allowed us to study the epidemiological profile of our patients and document that our institutional OS is superior to the state of Sao Paulo. This led us to conclude that an organized, dedicated oncology center is able to narrow the survival gap between Brazilian patients and their counterpart in the developed world.</p></sec><sec id="pbc26772-sec-1480"><label>O-117</label><title>Incidence and Determinants of Lost Diagnostic Opportunities for Children with Cancer in Argentina</title><p>E. Grynszpancholc<sup>1</sup>, <underline underline-style="single">V. Pinto</underline><sup>1</sup>, A. Ayoroa<sup>1</sup>, L. García<sup>1</sup>, G. Dran<sup>2</sup></p><p><italic><sup>1</sup>Fundación Natalie Dafne Flexer‐ Argentina, Fundación Natalie Dafne Flexer‐ Argentina, Buenos Aires, Argentina; <sup>2</sup>National Counsil For Scientific And Technologic Investigation CONICET, Facultad Latinoamericana de Ciencias Sociales FLACSO, Buenos Aires, Argentina</italic></p><p><bold>Background/Objectives</bold>: Disparities in accessing to accurate and timely childhood cancer diagnosis are usual in developing countries. Failed or delayed diagnoses are major causes of poor survival and quality of life. The Natali Dafne Flexer Foundation (FNDF) provides integral assistance to families facing pediatric cancer in Argentina. This study contains preliminary data from an ongoing study aimed to analyze the incidence and modulators of lost diagnostic opportunities (LDO) in those families assisted by the FNDF along a five‐year period.</p><p><bold>Design/Methods</bold>: Retrospective quali‐quantitative analysis. Families with 0‐20 y/o children who got cancer diagnoses between 2011 and 2015 were included. Demographic, disease and health insurance data, and medical institutions involved in the diagnoses process, were compared between groups with or without LDO. Additional data were extracted from parent`s narration.</p><p><bold>Results</bold>: A total of 572 families whose diagnostic trajectory was exhaustively registered were included. 56% of them reported to have one (36%), two (14%), three (3%) or more than three (3%) LDO. 91.5% were Argentinian, being the sample fairly representative of the distribution of childhood cancer in the Country regarding age, province of residence, sex and type of cancer. 30% had social/private health insurance and 69%, Public Health coverage. Retinoblastoma and low age positively correlated with absence of LDO (p<0.01). The Southern and Northern Regions, with vast provinces of low socioeconomic index and low population density, exhibited higher proportion of LDO than the mean for the Country. The type of institution (public/private) was independent of the presence of LDO, while consultations to private centers became more frequent as the number of LDO increased (p<0.05).</p><p><bold>Conclusions</bold>: A substantial number of families experience problems for obtaining childhood cancer diagnosis in Argentina. Disease and demographic determinants may influence the possibility of having LDO. Addressing such problems will help developing evidence‐driven, specific and local interventions to improve diagnoses process.</p></sec><sec id="pbc26772-sec-1490"><label>O-118</label><title>Improving Early Referral and Diagnosis of Brain Tumours in Children‐ Impact of National “lHeadSmart” Campaign in west of Scotland</title><p><underline underline-style="single">J. Sastry</underline><sup>1</sup>, A. Hafez<sup>1</sup></p><p><italic><sup>1</sup>Royal Hospital for Children, Haematology and Oncology, Glasgow, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: A nation‐wide campaign, “HeadSmart: Be Brain Tumour Aware”, was launched in 2011 in response to a national survey carried out in 2006 which indicated that referral practice in the UK for paediatric brain tumours ranked poorly in international comparisons. The aim of the campaign was to raise public and professional awareness in order to reduce the total diagnostic interval (TDI) from a pre‐campaign median of 14 (mean 35.4) weeks to less than 5 weeks so as to match the shortest published TDI. The audit was carried to evaluate the effectiveness of the campaign 5 years later and, in addition, to compare how local (Glasgow) referral practice aligns with national data.</p><p><bold>Design/Methods</bold>: Data was gathered from 19 patients under the age of 16 diagnosed with CNS tumours in Glasgow between May 2014 and March 2015. Data collection was performed by analysis of online patient records accessed through the NHSGGC clinical portal. TDI was calculated using various patient notes including GP letters and in‐patient hospital records.</p><p><bold>Results</bold>: Since the initial survey in 2006, there has been a considerable reduction in TDI to a median of 9 (mean 16.3) weeks in the patients in Glasgow investigated in this study. However, this is still higher than the national median of 6.7 (mean 21.3) weeks in 2013. The greatest observed improvement was in the time taken to diagnose patients after their first presentation to healthcare, for which the median reduced from 3.3 to 0.5 weeks between 2011 and Glasgow patients in 2014/2015.</p><p><bold>Conclusions</bold>: The increased public and professional awareness of brain tumours has led to a clear improvement in TDI nationwide since 2006. However, the data analysed in this study suggests that continued work and data collection is required in Glasgow to ensure that TDIs more closely resemble nationwide results.</p><p><bold>Acknowledgement</bold>: J Ferguson, Data manger</p></sec><sec id="pbc26772-sec-1500"><label>O-119</label><title>Factors Influencing Diagnostic Delays of Pediatric Cancers in Botswana</title><p><underline underline-style="single">K. Carpenter</underline><sup>1</sup>, A.K. Slone<sup>2,3</sup>, P.S. Mehta<sup>2,3</sup>, M.E. Scheurer<sup>4</sup>, J.S. Slone<sup>2,3</sup></p><p><italic><sup>1</sup>Botswana‐Baylor Children's Clinical Centre of Excellence, Adolescent Services, Gaborone, Botswana; <sup>2</sup>Texas Children's Cancer and Hematology Centers, Pediatrics, Houstan, USA; <sup>3</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>4</sup>Texas Children's Cancer and Hematology Centers, Childhood Cancer Epidemiology and Prevention Program, Houstan, USA</italic></p><p><bold>Background/Objectives</bold>: In low‐to‐middle income countries (LMICs), timely access to care is a major barrier in treatment of childhood cancer and may lead to patients presenting with more extensive disease. This study aims to elucidate factors influencing diagnostic and treatment delays within Botswana.</p><p><bold>Design/Methods</bold>: Utilizing the Botswana Pediatric Oncology Database (BPOD), this study retrospectively analyzed demographic and timeline data from pediatric oncology patients (ages 0‐18) presenting to Princess Marina Hospital (PMH) between January 2008‐December 2015.</p><p><bold>Results</bold>: Median total diagnostic delay, defined as date of symptom onset to date of diagnosis, was 10.7 weeks (IQR=5.1‐20.7) (N=69). Of these ten weeks, the time that it took patients to reach PMH following onset of symptoms accounted for the majority of the delay (med=9.6 weeks, IQR=4.1‐19.7) (N=66). Once patients presented to the tertiary care facility, the median time from biopsy to pathology result was 3 weeks (IQR=1.1‐4.3) (N=89). Presence of metastasis upon diagnosis was significantly correlated with longer total diagnostic delay (p=0.001). Age, sex, distance to a cancer center, HIV status, medical aid status, and cancer diagnosis did not have a significant effect on diagnostic delays.</p><p><bold>Conclusions</bold>: Pediatric cancer patients in Botswana experienced significant delays in presenting to PMH for treatment. The overall diagnostic delay was comparable to that found in reports from other LMICs. However, diagnostic delay was correlated with risk for having metastatic disease, a unique finding compared to existing literature. Further prospective research is necessary to fully understand factors influencing diagnostic and treatment delays and to develop strategies to address these factors.</p></sec></sec><sec id="pbc26772-sec-1510"><title>Free Paper Session: Leukemia and Lymphoma</title><sec id="pbc26772-sec-1520"><label>O-120</label><title>Safety and Feasibility of Administration of OEPA/COPDAC Chemotherapy and PET‐CT Based Strategy for Treating Hodgkin Lymphoma in a Developing Country</title><p><underline underline-style="single">D. Bansal</underline><sup>1</sup>, J. Ramamoorthy<sup>1</sup>, S. Mohapatra<sup>1</sup>, A. Trehan<sup>1</sup>, R. Jain<sup>1</sup>, B. Mittal<sup>2</sup>, A. Bhattacharya<sup>2</sup>, R. Kapoor<sup>3</sup>, R. Srinivasan<sup>4</sup>, A. Rajwanshi<sup>4</sup>, N. Kakkar<sup>5</sup>, A. Das<sup>5</sup></p><p><italic><sup>1</sup>Postgraduate Institute of Medical Education and Research, Pediatric Hematology‐Oncology unit‐ Dept. of Pediatrics‐ Advanced Pediatrics Centre, Chandigarh, India; <sup>2</sup>Postgraduate Institute of Medical Education and Research, Nuclear Medicine, Chandigarh, India; <sup>3</sup>Postgraduate Institute of Medical Education and Research, Radiotherapy, Chandigarh, India; <sup>4</sup>Postgraduate Institute of Medical Education and Research, Cytology, Chandigarh, India; <sup>5</sup>Postgraduate Institute of Medical Education and Research, Histopathology, Chandigarh, India</italic></p><p><bold>Background/Objectives</bold>: Protocols with reduced anthracycline/alkylating‐agent/bleomycin are currently favoured for Hodgkin lymphoma (HL). ABVD is popular in developing countries for ease/convention. There is lack of data on administration of ‘non‐ABVD’ protocols from developing countries.</p><p><bold>Design/Methods</bold>: The study was retrospective. Euronet‐PHL‐C1 based protocol was administered in a center in India from January‐2010 to March‐2016. A PET‐CT was performed at diagnosis and following OEPA‐2. Two/four courses of COPDAC were administered in Treatment Groups (TG) 2/3, respectively. Radiotherapy was indicated for inadequate (Deauville‐score ≥4) PET‐response.</p><p><bold>Results</bold>: One‐hundred‐and‐thirty‐five patients with HL were treated in the 6‐year‐period; 101 fulfilled the study criteria. The mean‐age of 101 patients was 7.6±2.4 years (range: 2‐13); 39% were underweight. The median observation time was 39 months (17, 61.5). An inadequate PET‐response was observed in 30/97 (31%) patients. Radiotherapy was administered to 15/30 patients. There were 36 episodes of febrile‐neutropenia in 22 patients, resulting in 4 deaths. All 4 treatment‐related‐mortalities and 33/36 (92%) episodes of febrile‐neutropenia were observed following the first‐course of OEPA. Other events included 9 relapses and 1 therapy‐related AML.</p><p>The 5‐year‐OS in TG 1, 2 and 3 was 96.8%, 100% and 91.1%, respectively. The 5‐year‐EFS and OS were 86.1% and 96%, respectively. The outcome compared favorably to the 5‐year‐EFS (77.7%) and OS (92.7%) of the centers earlier experience with ABVD/COPP in 206 patients. Relapse was associated with bulky disease (P=0.001) and ΔSUV<sub>max</sub><7 (P=0.01). Episodes of febrile‐neutropenia had a trend of association with anemia (P=0.074) and involvement of ≥4 nodal regions (P=0.095).</p><p><bold>Conclusions</bold>: Chemotherapy with OEPA/COPDAC and PET‐CT based response permitted reduction of therapy with a 5‐year‐EFS (86.1%) that compared favourably with the 5‐year‐EFS (77.7%) of patients who received ABVD/COPP in the center in the past. Febrile neutropenia and resultant mortality (4%) was concerning, and occurred commonly following the first‐course of OEPA. Supportive‐care systems should be well‐placed for administration of OEPA in developing countries.</p></sec><sec id="pbc26772-sec-1530"><label>O-121</label><title>Overview and Survival of Pediatric Advanced Stage Hodgkin Lymphoma Treated in Developing Countries; Children Cancer Hospital Egypt Experience</title><p><underline underline-style="single">R. Khedr</underline><sup>1</sup>, A. Hamouda<sup>1</sup>, S. Naguib<sup>2</sup>, M. khalaf<sup>3</sup>, S. fikry<sup>4</sup>, A. Elsayed<sup>5</sup>, H. taha<sup>6</sup>, M. zaghloul<sup>7</sup>, I. Attia<sup>1</sup></p><p><italic><sup>1</sup>National cancer institute ‐ Cairo university / Children's Cancer Hospital 57357, Pediatrics oncology, Cairo, Egypt; <sup>2</sup>Children's Cancer Hospital 57357, Clinical research Department, Cairo, Egypt; <sup>3</sup>National cancer institute ‐ Cairo university / Children's Cancer Hospital 57357, Radiodiagnosis Department, Cairo, Egypt; <sup>4</sup>Children's Cancer Hospital 57357, Clinical pharmacy Department, Cairo, Egypt; <sup>5</sup>National cancer institute ‐ Cairo university / Children's Cancer Hospital 57357, Nuclear Medicine, Cairo, Egypt; <sup>6</sup>National cancer institute ‐ Cairo university / Children's Cancer Hospital 57357, Surgical Pathology, Cairo, Egypt; <sup>7</sup>National cancer institute ‐ Cairo university / Children's Cancer Hospital 57357, Radiothaerapy Department, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: The major challenge in advanced stage Hodgkin Lymphoma is to optimize the balance between overall survival and treatment related toxicity. The aim of the study was to describe the pediatric population with advanced Hodgkin lymphoma (HL) in our country and their treatment outcome.</p><p><bold>Design/Methods</bold>: This is a retrospective single center study. Data analysis for children with advanced stage HL (IIB or IIIB with bulk disease, or stage IV) as done. Demographic data, staging, number of cycles (doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)) received and whether or not consolidation radiotherapy (RTH) was administered. Positron emission tomography (PET) was performed baseline and after the second cycle to detect early response without any change to treatment plan.</p><p><bold>Results</bold>: Three hundred and eighty‐one patients with newly diagnosed Hodgkin lymphoma were enrolled in the data analysis. Male (283) to female (98) ratio 3:1. B‐symptoms was present in 60% of patients. Ann Arbor staging distribution was as follows; 68 (17.8%) IIB, 97 (25.5%) IIIA, 96 (25.2%) IIIB, 55 (14.4%) IVA, 65 (17.1%) IVB. One hundred sixty‐five patients with early unfavorable and 216 with advanced‐stage disease were treated with ABVD ± RTH. One hundred twenty‐ nine (34%) patient did not receive RTH. The Five‐years Overall survival (OS) and the Event free survival (EFS) in these patients was 90.7 (95% CI: 85.4‐95.9 and 71.9% (95% CI: 63.6‐76.1) (p value 0.006) respectively. The OS and EFS of patient with advanced stage HL in the whole study population was 94.1 (95% CI: 91.5‐96.6) and 79.4 (95% CI 74.3‐84.4) respectively.</p><p><bold>Conclusions</bold>: More than 90% of patients are cured with risk‐based combined‐modality therapy, yet these therapies are frequently associated with risks for significant long term toxicities; innovative approaches are needed for those patients who have a high risk of failure with current therapies.</p></sec><sec id="pbc26772-sec-1540"><label>O-122</label><title>Diagnosis and Treatment of Anaplastic Large‐Cell Lymphoma in Children and Adolescents in China: A Retrospective Multicenter Survey Study</title><p><underline underline-style="single">Q. Mi</underline><sup>1</sup>, G. Yijin<sup>1</sup>, T. Jingyan<sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center, Hemotology amd Oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: This study was to provide a description review and improve our understanding of the treatment outcome of pediatric anaplastic large cell lymphoma (ALCL) in China.</p><p><bold>Design/Methods</bold>: The clinical data and outcomes of patients under16 years with newly histopathologically‐confirmed ALCL treated in 10 large single institutions in China between January 2009 and June 2013, were retrospectively analyzed. The event‐free survival (EFS) was analyzed using the Kaplan‐Meier method. The risk of disease progression or relapse was evaluated using logistic regression analysis. Significance was defined as <italic>P</italic> < 0.05.</p><p><bold>Results</bold>: Of the 80 eligible patients, the median age was 8.4 years (range, 1.3 ‐ 15.7 years). Two patients (3%) were Stage I, 9 (11%) Stage II, 64 (80 %) Stage III, and 5 (6%) Stage IV.The median time of follow‐up was 25.2 months (range, 7.1 ‐ 74.8 months), 55 patients survived without disease at the last of follow‐up, the 3‐year EFS was 65%±6%. Sixty‐five patients (81%) were treated with theCCCG‐BNHL‐2010regimen and 15cases (19%) treated with other regimens. The 3‐year EFS were 68%±5% vs.65%±20%(<italic>P=0.21</italic>).(,. The 3‐year EFS was 57%±7% and 78%±11% for patients with or without B symptoms<italic>(P=0.01)</italic>. Twenty‐four patients experienced disease progression or relapse. The median time from initial diagnosis to tumor failure was7.0 months (ranged, 1.5 ‐42.6 months) (median,). At the last evaluation, there were 5 patients still aliveafter disease progression and relapse. By univariate analysis, sex (P=0.04) and B symptoms (P=0.00) were identified as risk factors of disease progression or relapse. Nevertheless, only B symptoms (HR 5.60 95% CI 1.47∼21.27, <italic>P</italic>≤0.05) wererisk factors in multivariate analysis.</p><p><bold>Conclusions</bold>: The presenting features of children and adolescents with ALCL and EFS rates in this study were similar to those reported by western countries. Refinement of therapeutic strategies to improve survival for patients with disease progression or relapse should be the priority in future clinical study.</p></sec><sec id="pbc26772-sec-1550"><label>O-123</label><title>Preclinical Efficacy of Daratumumab in T‐Cell Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">K.L. Bride</underline><sup>1</sup>, T. Vincent<sup>1</sup>, L. Im<sup>1</sup>, T. Ryan<sup>1</sup>, T. Fuller<sup>1</sup>, D.M. Barrett<sup>1</sup>, S.L. Maude<sup>1</sup>, M.L. Hermiston<sup>2</sup>, S.A. Grupp<sup>1</sup>, B.L. Wood<sup>3</sup>, D.T. Teachey<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital of Philadelphia, Pediatrics, Philadelphia, USA; <sup>2</sup>UCSF Medical Center‐Mission Bay, Pediatrics, San Francisco, USA; <sup>3</sup>Seattle Children's Hospital, Pathology, Seattle, USA</italic></p><p><bold>Background/Objectives</bold>: Targeted immunotherapy has become critical for the successful treatment of many cancers, particularly therapeutic antibodies with cytotoxic abilities. No effective immunotherapies have been developed for T‐cell acute lymphoblastic leukemia (T‐ALL). CD38 is found on the cell surface of activated T cells, terminally differentiated B cells, but relatively low levels on normal lymphoid and myeloid cells. Daratumumab (dara) is a human monoclonal antibody that binds to CD38 and is successfully used in patients with refractory multiple myeloma.</p><p><bold>Design/Methods</bold>: To ensure CD38 is a relevant target, we measured CD38 expression by flow cytometry from 21 patients with T‐ALL (10 early T‐cell precursor (ETP) and 11 non‐ETP) at diagnosis and after induction chemotherapy. We also xenografted primary ALL blasts from 15 different patients, 7 with ETP‐ALL and 8 with non‐ETP T‐ALL. Mice were randomized to dara (200 μg /mouse intraperitoneally weekly) vs isotype (200 μg/mouse; 5 mice per arm for each sample) after they developed >1% peripheral blood (pb) blasts by FACS. Disease burden was assessed by FACS enumeration of pb blasts weekly and splenic blasts at sacrifice.</p><p><bold>Results</bold>: CD38 was expressed in all 21 patient samples and surface expression remained unchanged after induction (mean CD38 MFI at diagnosis vs end‐induction: 3.27 vs 3.19 log (p = 0.25).</p><p>All 7 ETP T‐ALL samples responded with marked improvement in disease burden. For 5 of 8 of the non‐ETP T‐ALL samples, mice with advanced disease died immediately after exposure to dara, presumably from tumor lysis. We repeated experiments treating after injection but prior to development of peripheral blasts with 7 of 8 non‐ETP ALL samples demonstrating efficacy to daratumumab (2 responded at high disease burden, 5 responded at low disease burden but had toxicity with high disease, and 1 did not respond).</p><p><bold>Conclusions</bold>: In summary, dara is a highly effective novel monotherapy for T‐ALL in preclinical models.</p></sec><sec id="pbc26772-sec-1560"><label>O-124</label><title>Therapeutic Targeting of Mutant P53 in Pediatric Acute Lymphobastic Leukemia</title><p>S. Demir<sup>1</sup>, Q. Sun<sup>1</sup>, E. Tausch<sup>2</sup>, S. Stilgenbauer<sup>2</sup>, G. te Kronnie<sup>3</sup>, C. Eckert<sup>4</sup>, L. Wiesmüller<sup>5</sup>, G. Selivanova<sup>6</sup>, K.M. Debatin<sup>1</sup>, <underline underline-style="single">L. Meyer</underline><sup>1</sup></p><p><italic><sup>1</sup>Ulm University Medical Center, Department of Pediatrics and Adolescent Medicine, Ulm, Germany; <sup>2</sup>Ulm University Medical Center, Internal Medicine III, Ulm, Germany; <sup>3</sup>University of Padova, Department of Women's and Children's Health, Padova, Italy; <sup>4</sup>Charité University Medicine, Department of Pediatric Oncology and Hematology, Berlin, Germany; <sup>5</sup>Ulm University Medical Center, Department of Obstetrics and Gynecology, Ulm, Germany; <sup>6</sup>Karolinska Institute, Department of Microbiology‐ Tumor and Cell Biology, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Mutations in the tumor suppressor gene <italic>TP53</italic> (<italic>TP53</italic>mut) are infrequent at initial diagnosis of pediatric acute lymphoblastic leukemia (ALL) but enriched at relapse and associated with inferior outcome. Here, we evaluate mutated p53 as target for directed therapy and investigate the effects of the p53‐targeting small molecule APR‐246.</p><p><bold>Design/Methods</bold>: Patient, patient‐derived xenograft (NOD/SCID/huALL) and cell line B‐cell precursor (BCP)‐ALL samples were analyzed for <italic>TP53</italic>mut (high‐performance liquid chromatography, Sanger sequencing). Sensitivities for the DNA damaging agent doxorubicin and the p53‐targeting small molecule APR‐246 (kindly provided by Aprea, Stockholm, Sweden) were investigated. Apoptosis (caspase‐3 activation, Annexin‐V/propidium iodide positivity), p53 restoration (immunoprecipitation with conformation‐specific antibodies) and activation (p53pSer15, expression of p53 downstream molecules) were analyzed. p53 deficient cells were generated by lentiviral shRNA mediated knock‐down. Xenograft ALL bearing NOD/SCID mice were treated with APR‐246 or vehicle.</p><p><bold>Results</bold>: In <italic>TP53</italic>mut leukemias, we observed a poor response to doxorubicin but sensitivity in <italic>TP53</italic>wt ALL. In contrast, <italic>TP53</italic>mut ALL were highly sensitive to APR‐246 while <italic>TP53</italic>wt leukemias showed insensitivity. APR‐246 induced structural restoration of mutant p53 and functional p53 activation as indicated by p53 wild‐type conformation, p53 phosphorylation and increased expression of p53 target molecules NOXA and PUMA, finally leading to leukemia cell apoptosis. Knockdown of p53 in <italic>TP53</italic>mut ALL led to abrogation of cell death, indicating that APR‐246 targets mutant p53. Moreover, a strong synergism and re‐sensitization to DNA‐damage induced cell death was observed upon combined APR‐246 and doxorubicin exposure. Importantly, in a preclinical setting we treated <italic>TP53</italic>mut ALL bearing recipient mice with APR‐246 and observed a significant reduction in leukemia load demonstrating clear <italic>in vivo</italic> activity of APR‐246.</p><p><bold>Conclusions</bold>: In BCP‐ALL, APR‐246 restores mutant p53 to wild type conformation and reactivates its tumor suppressor function leading to apoptosis induction. Targeting mutated p53 might provide an effective novel strategy for therapeutic intervention in this high‐risk subtype of ALL.</p></sec><sec id="pbc26772-sec-1570"><label>O-125</label><title>Treatment‐Related Veno‐Occlusive Disease in Children with De Novo Acute Lymphoblastic Leukemia During Intensification</title><p><underline underline-style="single">C. McAtee</underline><sup>1</sup>, N. Schneller<sup>1</sup>, J. Brackett<sup>1</sup>, M.B. Bernhardt<sup>2</sup>, S. Eric<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatric Hematology‐Oncology, Houston, USA; <sup>2</sup>Texas Children's Hospital, Pharmacology, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Veno‐occlusive disease (VOD) has been described following treatment of acute lymphoblastic leukemia (ALL) with 6‐thioguanine (6‐TG). Previous studies incorporating daily 6‐TG into maintenance chemotherapy demonstrated a high incidence of VOD, typically presenting after prolonged exposures to 6‐TG. 6‐TG continues to be used as a single, 14‐day burst during intensification, however, VOD associated with brief courses of 6‐TG is poorly described. We describe our single‐institution experience with VOD in this setting.</p><p><bold>Design/Methods</bold>: Subjects were identified from <italic>de novo</italic> patients with ALL at Texas Children's Cancer Center between 1/1/08 and 10/28/16 through medical record searches for those diagnosed with VOD within 60 days of receiving 14 days of 6‐TG. Subject demographic and clinical data were collected. Medians and ranges were calculated.</p><p><bold>Results</bold>: Of 680 new patients with ALL, 10 (1.5%) were identified with VOD. No predominant sex, ethnicity or race was noted. VOD was diagnosed 16.5 (6‐42) days from starting 6‐TG. Isolated thrombocytopenia was noted in 9/10 patients and presented 5 (0‐34) days prior to VOD, with 8/10 of these patients being clinically stable outpatients and 7/10 patients still taking 6‐TG. Refractoriness to platelet transfusions was noted in 8/10 patients, presenting 2 days prior to VOD with 7/8 of these being stable outpatients and 3/8 still taking 6‐TG. Fever was noted in 7/10 patients within 24 hours and 6/10 had documented or suspected infection in the 14 days prior to VOD. Intermediate thiopurine methyltransferase genotype was noted in 5/8 patients with data available.</p><p><bold>Conclusions</bold>: VOD generally presents early following initiation of 6‐TG in intensification phases of ALL treatment. Disproportionally severe thrombocytopenia and transfusion refractoriness typically preceded VOD diagnosis by several days, occurring in clinically stable outpatients. Identifying risk factors and early signs and symptoms of VOD in this population can hasten appropriate diagnosis/treatment, and in some cases, may allow for discontinuation of the offending 6‐TG.</p></sec></sec><sec id="pbc26772-sec-1580"><title>Free Paper Session: Liver Tumours and Rare Tumours</title><sec id="pbc26772-sec-1590"><label>O-126</label><title>Survival and Lates Effects of JPLT (Japanese Study Group for Rediatric Liver Tumor)‐2 Risk‐Stratified Study for Hepatoblastoma</title><p><underline underline-style="single">E. Hiyama</underline><sup>1</sup>, T. Hishiki<sup>2</sup>, K. Ida<sup>2</sup>, K. Watanabe<sup>2</sup>, Y. Tanaka<sup>2</sup>, Y. Aoki<sup>2</sup>, T. iehara<sup>2</sup>, T. Kazama<sup>2</sup>, K. Kihira<sup>2</sup>, T. Taguchi<sup>2</sup>, J. Fujimura<sup>2</sup>, K. Hoshino<sup>2</sup>, S. Honda<sup>2</sup>, K. Matsumoto<sup>2</sup>, M. Mori<sup>2</sup>, M. Yano<sup>2</sup></p><p><italic><sup>1</sup>Hiroshima University Hospital, Peditric Surgery, Hiroshima, Japan; <sup>2</sup>Japanese children cancer group, Liver tumor committee, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: The Japanese Study Group for Pediatric Liver Tumor (JPLT)‐2 study for hepatoblastoma (HBL) launched in 1999 and closed in 2012. The main aim of this study launched to evaluate the efficacy of cisplatin/pirarubicin in risk‐stratified HB: standard risk HB (a tumor involving three or fewer sectors of the liver), intermediate risk HB (a tumor involving all sectors of the liver or invasion into portal or hepatic vein) and high risk HB (a tumor involving all sectors of the liver or with metastasis).</p><p><bold>Design/Methods</bold>: Until 2012, 360 HB children who were younger than 15 years of age were eligible for inclusion in the JPLT2 study in which the cisplatin/pirarubicin regimen (CITA) is kept as the first line. In this study, we examined the outcome and late effects of the HB patients by the risk‐stratified three groups (standard, intermediate and high risk groups).</p><p><bold>Results</bold>: Among 360 cases, PRETEXT I was 25, II was 117, III was 134, and IV was 84 including 61 cases (17%) with metastatic tumors. The 5‐year EFS/OS of the cases with standard risk HB were 77/92%, while those of the cases with Intermediate and high risk HB was 59/74% and 38/46%, respectively. Except for 40 cases who underwent primary resection, complete resection of primary after CITA was performed 98% of standard risk, 76% of intermediate risk and 86% of high risk patients. And the late phase complications were 51 cases with maldevelopment, 20 with cardiac complications, 65 with ototoxicity and 8 with second malignancies.</p><p><bold>Conclusions</bold>: As compared with other multicenter cooperative protocols, CITA regimens achieved similar rates of survival and resectability in standard risk patients. More promising strategies including adequate liver transplantation and new targeting drugs should be developed for intermediate and high risk HBs.</p></sec><sec id="pbc26772-sec-1600"><label>O-127</label><title>AFP as a Biologic Marker and Prognostic Factor in Newly‐Diagnosed Completely Resected Hepatoblastoma</title><p><underline underline-style="single">A. O'Neill</underline><sup>1</sup>, M. Malogolowkin<sup>2</sup>, M.D. Krailo<sup>3</sup>, C. Xia<sup>4</sup>, M. Qayed<sup>5</sup>, M.R. Langham Jr<sup>6</sup>, R.L. Meyers<sup>7</sup>, H.M. Katzenstein<sup>8</sup></p><p><italic><sup>1</sup>Dana Farber Cancer Institute, Pediatric Oncology, Boston, USA; <sup>2</sup>University of California Davis Comprehensive Cancer Center, Pediatric Oncology, Sacramento, USA; <sup>3</sup>University of Southern California Keck School of Medicine, Research Preventive Medicine, Los Angeles, USA; <sup>4</sup>Statistics and Data Center‐ Children's Oncology Group, Statistics, Monrovia, USA; <sup>5</sup>Emory Winship Cancer Institute, Pediatric Oncology, Atlanta, USA; <sup>6</sup>Le Bonheur Children's Hospital and University of Tennessee, Department of Surgery, Memphis, USA; <sup>7</sup>Primary Children's Hospital and University of Utah, Department of Surgery, Salt Lake City, USA; <sup>8</sup>Vanderbilt University School of Medicine‐ Monroe Carell Jr. Children's Hospital, Pediatric Oncology, Nashville, USA</italic></p><p><bold>Background/Objectives</bold>: Hepatoblastoma (HB) is the most common pediatric liver neoplasm. Greater than 90% of newly diagnosed patients present with an elevated serum alpha feto‐protein (AFP) level. The decline of AFP levels throughout therapy is routinely utilized as a marker of response however the exact relationship between AFP decline and outcome is not well established.</p><p><bold>Design/Methods</bold>: Children's Oncology Group (COG) protocol AHEP0731 was designed for patients with newly diagnosed HB and included a stratum for low‐risk patients with disease that was resected at diagnosis and followed by two adjuvant cycles of cisplain, 5‐fluorouracil, and vincristine (C5V). AFP levels were obtained per protocol at diagnosis, during therapy, and at routine off‐therapy followup visits every 6 months. We analyzed AFP levels at diagnosis, and decline in response to therapy until normal, per institutional standards indicating “complete remission.“</p><p><bold>Results</bold>: Fifty‐one subjects were enrolled on the low‐risk stratum, 49 of whom were eligible for this analysis. Mean AFP at diagnosis was 70,582 ng/mL, excluding two patients that lacked baseline values (median: 15,881, range: 104‐391,410 ng/mL). AFP values normalized in subjects as follows: 6 patients during therapy, 26 patients at the end‐of‐therapy, and 14 and 1 patient(s) at 6 and 12 months off‐therapy, respectively. Two subjects failed to normalize AFP. There was no difference in outcome based on the timing of normalization of AFP levels. All patients who recurred had progressive re‐elevation of successive AFP levels. Minor transient increases (levels < 100 ng/ml) in AFP were observed and did not necessarily indicate relapse.</p><p><bold>Conclusions</bold>: In patients with upfront, resected disease, time‐to‐normalization of AFP levels was not predictive of overall outcome. AFP as an indicator of relapse is highly sensitive.</p></sec><sec id="pbc26772-sec-1610"><label>O-128</label><title>PARP1‐Dependent Chromosomal Domains Determine the Development of Aggressive Hepatoblastoma by Activating Multiple Pathways of Cancer</title><p><underline underline-style="single">L. Valanejad Kiefer</underline><sup>1</sup>, A. Cast<sup>1</sup>, M. Wright<sup>1</sup>, M. Weirauch<sup>2</sup>, N. Timchenko<sup>1</sup></p><p><italic><sup>1</sup>Cincinnati Children's Hospital Medical Center, Division of Pediatric General and Thoracic Surgery, Cincinnati, USA; <sup>2</sup>Cincinnati Children's Hospital Medical Center, Center for Autoimmune Genomics and Etiology, Cincinnati, USA</italic></p><p><bold>Background/Objectives</bold>: Hepatoblastoma (HBL) is a pediatric liver cancer that affects children under the age of three. Reduction of tumor suppressor proteins (TSPs) is seen in many types of liver cancer. Surprisingly, we found that aggressive, chemo‐resistant HBLs are characterized by an elevation of TSPs. Our goals were to determine mechanisms by which aggressive HBL neutralizes activities of elevated TSPs; elucidate mechanisms that elevate TSPs in aggressive cancer; and examine if the inhibition of these mechanisms inhibit HBL.</p><p><bold>Design/Methods</bold>: Using RNA‐Seq and biochemical approaches, we analyzed a large cohort of HBL samples. Post‐translational modifications of 5 TSPs (Rb, p53, C/EBPα, HNF4α and CUGBP1) and protein‐protein complexes of these TSPs were examined using HPLC‐based size exclusion chromatography, Co‐IP, and 2D gel electrophoresis. Changes in chromatin structure were examined using ChIP assays.</p><p><bold>Results</bold>: While HBL samples with a mild phenotype have reduced levels of TSPs, aggressive HBL is characterized by an elevation of TSPs that underwent post‐translational modifications eliminating their tumor suppression activities. We found that genes of each TSP contain a unique 250 base pair chromosomal domain (Aggressive Liver Cancer Domains (ALCDs)). The human genome contains 30 ALCDs located in chromosomal regions of 5 TSPs and certain cancer related genes, but ALCDs are not observed in the mouse genome. ALCDs and corresponding genes are activated by an elevation of PARP1/Ku80/Ku70 complexes, which bind directly to ALCDs. Inhibition of PARP1 in cultured hepatoblastoma cells eliminates PARP1/Ku80/Ku70 complexes and inhibits or normalizes expression of corresponding genes resulting in an inhibition of proliferation.</p><p><bold>Conclusions</bold>: Activation of ALCDs by PARP1 is a key event in the development of aggressive HBL. This phenotype also involves post‐translational modifications that block their tumor suppression activities. Activation of PARP1 is a mechanism for development of aggressive HBL suggesting that FDA‐approved PARP1 inhibitors might be used for treatment of chemo‐resistant HBL.</p></sec><sec id="pbc26772-sec-1620"><label>O-129</label><title>Genetic and Epigenetic Analyses of Hepatoblastoma Identify Subgroups with Different Clinical and Biological Features</title><p><underline underline-style="single">M. Sekiguchi</underline><sup>1</sup>, M. Seki<sup>1</sup>, T. Kawai<sup>2</sup>, T. Isobe<sup>1</sup>, K. Yoshida<sup>3</sup>, M. Yoshida<sup>1</sup>, N. Hoshino<sup>4</sup>, Y. Shiraishi<sup>5</sup>, R. Souzaki<sup>6</sup>, K. Watanabe<sup>7</sup>, Y. Arakawa<sup>7</sup>, K. Koh<sup>7</sup>, Y. Hayashi<sup>8</sup>, T. Taguchi<sup>6</sup>, M. Sanada<sup>9</sup>, Y. Tanaka<sup>10</sup>, S. Miyano<sup>5</sup>, K. Hata<sup>2</sup>, S. Ogawa<sup>3</sup>, J. Takita<sup>1</sup></p><p><italic><sup>1</sup>The University of Tokyo, Department of Pediatrics, Bunkyo‐ku, Japan; <sup>2</sup>National Research Institute for Child Health and Development, Department of Maternal‐Fetal Biology, Setagaya‐ku, Japan; <sup>3</sup>Kyoto University, Department of Pathology and Tumor Biology, Kyoto, Japan; <sup>4</sup>The University of Tokyo Hospital, Department of Pediatric Surgery, Bunkyo‐ku, Japan; <sup>5</sup>The Institute of Medical Science‐ The University of Tokyo, Human Genome Center, Minato‐ku, Japan; <sup>6</sup>Kyushu University, Department of Pediatric Surgery, Fukuoka, Japan; <sup>7</sup>Saitama Children's Medical Center, Department of Hematology/Oncology, Saitama, Japan; <sup>8</sup>Japanese Red Cross Gunma Blood Center, Director, Maebashi, Japan; <sup>9</sup>Nagoya Medical Center, Department of Advanced Diagnosis, Nagoya, Japan; <sup>10</sup>Kanagawa Children's Medical Center, Department of Pathology, Yokohama, Japan</italic></p><p><bold>Background/Objectives</bold>: Hepatoblastoma (HBL) is the most common liver tumor in children. Despite intensive multimodal therapy, the prognosis of high‐risk HBL remains poor, and this underscores the importance of understanding HBL pathogenesis and developing novel therapeutic modalities. However, as the mutation rate in HBL is relatively low and molecular targets except for Wnt/beta‐catenin pathway have not been established, our understanding of the molecular basis of HBL is still limited.</p><p><bold>Design/Methods</bold>: We performed methylation array analysis and single nucleotide polymorphism (SNP) array‐based copy number (CN) analysis on 38 samples of HBL. A part of the samples were also subjected to whole‐exome sequencing (WES, 10 samples) and RNA sequencing (RNA‐seq, 18 samples).</p><p><bold>Results</bold>: We identified mutations/deletions of <italic>CTNNB1</italic> in all samples subjected to WES/RNA‐seq. No other recurrent mutation or gene fusion was detected. Consensus clustering of 38 samples based on methylation data indicated the presence of 3 distinct clusters. Cluster 1 was characterized by high expression of <italic>LGALS1</italic> associated with the promoter hypomethylation and marked by low diagnostic age. Intriguingly, cluster 1 included most of the cases with uniparental disomy/trisomy of chromosome 11p. As for cluster 2, all but one case had 1q/2q gains. Cluster 2 included most of the cases staged as PRETEXT IV that required liver transplant. Cluster 3 exhibited low expression of <italic>NQO1</italic> with the promoter hypermethylation and less frequent CN alterations. Patients with relatively low serum AFP levels were enriched in this cluster. Being consistent with low expression of <italic>NQO1</italic>, known as a poor prognostic factor in several kinds of tumors, patients in cluster 3 showed better event‐free survival than the others (100% vs 56.0%, p = 0.046).</p><p><bold>Conclusions</bold>: Our integrated genome‐wide study of HBL identified methylation subgroups well correlated with biological and clinical features. It may be useful for clinical risk stratification and searching for new molecular targets.</p></sec><sec id="pbc26772-sec-1630"><label>O-130</label><title>Patterns of Care and Treatment Outcomes of Pancreatic Tumors in Children: an Analysis of the National Cancer Database</title><p>O. Picado<sup>1</sup>, J. Tashiro<sup>1</sup>, K. Rao<sup>1</sup>, J. Sola<sup>1</sup>, <underline underline-style="single">E. Perez</underline><sup>1</sup></p><p><italic><sup>1</sup>University of Miami ‐ Miller School of Medicine, Surgery, Miami, USA</italic></p><p><bold>Background/Objectives</bold>: Pancreatic tumors are rare in children and limited data is available. We aimed to describe patient and tumor characteristics and to report on survival of this disease.</p><p><bold>Design/Methods</bold>: Data from the National Cancer Database (2004‐2013) on children younger than 18 years with pancreatic tumors were analyzed. The association between treatment and hazard of death was assessed using Kaplan‐Meier method and Cox regression model.</p><p><bold>Results</bold>:We identified 86 children with pancreatic tumors; 52% were male, 56% white non‐Hispanic, and 90% insured. Median age at diagnosis was 14 (IQR: 9‐16) years. Tumors were distributed as follows, pseudopapillary neoplasm (27%, n=23), endocrine tumors (26%, n=22), pancreatoblastoma (17%, n=15), pancreatic adenocarcinoma (16%, n=14), sarcoma (8%, n=7) and neuroblastoma (6%, n=5). Sixty patients underwent surgery, 70% (n=42) achieved R0 resection. Most patients (75%, n=45) had lymph node examination, and 22% had positive samples. Twenty percent (n=17) received adjuvant therapies; 14% (n=12) chemotherapy and 6% (n=5) chemoradiation therapy, while 19% (n=16) received palliative treatment. Most pancreatoblastomas (80%, n=12) and sarcomas (57%, n=4) received chemotherapy and chemoradiation therapy, respectively. Five‐year overall survival for all pancreatic tumors was 61%. Five‐year overall survival by tumor histology were 95%, 75%, 70%, 51%, 43%, and 34% for pseudopapillary neoplasm, neuroblastoma, pancreatoblastoma, endocrine tumors, sarcoma and pancreatic adenocarcinoma, respectively. On univariate analysis, males (HR: 2.50, 95%CI: 1.07–5.80, p=0.03), sarcomas (HR: 13.48, 95%CI: 1.51–120.59, p=0.02), endocrine tumors (HR: 10.11, 95%CI: 1.26–80.90, p=0.03), adenocarcinoma (HR: 22.95, 95%CI: 2.81–187.20, p<0.01), and non‐surgical management (HR: 4.80, 95%CI: 2.15–10.71, p<0.001) were all significant predictors of worse survival. Though, non‐surgical management (HR: 4.07, 95%CI: 1.56–10.62, p<0.001) remained independent predictor of worse survival on multivariate analysis.</p><p><bold>Conclusions</bold>: Overall survival of children with pancreatic tumors is grim, with varying survival rates among different tumors. Surgical management of pancreatic tumors in children is associated with long‐term survival.</p></sec><sec id="pbc26772-sec-1640"><label>O-131</label><title>NUT Midline Carcinoma in Children and Adults: A Multicenter Retrospective Study</title><p><underline underline-style="single">L. Lemelle</underline><sup>1</sup>, G. Pierron<sup>2</sup>, P. Fréneaux<sup>3</sup>, S. Huybrechts<sup>4</sup>, A. Spiegel<sup>5</sup>, D. Plantaz<sup>6</sup>, M. Julieron<sup>7</sup>, S. Dumoucel<sup>8</sup>, A. Italiano<sup>9</sup>, F. Millot<sup>10</sup>, C. Le Tourneau<sup>11</sup>, G. Leverger<sup>12</sup>, P. Chastagner<sup>13</sup>, M. Carton<sup>14</sup>, D. Orbach<sup>15</sup></p><p><italic><sup>1</sup>Institut Curie, Department of Pediatric‐ Adolescent‐ Young Adults, Paris, France; <sup>2</sup>Institut Curie, Unité de Génétique somatique, Paris, France; <sup>3</sup>Institut Curie, Département de pathologie, Paris, France; <sup>4</sup>Hôpital Universitaire des Enfants Reine Fabiola‐ ULB Université libre de Bruxelles, Hematology‐Oncology Unit, Brussels, Belgium; <sup>5</sup>CHU Hautepierre, Department of Pediatric Hematology‐Oncology, Strasbourg, France; <sup>6</sup>Hôpital de Grenoble, Department of Pediatric Hematology‐Oncology, Grenoble, France; <sup>7</sup>Centre Oscar Lambret, Head and Neck Surgery department, Lille, France; <sup>8</sup>CHU Sainte Justine‐ University of Montreal, Department of Pediatric Hematology‐Oncology, Montreal, Canada; <sup>9</sup>Institut Bergonié, Department of Medical Oncology, Bordeaux, France; <sup>10</sup>Centre Hospitalier Universitaire Poitiers, Pediatric oncology departement, Poitiers, France; <sup>11</sup>Institut Curie, Medical oncology department‐ INSERM U900 Research unit‐ Saint‐Cloud, Paris, France; <sup>12</sup>Assistance Publique – Hôpitaux de Paris‐ Hôpital Armand Trousseau, 12Department of Pediatric Hematology and Oncology, Paris, France; <sup>13</sup>Hôpital d'Enfants de Brabois, Department of Pediatric Hematology‐Oncology, Vandoeuvre Les Nancy, France; <sup>14</sup>INSERM UMS 11, 14Population‐based Epidemiological Cohorts Unit, Villejuif, France; <sup>15</sup>Institut Curie, Department of Pediatric‐ Adolescent‐ Young Adults‐ French Pediatric Rare Tumor group groupe Fracture, Paris, France</italic></p><p><bold>Background/Objectives</bold>: <italic>NUT</italic> midline carcinoma is an aggressive tumor defined by the presence of <italic>NUT</italic> rearrangement (BRD3/4‐NUT fusion oncogene) with a poor prognosis. This rare cancer is underdiagnosed and poorly treated.</p><p>The primary objective of this study was to describe the clinical, radiologic and biological features of <italic>NUT</italic> midline carcinoma. The secondary objective was to describe the various treatments and assess their efficacy.</p><p><bold>Design/Methods</bold>: This retrospective multicenter study was based on review of the medical records of children and adults with <italic>NUT</italic> midline carcinoma with specific rearrangement or positive anti‐NUT nuclear staining (>50%).</p><p><bold>Results</bold>: This series of 12 patients had a median age of 18.1 years (ranges: 12.3 – 49.7 years). The primary tumor was located in the chest in 8 patients, the head and neck in 3 patients and 1 patient had a multifocal tumor. Nine patients presented regional lymph node involvement and 8 distant metastases. One‐half of patients were initially misdiagnosed and diagnosis of NMC was therefore subsequently corrected by targeted molecular biology analyses. Specific NUT antibody was positive in all cases tested. The specific BRD4‐NUT translocation was found in 10/12 patients. A transient response to chemotherapy was observed in 4/11 patients. Only 2 patients were treated by surgery and 5 received radiotherapy with curative intent. Three out of 12 patients received targeted therapy. At the end of follow‐up, only one patient was still in remission more than 12 years after the diagnosis. Median overall survival was 4.7 months (95%CI: 2.1‐17.7).</p><p><bold>Conclusions</bold>: <italic>NUT</italic> midline carcinoma is an aggressive disease refractory to conventional therapy. Early diagnosis by NUT‐specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma to identify the specific rearrangement of <italic>NUT</italic> gene is useful for diagnosis. It should lead to propose optimal therapeutic strategy with early inclusion in targeted therapy studies.</p></sec></sec><sec id="pbc26772-sec-1650"><title>Childhood Cancer International (CCI)</title><sec id="pbc26772-sec-1660"><label>O-132</label><title>A Childhood Cancer Parent's Guide to Transforming Pediatric Cancer Policy in Your State</title><p><underline underline-style="single">J. Bloyd</underline><sup>1</sup></p><p><italic><sup>1</sup>American Childhood Cancer Organization, Lexington, USA</italic></p><p><bold>Background/Objectives</bold>: The objective of this presentation is to empower parents of childhood cancer patients and survivors to effectively engage policy makers to raise awareness about childhood cancer and the need for additional resources. The presenter will share about her personal experience in forming partnerships with state legislators and the Governor to pass legislation making Kentucky a national model for change.</p><p>Mrs. Bloyd is the mother of a Burkitts Lymphoma Leukemia survivor, Paxton. She worked for KY Governor Ernie Fletcher as well as U.S. Senate Majority Leader Mitch McConnell in D.C., and as a grassroots advocacy lobbyist/consultant for the American Heart Association, Campaign for Tobacco Free Kids, and Americans for Non‐Smokers Rights prior to her son's diagnosis.</p><p><bold>Design/Methods</bold>: Mrs. Bloyd will use her experience as a case study to reveal pitfalls and pearls for effective grassroots advocacy.</p><p><bold>Results</bold>: Mrs. Bloyd led the way in Kentucky drafting legislation to create a new pediatric cancer research trust fund. This initiative is funded through an innovative approach giving Kentucky residents the opportunity to donate via their annual state income tax return. As a result of her leadership, Mrs. Bloyd was appointed by the Governor to the board and elected President. Mrs. Bloyd also led the way in changing Kentucky's Cancer Action Plan to include specific objectives regarding childhood cancer research and survivorship. To commemorate International Childhood Cancer Day Jamie recently partnered with Governor Matt Bevin and the First Lady in launching KY's first‐ever pediatric cancer advocacy day at the State Capitol.</p><p><bold>Conclusions</bold>: Although childhood cancer is the number one cause of death by disease for children, the issue goes largely unnoticed by state policy makers. Effective advocacy at the grassroots level has the power to change the political landscape in making childhood cancer a priority issue.</p></sec><sec id="pbc26772-sec-1670"><label>O-133</label><title>The Best Interests of the Paediatric Oncology Patient: A Case Study Where Medical Professionals and Carers do not Agree</title><p><underline underline-style="single">T. Di Lallo</underline><sup>1</sup></p><p><italic><sup>1</sup>Royal Children's Hospital, Parent's Advisory Group‐ Children's Cancer Centre, Parkville, Australia</italic></p><p><bold>Background / Objectives: Background</bold>: In December 2015, Oshin Kiszko was diagnosed with a rare brain tumour, <italic>medulloblastoma</italic>. Oshin was then six years old. He died in December 2016.</p><p>Following surgery in December 2015, curative treatment comprising intensive chemotherapy and craniospinal radiotherapy was indicated. Oshin's parents were advised accordingly.</p><p>Oshin's parents initially opposed the administration of chemotherapy. They subsequently agreed to limited chemotherapy, but otherwise preferred to pursue alternative therapies. They declined radiotherapy under any circumstances.</p><p>Litigation took place between Oshin's parents and the treating Hospital.</p><p><bold>Objectives</bold>: Consideration of the legal/ethical issues which emerge when legal guardians seek to limit medical treatment for the infant patient in the exercise of their parental entitlement to protect their child's welfare.</p><p>Identification of how the legal and ethical issues become especially acute where the indicated medical treatment takes the form of “special medical procedures” as that term is understood by law.</p><p>Analysis of why the Court ultimately deferred to the wishes of Oshin's legal guardians concerning on‐going medical treatment in preference to the recommendations of the child's treating medical professionals.</p><p><bold>Design/Methods</bold>: Nil.</p><p><bold>Results</bold>: Nil.</p><p><bold>Conclusions</bold>: The ‘bests interests’ approach to the consideration of patient welfare does not offer a specific hierarchy of values.</p><p>The application of the “best interests’ approach in the case of the individual patient is multifaceted and intricate, especially in the context of “special medical procedures”.</p><p>Best interests are values, not facts. Therefore, complex ethical and legal issues intrude into otherwise clinical questions.</p><p>The wishes of legal guardians are protected by law and cannot lightly be derogated from.</p></sec><sec id="pbc26772-sec-1680"><label>O-134</label><title>“Getting More Bang for Your Buck” ‐ The Perspective of a Not‐for Profit on Innovative Strategies to Get Better value for Money for Medical Assistance</title><p><underline underline-style="single">H. Gupta</underline><sup>1</sup>, A. Taluja<sup>2</sup>, K. Sawhney<sup>1</sup>, P. Bagai<sup>1</sup>, A. Mahajan<sup>1</sup></p><p><italic><sup>1</sup>Cankids...Kidscan, Medical Projects and Support Service Program, Delhi, India; <sup>2</sup>Cankids...Kidscan, Quality Control Research and Impact, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Drugs cost is a significant component of the overall financial burden in the management of childhood cancer. The diverse healthcare dynamics in India leads to a significant albeit variable part of this burden being passed on to the families. Cankids is a grassroots level organization providing holistic support to pediatric oncology patients at 45 centers in India. Support for medications currently constitutes the biggest outlay in our annual expenditure. It is therefore, vital for us to find ways to cut costs without compromising on the quality of treatment. The aim of this study was to quantify the cost reduction achieved using various strategies.</p><p><bold>Design/Methods</bold>: Medical Assistance team of cankids selects and procures chemotherapy/supportive drugs directly from pharmaceutical companies for all Cankids supported Hospital units. Drugs requiring cold‐chain are delivered through local stockists of parent company. As a general principle generics approved by Drug General Controller of India are procured. Bulk purchasing facilitates better negotiation in prices and value additions such as some complimentary vials and diagnostics. Billing centrally leads to avoidance of higher taxes at state level. Attempt was made for the purpose of this study to quantify the overall economic benefit using the above strategies for five commonly prescribed, key drugs L‐Asparaginase, Imatinib, Filgrastim, Voriconazole, Meropenem.</p><p><bold>Results</bold>: During the year 2015‐16 Cankids provided medical assistance to 4531 patients, with total outlay of $551,655. By using generics for 4 of these 5 drugs we had a cost reduction of 63%. For native Asparaginase only innovator product was used. Apart from this, by using above mentioned strategies, a reduction of 58% in the retail price of final purchased generic drugs was achieved.</p><p><bold>Conclusions</bold>: Significant cost reductions can be achieved in partnership with pharmaceutical industry enabling support groups to reach out to more patients.</p></sec><sec id="pbc26772-sec-1690"><label>O-135</label><title>Increasing Fundraising Capacity for Parent Run Organizations in LMICs</title><p><underline underline-style="single">M. Hamid</underline><sup>1</sup>, S. Choudhury<sup>1</sup></p><p><italic><sup>1</sup>ASHIC Foundation, Pediatric Oncology, Dhaka, Bangladesh</italic></p><p><bold>Background/Objectives</bold>: LMICs struggle with a multitude of indigenous socio‐economic issues, making it difficult to raise the fundraising capacity for small parent‐run organizations focused on a specific cause such as childhood cancer. In a country such as Bangladesh, malnutrition, education and communicable diseases receive the lion's share of public funding and attention. Specialized causes such as childhood cancer are forced to resort to private sources of funding. Unequal distribution of wealth keeps more than 90% of the country's wealth in the hands of the select few, who make their own decisions on what projects to fund. Most have causes in their own communities or extended families that they choose to support, and as a result specialized programs such as support for childhood cancer gets ignored.</p><p><bold>Design/Methods</bold>: With a track record of swindlers in the community, individuals are also slow to trust private non‐governmental organizations (NGOs) unless they have a personal connection with the administrators of the organization. Formed in 1994, ASHIC Foundation got its start with 100% of its small budget funded by private funds from the founders of the organization. Maheen Hamid, daughter of the founders Afzal & Salma Choudhury, will share the family's journey over the last two decades. This includes relationship building with the local medical communities, tapping into international networks/ partners, building credibility of ASHIC Programs by being consistent and dedicated service providers and many other factors that have helped to build the trustworthiness of the organization.</p><p><bold>Results</bold>: Today, the organization gets about ∼70% of its current ∼$100,000 annual budget from private donations, including those from individuals and institutions.</p><p><bold>Conclusions</bold>: Several parent run organizations in LMICs may be able to benefit from the effective strategies employed by ASHIC Foundation, and the organization's plans to leverage new marketing tools for increasing fundraising capacity.</p></sec><sec id="pbc26772-sec-1700"><label>O-136</label><title>Developing an Intelligent Resource Mobilization Strategy in Response to Rapid Growth of Programs Focussed on Change for Childhood Cancer in India</title><p><underline underline-style="single">A. Kumar</underline><sup>1</sup>, P. Bagai<sup>1</sup>, G. Nagar<sup>1</sup>, K. Sawhney<sup>1</sup></p><p><italic><sup>1</sup>CanKids...KidsCan, Resource Mobilisation Department, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: CanKids...KidsCan (CK) – a grassroot level not‐for‐profit organization works for Change for Childhood Cancer in India and You Are Not Alone (YANA) Social Support Protocol; executed through their social support teams working in 44 cancer centres across India providing holistic support ( Range of 18 services) to provide best standards of treatment, care and support. Hence, requires fundraising & implementable resource mobilization roadmap.</p><p><bold>Design/Methods</bold>:
<list list-type="order" id="pbc26772-list-0001"><list-item><p>Adaptive fundraising strategy
<list list-type="alpha-lower" id="pbc26772-list-0002"><list-item><p>Evolving corporate atmosphere has brought into limelight the corporate social responsibilities (CSR) of each organization. Project/programs created developed according to CSR needs</p></list-item></list></p></list-item><list-item><p>Building expertise by
<list list-type="alpha-lower" id="pbc26772-list-0003"><list-item><p>Working with different stakeholders,</p></list-item><list-item><p>Developing fundraising roadmap.</p></list-item><list-item><p>donor management tools‐ sales force ( 4616 donors)</p></list-item><list-item><p>Building corpus fund</p></list-item></list></p></list-item><list-item><p>Community involvement through
<list list-type="alpha-lower" id="pbc26772-list-0004"><list-item><p>Seven Care centers, for cancer children for focused interventions</p></list-item><list-item><p>Donation in kind – involving community through their time, food and supplies.</p></list-item></list></p></list-item><list-item><p>Events
<list list-type="alpha-lower" id="pbc26772-list-0005"><list-item><p>Awareness – through disease based national campaign, survivor specific campaigns and statewide car rallies</p></list-item><list-item><p>Networking through fundraising dinners</p></list-item></list></p></list-item><list-item><p>Other Fundraising tools
<list list-type="alpha-lower" id="pbc26772-list-0006"><list-item><p>Crowd & bite sized fundraising</p></list-item><list-item><p>Using network's network</p></list-item><list-item><p>fundraising target setting</p></list-item><list-item><p>Schools /institutional partnerships</p></list-item></list></p></list-item></list></p><p><bold>Results</bold>:
<list list-type="order" id="pbc26772-list-0007"><list-item><p>Five year trend:
<list list-type="alpha-lower" id="pbc26772-list-0008"><list-item><p>Increase in funds raised from USD 460,000 to USD 945,000 to 1,280,000USD to 1,450,000USD to USD 2,000,000</p></list-item><list-item><p>Number of hospitals supported has increased from 27 to 44</p></list-item></list></p></list-item><list-item><p>Previous two year comparison
<list list-type="alpha-lower" id="pbc26772-list-0009"><list-item><p>56% in 2015‐16 to 65% in 2016‐17 raised through project funds</p></list-item><list-item><p>Increase from previous year funds raised – 33% in 2015‐16 to 66% in 2016‐17</p></list-item></list></p></list-item><list-item><p>Strong database of continual group/ individual relationships for future</p></list-item></list></p><p><bold>Conclusions</bold>:
<list list-type="order" id="pbc26772-list-0010"><list-item><p>Donor focussed projects led to renewable partnerships, reducing reliance on foreign funding</p></list-item><list-item><p>Team strengthening is essential for sustainability</p></list-item><list-item><p>Multiple fundraising tools helped increase donations and flexibility to implement programs</p></list-item><list-item><p>Effective low cost models for fundraising.</p></list-item><list-item><p>Community involvement shoulders some burden of fundraising</p></list-item></list></p></sec><sec id="pbc26772-sec-1710"><label>O-137</label><title>Charity Role in International Paediatric Cancer Clinical Trials</title><p><underline underline-style="single">S. Kennedy</underline><sup>1</sup>, D. Ludwinski<sup>1</sup>, S. Richards<sup>2</sup>, N. Bird<sup>2</sup>, L. Knox<sup>2</sup>, J. Rogers<sup>2</sup></p><p><italic><sup>1</sup>Solving Kids' Cancer, Research Programs, New York, USA; <sup>2</sup>Solving Kids' Cancer Europe, Research Programs, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: International clinical trials are becoming increasingly important in paediatric cancers to facilitate faster accrual rates and provide wider access to children for testing new therapies. Challenges of increased design and monitoring complexities, regulatory burden, and cost remain significant. This presents an opportunity for charities to stimulate and support international collaborations between academia, industry, government agencies, and non‐profits.</p><p><bold>Design/Methods</bold>: Research advocacy by an international charity based in the US and UK identified unmet needs for children with neuroblastoma. A call for proposals was issued to the international research community to submit ideas for combination immunotherapy. An international panel of scientific reviewers selected a proposal to recommend for the award. Another clinical trial testing a targeted drug planned in a US consortium was expanded to include UK and Europe due to charity support and influence. Seven additional charities in the US and UK are supporting these trials.</p><p><bold>Results</bold>: Two international clinical trials testing novel therapies in neuroblastoma influenced and supported by charity advocacy are due to open in 2017. One is testing targeted radiotherapy 131I‐MIBG with immunotherapy combination using anti‐GD2 antibody dinutuximab‐beta and anti‐PD1 antibody nivolumab and will accrue relapsed and refractory neuroblastoma patients in US, UK, and Germany (NCT02914405). The second is a third‐generation ALK inhibitor lorlatinib for children with ALK‐positive neuroblastoma that will accrue patients in US, UK, and France.</p><p><bold>Conclusions</bold>: Charities advocating for and supporting innovative international clinical trials are providing an essential role in stimulating trials that will accrue in a timely manner and address the need for more therapeutic options across borders for children with cancer.</p></sec><sec id="pbc26772-sec-1720"><label>O-138</label><title>Have A Heart for Children with Cancer: A Campaign to Raise Awareness of and Funds for Children living with Cancer</title><p><underline underline-style="single">L. Moore</underline><sup>1</sup></p><p><italic><sup>1</sup>CHOC Childhood Cancer Foundation SA, Gauteng South Region, Saxonwold, South Africa</italic></p><p><bold>Background/Objectives</bold>: The non‐profit sector in South Africa has become increasingly more competitive which has resulted in a scramble for available funds. CHOC Childhood Cancer Foundation South Africa (CHOC), the largest childhood cancer NGO operating in the African continent, developed a national awareness and fundraising campaign entitled “Have a Heart for Children with Cancer” with the primary aim of raising awareness of childhood cancer and funds for the organisation.</p><p><bold>Design/Methods</bold>: The “Have a Heart for Children with Cancer” campaign is linked to ICCD on the 15<sup>th</sup> February, In 2015 CHOC identified the need to formalize and give structure to the campaign. The campaign went blue to align with the corporate identity of the organisation and merchandise was developed with the “heart” theme. A round plastic pin that could be worn on the days leading up to and on the 15<sup>th</sup> February was designed, together with a chocolate to fit the Valentine's day theme. Both items were branded with the “Have a Heart Children with Cancer” slogan. The campaign encourages people “go blue” on the day and wear their badges and pins – all in support of childhood cancer and CHOC. Linked to this was a national media, social media and advertising campaign, including the lighting up of Table Mountain in Cape Town and a National Monument in Pretoria in the blue colour theme.</p><p><bold>Results</bold>: There has been an increase in the number of people being made aware of CHOC and childhood cancer. This is evident in the number of media articles/interviews, the number of participants aligning themselves to the campaign and the increase in sales of “Have a Heart for Children with Cancer” merchandise.</p><p><bold>Conclusions</bold>: The “Have a Heart for Children with Cancer” campaign is an effective awareness and fundraising campaign that has seen increased support for both CHOC and childhood cancer.</p></sec><sec id="pbc26772-sec-1730"><label>O-139</label><title>Children Raising Funds for Children: Implementing an Effective Fundraising Campaign in Schools in Gauteng, South Africa</title><p><underline underline-style="single">L. Moore</underline><sup>1</sup></p><p><italic><sup>1</sup>CHOC Childhood Cancer Foundation SA, Gauteng South Region, Saxonwold, South Africa</italic></p><p><bold>Background/Objectives</bold>: It is important that non‐profit organisations leverage support from a wide variety of income sources. An effective way of doing this is implementing a holistic school giving programme that is mutually beneficial to both the organisation and the school. There is increased pressure on children today to be effective and contributing citizens of society. The opportunities for charities to get maximum benefit from this social movement are enormous and CHOC has been extremely successful in leveraging off these opportunities in its fundraising efforts.</p><p><bold>Design/Methods</bold>: This initiative is broken into four key sections: monetary activities, community service opportunities, social responsibility clubs and collections of in‐kind donations. Key activities promoted in schools include: civvies days, where children pay a donation to wear clothing of their choice to school (often linked to national/international awareness campaigns related to childhood cancer); collection of items that are needed to implement core programmes; opportunities for social responsibility clubs to engage with CHOC at its operational sites, assisting in various activities such as painting, cleaning, preparing meals and administration tasks and; providing opportunities for individual learners to gain both passive and active community hours through assisting with campaigns, events and fundraising initiatives.</p><p><bold>Results</bold>: There has been a steady increase in the number of schools and learners getting involved in CHOC initiatives. Monetary income has increased and currently accounts for 11% of overall income received. There has been over a 100% increase in the amount of in‐kind donations received which has a huge impact on reducing expenditure.</p><p><bold>Conclusions</bold>: A well planned and implemented schools fundraising campaign will see steady growth over a period of time and can comprise a significant portion of an organisations income. It opens opportunities to gain access to other income sources whilst assisting in shaping future leaders who will become active members of society contributing to social change.</p></sec><sec id="pbc26772-sec-1740"><label>O-140</label><title>Creating and Developing Games Throughout Interdisciplinarity and Patient Participation</title><p><underline underline-style="single">S. Mozzilli</underline><sup>1</sup>, E. Sassi<sup>2</sup>, L. Rossi<sup>3</sup>, V. Sonaglio<sup>4</sup>, F. Francisco<sup>4</sup>, A. Duarte<sup>5</sup>, L. Panzoldo<sup>4</sup>, G. Yabu<sup>2</sup>, D. Costa<sup>6</sup>, S. Sredni<sup>7</sup></p><p><italic><sup>1</sup>Instituto Beaba, Direction, Sao Paulo, Brazil; <sup>2</sup>Instituto Beaba, Creative, São Paulo, Brazil; <sup>3</sup>Mukutu Game Studio, Development, Santos, Brazil; <sup>4</sup>A.C. Camargo Cancer Center, Pediatric Oncology, São Paulo, Brazil; <sup>5</sup>Universidade de Brasília, Pediatric Oncology, Brasília, Brazil; <sup>6</sup>Mukutu Game Design, Development, Santos, Brazil; <sup>7</sup>Children's Memor Rsrch Ctr, Pediatric Oncology, Chicago, USA</italic></p><p><bold>Background/Objectives</bold>: In an increasingly technological world, digital information about childhood cancer that is easily accessible to pediatric patients, their families and healthcare providers is still missing.</p><p>In this scenario, we decided to bring all stakeholders – patients, caregivers, healthcare professionals, creatives and entrepreneurs together to create an application for tablet and mobile devices that would help children demystify cancer and its treatment.</p><p><bold>Design/Methods</bold>: 1 ‐ <bold>Interdisciplinarity</bold>: which involves the combination of two or more academic disciplines into one activity;</p><p>2 ‐ <bold>Design Thinking</bold>: a human centered methodology for a rapid ideation with the ability to visualize and adapt the results in near real time;</p><p>3 ‐ <bold>Agile UX</bold>: a methodology which integrates the user experience design and developer team;</p><p>4 ‐ <bold>Patient Centered Design</bold>;</p><p>5 ‐ <bold>Project Management Platforms</bold>;</p><p>6 ‐ <bold>Collaboration</bold> and <bold>Communication Tools</bold>.</p><p><bold>Results</bold>: 1 ‐ Development of an application with 20 minigames for iOS and Android platforms, in a language that is easily accessible to children with an attractive an colorful interface where the child can identify him/herself with a custom designed character that guides them through different steps of the treatment. The initiative was highlighted in the AppStore and resulted in almost 4 million views.</p><p>2 ‐ Acquisition and expansion of interdisciplinarity for all stakeholders.</p><p>3 ‐ And most importantly, development of empathy and compassion for our patients.</p><p><bold>Conclusions</bold>: The interdisciplinarity and the effective participation of all the stakeholders in the project, allowed an integrated access to information, facilitating the understanding, identification, codification and availability of information that resulted in generation of easily accessible knowledge to our targeted population.</p><p>The greatest transformation was not only in the technological advance itself, but in our new way to associate knowledge with human factors in order to educate, empower and improve the quality of life of children fighting cancer. <italic>www.beaba.org/games</italic></p></sec><sec id="pbc26772-sec-1750"><label>O-141</label><title>A Childhood Cancer Parent's Experience with CBD (Cannabidiol) HEMP Oil as a Substitute for Pain Relief and Anxiety</title><p><underline underline-style="single">D. Mujagic‐Cammett</underline><sup>1</sup></p><p><italic><sup>1</sup>Parent, n/a, Bethesda, USA</italic></p><p><bold>Background/Objectives</bold>: The objective of this presentation is to inform and empower the parents of childhood cancer patients of pain remedy and anxiety alternatives and to raise awareness among oncologists and researchers of the potential such natural alternatives could provide to patients who do not respond positively to conventional medicine. The presenter will share her personal experience introducing CBD hemp oil as a substitute for pain treatment and anxiety during her daughter Sabrina's treatment for Neuroblastoma.</p><p>Mrs. Mujagic‐Cammett is the mother of a Neuroblastoma patient, Sabrina who battled this disease on and off for nine years before passing in October 2016 at the age of 12.</p><p><bold>Design/Methods</bold>: Mrs. Mujagic‐Cammett will present her experience as a case study of the success she had introducing cannabidiol hemp oil to combat Sabrina's pain and anxiety in order to inform parents and to spark the interest of doctors and researchers to explore the potential benefits of substituting hemp oil or other naturally occurring substances for opioids to address pain and anxiety during inpatient procedures.</p><p><bold>Results</bold>: While treating Sabrina both at home and in the hospital, Mrs. Mujagic‐Cammett confirmed that utilizing a natural product could produce an equivalent response versus a pharmaceutical in Sabrina's case. During her treatment, Sabrina did not exhibit nor express discomfort while provided with CBD to manage pain as her decease progressed.</p><p><bold>Conclusions</bold>: Mrs. Mujagic‐Cammett believes such options should be added to those presented to parents as an alternative to providing pain relief and reducing anxiety for their child during treatment. Also, that more studies should be conducted to determine the relative effectiveness of CBD hemp oil or other naturally occurring medicines as another choice for parents and doctors.</p></sec><sec id="pbc26772-sec-1760"><label>O-142</label><title>Continuity of Oncology Care for Central American Migrant Children in the US</title><p><underline underline-style="single">M. Orjuela‐Grimm</underline><sup>1</sup>, L. Fu<sup>2</sup>, R. Martinez<sup>3</sup>, L. Onesi<sup>4</sup>, C. Batista<sup>5</sup>, J. Levine<sup>4</sup>, M. Barnett<sup>6</sup>, C. Urey<sup>7</sup>, B. Mejia<sup>8</sup>, Y. Gonzalez Cerdeira<sup>8</sup>, S. Blanco<sup>5</sup>, J.P. Medina‐Paez<sup>9</sup>, P. Satwani<sup>10</sup></p><p><italic><sup>1</sup>Columbia University Medical Center, Pediatrics‐Oncology & Epidemiology, New York City NYC, USA; <sup>2</sup>Hospital Escuela, Pediatric Oncology, Tegucigalpa, Honduras; <sup>3</sup>Hospital Mario Catarino Rivas, Pediatric Oncology, San Pedro Sula, Honduras; <sup>4</sup>Columbia University Medical Center, Pediatrics Oncology, New York CIty, USA; <sup>5</sup>Columbia University Medical Center, Pediatrics Oncology & Social Work, New York City, USA; <sup>6</sup>Columbia University Medical Center, Pediatrics Oncology & Psychology, New York City, USA; <sup>7</sup>Coalicion Mexicana/ Universidad Centro Americana, Red Jesuita de Servicio a Migrantes en NY, Managua, Nicaragua; <sup>8</sup>ERIC‐SJ, Investigación y Derechos Humanos, Progreso, Honduras; <sup>9</sup>Columbia University Medical Center, Epidemiology, New York City, USA; <sup>10</sup>Columbia University Medical Center, Pediatrics BMT, New York City, USA</italic></p><p><bold>Background/Objectives</bold>: During the past 4 years the numbers of Central American children migrating overland to the US has reached unprecedented levels, with > 93,000 migrating during 2016. Some children migrate while undergoing chemotherapy, interrupting intended care. We report a collaboration between pediatric oncology teams in sending and receiving countries permitting continuity of care despite complex legal circumstances.</p><p><bold>Design/Methods</bold>: A 4 year old girl undergoing maintenance therapy for B cell precursor standard risk ALL in Honduras, abandoned therapy, traveling overland to the US. After resettling in NYC she ran out of medications, developed fevers and was admitted in relapse at Columbia. After electronic discussion between NY and Honduran oncologists, she began relapse therapy, quickly achieving remission. Pre‐BMT unrelated donor search yielded only 9/10 HLA matches. Sibling testing revealed a 10/10 HLA match in one 9 year old brother living in a remote Honduran village. Because of the nature of the family's migration to the US, he was ineligible for a tourist visa, and stem cells from Honduras could not enter the US. The NY oncologists working closely with a Jesuit human rights organization, a NY community organization, Honduran oncologists, and a volunteer immigration lawyer petitioned for the boy's US entry.</p><p><bold>Results</bold>: The 10/10 HLA‐matched 9 year old was granted Humanitarian Parole by US Homeland Security within 3 months of HLA testing. Marrow donor assent and preparation for flying was done with video calling. The boy traveled 4 days later. BMT proceeded without complications. The girl was discharged on day +28. The donor returned to Honduras complying with his Parole. After day +180 the girl's family chose to return to Honduras where she is again followed by her Honduran oncologist, now in close electronic communication with the NY team.</p><p><bold>Conclusions</bold>: We propose technology facilitated binational oncologic continuity of care as a model for treatment during migration.</p></sec><sec id="pbc26772-sec-1770"><label>O-143</label><title>UNITE2CURE ‐ Breaking the 18 Year Age‐Limit Dogma</title><p><underline underline-style="single">N. Scobie</underline><sup>1</sup>, C. Copland<sup>2</sup></p><p><italic><sup>1</sup>Unite2Cure, Zoé4life, Sullens, Switzerland; <sup>2</sup>Unite2Cure, Parent representative, Sullens, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Unite2Cure is partnering with Accelerate in order to remove the “18 year age‐of entry dogma” within clinical trial designs. Ages of entry to adult trials should be flexible and based on considerations of biology and safety. Trials specifically for teenagers and young adults are less common even than for children.Adolescents tend to be grouped with children and thus are excluded from adult trials. We contend that inclusion in trials should be based on medical need rather than arbitrary age limits.</p><p><bold>Design/Methods</bold>:</p><p>1. The age of clinical trial entry should be reduced to 12 years in adult early phase cancer drug studies unless there are well‐justifiable medical/scientific reasons not to do so.</p><p>2. No upper or lower age limit criteria for Phase‐II and III trials– when AYA diseases present in both paediatric and adult populations– and have the same biology.</p><p>3. Trials enrolling adolescents should always be conducted in an age‐appropriate setting</p><p>4. Adolescents should still be included in paediatric Phase‐I, II and III trials– where relevant, to maximise therapeutic opportunities.</p><p>5. Young adults should be permitted to participate in paediatric Phase II‐III trials– especially for ‘paediatric’ type cancer.</p><p>6. The indication proposed in a regulatory marketing authorisation application for of a given cancer drug should include adolescents at the same time as the adult authorisation.</p><p><bold>Results</bold>: 1. Improved access of adolescents to new cancer drugs</p><p>2. Better understanding of biology and response of the MoA (Explore differences, if they exist, between adolescents and adults)</p><p>3. Positive influence in paediatric drug development (Early signs of activity in a paediatric disease present in adolescents)</p><p>4. Positive influence in adult drug development (Increased likelihood of achieving proof of concept/proof of principle for drugs with brand new mechanisms of action)</p><p><bold>Conclusions</bold>: Is it safe to recruit teenagers in adult early drug trials? YES, either in adult Phase 1 and Phase 2 trials</p></sec><sec id="pbc26772-sec-1780"><label>O-144</label><title>The Promote, Protect and Support Malnutrition (PPSN) Model for Delivering Nutritional Support to Childhood Cancer Patients in India</title><p><underline underline-style="single">A. Sharma</underline><sup>1</sup>, P. Bagai<sup>1</sup>, M. Khurana<sup>1</sup>, N. Joshi<sup>1</sup></p><p><italic><sup>1</sup>Cankids...Kidscan, Treatment Support Program, NEW DELHI, India</italic></p><p><bold>Background/Objectives</bold>: A survey of nutritional practices for children with cancer in India in 2014 established that there is a deficiency of provision of nutritional services and variability in existing practices of nutritional assessment and intervention. To address the problem, Cankids, a not for profit childhood cancer organisation, developed the PPSN model.</p><p><bold>Design/Methods</bold>: Using the SIOP PODC algorithm as a starting point for nutritional assessment and intervention, the PPSN model provides the necessary resources. The resources include
<list list-type="order" id="pbc26772-list-0011"><list-item><p>Dietitians and other staff.The dietician managed the nutrition status of the child through prospective assessment, 1 on 1 counselling and risk stratification.The social support team and a parent support group (PSG) worker work with the dietician to deliver the program.</p></list-item><list-item><p>Information education communication materials on nutrition and hygiene</p></list-item><list-item><p>Nutritional supplements,Desired home based and industrial supplementation are provided.</p></list-item><list-item><p>In addition, advocacy and stakeholder engagement is promoted through a national group called POSHAN.</p></list-item></list></p><p><bold>Results</bold>:
<list list-type="bullet" id="pbc26772-list-0012"><list-item><p>·6 dieticians were provided and supported in 11 cancer centers in India in the last 12 months.40 PSG workers were trained for nutritional assessment.</p></list-item><list-item><p>·144 sessions for awareness generation on nutrition and 288 session on hygiene maintenance were conducted.1 recipe exhibition was organised.15 Focus group discussions were conducted and equipment for anthropometric measurements were provided. A nutrition management guidebook for families in 3 languages and a snake and ladder game for child education was developed..</p></list-item><list-item><p>Feeding program was provided to 218 beneficiaries per month in 4 centers Supplementation support was provided to 400 patients based on risk stratification.</p></list-item><list-item><p>·488 parents and children participated in the nutrition awareness campaign across India. Nutrition week was celebrated for awareness generation at community level.</p></list-item></list></p><p><bold>Conclusions</bold>: The PPSN model is feasible to deliver nutritional support in resource‐limited settings. Studies to measure impact are being planned.</p></sec><sec id="pbc26772-sec-1790"><label>O-145</label><title>Enhancing Childhood Cancer Awareness through Road Show to the Urban Places in Indonesia</title><p><underline underline-style="single">A.U. Sudjoko</underline><sup>1</sup></p><p><italic><sup>1</sup>Yayasan Onkologi Anak Indonesia, Secretary, Jakarta Barat, Indonesia</italic></p><p><bold>Background/Objectives</bold>: To increase public awareness of children with cancer, the importance of early detection and subsequent care is the mission of the Indonesian Childhood Cancer Foundation or Yayasan Onkologi Anak Indonesia (YOAI). Indonesia is an archipelago of over 17.000 islands straddling the equator. Many are sparsely inhabited, some not at all. However, with a population over 250.000.000 there are very few oncologists or specialists for children with cancer and those are not found outside urban areas. Many children with cancer must travel far to find treatment in Jakarta, the capital of Indonesia. YOAI has taken the initiative to offer outreach by promoting seminars for laymen and professionals in our far flung communities with our Road Show.</p><p><bold>Design/Methods</bold>: Our road show gives informative presentations to public on awareness of children with cancer by cooperating with community health centers, schools and other relevant organizations. Scientific seminars are offered to doctors, nurses and students from academic medical institutions. We cooperate with hospitals and universities where the presentations are held.</p><p><bold>Results</bold>: Our Road Shows have helped raised awareness of children with cancer and their needs in regions outside urban areas and how to assist them in their forward needs. We also encourage doctors to become specialists in the field of childhood oncology.</p><p><bold>Conclusions</bold>: YOAI has been doing the Road Show for the past two years not only at the hospital in Jakarta but also in other cities such as Bandung, Jogyakarta, Solo, Surabaya, Padang, Medan, Garut and Cirebon. Our goal is to move on until we covered the whole provinces of Indonesia</p></sec><sec id="pbc26772-sec-1800"><label>O-146</label><title>Using Thunderclap to Raise Awareness about #Kidscancerpain Over Social Media</title><p><underline underline-style="single">P. Tutelman</underline><sup>1</sup>, C. Chambers<sup>1</sup>, J. Stinson<sup>2</sup>, J. Parker<sup>1</sup>, E.K. Drake<sup>9</sup>, M. Barwick<sup>2</sup>, F. Campbell<sup>3</sup>, C. Fernandez<sup>4</sup>, K. Irwin<sup>5</sup>, L. Jibb<sup>6</sup>, P. Nathan<sup>7</sup>, H. Witteman<sup>8</sup></p><p><italic><sup>1</sup>IWK Health Centre, Centre for Pediatric Pain Research, Halifax, Canada; <sup>2</sup>The Hospital for Sick Children, Child Health Evaluative Sciences, Toronto, Canada; <sup>3</sup>The Hospital for Sick Children, Anesthesia and Pain Medicine, Toronto, Canada; <sup>4</sup>IWK Health Centre, Hematology‐Oncology, Halifax, Canada; <sup>5</sup>Multimed Inc., Cancer Knowledge Network, Toronto, Canada; <sup>6</sup>University of Ottawa, Nursing, Ottawa, Canada; <sup>7</sup>The Hospital for Sick Children, Haematology/Oncology, Toronto, Canada; <sup>8</sup>Université Laval, Family & Emergency Medicine, Quebec City, Canada; <sup>9</sup>Independent Healthcare Consultant, Halifax, Canada</italic></p><p><bold>Background/Objectives</bold>: Social media is increasingly being used to disseminate health information, connect experts with patients, and raise awareness about medical conditions. Funded by the Canadian Cancer Society, #KidsCancerPain is a social media campaign in partnership with the Cancer Knowledge Network aimed at delivering evidence‐based information on pediatric cancer pain to parents. This study evaluated the use of Thunderclap, a crowdspeaking social media platform, to raise awareness about #KidsCancerPain.</p><p><bold>Design/Methods</bold>: A Thunderclap campaign introducing #KidsCancerPain was created. A Thunderclap is an organized social media event where supporters share a similar message via Twitter and/or Facebook on the same day at the same time. Supporters were invited via email/newsletter blasts, online promotion, and targeted invitations. To join, supporters authorized Thunderclap to send a pre‐programmed message (“<italic>No parent wants to see their child in pain. Help us in “Making Cancer Less Painful for Kids”. #KidsCancerPain</italic>”) via their Twitter/Facebook account on the set date/time.</p><p><bold>Results</bold>: Between July 13‐27 2016, 366 unique social media accounts (Twitter, 61.5%; Facebook, 38.5%) joined the #KidsCancerPain Thunderclap, held July 27, 2016, 9pm ET. This resulted in a social reach of 1,672,727 people, making it the largest childhood cancer Thunderclap to date. Supporters were individuals (84.7%) and organizations (15.3%) and included cancer, health, research/academic, and pain groups (e.g., Canadian Cancer Society, WEGO Health etc.). The majority of supporters were from Canada (60.1%), followed by the United States (24.6%), Australia (8.2%) and the United Kingdom (3.3%). During the Thunderclap, #KidsCancerPain trended on Twitter in Canada (i.e., became a viral topic). Most supporters used the pre‐programmed message (55.7%) and 11.7% modified the message. The content of the posts of 35.4% of supporters were unavailable due to privacy settings on accounts.</p><p><bold>Conclusions</bold>: Thunderclap was a novel and rapid way to build widespread awareness about pediatric cancer pain and the #KidsCancerPain campaign. Challenges and opportunities will be discussed.</p></sec><sec id="pbc26772-sec-1810"><label>O-147</label><title>Developing and Publishing a Guideline Titled “Siblings of Childhood Cancer Patients ‐Things You Need to Have in Mind When You are with Them”</title><p><underline underline-style="single">K. Yamashita</underline><sup>1</sup>, M. Ozawa<sup>2</sup></p><p><italic><sup>1</sup>Children's Cancer Association of Japan, Chairman, Minato‐ku, Japan; <sup>2</sup>St. Luke's International Hospital, Pediatrics, Cyuo‐ku‐ Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: Development and publication of various booklets and guidelines to serve the needs of patients and families is one of very important tasks of Children's Cancer Association of Japan known as CCAJ. Since 2000, four guidelines, i.e. “Support to patients and families”, “Educations of patients”, “Supporting survivors” and “Palliative care” were published. In 2013, a plan was started for developing the fifth guideline focusing “Siblings”, whose difficulties are well known but no enough attention has been given. The guideline was concluded in Dec. 2016 and published in Feb. 2017.</p><p><bold>Design/Methods</bold>: A working group was organized of which members are, a sibling of childhood cancer patient, a mother, a farther, a survivor, a pediatrician, a nurse, a social worker, a primary school teacher and a nursery teacher. Started in 2013 in total 13 meetings of WG were held and enthusiastic discussions were made until the conclusion in Dec. 2016. In addition, open discussions were made in the annual open symposium held in conjunction with annual congress of JSPHO and JSPON from 2013 through 2016, and reflected in the final draft.</p><p><bold>Results</bold>: The guideline titled “Siblings of childhood cancer patients –Things you need to have in main when you are with them” was published in Feb. 2017. The guideline is written in the manner addressing to those who care about siblings describing various situations siblings face during and after the treatment of patients. The last section is designed to address to siblings with a key message “you are not alone”. A card for the siblings to write and exchange messages is also enclosed as an attachment.</p><p><bold>Conclusions</bold>: The guideline is expected to be of helps to deepen understandings between siblings of childhood cancer patients and those who surround them including parents, and also to serve as a trigger for effective dialogue with siblings.</p></sec></sec><sec id="pbc26772-sec-1820"><title>Session 1: Neuroblastoma & Fertility</title><sec id="pbc26772-sec-1830"><label>O-148</label><title>Analysis of Surgery for Neuroblastoma in the Netherlands 1998 – 2014</title><p><underline underline-style="single">M. Jans</underline><sup>1</sup>, G. Tytgat<sup>2</sup>, S. Zwaveling<sup>3,4</sup>, C. van de Ven<sup>1,5</sup>, S. Terwisscha van Scheltinga<sup>1,5</sup>, R. van Baren<sup>6</sup>, M. Fiocco<sup>7</sup>, H. Heij<sup>1</sup>, M. Wijnen<sup>1,8</sup></p><p><italic><sup>1</sup>Prinsess Máxima Center, Pediatric Surgery, Utrecht, The Netherlands; <sup>2</sup>Prinsess Máxima Center, Pediatric Oncology, Utrecht, The Netherlands; <sup>3</sup>Academic Medical Center, Pediatric Surgery, Amsterdam, The Netherlands; <sup>4</sup>Vrije Universiteit Medical Center, Pediatric Surgery, Amsterdam, The Netherlands; <sup>5</sup>Erasmus Medical Center, Pediatric Surgery, Rotterdam, The Netherlands; <sup>6</sup>University Medical Center, Pediatric Surgery, Groningen, The Netherlands; <sup>7</sup>Leiden University, Mathematical Institute, Leiden, The Netherlands; <sup>8</sup>Radboud University Medical Center, Pediatric Surgery, Nijmegen, The Netherlands</italic></p><p><bold>Background/Objectives</bold>:
<list list-type="order" id="pbc26772-list-0013"><list-item><p>Establishing surgery related complications, mortality and long‐term sequelae in a large cohort of patients with neuroblastoma (NBL).</p></list-item><list-item><p>Evaluating impact of extent of resection on survival and local recurrence in high‐risk patients.</p></list-item></list></p><p><bold>Design/Methods</bold>: This retrospective multi‐center cohort study included all patients who underwent primary tumor resection for NBL in The Netherlands between 1998 and 2014, before the start of centralized care. Surgery related complications, mortality and long‐term sequelae were documented. For all high‐risk patients, five‐year overall survival (OS), five‐year event free survival (EFS), five‐year cumulative incidence of relapse (CIR) and total number of local recurrence (NLR) were estimated for complete, >95% and ≤ 95% resection.</p><p><bold>Results</bold>:
<list list-type="order" id="pbc26772-list-0014"><list-item><p>Surgery was performed in 301 children. Peroperative complication rate was 42%. Short‐term postoperative complication rate was 43%. PICU support for surgical complications was necessary in 5%. Secondary surgery was performed in 8%. Five children (2%) died of surgery related causes. Long‐term complications occurred in 9% of children, long‐term sequelae in 6%.</p></list-item><list-item><p>A total of 170 children (57%) were stratified as high‐risk patients. For complete resection, EFS was 25% (15% ‐ 35%), OS was 26% (15%‐36%), CIR was 72% (61% ‐ 82%), NLR was 15 (18%). For >95% resection, EFS was 24% (13% ‐ 34%), OS was 27% (15% ‐ 39%), CIR was 62.7% (50% ‐ 76%), NLR was 8 (14%). For ≤ 95% resection, EFS was 33% (16% ‐ 50%), OS was 45% (29% ‐ 64%), CIR was 53% (35% – 72%), NLR was 6 (20%).</p></list-item></list></p><p><bold>Conclusions</bold>:
<list list-type="order" id="pbc26772-list-0015"><list-item><p>A large series of surgery related adverse events in children treated for Neuroblastoma is presented. Surgery for neuroblastoma is associated with significant morbidity and mortality.</p></list-item><list-item><p>For high‐risk patients, no significant difference was found in overall survival, event free survival, cumulative incidence of relapse or total number of local recurrence for complete, >95% or ≤ 95% resection.</p></list-item></list></p></sec><sec id="pbc26772-sec-1840"><label>O-149</label><title>Surgical Complications of Kidney and Urinary Tract in Abdominal Neuroblastoma‐ A Retrospective Single‐Institutional Review of 521 Cases in 5 Years</title><p><underline underline-style="single">H. Wang</underline><sup>1</sup></p><p><italic><sup>1</sup>Beijing Children's Hospital‐ Capital Medical University, Surgical Oncology, BEIJING, China</italic></p><p><bold>Background/Objectives</bold>: Gross total resection(GTR) is survival‐beneficial even for advanced neuroblastoma. Although it is still controversial and may be relevant to higher rate of complications, GTR has been the goal of surgery for most cases. So it is important to know better about the possible complication, particularly the injury of kidney and urinary tract which is the most common in abdominal neuroblastoma.</p><p><bold>Design/Methods</bold>: 521 consecutive patients who underwent primary tumor resection enrolled hospitalization in our hospital from January 2011 to January 2015. By reviewing the medical records and follow‐up data, 66 cases was identified to have kidney and urinary tract injury.</p><p><bold>Results</bold>:
<list list-type="order" id="pbc26772-list-0016"><list-item><p>Of the 66 cases, patients aged from 6 months to 8 years. The INSS staging were 3 and 4. All the patients accepted preoperative chemotherapy.</p></list-item><list-item><p>10 cases underwent intraoperative nephrectomy and semi‐nephrectomy, 3 due to renal vascular encasement and 7 due to invasion to parenchyma. Nephrectomy were planed before operation.</p></list-item><list-item><p>21 cases were found in the following‐up to have ischemia and kidney atrophy. 7 of the 21 cases showed renal atrophy in three months postoperation, and the other 14 cases showed different amount of ischemia in the affected kidney.</p></list-item><list-item><p>27 cases showed hydronephrosis and dilation of ureter with normal renal function.</p></list-item><list-item><p>9 cases were found to have some minimal abnormalities, 2 with dislocation of kidney, 2 with renal caculus and calc deposition, 5 with outline of kidney undistinguished by adhesion.</p></list-item><list-item><p>2 cases underwent renal arterial reconstrution intraoperately because of severe injury of the artery and ischemia of the kiney. One showed normal blood supply to the kidney and the other with renal atrophy in the following‐up.</p></list-item></list></p><p><bold>Conclusions</bold>:
<list list-type="order" id="pbc26772-list-0017"><list-item><p>Surgical complications of kidney and urinary tract are common.</p></list-item><list-item><p>The continual improvement of manipulation of surgery is important.</p></list-item><list-item><p>Imaging indication helps to tailor the surgical strategy for neuroblastoma.</p></list-item></list></p></sec><sec id="pbc26772-sec-1850"><label>O-150</label><title>Our Experience with Neuroblastoma in Children ‐ Outcomes Based on Risk Stratification</title><p><underline underline-style="single">S.</underline><underline underline-style="single">Mishra</underline><sup>1</sup>, S. Jain<sup>2</sup>, G. Kapoor<sup>3</sup></p><p><italic><sup>1</sup>Rajiv Gandhi Cancer Institute and Research Centre, Pediatric Surgical Oncology, Delhi, India; <sup>2</sup>Rajiv Gandhi Cancer Institute and Research Centre, Pediatric Hematology Oncology, Delhi, India; <sup>3</sup>Rajiv Gandhi Cancer Institute and Research Centre, Pediatric Hematology and Oncology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: With few exceptions, the outcome of Neuroblastoma (NB) is dismal, especially in developing countries. The aim of this study was to analyze the overall survival (OS) and disease free survival (DFS) in Low, Intermediate and High risk groups of NB managed in our Institute in the last 7 years.</p><p><bold>Design/Methods</bold>: Retrospective analysis of hospital records of patients with NB was done from January 2009 to Dec 2016. In 57 patients with a median age of 3 yrs and M:F ratio of 1.19, primary sites were adrenal (n=39), paraspinal (n=5), retroperitoneal (n=3), mediastinal (n=3), olfactory (n=2), cervical (n=1) and unknown (n=4). Twenty‐four came only for opinion and and 7 were lost to follow up after the 1<sup>st</sup> admission (including 3 patients who came only for surgery or radiation). Remaining 26 were further studied.</p><p><bold>Results</bold>: INRG risk stratification showed Low risk (n=11), Intermediate risk (n=3) and High risk (n=12). IDRF was present in 7 patients. Two neonates with Stage IVS succumbed early. The remaining 12 Low and Intermediate risk patients did well with a combination of chemotherapy and surgery or close observation alone. Surgery was done in 21/26 patients. Spontaneous regression was seen in 3/11 low risk patients. Of the high risk group 9/13 underwent autologous stem cell transplant and differentiating therapy of which 4 are alive and well. Anti GD‐2 therapy was not available. The 2‐yr‐DFS in Low intermediate and high risk group patients was 80%, 100% and 40% respectively. The 4‐yr‐DFS dropped to 20% in the high risk group as 3 patients did not have long term follow up.</p><p><bold>Conclusions</bold>: Despite tremendous challenges in resource challenged nations, treatment of NB is feasible in high volume Pediatric Oncology centres with facilities for autologous stem cell transplant. The results are comparable to that published in literature.</p></sec><sec id="pbc26772-sec-1860"><label>O-151</label><title>Future Fertility: Giving Hope to Young People</title><p><underline underline-style="single">C. Elbourne</underline><sup>1</sup>, R. Parry<sup>2</sup>, J. Davies<sup>3</sup>, S. Lane<sup>4</sup>, K. Lakhoo<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital‐ The John Rafcliffe‐ Oxford, Department of Paediatric Surgery, Oxford, United Kingdom; <sup>2</sup>The Children's Hospital‐ The John Radcliffe‐ Oxford, Department of Paediatric Surgery, Oxford, United Kingdom; <sup>3</sup>The Children's Hospital‐ The John Rafcliffe‐ Oxford, Oxford Tissue Bank, Oxford, United Kingdom; <sup>4</sup>The Children's Hospital‐ The John Rafcliffe‐ Oxford, Department of Paediatric Oncology, Oxford, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Ten young people under the age of twenty‐five are diagnosed with cancer every day. Eight will be cured but one will become infertile as a result of their treatment. Cryopreservation of gonadal tissue to preserve fertility and endogenous hormone production has been extremely successful and is available to increasing numbers of children. We aim to share our experience of this ground‐breaking service.</p><p><bold>Design/Methods</bold>: Initially developed to provide women and girls with cancer the ability to preserve ovarian tissue while undergoing intensive treatment, the service has rapidly expanded incorporating testicular cryopreservation for pre‐pubertal boys and inclusion of children with non‐malignant haematological conditions undergoing curative bone marrow transplantation.</p><p>Referrals are received from across England and Wales and assessed by the specialist multidisciplinary team. Children and families receive pre‐operative counselling from a specialist paediatric consultant and surgical team. Where possible the retrieval of gonadal tissue, via testicular biopsy or laparoscopic unilateral oophorectomy, is performed concomitantly with other required procedures. Tissue is received directly from theatre and processed by the onsite tissue bank team. For most children, this is a day case procedure.</p><p><bold>Results</bold>: Since its beginning in 2013, 84 children have undergone gonadal tissue retrieval for cryopreservation. Testicular biopsy has been performed for 15 pre‐pubertal boys. Unilateral laparoscopic oophorectomy has been performed for 69 girls ages 1‐17. Of these, 28 have undergone concurrent procedures including central venous line insertion, lymph node biopsy and bone marrow aspiration. 53 were girls with cancer and 16 had non‐malignant haematological disease including 8 girls with sickle cell anaemia and 4 with thalassaemia.</p><p>The service has grown tenfold between 2013‐2016, and continues to expand.</p><p><bold>Conclusions</bold>: Laparoscopic oophorectomy and testicular biopsy facilitating gonadal tissue cryopreservation is a safe and effective service providing hope for children and their families undergoing treatment for cancer and non‐malignant haematological disease.</p></sec><sec id="pbc26772-sec-1870"><label>O-152</label><title>Laparoscopic Ovarian Cortical Strip Harvesting for Cryopreservation</title><p><underline underline-style="single">D. Baker</underline><sup>1</sup>, C. Clark<sup>1</sup>, F. Munro<sup>1</sup>, P. Hammond<sup>1</sup>, H. Wallace<sup>2</sup>, R. Anderson<sup>3</sup></p><p><italic><sup>1</sup>Royal Hospital for Sick Children, Paediatric Surgery, Edinburgh, United Kingdom; <sup>2</sup>Royal Hospital for Sick Children, Paediatric Oncology, Edinburgh, United Kingdom; <sup>3</sup>Royal Infirmary of Edinburgh, Reproductive Medicine, Edinburgh, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Advances in the treatment of childhood cancers show ever improving survival rates. The treatment of childhood malignancy can however lead to premature gonadal failure. We present our centre's experience of using cortical strip harvesting for ovarian tissue cryopreservation while retaining the remainder of the ovary in situ.</p><p><bold>Design/Methods</bold>: In this paper we describe the surgical technique and perioperative care regimen. We detail the demographic data for 24 cases over a ten year period and review complications. We discuss outcomes, and the method of cryopreservation used for the ovarian tissue.</p><p><bold>Results</bold>: Thirty patients were identified between 2006 and 2016 who have undergone laparoscopic ovarian cortical strip harvesting, of which follow‐up data was available for 24. Median age at operation was 13, range 4‐16. There was no significant bleeding, adhesional obstruction, or injury to other organs reported. No cases were converted to open procedures or returned to theatre. Early postoperative pain has been found to be a feature, thought to be secondary to gonadal trauma. Five patients have since died as a result of their underlying diagnosis. Three have menstruation documented at follow‐up. To date, two patients are known to have fallen pregnant naturally since their surgery, and one of these pregnancies progressed to childbirth.</p><p><bold>Conclusions</bold>: Laparoscopic ovary‐sparing ovarian cortical strip harvesting is a safe procedure, although it should only be performed as part of an integrated service with fertility and laboratory specialists with suitable accreditation and oversight. It offers the possibility of conceiving naturally or via reimplantation to patients who are at risk of early infertility as a result of their treatment.</p></sec></sec><sec id="pbc26772-sec-1880"><title>Session 2: Renal Tumours & Lung Metastasis</title><sec id="pbc26772-sec-1890"><label>O-153</label><title>Surgery of Bilateral Renal Tumors in Children Involving the Renal Hilus</title><p><underline underline-style="single">S.W. Warmann</underline><sup>1</sup>, A. Schmidt<sup>1</sup>, M. Ebinger<sup>2</sup>, S. Juergen<sup>3</sup>, J. Fuchs<sup>1</sup></p><p><italic><sup>1</sup>University Children's Hospital, Pediatric Surgery and Pediatric Urology, Tuebingen, Germany; <sup>2</sup>University Children's Hospital, Pediatric Oncology, Tuebingen, Germany; <sup>3</sup>University Hospital, Diagnostic and Interventional Radiology, Tuebingen, Germany</italic></p><p><bold>Background/Objectives</bold>: Bilateral nephron‐sparing surgery (NSS) is the surgical approach of choice in bilateral renal tumors in children. However, centrally located tumors with involvement of the renal hilus represent a surgical challenge.</p><p><bold>Design/Methods</bold>: We evaluated all children with bilateral renal tumors involving he renal hilus operated on at our center, which serves as surgical reference center for pediatric renal tumors.</p><p><bold>Results</bold>: Fifteen children were evaluated (8 girls, 7 boys) with a median age of 32 months (13‐67). All children had undergone neoadjuvant chemotherapy. Median operating time was 359 minutes (90‐383). We performed bilateral NSS in 10 cases, unilateral NSS in 3 children with single kidneys after contralateral tumor nephrectomy elsewhere, and unilateral NSS with contralateral tumor nephrectomy in 2 children. The reasons for the two nephrectomies were loss of function after NSS prior to referral in one case and cava thrombosis plus extrarenal disease in the other case. In all but one of the patients undergoing bilateral surgery we performed a single stage approach. Median vascular exclusion time in patients with hilus involvement was 19 minutes (5‐45). 2 children required redo‐surgery for urinary leakage. Histology revealed intermediate risk in 8 patients, high risk in 4 patients and nephroblastomatosis in 3 patients. One child with high risk nephroblastoma (blastemal type with diffuse anaplasia, cava thrombus and extra‐renal disease) had a combined pulmonal and abdominal relapse and died 16 months after surgery. All other patients are alive without evidence of disease and with their organs functioning after a median follow‐up of 25 months (0‐118).</p><p><bold>Conclusions</bold>: Children with bilateral renal tumors should be treated and especially undergo surgery in centers with special expertise in this field. Under this condition, surgery of central bilateral renal tumors can be executed with a satisfactory surgical, functional, and oncological outcome.</p></sec><sec id="pbc26772-sec-1900"><label>O-154</label><title>Feasibility of Complete Resection of Residual Lung Nodules After Chemotherapy in Patients with Stage IV Favorable Histology Wilms Tumor</title><p><underline underline-style="single">P. Ehrlich</underline><sup>1</sup>, E. Smith<sup>2</sup>, G. Khanna<sup>3</sup>, K. Gow<sup>4</sup>, T. Hamilton<sup>5</sup>, S.E.N. Servaes<sup>6</sup>, D. Barnhart<sup>7</sup>, R. Glick<sup>8</sup>, R. Dasgupta<sup>9</sup>, E. Mullen<sup>10</sup>, J. Geller<sup>11</sup>, C. Fernandez<sup>12</sup>, J. Kalapurakal<sup>13</sup>, E. Gratias<sup>14</sup>, J. Dome<sup>15</sup>, D. Dix<sup>16</sup></p><p><italic><sup>1</sup>University of Michigan, Surgery, Ann Arbor, USA; <sup>2</sup>University of Michigan, radiology, Ann Arbor, USA; <sup>3</sup>Washington University at St Louis, Radiology, St Lous, USA; <sup>4</sup>University of Washington, Surgery, Seattle, USA; <sup>5</sup>Harvard University, Surgery, Boston, USA; <sup>6</sup>Childrens Hospital of Philadelphia, Radiology, Philadelphia, USA; <sup>7</sup>Primary Childrens Hopsital, Surgery, Salt Lake City, USA; <sup>8</sup>Cohen Childrens Hopsital, Surgery, Long island, USA; <sup>9</sup>Cincinnati Childrens Hospital, Surgery, Cincinnati, USA; <sup>10</sup>Dana Farber, Oncology, Boston, USA; <sup>11</sup>Cincinnati Childrens Hospital, Oncology, Cincinnati, USA; <sup>12</sup>IWK Childrens Hospital, Oncology, Halifax, Canada; <sup>13</sup>Northwestern, Radiation Oncology, Chicago, USA; <sup>14</sup>Childrens Oncology Group, Renal Tumors, Philadelpahia, USA; <sup>15</sup>Childrens National Medical Center, Onoclogy, Washington DC, USA; <sup>16</sup>University of British Columbia, Oncology, Vancouver, Canada</italic></p><p><bold>Background/Objectives</bold>: Children's Oncology Group (COG) study AREN0533 showed that patients whose pulmonary lesions had a complete response (CR) by 6 weeks with vincristine, dactinomycin, and doxorubicin can avoid pulmonary XRT and have outstanding overall survival. Patients who did not achieve CR received pulmonary XRT, but it is possible that some of these patients had benign lesions, necrotic Wilms tumor, or well‐differentiated Wilms tumor that may not require XRT. The purpose of this exploratory study was to examine the feasibility and extent of surgical resection for PR/SD patients enrolled on AREN0533.</p><p><bold>Design/Methods</bold>: Patients enrolled on COG AREN0533 with stage IV WT due to pulmonary metastasis, and had either PR/SD with less than 10 lesions after 6 weeks of chemotherapy were eligible. The initial and 6 week chest CT were reviewed by surgeons and radiologists to evaluate number, location and resectability of residual lesions. For this study resection was considered “feasible” if lesions were peripheral, required only a wedge resection and could be performed thorascopically. Resections that would require a total lobectomy were not considered feasible.</p><p><bold>Results</bold>: 302 patients enrolled and at 6‐weeks, 189 had either PR/SD. Of these 93(49%) had less than 10 lesions (14 SD and 79 PR). 83 of 93 patients has 1‐3 residual lesions. In 23/93(28%) surgery was considered not feasible. In 67/93 (72%) thorascopic surgery was deemed feasible(35% of total, 67/189). Extent of surgery included a single wedge resection in 20 patients; between 2‐3 wedge sections in a single lobe in 5 patients; between 2‐3 wedge resections in different lobes in a single lung in 24 patients. 18 would require 2‐5 wedge resections in both lungs</p><p><bold>Conclusions</bold>: Thorascopic resection of pulmonary noldues was considered “feasible” in 35% of PD/SD after 6 weeks of cheotherapy. Selected PR/SD patient's maybe good candidates for surgery and could avoid XRT.</p></sec><sec id="pbc26772-sec-1910"><label>O-155</label><title>Cross‐Sectional and Longitudinal Study of Renal Function after Nephron‐Sparing Surgery Versus Nephrectomy for Unilateral Renal Tumor in Children</title><p><underline underline-style="single">D. Cozzi</underline><sup>1</sup>, S. Ceccanti<sup>1</sup>, S. frediani<sup>1</sup>, I. Falconi<sup>1</sup>, A. Cervellone<sup>1</sup>, F. Cozzi<sup>1</sup></p><p><italic><sup>1</sup>Sapienza University of Rome, Pediatric Surgery Unit, Rome, Italy</italic></p><p><bold>Background/Objectives</bold>: Pre‐operative renal dysfunction in children with unilateral renal tumor (URT) may be a surrogate marker of low nephrons number endowment. Therefore, we included baseline renal function among the matching criteria used to compare the renal function outcome after nephron‐sparing surgery (NSS) versus nephrectomy in more balanced pair‐matched groups of children with URT.</p><p><bold>Design/Methods</bold>: We reviewed our prospectively maintained database of children with URT treated at our institution between 1992 and 2016. Thirteen patients who underwent NSS were matched with thirteen patients who underwent nephrectomy. Propensity scores included age at surgery,stage, age at follow‐up, sex, histologic type, pre‐operative estimated glomerular filtration rate (eGFR), and number of preoperative patients with renal dysfunction (eGFR<90/ml/min/1.73m<sup>2</sup>). The renal function outcomes were evaluated by cross‐sectional and longitudinal study of eGFR.</p><p><bold>Results</bold>: Before surgery 5 patients in each group presented with renal dysfunction. At 20‐year follow‐up, cross‐sectional study showed a renal function advantage of NSS over nephrectomy (eGFR 117±18.4 vs. 99.5 ±22.1;p=0.03). The longitudinal study of eGFR showed a stable renal function after nephrectomy (p=0.64) and a significant increase after NSS (p=0.004). At last follow‐up, 6 patients after nephrectomy and none after NSS, presented with a renal dysfunction (p=0.01).</p><p><bold>Conclusions</bold>: Children with URT treated with NSS, in comparison with pair‐matched children treated with nephrectomy, may present after surgery a better recovery of renal function reaching at long‐term follow‐up values within the range of two kidneys renal function. At a similar follow‐up, 46% of children with URT treated with nephrectomy may present with renal dysfunction.</p></sec><sec id="pbc26772-sec-1920"><label>O-156</label><title>How do we Biopsy Renal Tumours?</title><p><underline underline-style="single">K. Elmalik</underline><sup>1</sup>, E. Gavens<sup>2</sup>, S. Marven<sup>2</sup>, R. Fisher<sup>2</sup>, J. Walker<sup>2</sup>, A. Raghavan<sup>3</sup>, D. Hughes<sup>3</sup>, L. Smith<sup>1</sup>, S. Nour<sup>1</sup>, F. Dickinson<sup>4</sup>, A. Rickett<sup>4</sup>, B. Davies<sup>5</sup>, D. Colliver<sup>5</sup>, M. Peeraully<sup>5</sup>, L. Morris<sup>5</sup>, R. Stewart<sup>5</sup></p><p><italic><sup>1</sup>East Midlands Children's and Young Persons’ Integrated Cancer Service, Paediatric Surgery, Leicester, United Kingdom; <sup>2</sup>Sheffield Children's Hospital, Paediatric Surgery, Sheffield, United Kingdom; <sup>3</sup>Sheffield Children's Hospital, Paediatric Radiology, Sheffield, United Kingdom; <sup>4</sup>East Midlands Children's and Young Persons’ Integrated Cancer Service, Paediatric Radiology, Leicester, United Kingdom; <sup>5</sup>East Midlands Children's and Young Persons’ Integrated Cancer Service, Paediatric Surgery, Nottingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: The management of Wilms tumour is unique in the UK. The SIOP protocol is followed however currently a biopsy is performed pre‐chemotherapy. The UKW3 team have investigated the potential influence of the biopsy on local recurrence. The aim of this study was to examine the technique of the biopsy.</p><p><bold>Design/Methods</bold>: This was a three centre retrospective data analysis between 2001‐2016 using medical records and Histopathology reports from three centres. Study limitations were due to variability in documentation within the three sites over a long period of time.</p><p><bold>Results</bold>: Hundred and forty cases of renal tumours were identified, 76 were females and 64 were males; average age was 3y 4m (5m – 15y4m). The diagnosis was Wilms Tumour in 95%, others; CCSK, Cystic Nephroma and Renal Cell Carcinoma. Stage I 34%, stage2 13%, stage 3 24%, stage 4 22% and stage 5 7%. Risk stratification showed 11% were high risk, 82% intermediate and 7% low risk. The approach to biopsy was open in 7% and percutaneous in 93%. In nine percutaneous cases a Co‐axial sheath was used. The needle gauge range was 14 to 18G. The radiologist performed the biopsy in 44% of cases while the surgeon did in 56%. Multiple cores were taken between 2‐11 samples. Ultrasound guidance was utilised in the majority to guide the biopsy. Only one patient developed bleeding from a biopsy however none underwent an emergency nephrectomy.</p><p><bold>Conclusions</bold>: This is the first study that looked into the technique of biopsy in renal tumours. The results showed that the technique is safe whether it is performed by a radiologist or a surgeon. Surgeons and radiologists need to improve their documentation of the fine details when performing percutaneous biopsies.</p></sec><sec id="pbc26772-sec-1930"><label>O-157</label><title>Inter‐Ethnic Differences in Wilms Tumors ‐ A Clinical, Pathological and Molecular Profile of a Multiracial Cohort</title><p>B.N. Loke<sup>1</sup>, K.D. Tawng<sup>2</sup>, C.H. Kuick<sup>3</sup>, M.K. Wong<sup>4</sup>, S. Jain<sup>3</sup>, Y.H. Zou<sup>5</sup>, V. Ganesan<sup>5</sup>, D.W.Q. Lian<sup>3</sup>, S.W. Sim<sup>6</sup>, Y.T. Lee<sup>6</sup>, F.K.C. Chin<sup>7</sup>, M.Y. Chan<sup>2</sup>, A.M. Tan<sup>2</sup>, S.Y. Soh<sup>2</sup>, K.T.E. Chang<sup>3</sup>, <underline underline-style="single">A.H.P. Loh</underline><sup>6</sup></p><p><italic><sup>1</sup>National University of Singapore, Faculty of Science, Singapore, Singapore; <sup>2</sup>KK Women's and Children's Hospital, Department of Paediatric Subspecialties Haematology Oncology Service, Singapore, Singapore; <sup>3</sup>KK Women's and Children's Hospital, Department of Pathology and Laboratory Medicine, Singapore, Singapore; <sup>4</sup>KK Women's and Children's Hospital, VIVA‐KKH Paediatric Solid Tumour Research Laboratory, Singapore, Singapore; <sup>5</sup>National University of Singapore, Yong Loo Lin School of Medicine, Singapore, Singapore; <sup>6</sup>KK Women's and Children's Hospital, Department of Paediatric Surgery, Singapore, Singapore; <sup>7</sup>National Cancer Centre Singapore, Division of Radiation Oncology, Singapore, Singapore</italic></p><p><bold>Background/Objectives</bold>: Wilms tumor demonstrates significant epidemiological, histological and outcome differences between ethnic groups, yet the clinicopathological and molecular profile is poorly studied in Asians. Also, the incidence of biological risk factors in Asian populations are not known. We aimed to characterize these features in Wilms tumor patients from a multiracial cohort.</p><p><bold>Design/Methods</bold>: Clinical charts and histological slides from patients with malignant renal tumors seen at our institution from January 1997 to December 2016 were reviewed. PCR‐based genotyping was used to identify loss of heterozygosity at 1p36 and 16q22. Clinicopathological and molecular characteristics, and survival outcomes of Asian and non‐Asian patients were compared.</p><p><bold>Results</bold>: Sixty‐seven of 80 malignant renal tumors were Wilms tumors; 53 (79.1%) were Asian and 14 (20.9%) were non‐Asians. Mean age at diagnosis was 4.1 years (s.d.: 3.4 years). There were more girls among non‐Asians than Asians (female:male=1.8 and 1.0, respectively). Unfavorable histology occurred more frequently in non‐Asians than Asians (25.0% and 4.2%, respectively, P=0.02). More non‐Asians had focal or diffuse anaplasia (8.3% and 6.7%) compared to Asians (2.2% and 2.2%, P=0.059), yet nephrogenic rests were encountered only in Asian patients (7 perilobar, 6 intralobar). More non‐Asians presented with advanced disease (National Wilms Tumor Study (NWTS) stage III, 6 (54.5%), stage IV, 3 (27.3%)) compared to Asians (stage III, 13 (27.1%), stage IV, 5 (10.4%)), but lymph node metastases rates were similar (non‐Asian 20.0%, Asian 19.1%). No Asian patients had bilateral tumors; only one non‐Asian patient had stage V disease. Following treatment on NWTS regimens, event‐free and overall survival did not differ between non‐Asian and Asian patients (P=0.660 and 0.782, respectively, Log‐rank test).</p><p><bold>Conclusions</bold>: Asian patients had more equal gender ratio, less unfavorable histology and anaplasia, and less advanced disease at presentation. The biological bases for these differences, and the potential implications on treatment recommendations for Asian patients warrants further study.</p></sec><sec id="pbc26772-sec-1940"><label>O-158</label><title>Combination Technique Image Guided Localisation Prior to Thoracoscopy Facilitates Accurate Identification and Biopsy of Suspiscious Pulmonary Lesions</title><p><underline underline-style="single">M. Collin</underline><sup>1</sup>, S. Murthy Chennapragada<sup>2</sup>, D. McDowell<sup>1,3</sup>, J. Karpelowsky<sup>4,5</sup></p><p><italic><sup>1</sup>The Children's Hospital at Westmead, Paediatric Surgery, Westmead, Australia; <sup>2</sup>The Children's Hospital at Westmead, Radiology, Westmead, Australia; <sup>3</sup>University of Sydney, Sydney Medical School, Sydney, Australia; <sup>4</sup>The Children's Hospital at Westmead, Paediatric Oncology and Thoracic Surgery, Westmead, Australia; <sup>5</sup>University of Sydney, Children's Cancer Research Unit, Sydney, Australia</italic></p><p><bold>Background/Objectives</bold>: Image guided localization of pulmonary lesions suspected for metastases or infection prior to thoracoscopic biopsy has aided identification during the minimally invasive approach. Techniques used to facilitate identification of the lesions at thoracoscopy have included methylene blue tattoo or hookwire localisation under CT guidance. We describe our surgical results using the techniques alone or in combination to improve the intra operative localisation of the lesions at thoracoscopy.</p><p><bold>Design/Methods</bold>: This retrospective audit included all cases of CT guided localisation and surgical excision of pulmonary lesions identified from our institution's surgical and radiology databases from 2006‐2016. We reviewed the method of CT localisation (single hookwire or methylene blue versus both), the intraoperative findings including success of the technique, ability to identify the lesion and histopathological findings.</p><p><bold>Results</bold>: Eighteen children (14 male and 4 female, age range 4‐17 years) underwent CT guided localization prior to surgical excision of pulmonary lesions. Eleven out of 18 cases involved the use of both hookwire and methylene blue, 6/18 cases used methylene blue only and 1/18 case used hook wire only. Histologically, there were 5 metastatic nodules, 1 fungal infection, the remaining 11 being non‐specific/infective changes or lymph nodes. Thoracoscopic resection of the suspicious lesion was possible in all except one case where methylene blue only was used and spilt throughout the thorax. In this case a previously unidentified pleural based lesion was biopsied which was diagnostic for infection. In two cases where both techniques were used, one of the techniques had failed (one hookwire and one methylene blue) however the lesions were successfully biopsied due to localization from the other technique.</p><p><bold>Conclusions</bold>: Preoperative image guided localisation of pulmonary lesions facilitates minimally invasive thoracoscopic identification for biopsy of these lesions. We recommend the use of both hookwire and tattoo to improve the chances of localising a lesion accurately for biopsy.</p></sec><sec id="pbc26772-sec-1950"><label>O-159</label><title>Prognostic Impact of Pulmonary Nodules Diagnosed at Initial Presentation in Patients with Osteosarcoma</title><p><underline underline-style="single">S. Irtan</underline><sup>1</sup>, L. Brugières<sup>2</sup>, H. Pacquement<sup>3</sup>, M.D. Tabone<sup>4</sup>, S. Piperno‐Neuman<sup>5</sup>, N. Gaspar<sup>2</sup>, M. Jimenez<sup>6</sup>, M. Larroquet<sup>1</sup>, S. Sarnacki<sup>7</sup>, J. Donadieu<sup>4</sup>, C. Cellier<sup>8</sup></p><p><italic><sup>1</sup>Armand‐Trousseau Hospital‐ APHP, Pediatric Surgery, Paris, France; <sup>2</sup>Gustave Roussy Institute, Pediatric Oncology, Villejuif, France; <sup>3</sup>Curie Institute, Pediatric Oncology, Paris, France; <sup>4</sup>Armand‐Trousseau Hospital‐ APHP, Pediatric Oncology, Paris, France; <sup>5</sup>Curie Institute, Oncology, Paris, France; <sup>6</sup>Unicancer, Pediatric Oncology, Paris, France; <sup>7</sup>Necker Enfants Malades ‐ APHP, Pediatric Surgery, Paris, France; <sup>8</sup>Curie Institute, Pediatric Radiology, Paris, France</italic></p><p><bold>Background/Objectives</bold>: Patients with metastatic osteosarcoma have a poor outcome but the surgical removal of all lung metastases is thought to improve survival. The dramatic increase of CT‐scan quality allows detecting endless smaller nodules whose exact nature remains difficult to assess. We aimed to determine if the presence of at least one nodule on CT‐scan at diagnosis has an impact on survival and to describe the evolution and management of lung nodules during the course of treatment.</p><p><bold>Design/Methods</bold>: The analysis was performed on patients from three centres included in OS2006 trial and treated with high‐dose methotrexate based chemotherapy from 2007 to 2013. Chest CT‐scans performed at diagnosis, before and after lung surgery, at the end of treatment and at relapse in case of recurrence were centrally reviewed.</p><p><bold>Results</bold>: Among 80 patients diagnosed at a median age of 13.5 years [3‐27], 8 patients (10%) had been classified at diagnosis as metastatic, 46 (57%) as localized and doubtful in 26 cases (32%). At central review, nodules were found at diagnosis in 46 (57%) patients: in all patients classified as metastatic or doubtful and in 12 patients considered localized. The median number of nodules per patient was 2 [1‐52]. Median size was 3 mm [1‐13]. Nodules were round in 77% of cases and calcified in 17%. At pre‐operative assessment, nodules were still detectable in 30/46 (65%) patients with nodules at diagnosis and appeared in one patient with no nodules at diagnosis. Among these 30 patients, 22 (73%) were operated on. The 5‐year overall and event‐free survival (OS/EFS) of patients with at least one nodule at diagnosis versus no nodule were respectively 70%(95%CI:50%‐84%)/55%(CI95%:35%‐71%) and 89%(95%CI:70%‐96%)/79% (95%CI:61%‐89%) (p=0.04 for OS and p=0.15 for EFS).</p><p><bold>Conclusions</bold>: The CT‐scan detection of lung nodules at diagnosis of osteosarcoma regardless of their evolution and management seems to negatively impact OS.</p></sec></sec><sec id="pbc26772-sec-1960"><title>(PBC‐Session): The Robert Arceci Best of IPSO</title><sec id="pbc26772-sec-1970"><label>O-160</label><title>Outcome of Patients Suffering from Rhabdomyosarcoma of the Female Genital Tract ‐ A Report from the Cooperative Weichteilsarkom Studiengruppe Trials CWS‐81, ‐86, ‐91, and ‐2002P</title><p><underline underline-style="single">G. Seitz</underline><sup>1</sup>, M. Matle<sup>2</sup>, M. Sparber‐Sauer<sup>3</sup>, J. Fuchs<sup>4</sup>, T. Klingebiel<sup>5</sup>, E. Koscielniak<sup>3</sup></p><p><italic><sup>1</sup>Center for Pediatric and Adolescent Medicine, Department of Pediatric Surgery, Marburg, Germany; <sup>2</sup>Center for Pediatric and Adolescent Medicine, Department of General Pediatrics and Neonatology, Marburg, Germany; <sup>3</sup>Klinikum Stuttgart ‐ Olgahospital‐ Zentrum für Kinder– Jugend‐ und Frauenmedizin, Pediatrics 5 Oncology‐ Hematology‐ Immunology, Stuttgart, Germany; <sup>4</sup>University Children´s Hospital, Department of Pediatric Surgery and Urology, Tuebingen, Germany; <sup>5</sup>University Hospital, Department of Pediatric Hematology and Oncology, Frankfurt/Main, Germany</italic></p><p><bold>Background/Objectives</bold>: Rhabdomyosarcoma (RMS) of the female genital tract is rare and vaginal tumors seem to have a more favorable prognosis. Local control may consist of surgery and/or radiotherapy, but might be associated with severe side effects in young children. The aim of the study was to evaluate treatment and outcome of patients treated within four Cooperative Soft Tissue Sarcoma (CWS) trials.</p><p><bold>Design/Methods</bold>: Fifty‐four patients suffering from localized RMS of the female genital tract (vagina/uterus) were enrolled and analyzed. All patients were treated according to the CWS study protocols.</p><p><bold>Results</bold>: The 5‐year overall survival rate was 84.6% and the 5‐year event free suvival (EFS) 71.5%. Median age was 2.5 years and the median follow‐up 7.85 years. 53 patients had embryonal and one patients alveolar histology. Forty patients were ≤10 years (EFS: 71.4%) and fourteen >10 years (EFS: 71.4%). Fourty tumors were located at the vagina (EFS: 68.9%) and 14 at the uterus (EFS: 78.6%). Tumors ≤5cm had a better EFS (n = 26; 84.3%) than those >5cm (n = 28; 59.3%). Positive lymph nodes at diagnosis were detected in 3 patients (EFS: 33.3%). Primary resection was carried out in 26 patients (EFS: 68%) and secondary resection in 33 patients (EFS: 65.3%). Completeness of resection did not influence the outcome. Radiotherapy was used in 20 patients (EFS: 42.1%). Only 3 patients were treated with solely chemotherapy.</p><p><bold>Conclusions</bold>: The outcome of patients suffering from RMS of the female genital tract is comparable to other localizations in the urogenital tract. Almost all patients had local control and tumors located at the uterus seem to have a trend towards a better EFS than those located in the vagina. Tumor size, but not patient´s age, is a positive predictive factor for outcome. The extent of surgical resection had no Impact on the outcome.</p></sec><sec id="pbc26772-sec-1980"><label>O-161</label><title>Pelvic Peritonectomy Prevents Recurrence of Desmoplastic Small Round Cell Tumor After CRS and HIPEC</title><p><underline underline-style="single">A. Hayes‐Jordan</underline><sup>1</sup>, B. Coakley<sup>1</sup>, L. Xiao<sup>2</sup>, C. Herzog<sup>3</sup>, P. Anderson<sup>4</sup>, W. Huh<sup>3</sup></p><p><italic><sup>1</sup>MD Anderson Cancer Center, Surgery, Houston Texas, USA; <sup>2</sup>MD Anderson Cancer Center, Biostatistics, Houston Texas, USA; <sup>3</sup>MD Anderson Cancer Center, Pediatrics, Houston Texas, USA; <sup>4</sup>The Cleveland Clinic, Pediatric Hematology Oncolgy and Blood and Marrow Transplantation, Cleveland‐ OH, USA</italic></p><p><bold>Background/Objectives</bold>: Desmoplastic small round cell tumor (DSRCT) is a rare form of sarcoma primarily affecting adolescents. Patients frequently present with hundreds of peritoneal tumor implants. Historically, only 30% of patients reach 3‐year overall survival. Inability to obtain a complete abdominal resection impacts long‐term survival in DSRCT. We use a combination of systemic chemotherapy, cytoreductive surgery with cisplatin‐based hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC) and adjuvant radiotherapy. As almost 100% of patients have pelvic tumors at diagnosis, we hypothesized that a pelvic peritonectomy, after neoadjuvant chemotherapy, was essential for control of the ‘primary’ tumor.</p><p><bold>Design/Methods</bold>: We reviewed 81 patients who underwent complete CRS‐HIPEC with cisplatin for DSRCT from 2006‐2016. Since pelvic peritonectomy was routinely performed after March 2013, we compared patients who received pelvic peritonectomy to those who did not, regardless of macroscopically visible disease in the pelvis. All patients received neoadjuvant and adjuvant chemotherapy. Most received adjuvant radiotherapy.</p><p><bold>Results</bold>: Patients ranged in age from 4 to 41 years and were followed postoperatively up to 7.7 years. Before pelvic peritonectomy was added to our standard operative approach, 39% of patients (18/46) developed a local recurrence. Of these recurrences, 33% (6/18) were located in the pelvis alone without distant disease. The local recurrence rate decreased to 6% (2/35) after making this change. Among 59 patients with at least 36 months follow‐up, the median recurrence‐free survival was 11.8 months and median overall survival was 36.1 months. Median postoperative survival (31.1 months vs. 18.1 months, p=0.04) was significantly longer in patients who had a CR0/CR1 CRS‐HIPEC than for patients who had a CR2 CRS‐HIPEC.</p><p><bold>Conclusions</bold>: Complete cytoreduction, including routine pelvic peritonectomy, substantially reduces local recurrence rates of DSRCT. With this technique, a 94% local control rate was achieved in DSRCT patients who underwent CRS‐HIPEC.</p></sec><sec id="pbc26772-sec-1990"><label>O-162</label><title>Outcome of Localized Liver‐Bile Ducts Rhabdomyosarcoma According to Local Therapy. A Report from the European Soft Tissue Sarcoma Group (EPSSG) RMS 2005 Study</title><p><underline underline-style="single">F. Guerin</underline><sup>1</sup>, G. Cecchetto<sup>2</sup>, T.N. Rogers<sup>3</sup>, S. Terwisscha Van Scheltinga<sup>4</sup>, G. Guillen Burrieza<sup>5</sup>, V. Minard‐Colin<sup>6</sup>, H. Mandeville<sup>7</sup>, A. Kelsey<sup>8</sup>, G.L. De Salvo<sup>9</sup>, G. Bisogno<sup>10</sup>, H. Martelli<sup>1</sup></p><p><italic><sup>1</sup>Bicetre hospital APHP, paediatric surgery, Le Kremlin Bicetre, France; <sup>2</sup>University Hospital of Padua, paediatric Surgery, Padova, Italy; <sup>3</sup>Royal hospital for Sick Children, Paediatric surgery, Bristol, United Kingdom; <sup>4</sup>Prinses Máxima Centrum voor Kinderoncologie, Paediatric Surgery, Utrecht, The Netherlands; <sup>5</sup>Hospital Universitari Vall d'Hebron, Paediatric Surgery, Barcelona, Spain; <sup>6</sup>Gustave Roussy Cancer Campus, Paediatric Oncology, Villejuif, France; <sup>7</sup>The Royal Marsden NHS Foundation Trust, Clinical Oncology, Sutton, United Kingdom; <sup>8</sup>Royal Manchester Children's hopsital, Pathology, Manchester, United Kingdom; <sup>9</sup>Istituto Oncologico Veneto IOV‐IRCCS, UOS Sperimentazioni Cliniche‐ Biostatistica e Nucleo Ricerca Clinica, Padova, Italy; <sup>10</sup>University Hospital of Padua, Paediatric Oncology, Padova, Italy</italic></p><p><bold>Background/Objectives</bold>: To evaluate the impact of local treatment therapy on outcome in patients with liver‐bile ducts rhabdomyosarcoma (BD‐RMS)</p><p><bold>Design/Methods</bold>: We analyzed the data of 28 patients (2 liver, 26 bile ducts) included in the RMS 2005 protocol until 2013. Delayed surgery and/or External Beam Radiation Therapy (EBRT) were performed after at least 4 courses of chemotherapy.</p><p><bold>Results</bold>: All but one patient had embryonal RMS, 13 had a tumour > 5cm, 5 were N1. Median age at diagnosis was 3 years (1‐8 years).</p><p><list list-type="simple" id="pbc26772-list-0018"><list-item><label>–</label><p>Six patients (21%) had primary surgery (1 IRS I, 4 IRS II, 1 IRS III): ) consisting of bile duct excision (BDE), 1 with Whipple procedure. Four of them also received EBRT. All are in first complete remission (CR1) except one (IRS II, EBRT+, local relapse, death)</p></list-item><list-item><label>–</label><p>Five patients (18%) received EBRT alone (one local relapse, death).</p></list-item><list-item><label>–</label><p>Seventeen patients (61%) underwent secondary surgery (7 with additional EBRT): 7 BDE including 2 with Whipple procedure, 7 BDE + partial hepatectomy, and 3 partial hepatectomies. Four R1 patients underwent EBRT without recurrence. Among 3 R0 patients who received EBRT, one had a metastatic relapse and died. Ten R0 patients did not receive EBRT: 3 relapsed locally, 2 died and 1 is in CR2.</p></list-item></list></p><p>In summary, local relapse occurred in 2 among 15 patients with EBRT and 3 among 12 without EBRT.</p><p>At a median follow‐up of 5 years (16 months‐10 years) 23 patients are alive, 22 in CR1. Five patients died (4 local, 1 metastatic relapse). 5‐years OS was 85% (CI:67‐94%) and 5‐years EFS was 75.6% (CI:55.3‐88.6%).</p><p><bold>Conclusions</bold>: Local relapse in BD‐RMS is often fatal. This analysis did not show any difference in outcome between surgery alone and EBRT+/‐ surgery. However possible long‐term sequelae of EBRT on hepatic pedicle could be balanced with the safety of BDE + Roux en Y loop.</p></sec><sec id="pbc26772-sec-2000"><label>O-163</label><title>Surgical and Interventional Treatments for Ruptured Hepatic Tumors in Japanese Study Group Experiences</title><p><underline underline-style="single">E. Hiyama</underline><sup>1</sup>, T. Hishiki<sup>2</sup>, K. Hoshino<sup>2</sup>, A. Yokoi<sup>2</sup>, Y. Takama<sup>2</sup>, T. Kazama<sup>2</sup>, S. Honda<sup>2</sup>, T. Taguchi<sup>2</sup>, S. Kurihara<sup>1</sup>, M. Kawashima<sup>1</sup>, Y. Ueda<sup>1</sup></p><p><italic><sup>1</sup>Hiroshima University Hospital, Peditric Surgery, Hiroshima, Japan; <sup>2</sup>Japan Children's Cancer Group, Liver tumor committee, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: We aimed to evaluate interventional and surgical treatments of spontaneous tumor rupture in hepatic tumors in the JPLT (Japanese study group for Pediatric Liver Tumors) ‐2 study (1999‐2012).</p><p><bold>Design/Methods</bold>: Of the 404 patients with hepatic malignancies who were enrolled in the JPLT‐2 study, 32 showed spontaneous tumor rupture at diagnosis. Age at diagnosis, sex, pathology of liver disease, PRETEXT classification, and clinical presentation were assessed. Embolization was performed in a selective fashion when possible. Treatments, complications, and survival were examined.</p><p><bold>Results</bold>: There were 7 PRETEXT I, 9 II, 10 III, and 6 IV, including 5 metastatic tumors. The age range at diagnosis was 2‐184 months, with 20 males and 12 females. Histological examination revealed 27 hepatoblastomas, 4 hepatocellular carcinomas, and 1 sarcoma. Transarterial embolization was performed in 27 cases, whereas 4 of them showed uncontrollable bleeding, with 2 of these cases dying of massive bleeding. In the remaining 30 cases, 11 PRETEXT I and II cases underwent primary resection of the tumors, 11 cases had a tumor biopsy followed by preoperative chemotherapy, and 8 cases received chemotherapy without a tumor biopsy. In the 19 cases with preoperative chemotherapy, 4 died of tumor progression before surgery, while the remaining 15 cases underwent tumor resection including 4 who received a liver transplantation. Postoperative chemotherapy was performed in all 30 cases, including 2 of high dose chemotherapy. However, 11 of these 30 cases showed recurrence and 6 cases died.</p><p><bold>Conclusions</bold>: Spontaneous tumor rupture is an unfavorable prognostic factor for pediatric liver tumors. Adequate surgical or interventional treatments to control tumor bleeding and more aggressive chemotherapy might be necessary to improve the outcomes of these patients.</p></sec></sec><sec id="pbc26772-sec-2010"><title>Rare Tumors (+ 1 education)</title><sec id="pbc26772-sec-2020"><label>O-164</label><title>Systematic Review and Meta‐Analysis of Appendiceal Carcinoid Tumours in Children</title><p><underline underline-style="single">I. Njere</underline><sup>1</sup>, L. Linnea<sup>1</sup>, D. Thurairasa<sup>1</sup>, M. Bisharat<sup>1</sup>, I. Jefffrey<sup>2</sup>, D. Rex<sup>1</sup>, Z. Mukhtar<sup>1</sup>, E. Nicholls<sup>1</sup>, B. Okoye<sup>1</sup>, C. Sinha<sup>1</sup></p><p><italic><sup>1</sup>St George's University of London, Paediatric Surgery, London, United Kingdom; <sup>2</sup>St George's University of London, Pathology, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: To determine if more invasive procedures are necessary following incidental finding of an appendiceal carcinoid tumour after appendicectomy</p><p><bold>Design/Methods</bold>: A search of Medline, Embase, Cinahl and Cochrane database of systematic reviews were undertaken of the English language literature. The mesh terms used were Carcinoid or neuroendocrine, tumour or tumor, appendix or appendicectomy or appendectomy, child or paediatric or paediatric. Of 369 articles found 37 met the inclusion criteria. Our hospital records and pathology database identified 11patients with confirmed histological diagnosis of appendicular carcinoids from January 1996 to December 2016.</p><p><bold>Results</bold>: A total of 958 cases were identified from the literature and our own experience. There were 566 females and 343 males giving us a ratio of 1.65:1. The frequency was 1 in 333.8 appendicectomies or 0.3% of appendicectomies. There was a twenty eight‐fold increase in risk of having a positive lymph node if tumour size was >2cm compared with the risk of having a positive lymph node if tumour size was ≤2cm. Of 189 patients that met the criteria for Right hemicolectomy (RHC) following appendicectomy, with a median follow‐up of 3.4years (range 0‐51years) no recurrence was noted in neither the 69 that had a secondary procedure nor the 120patients that were just observed. No mortality from carcinoid was noted in the 2 groups. No survival advantage was therefore conferred by another procedure. Mean follow‐up was 58.6months (4.8yrs) with a range of 0‐396months (33yrs).</p><p><bold>Conclusions</bold>: Appendicectomy alone is adequate treatment for an appendicular carcinoid in children, irrespective of size, position, lymph node or mesenteric involvement unless there are positive margins. Post‐appendicectomy investigations not helpful and long follow‐up unnecessary</p></sec><sec id="pbc26772-sec-2030"><label>O-165</label><title>Controversies in Surgical Management of Melanoma in Pediatric Age</title><p><underline underline-style="single">M. Ilari</underline><sup>1</sup>, G. Torino<sup>1</sup>, A. Zangari<sup>2</sup>, F. Nino<sup>1</sup>, G. Cobellis<sup>1</sup>, A. Martino<sup>1</sup></p><p><italic><sup>1</sup>"G. Salesi" Children's Hospital, Pediatric Surgery, Ancona, Italy; <sup>2</sup>San Camillo ‐ Forlanini General Hospital, Pediatric Surgery, Roma, Italy</italic></p><p><bold>Background/Objectives</bold>: Malignant melanoma (MM) in children is rare with an incidence of 0.7/million/year. The risk of melanoma development in large congenital nevi is widely accepted. Melanoma occurrence from intermediate congenital nevi has been reported. The purpose of this study is to discuss surgical indications of nevi and diagnosis and treatment of melanoma.</p><p><bold>Design/Methods</bold>: From 2003 to 2016 were retrospectively reviewed 145 children (aged 1 month to 14 years) underwent to surgical excision of 156 nevi. Indications for excision included clinical appearance, site of difficult monitoring or of exposure to frequent trauma. After diagnosis of MM, the patient was underwent to sentinel lymph‐node biopsy (SLNB) for melanoma thickness of ≥ 1 mm associated to excision of tumor site (with 2 cm margins) and primary closure or skin graft.</p><p><bold>Results</bold>: In all cases, first surgical excision included 2 mm margins of normal skin around the lesion. MM was diagnosed in 5 patients. One infant was underwent to partial excision of large congenital nevus but at 23 months follow‐up he was also submitted to excisional biopsy of an inguinal nodal mass resulting in metastatic melanoma and he died for cerebral metastasis. The other 4 patients were underwent to scar excision with 2 cm margins and SLNB for MM diagnosis. In 3 patients, the SLBN was positive and in 2 of them was performed an inguino‐iliac‐obturatory lymph‐node dissection showed micromestases, on the contrary, in the third patient the parents refused further surgical proposed treatment but she remains disease free at 8 months follow‐up. The remaining three patients are disease free at 16, 13 and 10 years respectively.</p><p><bold>Conclusions</bold>: MM in children is less rare than is commonly believed. The behaviour of this disease is different from that in adulthood. Clinical trials are needed to define the biological findings and the most suitable surgical treatment for MM in children.</p></sec><sec id="pbc26772-sec-2040"><label>O-166</label><title>Outcome After Surgery for Solid Pseudopapillary Pancreatic Tumors in Children: Report from Trep Project – Italian Rare Tumors Study Group</title><p><underline underline-style="single">A. Crocoli</underline><sup>1</sup>, C. Grimaldi<sup>1</sup>, M.D. De Pasquale<sup>2</sup>, G. Cecchetto<sup>3</sup>, C. Virgone<sup>3</sup>, S. Cesaro<sup>4</sup>, G. Bisogno<sup>5</sup>, V. Cecinati<sup>6</sup>, A. Narciso<sup>1</sup>, D. Alberti<sup>7</sup>, A. Ferrari<sup>8</sup>, P. Dall'Igna<sup>3</sup>, M. Spada<sup>1</sup>, A. Inserra<sup>1</sup></p><p><italic><sup>1</sup>Bambino Gesù Children's Hospital ‐ IRCCS, Surgery, Rome, Italy; <sup>2</sup>Bambino Gesù Children's Hospital ‐ IRCCS, Oncohematology, Rome, Italy; <sup>3</sup>University of Padova, Pediatric Surgery, Padova, Italy; <sup>4</sup>Policlinico G.B. Rossi, Hematology, Verona, Italy; <sup>5</sup>University of Padova, Pediatric Hematology and Oncology, Padova, Italy; <sup>6</sup>Ospedale Civile, Pediatric Hematology and Oncology, Pescara, Italy; <sup>7</sup>Spedali Civili, Pediatric Surgery, Brescia, Italy; <sup>8</sup>Istituto Nazionale Tumori, Pediatric Oncology, Milan, Italy</italic></p><p><bold>Background/Objectives</bold>: Solid pseudopapillary pancreatic tumors (SPPT) are an extremely rare entity in pediatric patients. Even if the role of radical surgical resection as primary treatment is well established, data about follow up in children undergone pancreatic resection are scant.</p><p><bold>Design/Methods</bold>: Retrospective review of Italian pediatric rare tumor registry (TREP) was performed. Short (<30 days) and long term complications of different surgical resections, as well as long term follow up were evaluated.</p><p><bold>Results</bold>: from January 1<sup>st</sup> 2000 to February 28<sup>th</sup> 2017, 40 patients (M:F=8:32) were enrolled. Median age at diagnosis was 13,5 years (range 7‐18). Median delay of diagnosis was 1 month (range 0‐7). Fourteen children had an occasional diagnosis, whereas 19 complained of abdominal pain and 7 were referred for recurrent vomiting. Tumors arose from head of pancreas (n=12) or from body/tail (n=28). Resection was complete in 38 patients (duodenocephalopancreasectomy n=11, spleen preserving distal resection n =24, distal resections with splenectomy n=3); 2 cases of microscopic spillage were recorded. At follow up (median 81 months, range 0‐188), local recurrence of disease occurred in one patient with intraoperative spillage. All patients are alive. Three pancreatic fistulas occurred in the body/tail group (conservative management), whereas 3 complications occurred in head group (one ileal ischemia undergone to endovascular treatment, one Wirsung duct stenosis undergone to surgical revision and one chilous fistula managed conservatively).</p><p><bold>Conclusions</bold>: Surgery proves as the therapeutic option for these tumors, hence complete resection is mandatory. Extensive resections, including duodenocephalopancreasectomy, are safe when performed in specialized centres. Long term follow up must be centered on oncologic radicality and residual pancreatic function.</p></sec><sec id="pbc26772-sec-2050"><label>O-167</label><title>Duodenum‐Preserving Pancreatic Head Resection (Modified Whipple's Procedure) for Tumors Localized to the Pancreatic Head in Children</title><p><underline underline-style="single">J. Wang</underline><sup>1</sup>, X. Chen<sup>1</sup>, M. Li<sup>1</sup>, J. Cai<sup>1</sup>, M. He<sup>1</sup>, J. Mao<sup>1</sup>, Q. Shu<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Surgical Oncology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: Pancreatic tumor is a rare neoplasm in children. Whipple's procedure is considered as a standard treatment for tumors localized to the pancreatic head. However, this radical procedure is still controversial in pediatric population, since most pancreatic tumors in children are benign or low‐grade malignant. Herein, we present 11 cases duodenum‐preserving pancreatic head resection (DPPHR) for tumors localized to the pancreatic head in children.</p><p><bold>Design/Methods</bold>: Retrospective single institution study was performed, 11 cases with tumors localized to the pancreatic head in our center from Jan. 2015 to Dec. 2016 were included. Tumor types were pancreatoblastoma (n=4, 1 male and 3 female, aged from 3m to 7y2m) and solid‐pseudopapillary tumor (SPT, n=7, 2 male and 5 female, aged from 8y2m to 13y4m). All cases underwent DPPHR procedure. Patients with pancreatoblastoma and 3 cases with SPT received postoperative chemotherapy and other 4 cases with SPT received close follow‐up without chemotherapy.</p><p><bold>Results</bold>: DPPHR was performed successfully and duodenum was kept intact in all cases. Eight cases underwent pancreaticojejunostomy only since common bile duct was not injured during pancreatic head resection. Two cases underwent pancreaticojejunostomy plus cholangiojejunostomy. Other 2 cases received tumor resection only. Pancreatic pseudocyst was observed in 1 case (tumor resection only group) and there was no other early postoperative complication. Follow‐up time from 3m to 27m, recurrence was observed in 1 case with pancreatoblastoma 6m after chemotherapy. Recurrent tumor localized to pancreatic body not duodenum wall was identified during the second operation.</p><p><bold>Conclusions</bold>: Duodenum‐preserving pancreatic head resection combined with appropriate chemotherapy is safe and effective for tumors localized to the pancreatic head in children.</p></sec><sec id="pbc26772-sec-2060"><label>O-168</label><title>Diagnosis and Treatment of Pediatric Thyroid Cancer – Experience in 38 Cases at a Fourth‐Level Institution</title><p><underline underline-style="single">J.P. Luengas</underline><sup>1</sup>, C. Correa<sup>1</sup>, O. Gil<sup>1</sup>, A. Holguín<sup>1</sup>, G. Veintemilla<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Cancerología, Cirugía Pediátrica, bogota, Colombia</italic></p><p><bold>Background/Objectives</bold>: To present our experience in the diagnosis and treatment of pediatric thyroid cancer at a Cancer Center in Bogota, Colombia.</p><p><bold>Design/Methods</bold>: We reviewed 48 cases referred to our institution from 2008‐2016 with pediatric thyroid cancer. Thirty‐eight had complete information on their charts for analysis. We analyzed the demographic characteristics, the symptom of presentation, diagnosis, treatment, recurrence, mortality, and delay between diagnosis and treatment.</p><p><bold>Results</bold>: Patients were between 8‐19 years old. Mean age at diagnosis was 12 years of age. Eighty‐two percent were female. Two patients had a positive family history for MEN‐2 Syndrome. 74% presented with a thyroid nodule, and 13% with cervical node. Fine needle aspiration biopsy was used for diagnosis in 71%. All patients underwent total thyroidectomy, papillary thyroid cancer was the most frequent histologic finding (87%), followed by medullary thyroid cancer (5%), clear cell and follicular carcinoma (3% each). Eighty‐six percent of patients had positive nodes and underwent cervical lymphadenectomy: 27% central compartment, and 73% central and modified radical lymphadenectomy. There was a complication rate of 13%, 26% recurrence, 29% metastasis, and 5% mortality in this series. Mean time between diagnosis and thyroidectomy was 4 months (range: 0‐38), and mean time to iodine ablative therapy was 5 months (range: 0‐36).</p><p><bold>Conclusions</bold>: Pediatric thyroid cancer is more frequent in adolescent females. It presents with a nodule or cervical node, and the most frequent histology is papillary carcinoma. Patients usually need some type of lymphadenectomy in addition to total thyroidectomy because of nodal disease. Mortality remains low even though many patients experienced a delay in surgical treatment and iodine ablative therapy due to healthcare issues.</p></sec><sec id="pbc26772-sec-2070"><label>O-169</label><title>Cytoreductive Surgery and Hyperthermic Intraperitoneal Perfusion with Chemotherapy in Children with Peritoneal Tumor Spreading: A French Nationwide Study Over 14 Years</title><p>A. Scalabre<sup>1</sup>, P. Philippe‐Chomette<sup>2</sup>, G. Passot<sup>3</sup>, D. Orbach<sup>4</sup>, D. Elias<sup>5</sup>, N. Corradini<sup>6</sup>, B. Laurence<sup>6</sup>, S. Msika<sup>7</sup>, M.D. Leclair<sup>8</sup>, S. Joseph<sup>8</sup>, C. Brigand<sup>9</sup>, F. Becmeur<sup>10</sup>, C. Soler<sup>11</sup>, D. Pezet<sup>12</sup>, J. Gagniere<sup>12</sup>, O. Glehen<sup>3</sup>, <underline underline-style="single">S. Sarnacki</underline><sup>13</sup></p><p><italic><sup>1</sup>University Hospital of Saint‐Etienne‐ Faculty of Medicine Jacques Lisfranc‐ PRES Lyon 42023‐ Jean Monnet University, Pediatric surgery, Saint‐Etienne, France; <sup>2</sup>University Paris 7 Denis Diderot‐ Hôpital Robert Debré‐ Assistance Publique ‐ Hôpitaux de Paris, Pediatric surgery, Paris, France; <sup>3</sup>CHU Lyon Sud‐ Hospices civils de Lyon‐ University of Lyon‐ France. EMR 37‐38‐ Lyon 1 University, Surgical Oncology, Lyon, France; <sup>4</sup>Institut Curie, Pediatric‐ Adolescent and Young Adult Oncology, Paris, France; <sup>5</sup>Gustave Roussy Cancer Center, Oncologic Surgery, Villejuif, France; <sup>6</sup>Gustave Roussy Cancer Center, Oncology for Child and Adolescents, Villejuif, France; <sup>7</sup>University Paris 7 Denis Diderot‐ Hôpital Louis Mourier‐ Assistance Publique ‐ Hôpitaux de Paris, Digestive surgery, Colombes, France; <sup>8</sup>Children University Hospital, Pediatric surgery, Nantes, France; <sup>9</sup>University Hospital, Digestive surgery, Strasbourg, France; <sup>10</sup>University Hospital, Pediatric surgery, Strasbourg, France; <sup>11</sup>Hôpital l'Archet‐ University Hospital, Hematology‐Oncology, Nice, France; <sup>12</sup>Université Clermont Auvergne‐ INSERM‐ CHU Clermont Ferrand, Digestive surgery, Clermont Ferrand, France; <sup>13</sup>University Paris Descartes‐ Hôpital Necker Enfants‐Malades‐ Assistance Publique ‐ Hôpitaux de Paris, Pediatric surgery, Paris, France</italic></p><p><bold>Background/Objectives</bold>: Efficacy and role of cytoreductive surgery and hyperthermic peritoneal perfusion with chemotherapy (HIPEC) remain unknown in pediatric tumors.</p><p><bold>Design/Methods</bold>: This retrospective multicentric national study analyzed all pediatric patients with peritoneal tumor spreading treated by cytoreductive surgery with HIPEC as part of a multimodal therapy in France from 2001 to 2015.</p><p><bold>Results</bold>: Twenty‐two patients (9 males and 13 females) were selected. The median age was 14.8 years (4.2‐17.6). Seven had peritoneal mesotheliomas, 7 desmoplastic small round cells tumors (DSRCT) and 8 other histologic types. Twenty (91%) patients received prior conventional chemotherapy before HIPEC. A complete macroscopic resection (CC‐0) was achieved in 16 cases (73 %). Incomplete resections were classified as CC‐1 in 4 cases (18%) and CC‐2 in 2 cases (9%). Fourteen (64%) patients had complications within 30 days from HIPEC, requiring an urgent laparotomy in 8 (36%) cases. Thirteen patients (59 %) received adjuvant chemotherapy and 4 (18%) received total abdominal radiotherapy after surgery. Fifteen patients (68%) had a relapse after a median time of 9.6 months (1.4‐86.4) after the procedure and 9 (41%) eventually died after a median time of 5.3 months (0.1‐36.1) from relapse. Six patients (27%) were alive with progressive disease at last‐news. Seven patients (32%) were alive and in complete remission after a median follow‐up of 25.0 months. The mean overall survival (OS) and disease free survival (DFS) were 57.5 months (CI95% [38.59‐76.32]) and 30.9 months (CI95% [14.96‐46.77]). Patients with a peritoneal mesothelioma had a significantly better OS (p=0.015) and DFS (p=0.028) than other histologic type</p><p><bold>Conclusions</bold>: In this French national series, outcomes of HIPEC are encouraging essentially for the treatment of peritoneal mesothelioma in children. International randomized trials evaluating the outcomes of cytoreductive surgery and HIPEC for the treatment of peritoneal tumor spreading in children are mandatory.</p></sec><sec id="pbc26772-sec-2080"><label>O-170</label><title>Minimally Invasive Surgery in Pediatric Surgical Oncology: A Developing Country Experience</title><p><underline underline-style="single">R.C. Ribeiro</underline><sup>1</sup>, V. Kremer<sup>1</sup>, W.E. Oliveira Júnior<sup>1</sup></p><p><italic><sup>1</sup>Barretos Childrens Cancer Hospital, Pediatric Surgery Department, Barretos, Brazil</italic></p><p><bold>Background/Objectives</bold>: The use of Minimally Invasive Surgery (MIS) has been been greatly expanded in pediatric surgery. However its application in pediatric cancer still is a matter of debate. Our purpose is to describe our experience using Minimally Invasive Surgery (MIS) techniques in tertiary center with specific oncological pediatric surgery unit.</p><p><bold>Design/Methods</bold>: A retrospective analysis of all patients undergoing MIS in a pediatric oncology surgery unit at a single institution from a developing country between July 2014 and February 2017. MIS procedures were considered made by laparoscopy with diagnostic, staging or therapeutic intent. Demographic features, primary diagnosis, surgical procedure, time length, complications and conversion rate were reviewed.</p><p><bold>Results</bold>: Forty‐two children, ranging from 3 to 256 months of age, underwent 45 MIS procedures during this period. Laparoscopy was performed for tumor resection in 23 cases (51,1%), diagnostic purposes in 9 cases (20%), and for staging in 3 cases (6,6%). Ten additional laparoscopic procedures (22,2%) were performed for complications of the malignancy or its treatment. Median surgical time length was 73 minutes, ranging from 20 to 420 minutes, with a proctocolectomy as the longest procedure. In all cases safety principles of oncological surgery were respected. There was only one conversion to open surgery related to a bleeding during a resection of a mesenteric cyst. Complications were observed only in the proctocolectomy patients, presenting anastomotic fistulae in one patient and an episode of bowel obstruction in another. No trocar site recurrences were observed.</p><p><bold>Conclusions</bold>: The application of MIS techniques to pediatric cancer patients is a safe and effective diagnostic, staging and treating modality. MIS techniques are safe, reproducible and fulfill the objectives of quality of cancer surgery. Proper equipment remains as a limiting factor, along with the challenge in maintain a learning curve with a wide diversity of procedures.</p></sec></sec><sec id="pbc26772-sec-2090"><title>Liver Tumors, GCT and RMS (+ 1 education)</title><sec id="pbc26772-sec-2100"><label>O-171</label><title>Multidisciplinary Management of Hepatoblastoma: 8 Year Experience</title><p><underline underline-style="single">A. Elgendy</underline><sup>1,2</sup>, S. Fadel<sup>3,4</sup>, I. Zaky<sup>5</sup>, A. Younis<sup>1</sup></p><p><italic><sup>1</sup>Children's Cancer Hospital 57357 ‐ Egypt, Surgical Oncology Department, Cairo, Egypt; <sup>2</sup>Tanta University, Surgical Oncology Unit, Tanta, Egypt; <sup>3</sup>Children's Cancer Hospital 57357 ‐ Egypt, Pediatric Oncology Department, Cairo, Egypt; <sup>4</sup>National Cancer Institute‐ Cairo University, Pediatric Oncology Department, Cairo, Egypt; <sup>5</sup>Children's Cancer Hospital 57357 ‐ Egypt, Radiology Department, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: To evaluate the outcome of patients with hepatoblastoma treated by surgical resection at our hospital in 8 years.</p><p><bold>Design/Methods</bold>: Prospective study from January 2008 to December 2015. Evaluation was done by pretreatment extent staging system (PRETEXT), tumor biopsy and serum alpha fetoprotein. Overall survival (OS), event free survival (EFS) and univariate prognostic factors were estimated using kaplan‐meier and log rank test. Recurrence or death was considered as event.</p><p><bold>Results</bold>: The study included 87 patients (52 males, 35 females). Median age at diagnosis was 1.05 years (0.5 – 12.86). There were 3 (3.4%), 62 (71.3%) and 22 (25.3%) PRETEXT I, II and III respectively. Sixty four patients (73.56%) were standard risk (SR) and 23 (26.44%) high risk (HR). Thirteen patients were metastatic at diagnosis (11 lung, 2 bone). Upfront resection was done in 5 patients (5.75%) whereas, the other 82 (94.25%) underwent surgery after neoadjuvant chemotherapy according to their risk stratification. Fifty two patients (59.77%) underwent hemi‐hepatectomy (33 right, 19 left), 26 (29.88%) segmentectomy, 5 (5.75%) mesohepatectomy and 4 (4.6%) trisegmentectomy. Follow up till the end of June 2016 with a median of 23.5 months (6.46 – 100) revealed that 21 patients (24.1%) had events, among them 12 local recurrence, 7 distant relapse (6 lung, 1 brain) and 2 patients died postoperatively. The 5 years OS was 80.4% [85.3% for SR; 66.6% for HR (P= 0.037)], [82.2% for non‐metastatic; 45.5% for metastatic (P=0.018)].The 5 years EFS was 68.7% [77.8% for SR; 48.7% for HR (P=0.024)], [73.3% for non‐metastatic; 46.2% for metastatic (P=0.029)].</p><p><bold>Conclusions</bold>: Surgical resection combined with systemic chemotherapy is fundamental for improved outcome with 5 years OS and EFS 80.4% and 68.7% respectively. SIOPEL risk stratification and distant metastasis were independently impacted on the survival rates.</p></sec><sec id="pbc26772-sec-2110"><label>O-172</label><title>Laparoscopic Liver Resections in Children with Liver Tumors</title><p><underline underline-style="single">P. Kerimov</underline><sup>1</sup>, A. Kazancev<sup>1</sup>, M. Rubanskaya<sup>1</sup>, D. Rybakova<sup>1</sup></p><p><italic><sup>1</sup>Russian Cancer Research Center. NN Blokhina, Surgical separation of tumors of thoracoabdominal localization, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Laparoscopic liver resections for tumor liver pathology in children have been used relatively recently. In the literature, there are very few reports of laparoscopic liver resections in children with tumor organ pathology.</p><p><bold>Design/Methods</bold>: In our clinic from 2007 to 2016, 20 patients aged 3 months to 16 years underwent radical laparoscopic resections of the liver. Boys ‐ 14, girls ‐ 6, the average age of patients was 4 years. The following pathologies are diagnosed: hepatoblastoma ‐ 14 cases, liver hyperplasia ‐ 4 cases, metastasis of neuroblastoma ‐ 1 case and hemangioma of the liver ‐ 1 case.</p><p><bold>Results</bold>: Hemihepatectomy was performed in 6 patients, 5 patients had a diagnosis of hepatoblastoma, in 1 child nodular hyperplasia. The average duration of operations was 90 minutes, the average blood loss was 120ml. No conversions. Staying in the intensive care and reanimation room was 3 days.Segmentation was performed in 14 patients, in 9 patients hepatoblastoma was detected, hyperplasia ‐ 3 cases, neuroblastoma ‐ 1 case of hemangioma in 1 case. The average duration of operations was 60 minutes, the average blood loss was 0‐50 ml. No conversions. Staying in the intensive care unit and intensive care was 2 days. There were no immediate and remote postoperative complications. Among 15 patients with malignant liver diseases, there was no progression of the disease during the entire follow‐up period. Median follow‐up was 60 months.</p><p><bold>Conclusions</bold>: In the case of malignant pathology, strict selection of patients is required according to the indications, as well as compliance with all principles of "open" surgery and, first of all, radical intervention. Laparoscopic operations allow minimizing postoperative complications, shortening the course of the postoperative period, which in turn makes it possible to start a special antitumor treatment in the shortest possible time and positively influence the long‐term results of therapy</p></sec><sec id="pbc26772-sec-2120"><label>O-173</label><title>Current Surgical Intervention for Pediatric Giant Mediastinal Germ Cell Tumors</title><p><underline underline-style="single">S. Fumino</underline><sup>1</sup>, K. Sakai<sup>1</sup>, M. Higashi<sup>1</sup>, S. Aoi<sup>1</sup>, T. Furukawa<sup>1</sup>, M. Yamagishi<sup>2</sup>, M. Inoue<sup>3</sup>, T. Iehara<sup>4</sup>, H. Hosoi<sup>4</sup>, T. Tajiri<sup>1</sup></p><p><italic><sup>1</sup>Kyoto Prefectural University of Medicine, Pediatric Surgery, Kyoto, Japan; <sup>2</sup>Kyoto Prefectural University of Medicine, Pediatric Cardiovascular Surgery, Kyoto, Japan; <sup>3</sup>Kyoto Prefectural University of Medicine, Thoracic Surgery, Kyoto, Japan; <sup>4</sup>Kyoto Prefectural University of Medicine, Pediatrics, Kyoto, Japan</italic></p><p><bold>Background/Objectives</bold>: Giant mediastinal germ cell tumors (MGCTs) in children are rare tumor and often form large mass at diagnosis. Especially, malignant MGCTs invade surrounding vital tissues, then, they require a well‐planned advanced surgical approach. We retrospectively reviewed our surgical strategy for giant MGCT.</p><p><bold>Design/Methods</bold>: Five children with a median age of 5 years (range 1‐15) with giant MGCT were treated in our institute from 2012 to 2016. The medical charts were retrospectively reviewed.</p><p><bold>Results</bold>: The initial diagnosis was made by tumor markers and image inspection in all cases. Benign teratomas (2 girls) were treated with upfront surgery, and malignant MGCT (3 boys) showed elevated alpha‐fetoprotein and underwent radical tumorectomy after neo‐adjuvant chemotherapy. After detailed 3D‐CT, radical tumor excision was performed supported by a skilled pediatric cardiovascular surgeon. The basic approach was as follows: under cardiopulmonary support (CPS) (or with CPS on standby), via median sternotomy, the pericardium and phrenic nerve were resected <italic>en bloc</italic> with the tumor, followed by diaphragmatic plication. Open biopsy was performed via lateral thoracotomy in 1 patient with malignancy, who showed dense adhesion and fistula formation in the lung at radical resection; lobectomy via hemi‐clamshell incision was required. Although major postoperative complications including pericardial effusion, chylothorax requiring thoracoscopic repair, hoarseness, and pyothoraxchylothorax were noted, no deaths or severe sequelae occurred in this series.</p><p><bold>Conclusions</bold>: MGCTs could be initially diagnosed based on tumor markers and imaging findings. Therefore, open biopsy should be avoided because of severe adhesion at surgery. Preoperative 3D‐CT and CPS can ensure safety during advanced surgery. Well‐functioned surgical team including not only pediatric surgeons but also pediatric cardiovascular surgeons and thoracic surgeons is required for successful treatment.</p></sec><sec id="pbc26772-sec-2130"><label>O-174</label><title>Incidence, Treatment and Outcome of Recurrent (REC) Malignant Germ Cell Tumors (MGCT): A Single Institution Experience</title><p><underline underline-style="single">S. Agarwala</underline><sup>1</sup>, S. Bakhshi<sup>2</sup>, A. Dhua<sup>1</sup>, M. Sirnivas<sup>1</sup>, S. Thulkar<sup>3</sup>, M. Jana<sup>4</sup>, K. Devasenathipathy<sup>4</sup>, A.K. Bisoi<sup>5</sup>, V. Bhatnagar<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Pediatric Surgery, Delhi, India; <sup>2</sup>BRAIRCH‐ All India Institute of Medical Sciences, Medical Oncology, Delhi, India; <sup>3</sup>BRAIRCH‐ All India Institute of Medical Sciences, Radiology, Delhi, India; <sup>4</sup>All India Institute of Medical Sciences, Radiodiagnosis, Delhi, India; <sup>5</sup>CN Center‐ All India Institute of Medical Sciences, Cardiovascular and Thoracic surgery, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: To evaluate the incidence and the outcome of treatment of recurrent (REC) malignant germ cell tumors (MGCT).</p><p><bold>Design/Methods</bold>: Prospectively maintained data of patients of MGCT managed in the pediatric solid tumor clinic from June 1994 through December 2016 was analyzed to evaluate the incidence of recurrence. Outcome was evaluated in terms of 5‐year overall survival (OS) and disease free survival (DFS).</p><p><bold>Results</bold>: Of the 152 MGCT cases (83 gonadal; 69 extragonadal)treated in this period, there were 49(32.2%) recurrences. 113 of 152(74.3%) were primarily treated by us and of these 18(15.9%) recurred. Thirty‐nine(25.7%) were referred to us after resection and of these 31(79.5%)were with recurrence. The incidence of recurrence was similar among gonadal(27/83‐32.5%) and extra‐gonadal tumors(22/69‐31.9%). The incidence of recurrence was maximum for testicular and least among the ovarian tumorts(Testicular: 53.3%; Sacrococcygeal:41.7% and ovarian:7.9%). The 5‐year OS and RFS for the 152 patients was 0.9(95CI 0.83‐0.94) and 0.61(95CI 0.52‐0.69). Among the 49 REC‐MGCT, 42(85.7%) were alive and 7(14.3%) had died giving a 5‐year OS of 0.75(95CI 0.51‐0.89). However, of these 42 survivors only 21(50%) were DFS, while the remaining 21 had progressive disease at last follow‐up and chose to discontinue treatment. The 5‐yr OS was 0.67 for extragonadal and 0.82 for gonadal recurrences (p=0.25). Of the 18 recurrences after primary treatment by us, 14 were alive (5‐yr OS 0.49) but only 3 were DFS. Among the 31 REC‐MGCT referred after surgery elsewhere, 28 were alive (5‐yr OS 0.89) and 18 achieved DFS.</p><p><bold>Conclusions</bold>: The incidence of REC‐MGCT was 32% and it was similar for gonadal and extra‐gonadal tumors (32.5% vs 31.9%). Though the 5‐year OS for REC‐MGCT was 0.75, only 50% achieved DFS. The OS was better (0.89 vs 0.49) for patients who were operated elsewhere and came to us with recurrence (chemo naïve patients) than our own patients (heavily pre‐treated).</p></sec><sec id="pbc26772-sec-2140"><label>O-175</label><title>Methadone Potentiates the Cytostatic Effect of Doxorubicin in Rhabdomyosarcoma and Rhabdoid Tumors</title><p><underline underline-style="single">E. Schmid</underline><sup>1</sup>, A.S. Raible<sup>1</sup>, M.J. Stagno<sup>1</sup>, R. Handgretinger<sup>2</sup>, S.W. Warmann<sup>1</sup>, J. Fuchs<sup>1</sup></p><p><italic><sup>1</sup>University Hospital, Department of Pediatric Surgery and Pediatric Urology, Tuebingen, Germany; <sup>2</sup>University Hospital, Department of Pediatric Oncology and Haematology, Tuebingen, Germany</italic></p><p><bold>Background/Objectives</bold>: Rhabdoid tumors (RTs) and Rhabdomyosarcoma (RMS) are aggressive pediatric malignancies. Both entities show an intrinsic refractoriness to standard chemotherapy in advanced tumor stages, which is associated with poor prognosis. Alternative therapeutic approaches and optimization of already established treatment protocols are urgently needed in these conditions. The μ‐opioid receptor (OPRM1) agonist D,L‐Methadone is frequently used for analgesia in oncological patients. Recently it has been proposed that D,L‐Methadone exert a role in influencing tumor cell growth and could be a promising candidate for optimization of already established treatments. So far there are no related data in pediatric solid tumors.</p><p><bold>Design/Methods</bold>: Effects of combined D,L‐Methadone and doxorubicin treatment on two rhabdomyosarcoma and two rhabdoid tumor cell lines were measured using the following outcome data: cell growth inhibition (MTT‐assay), doxorubicin uptake and efflux, apoptosis and reactive oxygen species (ROS) production (flow cytometry), gene expression studies (real‐time PCR), cell migration (wound healing assay) and apoptosis and expression of the OPRM1 receptor (Western Blot).</p><p><bold>Results</bold>: Exposure of doxorubicin significantly increased the OPRM1 expression, whereas D,L‐Methadone increased doxorubicin uptake and decreased doxorubicin efflux. Moreover, combined treatment with D,L‐Methadone and doxorubicin resulted in a suppressed tumor cell growth and enhanced apoptosis in all cell lines, which was mediated by increased generation of ROS and through down‐regulation of apoptosis proteins. Furthermore treatment with D,L‐Methadone and doxorubicin resulted in a significant decrease of migration in comparison to D,L‐Methadone or doxorubicin alone.</p><p><bold>Conclusions</bold>: In summary, this new and innovative therapeutic approach displayed a strong anti‐tumor effect in rhabdomyosarcoma and rhabdoid tumor cell lines. The combination therapy of doxorubicin and D,L‐Methadone merits further investigation as an auspicious anticancer drug in RTs and RMS, especially when conventional treatment regimens show limited effects in the clinical setting.</p></sec><sec id="pbc26772-sec-2150"><label>O-176</label><title>Development of a National Competency‐Based Board Certification in Pediatric Surgical Oncology, the Coming‐of‐Age of a Subspeciality. Is There Room for a Global Curriculum?</title><p><underline underline-style="single">P. Lezama‐del Valle</underline><sup>1</sup></p><p><italic><sup>1</sup>Hospital Infantil De Mexico Federico Gomez, SURGERY / SURGICAL ONCOLOGY SERVICE, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: The surgical treatment of complex pediatric oncology cases is often beyond the scope of expertise of general Pediatric Surgeons. To overcome this situation, formal training in Pediatric Surgical Oncology (PSO) has been established in several comprehensive cancer centers across various countries, but formal Assessment for Credentialing and Certification has not been established before. The goal of this paper is to present the process of developing the Competency‐based Board Certifying Exam.</p><p><bold>Design/Methods</bold>: A Model of Clinical Practice in PSO was defined, stratifying which patients could be under the care of General Pediatric Surgeons and which ones should be referred to PSO specialists. The competencies for PSO fellows and specialists were identified and integrated in a profile, and a Certifying Process was planned, with the Mexican Board of Oncology and the National Committee for Specialty Boards.</p><p><bold>Results</bold>: A team of examiners was assembled, and Item banking was done in sufficient amount to have a 150 MCQ test, and clinical vignettes were designed for the oral exam. The blueprinting for both components of the examination was completed and pilot tested. The actual examination took place in a two‐day session in Mexico City, Mexico, in February 2017. Psychometric analysis of the MCQ items was conducted and the pass‐fail standard was established. Three examinees sat for this first iteration, 2/3 obtained a passing score.</p><p><bold>Conclusions</bold>: Where there is overlapping of competencies between two or more specialties, constructing a Clinical Model of Practice involving the stakeholders can avoid potential conflict. This model allowed us to clarify boundaries and develop the competencies and facilitated blueprinting. The performance of examinees was as expected. The competency‐based profile and the contents of the specifications could be discussed within the IPSO community to assemble a proposal for a global curriculum in this subspeciality.</p><p><bold>Acknowledgment</bold>: this work had the support of the FAIMER Institute.</p></sec></sec><sec id="pbc26772-sec-2160"><title>Treatment and Care ‐ Nursing</title><sec id="pbc26772-sec-2170"><label>O-177</label><title>Key Worker Role in End‐of‐Life Care: ‘I'D Call it Knitting….Making Sure That The Five or Six Elements That We Needed, They Were Knitted Together… Coordinated’</title><p><underline underline-style="single">S. Aldiss</underline><sup>1</sup>, A. Martins<sup>2</sup>, F. Gibson<sup>1,3</sup></p><p><italic><sup>1</sup>University of Surrey, School of Health Sciences‐ Faculty of Health and Medical Sciences, Guildford, United Kingdom; <sup>2</sup>University College London Hospitals NHS Foundation Trust, Cancer Clinical Trials Unit, London, United Kingdom; <sup>3</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, Centre for Outcomes and Experience Research in Children's Health‐ Illness and Disability, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: The delivery of end of life care requires a broad range of health and other care services, this may include hospitals, hospices, primary care and community professionals, ambulance services, dedicated palliative care teams, and other support providers. Essential to this delivery are good communication, care coordination, and effective networking: the specialist nurse key worker role has been identified to provide this service. The aim was to evaluate the role of the key worker in end of life care of children and young people with cancer from the perspective of parents and key workers.</p><p><bold>Design/Methods</bold>: In depth semi‐structured interviews with eight parents and fourteen key workers. Interview transcripts were analysed using framework analysis.</p><p><bold>Results</bold>: Four main themes were identified: coordination of care; continuity of care; positive relationships and communication. Key workers provided clinical, emotional, educational and practical support to families, through the coordination of care, their clinical experience and expertise and their relationships with families and other professionals. Having a key worker facilitated professionals and parents to get to know one another and become emotionally close. Positive relationships with key workers were built on trust and open and honest communication, through which parents were provided with individualised support and reassurance. This support and reassurance in conjunction with key workers’ coordination of resources enabled parents and children to have the choice of where to receive their care. Support in the palliative phase has its own challenges: lack of out of hours palliative care available in the community, establishing complex palliative care packages in the home and providing effective bereavement support for families. Some key workers offered a 24 hour on call service for these families.</p><p><bold>Conclusions</bold>: Having a key worker facilitated individualised and coordinated care and support. The positive key worker‐parent relationship is central to the support given to and received by parents.</p></sec><sec id="pbc26772-sec-2180"><label>O-178</label><title>Trajectories of Procedure‐Related Distress in Children with Cancer: Risk Factors and Impact of Persistent Distress on Long‐Term Quality of Life</title><p><underline underline-style="single">J. Bai</underline><sup>1</sup>, F.W.K. Harper<sup>2,3</sup>, L. Penner<sup>2,3</sup></p><p><italic><sup>1</sup>Emory University, NHW School of Nursing, Atlanta, USA; <sup>2</sup>Wayne State University, School of Medicine, Detroit, USA; <sup>3</sup>Wayne State University, Karmanos Cancer Institute, Detroit, USA</italic></p><p><bold>Background/Objectives</bold>: Children with cancer undergo distressing treatment‐related procedures such as port starts. Traumatic experiences with these procedures can result in negative healthcare outcomes in children with cancer. Limited data exist on the trajectories of distress over time and the impact of distress trajectories on children's quality of life (QOL) in cancer. This study aimed to characterize the longitudinal trajectories of distress in children with cancer and identify the risk factors of persistent distress and the relationships between distress trajectories and children's QOL.</p><p><bold>Design/Methods</bold>: Forty‐three children with cancer were selected from a parent study (R01CA138981). These children underwent 2‐3 continuous port start procedures. Child distress levels during these procedures were assessed by multiple raters using the Revised Wong‐Baker Faces Scale (T1, T2 and T3). The assessed risk factors included: demographic and clinical variables at baseline (T0) and parent dispositional attributes (Empathic concern, depression, negative and positive emotions) at T0‐T3. Parents reported children's QOL using PedsQL<sup>TM</sup> Cancer Module at 3‐month and 9‐month after the last procedure (T4 and T5). The group‐based trajectory modeling was used to identify the child distress clusters; the logistic regression analyzed the risk factors of the distress trajectory clusters; the Mann‐Whitney U test was conducted to examine the associations between the distress trajectory groups and QOL.</p><p><bold>Results</bold>: The group‐based trajectory modeling found two distinct trajectory clusters of distress: low distress group (n=24) and persistent distress group (n=19). The logistic regression showed that parent negative emotions at T3 can predict a significantly higher distress level (Odds Ratio=1.2, p=0.046). The Mann‐Whitney test showed that the persistent distress group had a lower procedural anxiety at T4 (p=0.004) and at T5 (p=0.005), but more pain/hurt at T5 (p=0.023) and more worries at T4 (p=0.023) and at T5 (p=0.042).</p><p><bold>Conclusions</bold>: Targeted interventions toward parents may help improve QOL for children with the persistent distress following painful procedures.</p></sec><sec id="pbc26772-sec-2190"><label>O-179</label><title>Does Parent Distress = Child Distress in Pediatric Cancer? A Review of the Literature</title><p><underline underline-style="single">D.M. Bakula</underline><sup>1</sup>, C.M. Sharkey<sup>1</sup>, M.N. Perez<sup>1</sup>, K.L. Gamwell<sup>1</sup>, H.C. Espeleta<sup>2</sup>, J.M. Chaney<sup>1</sup>, L.L. Mullins<sup>1</sup></p><p><italic><sup>1</sup>Oklahoma State University, Psychology, Stillwater, USA; <sup>2</sup>Oklahoma State Univeristy, Psychology, Stillwater, USA</italic></p><p><bold>Background/Objectives</bold>: The burden and stress of pediatric cancer leaves both parents and children vulnerable to psychological distress (e.g., depression, anxiety, posttraumatic stress). Extant research suggests that a relationship exists between parental distress and child distress, such that parents who are more distressed tend to have children who are more distressed. Although Drotar (1997) reviewed this relationship, the studies reviewed may no longer be considered contemporary. The aim of this project is to provide a current and comprehensive review of literature on this important relationship.</p><p><bold>Design/Methods</bold>: A review of published pediatric psycho‐oncology literature was conducted via PsychInfo and PubMed. Articles were chosen for review if they examined both parent and child distress, were available in English, and were peer‐reviewed.</p><p><bold>Results</bold>: Forty‐one articles were identified as meeting inclusion criteria, of which 26 articles reported a significant positive relationship between parent distress and child distress, 5 articles reported that no relationship existed between parent and child distress, and 10 articles did not report an assessment of the relationship between parent and child distress. Articles that supported the existence of a relationship had sample sizes ranging from N=22‐N=309, utilized both cross‐sectional (n=22) and longitudinal (n=4) designs, and reported modest correlational coefficients (r=.10‐.60).</p><p><bold>Conclusions</bold>: Available research indicates that there is indeed a relationship between parent psychological distress and child psychological distress. Although it is unclear whether the relationship is directional or transactional in nature, findings are consistent with transactional stress and coping models of adjustment to chronic health conditions. Although meta‐analyses of parent‐targeted interventions have not shown consistent reduction of subsequent child distress (e.g., Pai et al., 2006), this review suggests that parent‐targeted interventions may be capable of reducing child distress. However, given that not all studies reported analyses on this relationship, findings may be incomplete. Further research is needed to assess the mechanisms through which this relationship exists.</p></sec><sec id="pbc26772-sec-2200"><label>O-180</label><title>High Levels of Intensity of Moral Distress among Healthcare Professionals– A National Study in Pediatric Oncology</title><p><underline underline-style="single">C. Bartholdson</underline><sup>1</sup></p><p><italic><sup>1</sup>Karolinska Institutet, Women and Children´s Health, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Caring for children with cancer involves complex decisions about life and death. Moral distress occurs when one has an idea of what is ethically correct but cannot act accordingly, as well as when one does not know what is ethically correct but has to make a decision. Studies of moral distress in pediatrics are rare. The overall aim was to describe healthcare professional's experiences of moral distress in pediatric oncology in Sweden.</p><p><bold>Design/Methods</bold>: Data collection was performed by using a translated and culturally adapted paediatric version of the Moral Distress Scale‐Revised (MDS‐R).The instrument contains statements about difficult ethical situations. Healthcare professionals from all pediatric cancer centers (n=6) in Sweden completed the questionnaire by rating both level of disturbance and frequency related to each statement. Total moral distress score was calculated by summing the composite scores (i.e. level of disturbance x frequency). Descriptive analysis of data was conducted using Package for Social Sciences (SPSS).</p><p><bold>Results</bold>: In total 279 participants answered the questionnaire (response rate > 80%). Nurses and nurse‐assistants reported similar level of disturbance (intensity) whereas physicians reported slightly lower scores; the mean value for all professional groups was notably high. Furthermore nurses stated higher frequencies of distressing events compared to physicians and nurse‐assistants; the mean value for all professional groups was at the lower end of the scale. Nurses also reported higher level of total moral distress scores compared to other professions.</p><p><bold>Conclusions</bold>: Ethically distressful situations disturbs healthcare professionals a lot in pediatric cancer care in Sweden, however the situations does not occur very often. Nurses seem to experience the situations more distressful than the others. By understanding the experiences related to moral distress, ethical support can be tailored to assist healthcare professionals.</p></sec><sec id="pbc26772-sec-2210"><label>O-181</label><title>Children's Participation in Decisions, Discussions, and Actions in a Pediatric Oncology Setting in New Delhi, India: A Focused Ethnography</title><p><underline underline-style="single">J. Behan</underline><sup>1</sup>, A. Tsimicalis<sup>1</sup>, F. Carnevale<sup>1</sup>, S. Bakhshi<sup>2</sup>, B. Bhattacharjee<sup>2</sup>, R.S. Arora<sup>3</sup></p><p><italic><sup>1</sup>McGill University, Ingram School of Nursing, Montreal, Canada; <sup>2</sup>Dr. B. R. A. Institute Rotary Cancer Hospital‐ All India Institute of Medical Sciences, Department of Medical Oncology, New Delhi, India; <sup>3</sup>Max Super Speciality Hospital, Paediatric Oncology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: A participatory approach was adopted to better understand children's actual and desired participation in decisions, discussions, and actions in a pediatric oncology setting in New Delhi, India. Nested within an emerging field of childhood ethics, this study was guided by a moral experience framework, which seeks to understand how children's values or beliefs are being realized, or not, in their everyday lives.</p><p><bold>Design/Methods</bold>: A focused ethnography was conducted in 3 pediatric oncology settings including private, public, and not‐for‐profit hospitals. Over a 3‐month period, key informant interviews were conducted, followed by a series of participant observations and semi‐structured interviews with children with cancer, and retrieval of key documents. Data were consolidated between sources, open‐coding was conducted within/between sources, emerging codes categorized, and themes comparatively analysed.</p><p><bold>Results</bold>: 7 key informants were consulted to share their understanding of the moral experience of children with cancer. Key text analysis informed the contextual descriptions of the settings. Semi‐structured interviews were conducted with 22 children, 11 of which were observed during their cancer care. Participants, with varying cancer diagnoses, ranged in age from 3 to 17 years‐old. A conceptualization of participation was developed based on how the children actually or desire to navigate their worlds within the pediatric oncology setting. Children verbally and nonnegativerbally expressed their preferences for participation and elicited various dimensions to decision‐making, discussions, and actions. Children expressed varying views with regards to decision‐making concerning their health, cancer treatment, assent, nutrition, and housing. Children's participation varied in discussions and involved asking questions, listening, body language/facial expressions, and speaking. Children's actions included developing an understanding of their illness, expressing likes/dislikes and desires, addressing problems, recollecting their experiences, receiving treatment, and engaging in teaching and play.</p><p><bold>Conclusions</bold>: Children actively participate in matters affecting them. An advanced understanding of their values and beliefs may enhance their clinical encounters.</p></sec><sec id="pbc26772-sec-2220"><label>O-182</label><title>Intravenous Chemotherapy at Home: standard care?! Intravenous Chemotherapy at Home for Children with Cancer. A Pilot Study</title><p><underline underline-style="single">A. Beukhof</underline><sup>1</sup>, N. Kok<sup>1</sup>, M. van de Wetering<sup>1</sup></p><p><italic><sup>1</sup>Emma Children's Hospital/Academic Medical Center, Pediatric Oncology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: The treatment of a child with leukemia currently takes place in the hospital, which means that the child has to come to the hospital daily or weekly for treatment for a period of at least 2 years. In January 2017, a pilotstudy was started in these children to receive intravenous chemotherapy at home, with the aim to give the chemotherapy safe and efficient at home and improve the quality of life for children and families.</p><p><bold>Design/Methods</bold>: Through a partnership between the Department of Pediatric Oncology at the Emma Children's Hospital in Amsterdam, ‘Kinderthuiszorg’ (Children's home care organization ) and ‘Mediq Tefa’ (specialist in medical devices) it's possible to give intravenous chemotherapy at home.</p><p>We performed an explorative comparative study, using questionnaires about the social impact of the treatment and a shortened validated Quality‐Of‐Life‐list. As a baseline the questionnaires were taken before the start of the pilot, and will be repeated after 6 weeks and at the end of the pilot (at 3 months).</p><p>This pilot consisted of 30 parents and 10 children (>12 years) and took place from January 2017‐april 2017</p><p><bold>Results</bold>: The baseline results showed that 100% of the children and 86.6% of the parents are enthusiastic when chemotherapy is given at home. When they will get treatment at home 90% of the children and 83.3% of the parents expected to plan their life better, only 30% of parents expected to take time off work and 83.3% expected that the child will not miss school. The results of the pilot will be presented at the SIOP 2017.</p><p><bold>Conclusions</bold>: Because of specialized nurse practitioners in pediatric oncology both in the hospital and at home the possibility is created to administer the chemotherapy for these children at home and we hope this will be standard of care in the future!</p></sec><sec id="pbc26772-sec-2230"><label>O-183</label><title>Home Care Services for Sick Children: Health Care Professionals’ Conceptions of Challenges and Facilitators</title><p><underline underline-style="single">C. Castor</underline><sup>1</sup>, I. Hallström<sup>1</sup>, H. Hansson<sup>2</sup>, K. Landgren<sup>1</sup></p><p><italic><sup>1</sup>Lund University, Department of Health Sciences, Lund, Sweden; <sup>2</sup>Copenhagen University Hospital Rigshospitalet, Paediatrics and Adolescent Medicine, Copenhagen, Denmark</italic></p><p><bold>Background/Objectives</bold>: Families often prefer home care to hospital care and the number of home care services for children is increasing. The aim of this study was to explore healthcare professionals’ conceptions of caring for sick children in home care services.</p><p><bold>Design/Methods</bold>: An inductive qualitative design was used. Seven focus group interviews with 36 healthcare professionals from multidisciplinary home care services were performed. Data was analysed stepwise using a phenomenographic analysis.</p><p><bold>Results</bold>: Three description categories emerged <italic>“A challenging opportunity”, “A child perspective”, “Re‐organise in accordance with new prerequisites”</italic>. Providing home care for children was a challenging but rewarding task for healthcare professionals used to care for adults conceived to evoke both professional and personal challenges such as feelings of inadequacy and fear, and professional growth such as increased competence and satisfaction. Conceptions of whether the home or the hospital was the best place for care differed. Adapting to the child's care was conceived as important. Cooperation with paediatric departments and a well‐functioning teamwork were important organisational aspects.</p><p><bold>Conclusions</bold>: A sufficient number of referred children and enabling healthcare professionals to be part of the re‐organising and implementation processes might facilitate the home care services for sick children. Enough time and good teamwork must be emphasised. Early referrals, continuous cooperation with paediatric clinics complemented with individualised support when a child is referred were prerequisites that make up for the low number of paediatric patients and facilitate confidence and competence. The study was funded by the Swedish Childhood Cancer Foundation and The Swedish Research Council for Health, Working Life and Welfare.</p></sec><sec id="pbc26772-sec-2240"><label>O-184</label><title>How do Children with Cancer Experience the Needle Insertion Into Venous Access Port ?</title><p><underline underline-style="single">S.E. Egeland</underline><sup>1</sup>, H. Lie C<sup>2</sup>, E. Ruud<sup>1</sup></p><p><italic><sup>1</sup>Oslo University Hospital‐ 0027 Oslo‐ Norway., Department of Paediatric Haematology and Oncology‐ Unit of Paediatric and Adolescent Medicine., Oppegård, Norway; <sup>2</sup>University of Oslo, Oslo University Hospital‐ 0027 Oslo‐ Norway., Oslo, Norway</italic></p><p><bold>Background/Objectives</bold>: Many children with cancer fear painful needle‐related procedures. VAP is commonly used during cancer treatment, yet little is known about how children experience VAP needle insertion procedures.</p><p><bold>Aim</bold>: The aims were to 1) explore levels of <italic>distress before</italic> and <italic>pain</italic><italic>after</italic> the VAP‐ needle insertion among young patients, and 2) to explore how patients’ self‐report of distress and pain correlate with the proxy‐reports by parents and nurses.</p><p><bold>Design/Methods</bold>: The sample included 43 patients, aged1‐16 years with cancer, treated at two Norwegian hospitals and who had VAP for 2‐6 months. The patient (if old enough), parent and nurse performing the procedure completed a questionnaire before and after the procedure. The questionnaire consisted of three developmentally‐appropriate 10‐point distress and pain scales (higher scores indicate greater distress/pain). Data were analysed using descriptive statistics and non‐parametric correlations.</p><p><bold>Results</bold>: For the young children (1‐5 years), the median distress score was 8 (range 0‐9) and pain score was 4 (range 0‐10). Median distress and pain scores for the school‐age children (6‐12 years) were 3 (range 0‐9) and 1 (range 0‐10), and for the adolescents (age 13‐16) were 0 (range 0‐6) and 1 (range 0‐5) respectively. Ten children (23%) reported high distress and/or pain scores (7‐10). The distress level did not correlate with the pain level for the patient's ratings (rho=0.19, p=0.286) or nurses ratings (rho=0.33, p=0.062), but did for the parent ratings (rho=0.42, p=0.015). Patients’ ratings of distress and pain correlated with the proxy ratings of parents (rho=0.83, p<0.001 and rho=0.92, p<0.001) and nurses (rho=0.89, p<0.001 and rho=0.88, p<0.001).</p><p><bold>Conclusions</bold>: Reported distress and pain associated with VAP needle‐inserting procedures were greater among the youngest children compared to the older children. However, clinicians should be aware of the great individual differences and offer a CVK that does not involve needle‐ insertion to highly distressed children.</p></sec><sec id="pbc26772-sec-2250"><label>O-185</label><title>Age‐Appropriate Preparations for Children with Cancer Undergoing Radiothearpy ‐ A Feasibility Study</title><p><underline underline-style="single">J. Gardling</underline><sup>1</sup>, E. Törnqvist<sup>1</sup>, M. Edwinson Månsson<sup>1</sup>, I. Hallström<sup>1</sup></p><p><italic><sup>1</sup>Faculty of Medicine‐ Lund university, Department of Health Sciences, Lund, Sweden</italic></p><p><bold>Background/Objectives</bold>: Due to the need for complete immobility during radiotherapy children often require daily general anesthesia for several weeks. The aim of this study was to test age‐appropriate information and preparation procedures for children with cancer undergoing radiotherapy for feasibility and effectiveness in terms of the need for general anesthesia and anxiety.</p><p><bold>Design/Methods</bold>: In a quasi‐experimental controlled clinical trial, 17 children aged 3 to 18 years receiving age‐appropriate preparation including seven parts were compared with 16 children in a control group receiving traditional care. Feasibility in terms of recruitment, compliance and acceptability was assessed. Effectiveness was assessed by the primary outcomes: number of children who underwent treatment without general anesthesia and their respective fractions. Validated instruments measured the children's anxiety and emotional behavior as secondary outcomes.</p><p><bold>Results</bold>: The preparation parts were delivered as intended without any additional staff and without dropouts in the intervention group and therefore found feasible and acceptable. Three children planned for general anesthesia in the intervention group completed their treatments including 73 fractions awake. Children receiving general anesthesia, regardless of group, showed significantly higher negative emotional behavior. No statistic significances were found concerning the number of children receiving general anesthesia or anxiety.</p><p><bold>Conclusions</bold>: Avoiding general anesthesia for children with cancer going through radiotherapy gives benefits in terms of fewer risks and restrictions in life for the child, fewer disturbances in daily life for the family and lower costs for health care. Giving children individualized preparation may decrease the need for general anesthesia during radiotherapy treatment.</p><p><bold>Acknowledgements</bold>: We would like to express our gratitude to the participating children and to the Swedish Childhood Cancer Foundation for funding.</p></sec><sec id="pbc26772-sec-2260"><label>O-186</label><title>Effects of Age‐Appropriate Preparations for Children with Cancer Undergoing Radiotherapy on Parents’ and Family Functioning, Parents’ Anxiety and Hospital Costs</title><p><underline underline-style="single">J. Gardling</underline><sup>1</sup>, M. Edwinson Månsson<sup>1</sup>, E. Törnqvist<sup>1</sup>, I. Hallström<sup>1</sup></p><p><italic><sup>1</sup>Faculty of Medicine‐ Lund university, Department of Health Sciences, Lund, Sweden</italic></p><p><bold>Background/Objectives</bold>: The aim was to explore if age‐appropriate information and preparation procedures for children with cancer undergoing radiotherapy 1) decrease the impact on parents’ and family functioning, parents’ anxiety and 2) reduce hospital costs compared to traditional care.</p><p><bold>Design/Methods</bold>: The study was a part of a quasi‐experimental controlled clinical trial consisting of a control group including 31 parents to 16 children receiving traditional care and an intervention group including 32 parents to 17 children receiving age‐appropriate preparation including seven parts. Validated instruments measured the parents’ and family functioning and parents´ anxiety. Hospital costs were calculated.</p><p><bold>Results</bold>: Parents in the intervention group showed statistic significantly better communication throughout their child's radiotherapy. At their child´s last fraction, parental social functioning showed to have improved with a statistical significance. Parents of children receiving general anesthesia, regardless of group, showed statistically significant higher levels of anxiety. Hospital costs were lower in the intervention group.</p><p><bold>Conclusions</bold>: If only few children are able to go through RT without GA it imply for the individual child fewer risks and restrictions. For the parents´ and family, the benefits are in terms of less impact on their functioning and less anxiety. For the hospital, it means lower costs and increased availability of anesthesia personnel, enabling to prioritize other areas of care.</p><p><bold>Acknowledgements</bold>: We would like to express our gratitude to the participating parents and to the Swedish Childhood Cancer Foundation for funding.</p></sec><sec id="pbc26772-sec-2270"><label>O-187</label><title>Preparing Children for Blood Tests: Using Arts‐Based Techniques in Creative Research and App Development</title><p><underline underline-style="single">F. Gibson</underline><sup>1</sup>, N. Oldrieve<sup>2</sup>, J. Bayliss<sup>3</sup>, S. Hall<sup>4</sup>, V. Jones<sup>5</sup>, I. Manning<sup>4</sup>, L. Shipway<sup>6</sup>, K. Oulton<sup>7</sup></p><p><italic><sup>1</sup>Great Ormond Street Hospital for Children NHS Foundation Trust and University of Surrey, Centre for Outcomes and Experience Research in children's Health‐ Illness and Disability Orchid and School of health Sciences, London, United Kingdom; <sup>2</sup>St Georges Hospital, Community Children's Nurse in Children's Services, London, United Kingdom; <sup>3</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, The Louis Dundas Centre Oncology Outreach and Palliative Care, London, United Kingdom; <sup>4</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, GOSH Arts, London, United Kingdom; <sup>5</sup>Freelance Consultant, N/A, Melbourne, Australia; <sup>6</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, Charles West Division, London, United Kingdom; <sup>7</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, Centre for Outcomes and Experience Research in Children's Health‐ Illness and Disability ORCHID, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Blood tests can be distressing for children and prove detrimental to their psychological well‐being with some developing needle phobia, or anticipatory/procedural distress. Preparation for blood taking at the onset of illness is therefore invaluable in minimising such distress.</p><p><bold>Design/Methods</bold>: Our aim was to develop a ‘tool’ to help prepare children for blood tests. This was a two‐phased study. A user‐experience design, using creative arts/art making was utilized. In Phase 1, through a range of activities, children looked at the importance of blood within the body, and why we need to take blood. Participants made some blood of their own using some unconventional ingredients. They invented comical ‘blood’ characters and made life‐size maps of their own bodies. The ‘BLOOD QUEST’ game was subsequently developed. In Phase 2 we assessed its usefulness and effectiveness with a small group of children (and parents) with haematological disorders who were in/attending hospital. From this foundation work the ‘app’ prototype emerged.</p><p><bold>Results</bold>: Phase 1: 7 hospitalised children aged 4‐12 participated in a range of creative activities, drawing on their own experience to help design what the ‘BLOOD QUEST’ game looked like. Phase 2: 15 children played the game prior to having blood taken and completed a questionnaire about its usefulness and effectiveness. Most children who tested the game found it fun and informative. Half reported that playing the game made them feel better about having their blood taken and half felt the same. The game was more suited to children aged 4‐7.</p><p><bold>Conclusions</bold>: The collaboration between children and an illustrator enabled ‘idea elaboration’ allowing children to have genuine influence in research and in shaping the prototype game into the ‘app’. This presentation will focus on the creative steps that resulted in the Blood Quest ‘app’, available for the ipad and now free to download from the Apple App Store.</p></sec><sec id="pbc26772-sec-2280"><label>O-188</label><title>Multilingual Encounters in Paediatric Cancer Care – Risking Patient Safety by Insufficient use of Interpreters</title><p><underline underline-style="single">J. Granhagen Jungner</underline><sup>1</sup>, E. Tiselius<sup>2</sup>, K. Blomgren<sup>1</sup>, P. Pergert<sup>1</sup></p><p><italic><sup>1</sup>Karolinska Institutet, Women's and children's health, Stockholm, Sweden; <sup>2</sup>Stockholm University‐ Institute for Interpreting and Translation Studies, Department of Swedish Language and Multilingualism, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Overcoming language barriers in multilingual paediatric cancer care will improve the care situation and reduce costs, but knowledge is needed about how communication is performed and facilitated in situations with language barriers as well as how these situations can be improved. The purpose of this study was to investigate communication over language barriers between healthcare professionals (HCP) in paediatric cancer care and patients/families with limited proficiency in the country's official language.</p><p><bold>Design/Methods</bold>: We combine communication and interpreting sciences with medical and nursing sciences in an interdisciplinary project to increase knowledge about the complexity of communication over language barriers. A national multi‐site cross‐sectional survey has been performed using the Language Barriers and Communication Questionnaire (LBCQ). HCP (physicians, registered nurses, and nurse assistants) at all paediatric cancer centres (n=6) in Sweden were invited to participate and statistical analyses were performed using SPSS.</p><p><bold>Results</bold>: A total of 281 questionnaires have been collected (response rate > 80%). A majority of the respondents reported that the use of interpreters to a high degree increase patient safety (87%) and patient/parent participation in care (83%). Despite this, 50% of the respondents reported that they never or seldom use interpreters to take arrival status or medical history, and 48% report that they never or seldom use interpreters when they educate the patients and families.</p><p><bold>Conclusions</bold>: By identifying weaknesses in communication between HCP and patients/families with limited proficiency in the official language, we identified areas in this communication which needed to be strengthened. Results showed that HCP were aware that the use of interpreters increases patient safety and participation in paediatric cancer care. However, there is an insufficient use of interpreters, for example when taking arrival status and medical history or educating patients and the families, representing a risk to patient safety.</p></sec><sec id="pbc26772-sec-2290"><label>O-189</label><title>Symptom Trajectories in Children Receiving Treatment for Leukemia: A Latent Class Growth Analysis with Multitrajectory Modeling</title><p><underline underline-style="single">M.C. Hooke</underline><sup>1</sup>, M.J. Hockenberry<sup>2</sup>, C. Rodgers<sup>2</sup>, O. Taylor<sup>3</sup>, K.M. Koerner<sup>4</sup>, I. Moore<sup>4</sup>, M.E. Scheurer<sup>3</sup>, P. Mitby<sup>5</sup>, W. Pan<sup>2</sup></p><p><italic><sup>1</sup>University of Minnesota, School of Nursing, Minneapolis, USA; <sup>2</sup>Duke University, School of Nursing, Durham‐ NC, USA; <sup>3</sup>Baylor College of Medicine, Hematology/Oncology, Houston‐ TX, USA; <sup>4</sup>University of Arizona, School of Nursing, Tucson‐ AZ, USA; <sup>5</sup>Children's Minnesota, Cancer and Blood Disorders Program, Minneapolis‐ MN, USA</italic></p><p><bold>Background/Objectives</bold>: Cancer treatment symptoms play a major role in determining the health of children with cancer. Symptom toxicity often results in complications, treatment delays, and therapy dose reductions that can compromise leukemia therapy and jeopardize chances for long‐term survival. Critical to understanding symptom experiences during treatment is the need for exploration of “why” inter‐individual symptom differences occur; this will determine who may be most susceptible to symptom toxicities. The objective of this study was to examine specific symptom trajectories during the first 18 months of childhood leukemia treatment.</p><p><bold>Design/Methods</bold>: A repeated‐measures research design was used to evaluate treatment‐related symptom associations experienced by patients, ages 3 to 18 years, receiving treatment for a new diagnosis of acute lymphoblastic leukemia at four sites. Symptom trajectories were explored over four time periods: initiation of post‐induction therapy, 4, 8 and 12 months into post‐induction therapy. Self‐report symptom measures included fatigue, sleep disturbances, pain, nausea, and depression. Parents of children ages 3 to 6 completed proxy measurements. Latent class growth analysis was used to classify patients into distinctive groups with similar symptom trajectories based on response patterns on the self‐report measures over time.</p><p><bold>Results</bold>: Among 236 participants, 48% were ages 3 to 6 years, 33% were 7 to 12 years, and 19% were 13 to 18 years. Sex was evenly distributed; 46% were Hispanic. Three latent classes of symptom trajectories were identified and classified into mild, moderate, and severe symptom trajectories. The only demographic characteristic with a significant relationship to membership in the latent class symptom trajectories was race/ethnicity. Other demographic characteristics including leukemia risk levels showed no significant relationships.</p><p><bold>Conclusions</bold>: This study is unique in that groups of patients with similar symptoms were identified rather than groups of symptoms. Further research using latent class growth analysis is needed.</p><p>Funding: National Institutes of Health RO1 CA 1693398</p></sec><sec id="pbc26772-sec-2300"><label>O-190</label><title>Three‐Phase Intervention Study of the Need for Systematic Prevention and Treatment of Constipation in Children and Adolescents with Cancer</title><p><underline underline-style="single">M.D. Jeppesen</underline><sup>1</sup>, N. Panduro<sup>1</sup>, H. Haslund<sup>2</sup></p><p><italic><sup>1</sup>Aalborg University Hospital, Department of pediatric oncology, Aalborg, Denmark; <sup>2</sup>Aalborg University Hospital, Clinical nursing research unit, Aalborg, Denmark</italic></p><p><bold>Background/Objectives</bold>: Children and adolescents with cancer often suffer from constipation due to chemotherapy and treatment with opioids. Constipation may cause pain, anal fissures, septicemia and delays in therapy. Studies also show that constipation contributes to poor quality of life. Because of the many specialized tasks requiring the attention of nurses and doctors, management of constipation may be neglected. Furthermore, nausea and pain may make oral intake of laxatives difficult.</p><p><bold>Design/Methods</bold>: The aim of the study is to reduce severe complications caused by constipation in children and adolecents with cancer. The study is a three‐phase intervention study. In the first phase the problem is explored through audit of 15 patient records, parent reported “stool diaries” using the Bristol Scale, focus group interviews with pediatric oncology doctors and nurses, and interviews with parents and patients. In the second phase a practice guideline will be developed based on the results of phase one, and in the third phase the interventional guideline is implemented.</p><p><bold>Results</bold>: In phase one data from parents showed that it was difficult to accommodate extensive oral information at the time of diagnosis, and that it is difficult to ensure sufficient intake of laxatives. The diary has helped clarify stool patterns and has stressed the importance of using a common assesment tool. Data from health care professionals demonstrates the importance of systematic observation, documentation and care of constipation.</p><p><bold>Conclusions</bold>: Phase one has shown that systematic management of constipation is needed and that the use of an assesment tool by both parents and health care professionals may support this. In phase two the guideline will be developed, integrating the continuous use of Bristol scale to maintain focus on constipation care. In addition, we will write an information pamphlet for parents and promote the use of a stool diary.</p></sec><sec id="pbc26772-sec-2310"><label>O-191</label><title>Why all the Questions? Parent descriptions of the Role of Question‐Asking in Their Learning: A Report from the Children's Oncology Group</title><p><underline underline-style="single">K. Kelly</underline><sup>1</sup>, J. Withycombe<sup>2</sup>, K. Stegenga<sup>3</sup>, C. Rodgers<sup>4</sup></p><p><italic><sup>1</sup>Children's National Health System, Nursing Research and Quality Outcomes, Washington DC, USA; <sup>2</sup>Emory University, Nell Hodgson Woodruff School of Nursing, Atlanta GA, USA; <sup>3</sup>Children's Mercy Hospital, Division of Hematology‐ Oncology and Bone Marrow Transplant, Kansas City MO, USA; <sup>4</sup>Duke University, School of Nursing, Durham NC, USA</italic></p><p><bold>Background/Objectives</bold>: Question‐asking is used by researchers to evaluate parent understanding of their child's cancer and by clinicians to assess parents’ response to education. During qualitative research to describe parent perceptions of new diagnosis education (Rogers et.al., 2016), we noted a preponderance of interview data related to parent and clinician question‐asking. Because question‐asking was not related to our original study aim, we returned to our data to complete this secondary analysis of parent descriptions of questioning after diagnosis of their child's cancer.</p><p><bold>Design/Methods</bold>: Using secondary qualitative analysis we reviewed the dataset (n=20 parents) to assure adequate fit between our research question and the data and then conducted a retrospective interpretation. Data were first independently coded by two members of the study team. After this, all coding decisions were discussed during weekly investigator calls with consensus agreement reached by all investigators.</p><p><bold>Results</bold>: Question‐asking was not a straightforward process. A negative response to, “Do you have any questions?” was not always an accurate assessment of parent understanding. Parents sometimes reported being too confused or overwhelmed to ask. Parent questioning indicated unmet information needs or that parents were learning, e.g. parents who asked many questions were verifying their understanding with clinicians. Parents quickly learned from whom or where they could get their questions answered, which included written or online educational materials. Parents also expressed questions that they asked of themselves which included worries about their child's diagnosis and treatment or their ability to care for their child while balancing other life events.</p><p><bold>Conclusions</bold>: Understanding and responding to the reasons behind parent question‐asking could facilitate parent learning and coping. Given the nuances ascribed to question‐asking in parents, research is needed to also understand question‐asking in children and adolescents with cancer.</p><p>Funding: Children's Oncology Group‐National Cancer Institute/National Clinical Trials Network Group Operations Center Grant (U10CA180886: PI‐Adamson); Alex's Lemonade Stand Foundation.</p></sec><sec id="pbc26772-sec-2320"><label>O-192</label><title>Oncology Rounds Checklist Enhances Safety by Promoting Closed Loop Communication</title><p>E. Lambrinos<sup>1</sup>, L. Morrissey<sup>1</sup>, <underline underline-style="single">A. Federico</underline><sup>1</sup></p><p><italic><sup>1</sup>Boston Children's Hospital, Oncology, Boston‐ MA, USA</italic></p><p><bold>Background/Objectives</bold>: Communication breakdown between clinicians is a leading cause of medical errors. Dr. Atul Gawande describes that the implementation of checklists improves team communication and ultimately decrease patient complications[i]. At our institution, oncology rounds offer dedicated time when the multidisciplinary team and family gather to set daily goals. Interruptions are common, creating risk for lost or misinterpreted information. In response, a daily rounds checklist was designed to promote closed loop communication at the conclusion of rounds.</p><p>[i] Gawande, A. (2010). <italic>Checklist Manifesto, The (HB)</italic>. Penguin Books India.</p><p><bold>Design/Methods</bold>: In 2013, a paper‐based checklist was piloted, providing a tool to prompt the oncology team to summarize and confirm the patient plan before leaving the bedside. The checklist is read aloud and takes 20‐30 seconds to complete, summarizing patient information including treatment plan, upcoming diagnostic tests/procedures, antimicrobials, fever plan, nutrition, lines/tubes, labs, and discharge planning. Once the feasibility of a rounds checklist was established, a web‐based checklist was created which interfaces with the patient medical record, offering the capability to store patient information and access medication lists, labs, and other current information.</p><p><bold>Results</bold>: A rounds checklist prompts the team to pause and recap the plan for the day, promoting clear communication and ensuring that responsibilities are clearly delineated. Clinicians report that potential errors are identified, discharge planning is initiated earlier, and unnecessary or redundant labs, tests and medications are intercepted.</p><p><bold>Conclusions</bold>: Checklists are cost effective tools that improve patient outcomes and decrease untoward complications. At our institution, a daily rounds checklist has been found to improve the efficiency of rounds while promoting a climate of safety and family centered care. Future directions include the development of quality reports to determine the checklist's impact on safety, patient and staff satisfaction, clear delineation of roles and responsibilities, and cost savings.</p></sec><sec id="pbc26772-sec-2330"><label>O-193</label><title>Caregiver ‐ Burden and Coping Strategies in a Low Resource Country: A Quantitative and Exploratory Study Conducted in an Indian Pediatric Oncology Unit</title><p><underline underline-style="single">A. Mahajan</underline><sup>1</sup>, M. BODHANWALA<sup>2</sup>, B. AGARWAL<sup>3</sup>, Y.K. AMDEKAR<sup>2</sup></p><p><italic><sup>1</sup>B.J.Wadia Hospital for Children, Paediatric Hemato‐Oncology department., Mumbai, India; <sup>2</sup>B J Wadia Hospital For Children, Administration, Mumbai, India; <sup>3</sup>B J Wadia Hospital For Children, Pediatric Hematology Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Caregivers often experience difficulty in helping children with cancer to cope with the emotional impact of the illness because of their own psychological distress. In a low resource country, the child and family often stagger from hospital to hospital and city to city seeking care, thus creating emotional and financial hardships. We assessed the level of burden and coping among caregivers of children diagnosed with cancer in one Mumbai hospital.</p><p><bold>Design/Methods</bold>: A quantitative and exploratory study (by questionnaire) was conducted in 2015‐2016, with 100 caregivers, to measure their physical, psychological, social, occupational, spiritual and economic burden and coping strategies. Level of burden and coping strategies were co‐related with selected demographic variables. Data was analysed and measured using t‐ test and coefficient of correlation techniques.</p><p><bold>Results</bold>: Ninety‐five per cent of caregivers were parents; (mothers 60% fathers 35%) and others 5%. A high level of burden among caregivers was observed mainly in parents. Mothers’ emotional strain due to the child's illness and their ability to manage it and family cohesion were predictive of distress, both concurrently and prospectively. The greater use of self ‐directed coping strategies was related to higher levels of distress, for the fathers, and high levels of burden due to financial and employment problems were related to number hospital admissions for the child were significant.</p><p><bold>Conclusions</bold>: Findings shows that long‐term cancer treatment attributes to an increase in caregiver burden and the impact of stress on parental quality of life. Unfortunately, caregiver adopted coping strategies can be fleeting due to fears of relapse and the uncertainty about their child's disease condition. Health care providers can identify gaps in the provision of a holistic clinical and psycho‐social care to overcome caregiver burden and support caregivers to adopt appropriate coping strategies.</p></sec><sec id="pbc26772-sec-2340"><label>O-194</label><title>Evaluation of Parent‐Child Conversations Surrounding Li Fraumeni Syndrome Genetic Testing</title><p><underline underline-style="single">M. Belinda</underline><sup>1</sup>, J. Valdez<sup>2</sup>, J. Gattuso<sup>1</sup>, S. Ogg<sup>1</sup>, B. Walker<sup>1</sup>, J. Bosi<sup>1</sup>, K. Nichols<sup>2</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Division of Nursing Research, Memphis, USA; <sup>2</sup>St. Jude Children's Research Hospital, Division of Cancer Predisposition, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Advances in genetic technologies have revealed a growing number of heritable disorders associated with an increased risk to develop cancer during childhood. Dialogues about cancer genetic testing and the implications of genetic risk status on children rest primarily with parents. It is vital to understand if, when and how parents and children communicate about genetic testing for heritable cancer.</p><p>The study objective is to determine whether and how parents communicate with their children about genetic testing for Li‐Fraumeni syndrome (LFS), a rare and highly penetrant cancer predisposing condition.</p><p><bold>Design/Methods</bold>: Semi‐structured interviews examined parents’ decisions regarding the pursuit of LFS testing for their children and the communications surrounding test results. Transcripts were evaluated using a grounded theory approach to determine parents decision to initiate a conversation with their children and their self‐efficacy for holding this conversation.</p><p><bold>Results</bold>: This study evaluated interviews from 14 parents whose children tested positive for LFS. All 14 parents emphasized the importance of involving their child(ren) in conversations about undergoing LFS genetic testing and disclosure of the test results. Many parents self‐identified as being from a “cancer family”. Based on negative past experiences consisting of exclusion from conversations regarding cancer, these parents stated that they would approach communications about cancer with their children in a more open and inclusive manner. Nevertheless, evaluation of the interviews showed that only 9 of 14 parents (64%) actually disclosed the LFS test result to their child(ren).</p><p><bold>Conclusions</bold>: While parents express a desire for open conversations with their child(ren) regarding LFS genetic testing, such discussions do not always occur. Communication is essential to enable understanding of genetic risk status and compliance with treatment, prevention and surveillance measures. Development of educational materials and other interventions to facilitate age‐appropriate parent‐child conversations about genetic testing and genetic risk status for cancer is needed.</p></sec><sec id="pbc26772-sec-2350"><label>O-195</label><title>Oncology Nurse Case Managers: Improving Care for Children in Sub‐Saharan Africa</title><p><underline underline-style="single">N. Mariam</underline><sup>1</sup></p><p><italic><sup>1</sup>Uganda Cancer Institute, Nursing, kampala, Uganda</italic></p><p><bold>Background/Objectives</bold>: Treatment adherence plays a critical role in cancer management and leads to better clinical outcomes. Treatment adherence is a significant issue at the Uganda Cancer Institute (UCI), with many patients abandoning treatment before it is complete. The primary reasons for this, we believe, are poor communication, lack of social and financial supports. The role of nurse case manager (CM) was developed to improve patient outcomes by addressing these issues.</p><p><bold>Objectives</bold>:</p><p>1. Describe the role of nurse case managers in improving treatment adherence and clinical outcomes for patients treated at the Uganda Cancer Institute.</p><p><bold>Design/Methods</bold>: Barriers to treatment adherence were identified and the role of CM was developed to address these issues. based on personal experience as a CM on the pediatric ward for 4 years at the UCI.</p><p><bold>Results</bold>: UCI is the only cancer treatment center in Uganda, treating over 30,000 patients annually from Uganda and surrounding countries. Treatment begins 2 to 4 weeks after diagnosis due to the complex health care navigation processes and limited resources of families. Before CM, these ongoing challenges frequently led to treatment abandonment. Now, the CM is the first contact for patients when they arrive at UCI and are given our contact information so they can contact us. We assess the family's social and financial resources, explain the diagnosis, treatment plan including the number of hospital visits and treatment duration. We closely monitor the patients’ progress and facilitate communication between the patient, family, and clinicians. We follow‐up between hospital visits, provide counseling, and direct nursing. Most importantly, we advocate for our patients by relaying patient concerns to clinicians, mobilizing funds when possible, and connecting families with community resources.</p><p><bold>Conclusions</bold>: Oncology treatments are increasingly complex, and present unique challenges for oncology nurses in resource limited countries like Uganda. Nurse case managers will play an important role in improving outcomes.</p></sec><sec id="pbc26772-sec-2360"><label>O-196</label><title>Survey Reveals Barriers to the Delivery of Quality Pediatric Oncology Nursing Care in Low‐ and Mid‐Income Countries (L&MIC)</title><p><underline underline-style="single">L. Morrissey</underline><sup>1</sup>, M. Lurvey<sup>1</sup>, C. Sullivan<sup>2</sup>, S. Day<sup>3</sup>, L. Abramowitz<sup>4</sup>, J. Challinor<sup>5</sup>, R. Hollis<sup>6</sup>, G. Afungchwi<sup>7</sup>, P. Rehana<sup>8</sup></p><p><italic><sup>1</sup>Boston Children's Hospital, Hematology/Oncology Nursing, Boston, USA; <sup>2</sup>St. Jude Research Hospital, Internationa Outreach Program, Memphis, USA; <sup>3</sup>St. Jude Research Hospital, International Outreach Program, Memphis, USA; <sup>4</sup>University of California at San Francisco UCSF Hospital, Nursing, San Francisco, USA; <sup>5</sup>Unaffiliated, Unaffiliated, Amsterdam, Netherlands Antilles; <sup>6</sup>Leeds Teaching Hospitl NHS Trust, Nursing, London, United Kingdom; <sup>7</sup>Banso Baptist Hospital, Oncology Nursing, Banso, Cameroon; <sup>8</sup>Indus Childrens CAncer Hospital, Oncology Nursing, Karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: In 2014, the SIOP PODC Nursing Workgroup published baseline standards describing elements of nursing care essential to promote optimal patient outcomes. The SIOP Baseline Standards Taskforce developed a validated survey to measure the degree to which nursing standards are being met in paediatric oncology programs worldwide, and to compare responses from low, mid and high income countries (HIC) to identify trends by income level.</p><p><bold>Design/Methods</bold>: A validated survey addressing the six baseline standards was electronically distributed to a convenience sample of 208 pediatric oncology nurses from 64 countries. The survey was translated into four languages and administered in REDCap.™ Responses were compared based on World Bank defined income levels.</p><p><bold>Results</bold>: A 50% response rate from 104 nurses from 56 countries was achieved. Results revealed that nurse staffing levels on oncology wards and intensive care units in L&MIC are significantly lower than HIC (p < .0001). Nurses in LIC nurses caring for oncology patients are rotated more frequently (65% vs. 97%, p = .002) and are less likely to receive formal orientation programs. Significant differences exist in the inclusion of nurses in multidisciplinary meetings (p < .0001). Resources for safe care such as infusion pumps and personal protective equipment are often insufficient in L&MIC. Evidence based policies are available in 64.5% of reporting LIC, compared to 96.7% in HIC (p = .003).</p><p><bold>Conclusions</bold>: Results from the SIOP PODC Baseline Standards survey indicate that significant gaps exist in staffing levels, education, resources and institutional support for L&MIC pediatric oncology nurses. Survey results will be used to advocate for increased nursing support in L&MIC pediatric cancer units. Further research will determine if adherence to the baseline standards for pediatric oncology nurses is linked to favorable patient outcomes.</p></sec><sec id="pbc26772-sec-2370"><label>O-197</label><title>Pediatric Oncology Nurses' Experiences with Prognosis‐Related Communication</title><p><underline underline-style="single">A. Newman</underline><sup>1</sup></p><p><italic><sup>1</sup>Medical College of Wisconsin, Pediatric Oncology, Milwaukee, USA</italic></p><p><bold>Background/Objectives</bold>: Providers in pediatric oncology are faced with the challenge of communicating the devastating news of a cancer diagnosis and prognosis. While the initial conversation regarding prognosis is generally considered the responsibility of the physician, patients and family members will subsequently turn to nurses for clarification of the information presented. If nurses are excluded from initial conversations, they may feel as though they are “working in the dark,” trying to answer questions while not contradicting what the physician said. Little has been reported regarding pediatric oncology nurses’ experiences with such communication. The purpose of this research was to examine nurses’ experiences with prognosis‐related communication (PRC) and the associations with interprofessional collaboration, quality of care, and nurse moral distress.</p><p><bold>Design/Methods</bold>: A mixed‐methods approach utilizing an online survey incorporating validated measures of PRC, interprofessional collaboration, quality of care, and moral distress accompanied by focus groups was used to meet study objectives.</p><p><bold>Results</bold>: Findings demonstrated that nurses strongly agreed that prognostic disclosure is critical for decision making, but are challenged in determining their role. Nurses who had more years of experience, more training in PRC, worked outpatient or inpatient/outpatient, and indicated higher levels of collaboration reported more positive experiences with PRC. A significant correlation was identified between experiences with PRC and collaboration, and both were significantly associated with measures of quality of care and moral distress.</p><p><bold>Conclusions</bold>: Nurses should work to be active participants in PRC. When nurses sense that prognostic discussions have not occurred or if clarity is needed, nurses should feel confident in approaching physician colleagues to ensure parent understanding and satisfaction around communication. Future research and education should aim to develop interprofessional training to enhance communication and collaboration among nurses and physicians to ensure the highest quality of communication and care to patients and families.</p></sec><sec id="pbc26772-sec-2380"><label>O-198</label><title>Accidental Dislodgment and Obstruction of Central Venous Catheters as a Nursing Care Indicator at an Brazilian Pediatric Oncology Hospital</title><p><underline underline-style="single">R.C. Ribeiro</underline><sup>1</sup>, A. Ribeiro<sup>1</sup>, L. Lima<sup>1</sup>, F.F. Gonçalves<sup>2</sup>, V. Kremer<sup>2</sup>, W.E. Oliveira Júnior<sup>2</sup></p><p><italic><sup>1</sup>Barretos Childrens Cancer Hospital, Quality Department, Barretos, Brazil; <sup>2</sup>Barretos Childrens Cancer Hospital, Pediatric Surgery Department, Barretos, Brazil</italic></p><p><bold>Background/Objectives</bold>: Use of Central Venous Catheters (CVC) is essential in children when treating malignant diseases. The maintenance of catheter reflects the quality of nursing care. Catheter obstruction or accidental dislodgement due to traction are non‐infectious complications and can be considered as a quality indicator in an oncologic pediatric hospital setting. Our purpose was analyze those complications related to CVC removal in a hospitalized pediatric oncology patients from a developing country hospital.</p><p><bold>Design/Methods</bold>: A prospective analysis using the reporting system (SAS Interact ®) from a pediatric oncology hospital at a developing country database between February 2016 to August 2016. We analyzed demographic features, rate of CVC removal due to non‐infectious complications (accidental dislodgment or catheter obstruction) and the number of patients with CVC per day, multiplied by 100.</p><p><bold>Results</bold>: Hundred‐fourteen CVC were inserted into 110 children during the 6‐month period. From 110 catheters removed, thirteen were due to non‐infectious reasons, nine related to accidental dislodgment, four to obstruction. Average catheter life was 12.8 days, with a total of 911 catheter days. Regarding CVC events, the pediatric ward had an average of 143 CVC insertions per month, and an incidence of CVC removal of 0.85 per 100 catheter‐days. At Bone Marrow Transplant Unit had an average of 59 CVC patients per month, and removal incidence of 1.07 per 100 catheter days. The Pediatric Intensive Care Unit had an average of 118 CVC patients per month, what represented 60% of it occupation, and removal incidence of 0.11 per 100 catheter days. Overall hospital CVC removal incidence was 0.41 per 100 catheter days.</p><p><bold>Conclusions</bold>: Non‐infectious CVC removal can be used as an indicator of nursing care at pediatric oncology hospitals and give an assertiveness related of improvements, to decrease this rate improving children nursing care.</p></sec><sec id="pbc26772-sec-2390"><label>O-199</label><title>Telephone Triage: Standardized Practice in Paediatric Oncology</title><p><underline underline-style="single">L. Ollett</underline><sup>1</sup>, K. O'Driscoll<sup>1</sup>, S. Forrest<sup>1</sup>, J. Palmer<sup>1</sup></p><p><italic><sup>1</sup>Great North Childrens Hospital, Paediatric Oncology, Newcastle, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Paediatric Oncology nurses are often the first point of contact for overwhelmed parents. Patients are often assessed over the telephone with regards to acute oncology emergencies and advice/symptom management. Nurses are expected to make clinical decisions regarding patient care without visually assessing the patient or using a systematic uniformed approach. The Great North Children hospital, a principal treatment centre (PTC) has adopted the use of the United Kingdom Oncology Nursing Society (UKONS) Telephone Triage Kit. An audit as to the effectiveness of the tool was conducted.</p><p><bold>Design/Methods</bold>: The UKONS telephone triage kit provides a pathway for a nurse assessment over the telephone. The nurse will use a traffic light toxicity grading system to initiate emergency treatment or advice. In addition, patients who score an amber toxicity are required a 24 hour call back to promote early intervention and patient safety. A retrospective peer review of telephone triage calls were evaluated including diagnosis, time of call, duration of call, main complaint, toxicity grading and patient journey over a four month period from January 2016.Nurses perceptions and challenges of using the tool in the clinical environment were also explored.</p><p><bold>Results</bold>: 384 calls were received within the four month period, this having a significant impact on service provision as the average call lasted ten minutes. Data indicated nursing staff gave concise advice and symptom management using a valid tool. Nurses reported using toxicity grading gave them confidence and consistency in the advice offered. Highlighted areas for improvement included documentation regarding patient details and establishing contact within 24 hours after the initial telephone call.</p><p><bold>Conclusions</bold>: The UKONS triage tool is an invaluable resource within PTC setting. Data collected was discussed with management to allocate resources appropriately. Further educational and peer review sessions to highlight the importance of documentation and telephone call back are recommended.</p></sec><sec id="pbc26772-sec-2400"><label>O-200</label><title>AYA Involvement in Cancer Treatment Decision Making: An Ethnographic Study</title><p><underline underline-style="single">K. Pyke‐Grimm</underline><sup>1</sup>, B. Halpern‐Felsher<sup>2</sup>, L. Franck<sup>3</sup>, R. Goldsby<sup>4</sup>, R. Rehm<sup>3</sup></p><p><italic><sup>1</sup>Lucile Packard Children's Hospital, Center for Nursing Excellence, Stanford, USA; <sup>2</sup>Stanford, Department of Pediatrics, Palo Alto, USA; <sup>3</sup>UCSF, School of Nursing, San Francisco, USA; <sup>4</sup>UCSF, Department of Pediatrics, San Francisco, USA</italic></p><p><bold>Background/Objectives</bold>: Survival rates among adolescent and young adult (AYA) cancer patients have improved minimally over the past decade. AYAs experience treatment non‐adherence rates as high as 60% that can lead to relapse and even death. Open communication, positive family relationships and involvement of AYAs in treatment decisions and illness management support treatment adherence. However, there is limited research exploring AYA involvement and experiences in treatment decision‐making (TDM). The purpose of this ongoing study is to explore and describe AYA experiences with cancer TDM.</p><p><bold>Design/Methods</bold>: Twelve AYAs on treatment for cancer and within one year of their diagnosis participated in an interpretive ethnographic study that included interviews and informal participant observation. Participants were asked to reflect on a major TDM experience (e.g., clinical trial or surgery) and other decisions since diagnosis. Analysis included field notes, analytic memos and coding of interview transcripts using Atlas.ti.</p><p><bold>Results</bold>: Preliminary findings were drawn from 22 interviews with 12 AYAs (6 male, 5 female, 1 non‐binary) between 15 and 20 years old. AYAs distinguish between major treatment decisions and care preferences. Involvement in decision‐making varied from having no involvement in the decision, accepting the decision, being involved in discussions and assuming a shared or primary role in decision‐making and for some, changed over time. AYAs preferred parental involvement and appreciated their support in TDM. Friends and other family members were supportive but not involved in TDM. Factors influencing TDM included uncertainty about the treatment, altruism and quality of life.</p><p><bold>Conclusions</bold>: Findings highlight the range of involvement of the AYA in TDM. Overall, they felt informed, part of discussions and viewed themselves as sharing in or making treatment decisions. AYA preferences for participation in TDM may vary over time and by type of decision. Parents play a particularly important supportive role.</p></sec><sec id="pbc26772-sec-2410"><label>O-201</label><title>Intervention to Improve Adherence to the Use of Personal Protective Equipment for the Administration of Chemotherapy</title><p>L. Segovia<sup>1</sup>, <underline underline-style="single">L. Rojas</underline><sup>1</sup>, P. Francisca<sup>1</sup>, A. Torelli<sup>1</sup></p><p><italic><sup>1</sup>Hospital Luis Calvo Mackenna, Unidad de Oncologia, Santiago, Chile</italic></p><p><bold>Background/Objectives</bold>: Chemotherapy administration is a high risk procedure for nursing staff because of the potential teratogenic, carcinogenic, mutagenic damage and other toxic effects associated with exposure. In the oncology unit of the Hospital Luis Calvo Mackenna there are protocols of administration, based on the recommendation of international organisms. The unit has all the necessary personal protective elements (PPE) for safe administration. Every nurse who joins the unit receives a comprehensive four‐week orientation program that emphasizes the safe administration of chemotherapy, content that is reinforced annually in the continuing education program. Adherence to protocol compliance is monitored monthly by applying a checklist. This checklist assesses aspects of safety management for both the patient and the nursing staff. The item related to staff protection assesses whether the nurses use all the PPE described in the protocol. Monitoring conducted in August 2016 shows that 100% of nurses are not using all the PPE defined in the protocol.</p><p><bold>Design/Methods</bold>: In September 2016, an educational intervention to 100% of the Oncology Nurses was carried out focused on chemotherapy safe handling and administration. In October of the same year the checklist is reapplied.</p><p><bold>Results</bold>: 83% of the Oncology Nurses do not use all the PPE according to the Chemotherapy Administration Protocol. 100% of the nurses assesses do not use eye protection and 17% do not use gloves.</p><p><bold>Conclusions</bold>: Despite all the information and training that nurses receive, there is a low adherence to the policy and protocol, which mainly impacts on a potential risk to the health of nurses. A new intervention is proposed to know the reason for this low adherence by the nurses.</p></sec><sec id="pbc26772-sec-2420"><label>O-202</label><title>Parental Distress 6 Months After a Pediatric Cancer Diagnosis in Relation to Family Psychosocial Risk at Diagnosis</title><p><underline underline-style="single">S. Schepers</underline><sup>1,2,3</sup>, S.M. Sint Nicolaas<sup>4</sup>, H. Maurice‐Stam<sup>3</sup>, L. Haverman<sup>3</sup>, C.M. Verhaak<sup>4</sup>, M.A. Grootenhuis<sup>2,3</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Department of Psychology, Memphis, USA; <sup>2</sup>Princess Maxima Center for pediatric oncology, Psychosocial Research and Care Innovation, Utrecht, The Netherlands; <sup>3</sup>Emma Children's Hospital‐ Academic Medical Center, Psychosocial Department, Amsterdam, The Netherlands; <sup>4</sup>Amalia Children's Hospital‐ Radboud University Medical Center, Medical Psychology, Nijmegen, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Parents of children with cancer are at increased risk for experiencing distress and it is important to identify families that are in need for support at an early stage. This study aimed to (1) assess fathers’ and mothers’ distress as measured by the Distress Thermometer for parents (DT‐P) at 6 months post‐diagnosis (T2), and (2) assess if distress at 6 months post‐diagnosis could be predicted from Psychosocial Assessment Tool (PAT) risk profiles at approximately one month post‐diagnosis (T1).</p><p><bold>Design/Methods</bold>: A sample of 119 mothers and 98 fathers completed the DT‐P at T2. The sample was compared to a healthy reference group of 671 mothers and 463 fathers. The DT‐P consists of a thermometer score (ranging from 0‐10, >= 4 is clinical distress), and problem domains (total, practical, social, emotional, physical, cognitive, and parenting <2 years and ≥2 years of age). The PAT, a family psychosocial risk screener, was assessed at T1. Within the pediatric cancer group, DT‐Ps of parents with elevated total PAT‐scores (targeted/clinical) were compared to DT‐Ps of parents with low PAT‐scores (universal).</p><p><bold>Results</bold>: Parents of children with cancer more often reported clinical distress than parents of healthy children on the DT‐P thermometer score (fathers: 59.2% versus. 32.3%, <italic>p</italic><.001, mothers: 63% versus 42.3%, <italic>p</italic><.001) and reported more problems on all DT‐P domains (<italic>p</italic><.001‐.042), except for the parenting domain for children <2 years of age. Furthermore, parental distress at T2 was predicted from family psychosocial risk at T1, as parents with elevated total PAT‐scores reported more problems than parents with low PAT‐scores on the DT‐P thermometer score (fathers: <italic>p</italic>=.026, mothers <italic>p</italic>=.018) and on most of the DT‐P domains (<italic>p</italic><.001‐1.00).</p><p><bold>Conclusions</bold>: The results of this study point towards the importance of family psychosocial risk screening at diagnosis, and the need for applying tailored interventions, such that later parental distress can be reduced or prevented.</p></sec><sec id="pbc26772-sec-2430"><label>O-203</label><title>The Interventions Core to Pediatric Oncology Nursing: A National Survey of Clinical Application in China</title><p>J. Sun<sup>1</sup>, <underline underline-style="single">N. Shen</underline><sup>2</sup>, H. Lu<sup>2</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center, Nursing, Shanghai, China; <sup>2</sup>Shanghai Children's Medical Center, Nursing, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: In our previous study, we investigated the application frequency of 5 hospitals in 4 regions, and found that there had differences between the hospital in North China and the others, but the single hospital can not fully represent the region. Thus, in this study, we want to know national clinical application of the core interventions performed by pediatric oncology nurses and analysis its variance of region.</p><p><bold>Design/Methods</bold>: An online survey of application frequency of 82 core interventions, conducted by experts consensus based on Nursing Interventions Classification (NIC) was send to all the pediatric oncology nurses from 18 nation wide selected hospitals in January to February 2016.</p><p><bold>Results</bold>: 444 clinical nurses completed the questionnaire. The application rate of 82 core interventions were from 74.1% to 100%. As to domains, there were differences in basic and complex physiology domain (North China vs East, West China, p<0.05), behavioral and family domain (North China vs East China, p<0.05), health system domain (North China vs West China, p<0.05). As to classes, nurses in different region performed different frequently (p<0.05) in elimination, immobility management, nutrition support, self‐care promotion, electrolyte and acid‐base management, respiratory management, skin/wound management, thermoregulation, tissue perfusion management, Patient Education, Psychological Comfort Promotion, lifespan care.</p><p><bold>Conclusions</bold>: Core interventions of pediatric oncology nursing were frequently performed in practice, showing difference by the groups of regions, especially North China. When doing the homogenization training, trainers need to think about the reasons for the different clinical application by regions as shown in this study, in order to develop different proportion of training content.</p><p><bold>Found</bold>: Shanghai Municipal Education Commission – Gaoyuan Nursing Grant Support (Hlgy16073qnhb)</p></sec><sec id="pbc26772-sec-2440"><label>O-204</label><title>Development of a Pediatric Oncology Nursing Curriculum in Cambodia</title><p><underline underline-style="single">E. Sniderman</underline><sup>1</sup>, P. Johnson<sup>2</sup>, S. Sath<sup>3</sup></p><p><italic><sup>1</sup>Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Hematology‐ Oncology‐ Stem Cell Transplant, Chicago, USA; <sup>2</sup>Children's Mercy Hospital, Pediatric Oncology, Kansas City, USA; <sup>3</sup>Angkor Hospital for Children, Pediatrics/Pediatric Oncology, Siem Reap, Cambodia</italic></p><p><bold>Background/Objectives</bold>: The Angkor Hospital for Children (AHC) is one of two facilities in Cambodia that offers comprehensive cancer care for children, however treatment is currently limited to retinoblastoma and Wilms tumor, partially due to nursing limitations. AHC's pediatric oncology program is currently expanding. As part of the hospital's five‐year strategic plan, the development of a nursing curriculum and ongoing mentoring and training of oncology nurses were identified as priorities.</p><p><bold>Design/Methods</bold>: In conjunction with ASCO‐Health Volunteers Overseas, volunteer oncology Nurse Practitioners (NPs) visited AHC over a two year period. A formal assessment of the current knowledge base, resources, and challenges of the pediatric oncology nurses was performed using the SIOP PODC Baseline Standards for Paediatric Oncology Nursing Care in Low and Middle Income Countries. AHC nurses, educators, and other oncology team members collaborated in the assessment process.</p><p><bold>Results</bold>: The formal assessment identified gaps in knowledge, unsafe chemotherapy administration practices, and misconceptions regarding chemotherapy safety. This informed the creation of a curriculum adapted to the needs and resources of the hospital. Seven modules were created to be taught over 6 months. Content includes an introduction to childhood cancer/diseases, chemotherapy, supportive care and symptom management, infection control, emergencies, palliative care and pain management, and psychosocial considerations. Future modules will focus on late effects and central line care. Several interactive teaching strategies help create a dynamic teaching environment. Modules will be taught by the director of education and pediatric oncologist at AHC as well as by visiting international nurses/NPs.</p><p><bold>Conclusions</bold>: Nurses with specialized education and training in pediatric oncology are essential for successful comprehensive cancer care. Formal assessment using internationally accepted standards of pediatric oncology nursing care, adaptation of education to the limited resource setting, and collaboration with local team members were key steps in ensuring high quality cancer care will be provided to the children of Cambodia.</p></sec><sec id="pbc26772-sec-2450"><label>O-205</label><title>Evaluation of a Teenage and Young Adult (TYA) Long Term Follow‐Up (LTFU) Service for Survivors of Cancer in Childhood</title><p><underline underline-style="single">L. Soanes</underline><sup>1</sup>, E. Potter<sup>2</sup></p><p><italic><sup>1</sup>University College London, Children& Young People Services, London, United Kingdom; <sup>2</sup>The Royal Marsden NHS Foundation Trust, Oak Centre for Children & Young People, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Each year 1600 children are diagnosed with cancer in the United Kingdom; the survival rate for whom is now 80% (1). Survivors are known to be at increased risk of poorer psychosocial and physical outcomes than their peers (2). These effects occur soon after treatment or many years later (3), therefore it is recommended survivors follow a risk‐stratified pathway of LTFU for life (4, 5). A crucial stage of this pathway occurs in late adolescence as patients move from child to adult services, a process that should be one of proactive transition rather than sudden transfer (6).</p><p>To meet these recommendations a model of transition was introduced to children's and TYA principal treatment centre over a two year period. In 2016 a service evaluation was carried out to assess the acceptance and effectiveness of this model.</p><p><bold>Design/Methods</bold>: Using a mixed methods approach a sample of TYA aged 16‐25 years olds attending the TYA LTFU clinics were identified and data collected to measure acceptance and effectiveness of the mode through:
<list list-type="bullet" id="pbc26772-list-0019"><list-item><p>online patient experience survey</p></list-item><list-item><p>1:1 patient telephone interviews</p></list-item><list-item><p>qualitative and quantitative analysis of clinic consultations</p></list-item><list-item><p>qualitative and quantitative analysis of patient contact to the CNS for LTFU outside clinics.</p></list-item></list></p><p><bold>Results</bold>: The model of transition though largely accepted was for some a significant challenge; at times this went beyond the patient to the family, in particular mothers whose role as carer was also in transition. The need for time, a multidisciplinary and multi‐method of approach to facilitate patient knowledge and self confidence in transition was identified as a key factor in both acceptance and effectiveness of the model.</p><p><bold>Conclusions</bold>: This service evaluation has highlighted key factors in establishing a transition model and identified areas to ensure transition is truly holistic.</p></sec><sec id="pbc26772-sec-2460"><label>O-206</label><title>Sustainable Model for Nursing Education in Latin America: 10 Years Later</title><p><underline underline-style="single">C. Sullivan</underline><sup>1</sup>, L. Segovia Weber<sup>2</sup>, P. Viveros Lamas<sup>3</sup>, S. Day<sup>4</sup>, G. Rivera<sup>1</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Dept. of Global Pediatric Medicine, Memphis, USA; <sup>2</sup>Luis Calvo Mackenna Hospital, Latin American Center for Pediatric Oncology Nurisng Education, Santiago, Chile; <sup>3</sup>Luis Calvo Mackenna Hospital, Latin American Center for Pediatric Oncology Nursing Education, Santiago, Chile; <sup>4</sup>St. Jude Children's Research Hospital/University of Tennesse Health Science Center, Dept. of Global Pediatric Medicine/College of Nursing, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Ten years ago, the Latin American Center for Pediatric Oncology Nursing Education was created at Calvo Mackenna Hospital in Santiago, Chile as an initiative of the International Outreach Program at St Jude Children´s Research Hospital (SJCRH), to enhance the quality of pediatric oncology nursing care in Latin America through establishing the pediatric oncology nurse educator role.</p><p><bold>Design/Methods</bold>: The program consists of 4 weeks theoretical/skills training and clinical observation (176 hours) in pediatric oncology nursing, supportive care, and education. Theoretical portions include expositive‐participative lectures in pediatric oncology and education, using adult learning principles. Onsite and ongoing mentoring is provided in development of tailored education programs and quality projects. Program evaluation consists of pre‐/post‐tests and successful demonstration of curriculum development and delivery.</p><p><bold>Results</bold>: To date, 25 nurse educators from Mexico, Central America, South America, and the Caribbean completed the program. A network of Latin American nurse educators developed through ongoing mentoring/collaboration with graduates. Active members represent 13 hospitals in 8 countries and presently impact over 800 nurses. Additionally, quality improvement projects for correct patient identification are ongoing at several sites.</p><p><bold>Conclusions</bold>: The Latin American Center for Pediatric Oncology Nursing Education has proven to be a successful and sustainable model to promote excellence in pediatric oncology nursing education and quality in Latin America through development of the pediatric oncology nurse educator role.</p></sec><sec id="pbc26772-sec-2470"><label>O-207</label><title>Promoting Standardized Chemotherapy/Biotherapy Education in Latin America: An Aphon Initiative</title><p><underline underline-style="single">C. Sullivan</underline><sup>1</sup>, K. Belderson<sup>2</sup>, L. Segovia Weber<sup>3</sup>, P. Viveros Lamas<sup>4</sup>, J. Avila<sup>5</sup>, R. Ramos<sup>6</sup>, D. Navarro Diaz<sup>7</sup>, J. Challinor<sup>8</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Dept. of Global Pediatric Medicine, Memphis, USA; <sup>2</sup>Children's Hospital Colorado, Nursing Education, Denver, USA; <sup>3</sup>Luis Calvo Mackenna Hospital, Latin American Center for Pediatric Oncology Nurisng Education, Santiago, Chile; <sup>4</sup>Luis Calvo Mackenn Hospital, Latin American Center for Pediatric Oncology Nursing Education, Santiago, Chile; <sup>5</sup>Renaissance Doctors Hospital, Compliance, Edinburg, USA; <sup>6</sup>Stanford Children's Hospital, Hematology/Oncology, Palo Alto, USA; <sup>7</sup>Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Pediatric Oncology/Education, Guadalajara, Mexico; <sup>8</sup>UCSF, Nursing, Amsterdam, Netherlands Antilles</italic></p><p><bold>Background/Objectives</bold>: Association of Pediatric Hematology Oncology Nurses (APHON) has received numerous inquiries from nurses in low‐ and middle‐income countries (LMIC) interested in the Chemotherapy/Biotherapy certification course. APHON certification is recommended by the American Academy of Pediatrics and aligns with SIOP PODC Nursing baseline standards recommendation for formalized training in chemotherapy preparation and handling globally. In response to international interest, the International Task Force set out to evaluate the feasibility of adapting and piloting Spanish courses throughout Latin America.</p><p><bold>Design/Methods</bold>: A survey of nurses in Latin America verified interest and need for the course in 2015. Recommendations for adaptation were incorporated from two bilingual Chilean nurse educators, who took the English course at St. Jude Children's Research Hospital (SJCRH). The Task Force, Chemotherapy Committee, and Spanish WG modified/expanded the course over the next year, and materials were professionally translated with support from SJCRH. Spanish‐fluent APHON‐certified instructors were identified to teach the courses.</p><p><bold>Results</bold>: An inaugural two‐cohort pilot was held in Chile (32 nurses, April‐May 2016), followed by a second pilot with Central American nurses and an English instructor course (Associación Hemato/Oncología Pediátrica de Centro America pre‐conference at SJCRH (24/6 nurses, February 2017)). Additional pilots are scheduled in Argentina (Sociedad Latina Americana de Oncología Pediátrica (110 nurses, April 2017)) and Mexico (55 nurses, May 2017). All nurses of the Chilean pilots and 82% of nurses of the AHOPCA pilot passed the exam. Comparison of results for the four pilots will be presented.</p><p><bold>Conclusions</bold>: Since 80% of children and adolescents with cancer live in LMIC, it is paramount that their nurses have specialized training in chemotherapy/biotherapy. The APHON survey documented interest and need for standardized chemotherapy/biotherapy education across Latin America. Pilots have demonstrated course appropriateness for nurses’ practice. Future plans include developing an instructor community to promote sustainable, standardized Spanish courses and exploring expansion to other regions.</p></sec><sec id="pbc26772-sec-2480"><label>O-208</label><title>Analysis of the Interventions Performed in Pediatric Hematology‐Oncology Unit Based on Nursing Interventions Classification (NIC‐6TH)</title><p><underline underline-style="single">J. Sun</underline><sup>1</sup>, N. Shen<sup>2</sup>, H. Lu<sup>2</sup>, M. He<sup>3</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center, Nursing, Shanghai, China; <sup>2</sup>Shanghai Children's Medical Center, Nursing, Shanghai, China; <sup>3</sup>Shanghai Children's Medical Center, Pediatric Hematology‐Oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: In previous study, we used experts consensus to identify the core interventions done by pediatric hematology‐oncology nurses, but core interventions was just the interventions which nurses mostly performed in discipline.Therefore, this study was to identify all the interventions performed by pediatric hematology‐oncology nurses through records in hospital information system (HIS) and analysis its characteristic.</p><p><bold>Design/Methods</bold>: The research team selected a 42 beds pediatric hematology‐oncology unit, and drawn all the nursing interventions in nursing record and doctor's order from our HIS from 1 September 2016 to 30 December 2016, using Nursing Interventions Classification (NIC) to do the matching and then counting their frequencies.Then giving each intervention its own time and difficulty code according to NIC Time code refers to the average time needed to perform the intervention, 1=15 minutes or less; 2=16 to 30 minutes; 3=31 to 45 minutes; 4=46 to 60 minutes; 5=more than 1 hours. Difficulty code refers to the minimal education level necessary to perform the intervention in most cases, 1=nursing assistant; 2=RN ; 3=RN with post‐basic education or certification.</p><p><bold>Results</bold>: 4044 unique statements (1908 from nursing record, 2136 from doctor's order) were drawn from HIS matching to 77 interventions (56 from nursing record, 61 from doctor's order, 30 were the same).77 interventions belonged to 6 domains and 20 classes. The average difficulty was 1.88 and average time was 2.06.</p><p><bold>Conclusions</bold>: Nurses in pediatric hematology‐oncology unit performed totally 77 interventions. There still had some interventions just needed by nursing assistant but done by nurses, which should call for nurse managers to think about the suitable stuffing. The result of this study was expected to be useful in understanding how to improve pediatric hematology‐oncology nursing and the standardization of nursing interventions.</p><p><bold>Found</bold> Clinical Management Optimization Project of Shanghai Shen Kang Hospital Development Center(SHDC2014615);Shanghai Municipal Education Commission ‐ Gaoyuan Nursing Grant Support (Hlgy16073qnhb)</p></sec><sec id="pbc26772-sec-2490"><label>O-209</label><title>Checking In: The Next Generation of Pediatric Oncology Distress Screening</title><p><underline underline-style="single">L. Wiener</underline><sup>1</sup>, S. zadeh bedoya<sup>1</sup>, M. Pao<sup>2</sup></p><p><italic><sup>1</sup>NCI, Pediatric Oncology Branch, Bethesda, USA; <sup>2</sup>National Institute of Mental Health, Office of the Director, Bethesda, USA</italic></p><p><bold>Background/Objectives</bold>: An interdisciplinary group of experts and stakeholders developed evidence‐based standards for psychosocial care in pediatric cancer. One standard, supported by 149 high quality papers, recommends that youth with cancer and their family members routinely receive systematic assessments of their psychosocial needs. While valid and reliable measures are available for parents to report on their family and child's psychosocial needs, there are limited psychometrically valid self‐report measures to assess distress in medically ill children. A multi‐phase study guided the development of a brief electronic distress screen called <italic>Checking In</italic>.</p><p><bold>Design/Methods</bold>: Phase I: 281 Patient‐Caregiver‐Provider triads, with youth aged 7‐21 with cancer and other chronic illnesses completed the Distress Thermometer (DT) and measures of depression, anxiety, pain, and fatigue. Findings identified items to include in a new version of a pediatric distress screen. Phase II: 15 cognitive interviews were conducted with patients in each age group (8‐12; 13‐17; 18‐21). Health care providers gave input on development of a summary report.</p><p><bold>Results</bold>: Substantial discrepancy between parent and child specific distress symptoms on the DT indicated that parent input alone is not sufficient to identify child distress or to guide referrals. 15 most frequently endorsed symptoms were included in <italic>Checking In</italic>. Cognitive interviews tested the accuracy and quality of the items and identified errors in the response choices. Differences in wording recommendations based on age were found. Suggestions for design, format, and response options were incorporated.</p><p><bold>Conclusions</bold>: <italic>Checking In</italic> assesses emotional, physical, social, practical, and spiritual concerns of pediatric patients as well as suicidal ideation and adherence. An accompanying provider document summarizes patient and caregiver report of the child's distress in real time, to allow providers to triage services. Testing the reliability, validity, measurement variance, and responsiveness of <italic>Checking In</italic> and assessment of concordance of symptom ratings by patients and caregivers will follow.</p></sec></sec><sec id="pbc26772-sec-2500"><title>Educational Day ‐ Fertility</title><sec id="pbc26772-sec-2510"><label>O-210</label><title>Decision Support Tools in Paediatric and Adolescent Oncofertility for Clinicians and Parents</title><p><underline underline-style="single">Y. Jayasinghe</underline><sup>1</sup>, M. Kemertzis<sup>1</sup>, M. Hand<sup>2</sup>, C. Allingham<sup>3</sup>, L. Gillam<sup>4</sup>, L. Orme<sup>5</sup>, S. Jayasuriya<sup>6</sup>, M. Zacharin<sup>7</sup>, Y. Heloury<sup>8</sup>, M. McCarthy<sup>5</sup>, M. Sullivan<sup>5</sup>, M. Peate<sup>2</sup></p><p><italic><sup>1</sup>Royal Children's Hospital, Gynaecology, Melbourne, Australia; <sup>2</sup>University of Melbourne, Obstetrics & Gynaecology, Melbourne, Australia; <sup>3</sup>Notre Dame University, Medicine, Sydney, Australia; <sup>4</sup>Royal Children's Hospital, Clinical Ethics Service, Melbourne, Australia; <sup>5</sup>Royal Children's Hospital, Children's Cancer Centre, Melbourne, Australia; <sup>6</sup>Monash University, Medicine, Melbourne, Australia; <sup>7</sup>Royal Children's Hospital, Endocrinology, Melbourne, Australia; <sup>8</sup>Royal Children's Hospital, Surgery, Melbourne, Australia</italic></p><p><bold>Background/Objectives</bold>: Fertility preservation decisions for children are difficult and there is a need for decision support for clinicians and families. Our aim was to develop and evaluate electronic decisional support tools for clinicians and parents of children with cancer at The Royal Children's Hospital, Melbourne.</p><p><bold>Design/Methods</bold>: Electronic decision support systems were developed based on the literature and consultation with stakeholders. The clinician tool outlined clinician roles and responsibilities, linked to educational guidance, and included 'alerts' for best practice. Clinicians completed a survey on acceptance, and results were compared to a previous survey of 56 clinicians in 2014. The parent decision aid was based on International Patients Decision Aids Standards. Parents’ of children with cancer who had previously made a fertility preservation decision were invited to complete surveys before and after review of the decision aid.</p><p><bold>Results</bold>: Thirty‐nine oncofertility clinicians (18% involved in over 100 fertility consultations) reviewed the clinician decision support system. Compared to 2014, clinician satisfaction with fertility consults increased from 33% to 54%, and confidence from 40‐70% (p<0.005). Most (92%) wanted to improve their fertility consultation skills, and stated the clinician tool clearly outlined responsibilities, with 88% stating they would always or often use it. Thirty‐four parents consented to the decision aid study, of whom 15 reviewed the parental tool. They reported it was appealing, 'very clearly' presented (73%), 'clearly' or 'very clearly' explained their child's fertility choices (87.0%). The tool improved fertility related knowledge by 15% (p=0.04) and 87% of parents reported it would have been 'helpful', 'very helpful' or 'extremely helpful' if available when making a fertility preservation decision.</p><p><bold>Conclusions</bold>: The clinician tool appeared acceptable to clinicians however further development is required. The parental decision aid was very acceptable and improved knowledge in parents. Prospective assessment in a clinical setting is planned.</p></sec><sec id="pbc26772-sec-2520"><label>O-211</label><title>Factors Associated with Fertility‐Related Knowledge in Survivors of Pediatric Cancer</title><p><underline underline-style="single">A.C. Ferrante</underline><sup>1</sup>, N.M. Caltabellotta<sup>1</sup>, L. Nahata<sup>1</sup>, C. Gerhardt<sup>1</sup>, V. Lehmann<sup>2</sup></p><p><italic><sup>1</sup>The Research Institute at Nationwide Children's Hospital, Center for Biobehavioral Health, Columbus‐ OH, USA; <sup>2</sup>St. Jude's Children's Research Hospital, Department of Psychology, Memphis‐ TN, USA</italic></p><p><bold>Background/Objectives</bold>: Infertility is one of the most common late effects of certain cancer treatments. However, there is limited research on infertility in survivors of pediatric cancer. Thus, we assessed knowledge of cancer‐related infertility risk, perception of personal infertility risk, and knowledge of current fertility status and examined associations with demographic (i.e. gender, age, income level) and medical factors (i.e. diagnosis type, neurotoxicity of treatment).</p><p><bold>Design/Methods</bold>: Ninety‐one survivors of pediatric cancer (<italic>M</italic>=29.82 years) participated in an online survey assessing knowledge of cancer‐related infertility risk, perception of personal infertility risk, and knowledge of current fertility status. All participants were ages 20‐40, diagnosed between ages 5‐18 with leukemia (<italic>n</italic>=25), lymphoma (<italic>n</italic>=22), pediatric brain tumor (<italic>n</italic>=26), or other solid tumors (<italic>n</italic>=18), and at least 5 years post‐diagnosis.</p><p><bold>Results</bold>: Most survivors were aware of their general risk for cancer‐related infertility (n=79, 87%), which varied by type of diagnosis (<italic>p<</italic>0.001) and treatment (<italic>p=</italic>0.032), such that survivors of brain tumors and those who received high‐dose neurotoxic treatment were less likely to know. Forty‐seven survivors (52%) perceived that they were personally at risk for infertility, which was unrelated to examined factors. Almost half of all survivors (n=44; 48%) did not know their current fertility status, which was more common for younger survivors (<italic>p</italic><0.001), survivors of brain tumors (31%; <italic>p=</italic>0.012), and those with lower income (<italic>p=</italic>0.013).</p><p><bold>Conclusions</bold>: Most adult survivors of pediatric cancer were aware of the general risk for cancer‐related infertility, and about half perceived themselves at risk or knew their fertility status. Several demographic and medical factors were related to knowledge in these domains. Future research should continue to identify strategies to provide reproductive counseling to survivors of pediatric cancer before and after treatment, and optimize fertility preservation rates for those at risk.</p><p><bold>Acknowledgements</bold>: Thank you to The Research Institute at Nationwide Children's Hospital and CTSA Grant (UL1TR001070) for providing resources.</p></sec><sec id="pbc26772-sec-2530"><label>O-212</label><title>Development of Web Based Tailored Treatment Information to Enable Patient Participation and Empowerment. A Pilot Study in Wilms Tumor Patients and Families</title><p><underline underline-style="single">J.E. Dijkstra Pinto Leite</underline><sup>1</sup>, M.A. Grootenhuis<sup>2</sup>, J.G. de Ridder‐Sluiter<sup>2</sup>, R.L. Kamman<sup>3</sup>, E.M.M. van den Bergh<sup>4</sup>, W.C. Alers<sup>5</sup>, I. Sieswerda<sup>5</sup>, M.C. Naafs‐Wilstra<sup>6</sup>, Y. Wiersma<sup>7</sup>, S.J. Uitdehaag<sup>4</sup>, M.E. van der Veen<sup>5</sup>, M.A. Brouwer‐ van de Poll<sup>4</sup>, M.M. van den Heuvel‐Eibrink<sup>5</sup>, A.M.C. Mavinkurve‐Groothuis<sup>5</sup></p><p><italic><sup>1</sup>Princess Máxima Center, User Experience Design ICT, Utrecht, The Netherlands; <sup>2</sup>Princess Máxima Center, Psychosocial Research, Utrecht, The Netherlands; <sup>3</sup>Princess Máxima Center, ICT, Utrecht, The Netherlands; <sup>4</sup>Princess Máxima Center, Psychosocial Care, Utrecht, The Netherlands; <sup>5</sup>Princess Máxima Center, Paediatric Oncology, Utrecht, The Netherlands; <sup>6</sup>VOKK, CEO, Nieuwegein, The Netherlands; <sup>7</sup>Princess Máxima Center, Children's advisory council, Utrecht, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: In the Princess Máxima Center for pediatric oncology stimulating development is leading in care. Key principles are reduction of medical traumatic stress, adequate communication and family focus. Treatment of children with cancer is stressful for the child and the family. They are often overloaded with information, which is not always tailored to their needs. Their daily life is taken over by hospital visits and missing overview and control can lead to avoidable medical traumatic stress. Our aim is to design a tool that provides overview and tailored information of the treatment schedule.</p><p><bold>Design/Methods</bold>: In the first phase we analyzed the needs of different families. Personas were created with a focus group of 6 healthcare professionals to profile different family types. Contextual inquiry is performed to map activities in different stages of treatment. It will lead to knowledge on how and when information is shared with the families. In depth interviews will provide insights on preferences children and their families have in obtaining information about their disease and treatment.</p><p><bold>Results</bold>: We discussed and grouped 23 families with the focus group and identified 6 personas; reflecting differences in how families deal with disease, disease information and how they interact with health care professionals. The studies in the first phase lead to guidelines for a tool to communicate the Wilms Tumor treatment schedule addressing these differences.</p><p><bold>Conclusions</bold>: The result will be a visual, web‐based, tailored treatment information tool, to increase patient participation and empowerment. By creating overview of the treatment program, understandable for children and their parents, we aim to support them in making decisions and preparing for procedures. We use personas to profile different families and address their specific needs. The next step is to design the tool and investigate whether this tool will lead to reduction of medical traumatic stress.</p></sec><sec id="pbc26772-sec-2540"><label>O-213</label><title>Attitudes and Concerns About Parenthood and Fertiltiy Preservation among Adolescent and Young Adult Males and Their Parents During Cancer Survivorship</title><p><underline underline-style="single">N. Caltabellotta</underline><sup>1</sup>, A. Ferrante<sup>1</sup>, C. Gerhardt<sup>1</sup>, V. Lehmann<sup>2</sup>, S. Whiteside<sup>3</sup>, N. Yeager<sup>3</sup>, L. Nahata<sup>1</sup></p><p><italic><sup>1</sup>Nationwide Children's Hospital, Center for Biobehavioral Health, Columbus, USA; <sup>2</sup>St. Jude Children's Research Hospital, Department of Psychology, Memphis, USA; <sup>3</sup>Nationwide Children's Hospital, Division of Hematology/Oncology, Columbus, USA</italic></p><p><bold>Background/Objectives</bold>: One in three males experiences fertility problems after pediatric cancer treatment yet less than 25% of pubertal males pursue fertility preservation (FP) before treatment. Although parents are responsible for making the majority of health‐related decisions (including FP) during pediatric illness, it is unknown if parents are discussing parenthood and FP with their sons and are aware of their attitudes and concerns. The aims of this study were to examine attitudes about parenthood and FP among AYA males and their parents within the first seven years of cancer survivorship.</p><p><bold>Design/Methods</bold>: Ninety‐one participants (35 AYA males, 31 mothers, 25 fathers) completed questions based on the Health Belief Model. Participants ranked items on a 5‐point Likert scale for themselves (if an AYA male) or their sons (if a parent). Analyses compared attitudes of male AYA survivors (15‐25 years, <italic>M</italic>=18.94) and parents as two distinct groups, and within 26 mother‐son pairs and 20 father‐son pairs on items pertaining to parenthood and benefits/barriers to FP.</p><p><bold>Results</bold>: Eighty percent of AYA males endorsed wanting a biological child, and 51% of survivors agreed a future without a child would make them sad. Thirty‐one percent of AYA males thought speaking about FP with their parents would be embarrassing; a minority reported having conversations with their mothers (23%) and/or their fathers (17%) about sperm banking. Although 51% of AYA males were concerned they could pass on their cancer to their future children; neither mothers (p=0.003) nor fathers (p=0.002) shared this concern.</p><p><bold>Conclusions</bold>: Although most male AYA survivors desire biological children after treatment, they report difficulties discussing this with their parents and report barriers to FP of which their parents may be unaware. Future research needs to identify factors that contribute to these perceived barriers and strategies to facilitate conversations about parenthood and FP between AYA males and their parents.</p></sec></sec><sec id="pbc26772-sec-2550"><title>Haematology ‐ Acute Lymphoblastic Leukaemia</title><sec id="pbc26772-sec-2560"><label>PD-001</label><title>The Cost‐Effectiveness of Pegaspargase for First‐Line Treatment of Acute Lymphoblastic Leukaemia: A Cost‐Utility Analysis</title><p>S. Basu<sup>1</sup>, <underline underline-style="single">P. Lin</underline><sup>2</sup>, C. Rowntree<sup>3</sup>, V. Saha<sup>4,5</sup></p><p><italic><sup>1</sup>Shire, Head of Medical Affairs Oncology, Staines upon Thames, United Kingdom; <sup>2</sup>Shire, Global HEOR Lead‐ Oncology, Cambridge, USA; <sup>3</sup>University Hospital of Wales, Consultant Haematologist, Cardiff, United Kingdom; <sup>4</sup>University of Manchester, Paediatric Oncology, Manchester, United Kingdom; <sup>5</sup>Tata Medical Center, Senior Consultant in Paediatric Oncology, New Town‐ Kolkata, India</italic></p><p><bold>Background/Objectives</bold>: Asparaginase is a key component in the treatment of patients with acute lymphoblastic leukemia (ALL). In the UK, patients with newly diagnosed ALL receive PEG‐ASP followed by Erwinia‐derived asparaginase (ERW‐ASP) in cases of hypersensitivity. Although native ASP is no longer used as the first choice of asparaginase therapy, it was the standard of care before PEG‐ASP was available. This analysis evaluates the cost‐effectiveness of PEG‐ASP in patients with newly diagnosed ALL compared to native asparaginase (native‐ASP).</p><p><bold>Design/Methods</bold>: A combined decision tree/health state transition Markov model was developed to compare treatment sequences starting with PEG‐ASP versus native‐ASP, followed by ERW‐ASP in cases of hypersensitivity. Pediatric, young adult (≤25 years), and adult (26‐65 years) patients were modelled using UKALL2003 and UKALL14 protocols. Analyses were stratified by high‐, intermediate‐, and standard‐risk in pediatric patients, between patients aged ≤40 vs. ≥41 years, and on transplantation eligibility in the adult model. Key model parameters (survival, risk of hypersensitivity) were publication‐based with clinical input from key experts. In the base‐case analysis, OS and EFS were assumed equivalent for PEG‐ASP, native‐ASP, and ERW‐ASP, with 1,000IU/m<sup>2</sup> dosing (per UKALL protocols) used for PEG‐ASP. In scenario analyses, 2,500 IU/m<sup>2</sup> of PEG‐ASP was examined (per SmPC), including variations in comparative survival and hypersensitivity rates. Incremental cost‐effectiveness ratios (ICER; incremental costs/quality‐adjusted life years [QALYs] gained) were produced.</p><p><bold>Results</bold>: The base‐case scenario demonstrated that PEG‐ASP followed by ERW‐ASP resulted in reduced costs and increased QALYs (total cost savings, £4,741; total QALYs gained, 0.05) versus native‐ASP followed by ERW‐ASP. Scenario analyses highlighted the robustness of the results. Differences in total QALYs between PEG‐ASP and native‐ASP were driven primarily by the difference in hypersensitivity rates.</p><p><bold>Conclusions</bold>: This analysis demonstrates that PEG‐ASP, as part of multi‐drug chemotherapy, is cost‐effective compared to native‐ASP for children, young adults, and adults with newly diagnosed ALL.</p></sec><sec id="pbc26772-sec-2570"><label>PD-002</label><title>Consequences of Decreasing Asparginase and Dexamethasone Theray to Avoid Excessive Toxicity in Childhood Acute Lymphoblastic Leukemia: A Prospective Trial from a Middle‐Income Country</title><p><underline underline-style="single">K. Ghanem</underline><sup>1</sup>, D. El Tabech<sup>1</sup>, C. Al‐Aridi<sup>1</sup>, N. Tarek<sup>1</sup>, R. Saab<sup>1</sup>, M. Abboud<sup>1</sup>, H. El‐Solh<sup>1</sup>, S. Muwakkit<sup>1</sup></p><p><italic><sup>1</sup>American University of Beirut, Department of Pediatrics and Adolescent Medicine, Beirut, Lebanon</italic></p><p><bold>Background/Objectives</bold>: The best outcome of childhood acute lymphoblastic leukemia (ALL) is achieved through an adequate balance between disease control and treatment‐related toxicities. At the Children's Cancer Center of Lebanon, we implemented the St Jude Total‐XV protocol with minor modifications to treat patients with ALL 1‐18 years old. Between 2002‐2013 (period‐I), the protocol resulted in an excellent 5‐year overall (92.3%) and disease‐free survival (88.6%), however, excessive toxicities were observed, including CMV retinitis (3.5%), disseminated varicella (6%) and CNS thrombosis (6.2%).</p><p><bold>Design/Methods</bold>: Between 2013‐2015 (period‐II), and in a prospective, non‐randomized trial, we decreased dexamethasone dosage during continuation and intensification therapy by 25% for low‐risk and 33% for intermediate/high risk patients and stopped monthly dexamethasone pulses at 1.3 years instead of 2 years from initiation of continuation therapy. Asparaginase dose was decreased by 40% in induction for all patients, and 40% in intensification therapy for low‐risk patients. No prophylactic cranial irradiation was given.</p><p><bold>Results</bold>: The number of enrolled patients was 156 in period‐I and 61 in period‐II. After a median follow‐up of 88 months (range: 24‐177 months), the 3‐year cumulative incidence of isolated CNS relapse increased from 1.3% (n=2) (SE 0.01%) in period‐I to 10.2% (n=5) (SE 0.4%) in period‐II (Gray <italic>P</italic>: 0.003). In period‐II, 3/5 patients with CNS relapse were low‐risk, without initial CNS involvement. All five patients achieved second remission. One patient is currently in third remission after developing a second isolated CNS relapse. All CNS relapses occurred after 1.7 years from treatment initiation. The incidence of CMV retinitis, disseminated varicella, and CNS thrombosis decreased to 0%, 0% and 1.4%, respectively. The 3‐year cumulative incidence of death was not statistically different between the two periods (7.7 versus 9.3%, Gray <italic>P</italic>: 0.32).</p><p><bold>Conclusions</bold>: Decreasing dexamethasone and asparaginase dosages during childhood ALL therapy aiming to avoid treatment‐related toxicities resulted in significant increase in isolated CNS relapse.</p></sec><sec id="pbc26772-sec-2580"><label>PD-003</label><title>Molecular Genetic Profile in BCR‐ABL1 Negative Pediatric B‐Cell Acute Lymphoblastic Leukemia Can Further Refine Outcome Prediction in Addition to That by End‐Induction Minimal Residual Disease</title><p><underline underline-style="single">S. Gupta</underline><sup>1</sup>, S. Bakhshi<sup>2</sup>, A. Chopra<sup>1</sup>, R. Kumar<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences AIIMS‐ New Delhi, Lab Oncology, New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences AIIMS‐ New Delhi, Medical Oncology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Many patients with B‐cell Acute Lymphoblastic Leukemia (B‐ALL) don't respond satisfactorily to the standard therapy. Currently, the poor responders are subjected to aggressive chemotherapy based on minimal residual disease (MRD) status. Recently, Moorman et al (2014) proposed molecular genetic criteria for better risk‐prediction in B‐ALL. We undertook this study to assess their utility in <italic>BCR‐ABL1</italic> negative pediatric B‐ALL, particularly with respect to the end‐induction MRD status.</p><p><bold>Design/Methods</bold>: The new cases of <italic>BCR‐ABL1</italic> negative, pediatric B‐ALL, enrolled over 18 months were classified as standard, intermediate, high risk and treated as per the institutional protocol. The patients with MRD positivity (>0.01%) by flow cytometry, at the end of induction chemotherapy were treated as high risk. The genomic DNA was analyzed for copy number alterations (CNAs) in <italic>CDKN2A/B</italic>, <italic>PAX5</italic>, <italic>IKZF1</italic>, and other genes using multiplex ligation dependent probe amplification. The genetic‐profile was assessed using Moorman criteria. Event free survival (EFS) and overall survival (OS) were noted.</p><p><bold>Results</bold>: Seventy‐six cases with median age 7 years (2 months‐18 years) were finally analyzed. CNAs were detected in 49 (64.5%) cases. 24 cases were MRD positive, remaining were MRD negative‐ low (20), intermediate (20), high risk (12) cases. The genetic profile could identify two subgroups with significantly different EFS (p=0.045) and OS (p=0.037) in the MRD negative intermediate risk group. The genetic profile also separated two subgroups with significantly different EFS (p=0.036) in the MRD positive group, however the OS was not different (p=0.293). The analysis in other subgroups did not reveal any significant differences.</p><p><bold>Conclusions</bold>: The genetic profile identified distinct subgroups in MRD‐negative intermediate‐risk and MRD‐positive cases of B‐ALL. This indicates that the intermediate‐risk patients can be further segregated for therapy assignment, based on the genetic‐profile. More importantly, the empirical therapy up‐gradation in MRD positive cases may not be appropriate or adequate, particularly in those with poor molecular genetic‐profile.</p></sec><sec id="pbc26772-sec-2590"><label>PD-004</label><title>Insert Vincristine and Dexamethasone During the Maintenance Therapy of Non‐High Risk Pediatric Acute Lymphoblastic Leukemia was Unnecessary: A Randomized Controlled Trial Study from Single Center</title><p>L.B. Huang<sup>1</sup>, <underline underline-style="single">L. xue‐qun</underline><sup>1</sup>, K. Zhi‐Yong<sup>1</sup>, T. Hui‐Zhen<sup>1</sup>, Z. Xiao‐li<sup>1</sup></p><p><italic><sup>1</sup>the first affiliated hospital of SUMS, Pediatrics, Guangzhou, China</italic></p><p><bold>Background/Objectives</bold>: The benefit of vincristine (VCR) plus dexamethasone (DXM) during maintenance in ALL is controversial. A multicenter clinical trial, GD‐2008 (NCT00846703), which is based on the ALL IC‐BFM 2002 protocol, was designed to evaluate the benefit of VCR and DXM pulses in the maintenance therapy. Here, we report the results from our single center.</p><p><bold>Design/Methods</bold>: 194 children, diagnosed with ALL with non‐high‐risk features, were enrolled in our department from Aug 1, 2008 to Dec 31, 2014. All were treated with the same protocols based on the ALL IC‐BFM 2002 protocol, which included induction, consolidation, re‐induction, and maintenance therapy. At the beginning of the maintenance therapy, those patients in complete remission were randomly assigned to either protocol A or protocol B. In protocol A, patients were given conventional 6‐mercaptopurine (6MP) and methotrexate (MTX). Patients in protocol B were given 6MP and MTX for 7 weeks, and then substituted by VCR and DXM for 1 week, and every 8 weeks as a cycle. The primary outcome measure was disease‐free survival. The study is registered at http://www.clinicaltrials.gov with the identifier NCT00846703.</p><p><bold>Results</bold>: 4 patients (2.1%) died during the therapy before randomization. Of the remaining 190 patients, 177 (93.1%) were randomly assigned: 93 to protocol A and 84 to protocol B. With median follow‐up of 60 months, 10 children in protocol A and 17 in protocol B had relapses, and 1 child in the protocol A died of infection during maintenance treatment. The 5‐year event‐free survival (EFS) were 87.0%±3.7% in protocol A and 78.9% ±4.8% in protocol B, respectively (p=0.126). The 5‐year overall survival (OS) were 94.1%±2.6% in protocol A and 85.4%±4.2% in protocol B, respectively (p=0.04).</p><p><bold>Conclusions</bold>: There are no benefits that intermit the MM maintenance therapy with vincristine and dexamethasone in children with non‐high risk ALL who received chemotherapy based on BFM protocols.</p></sec><sec id="pbc26772-sec-2600"><label>PD-005</label><title>Favorable Outcome of TCF3‐PBX1 Genetic Translocation in Acute Lymphoblastic Leukemia in Chinese Children: CCLG2008 Study</title><p><underline underline-style="single">C. Li</underline><sup>1</sup>, L. Cui<sup>2</sup>, Z. Li<sup>2</sup>, Y. Chai<sup>3</sup>, J. Yu<sup>4</sup>, J. Gao<sup>5</sup>, X. Zhu<sup>6</sup>, R. Jin<sup>7</sup>, X. Shi<sup>8</sup>, L. Zhang<sup>9</sup>, Y. Gao<sup>10</sup>, R. Zhang<sup>2</sup>, H. Zheng<sup>2</sup>, S. Hu<sup>3</sup>, Y. Cui<sup>4</sup>, C. Zhou<sup>5</sup>, Y. Zou<sup>6</sup>, M.H.L. NG<sup>11</sup>, T. Wang<sup>2</sup>, M. Wu<sup>2</sup></p><p><italic><sup>1</sup>The Chinese University of Hong Kong, Paediatrics, Hong Kong, Hong Kong S.A.R.; <sup>2</sup>Beijing Children's Hospital of Capital Medical University, Hematology Oncology, Beijing, China; <sup>3</sup>Children's Hospital of Soochow University, Hematology Oncology, Suzhou, China; <sup>4</sup>Children's Hospital of Chongqing Medical University, Hematology Oncology, Chongqing, China; <sup>5</sup>West China Second University Hospital‐ Sichuan University, Hematology Oncology, Chengdu, China; <sup>6</sup>Institute of Hematology & Hospital of Blood Disease‐ Chinese Academy of Medical Science & Peking Union Medical College, Pediatric Hematology, Tianjin, China; <sup>7</sup>Union Hospital‐ Tongji Medical College‐ Huazhong University of Science and Technology, Pediatrics, Wuhan, China; <sup>8</sup>Capital Institute of Pediatrics, Hematology Oncology, Beijing, China; <sup>9</sup>Peking University People's Hospital, Pediatrics‐, Beijing, China; <sup>10</sup>Children's Hospital of Fudan University, Hematology Oncology, Shanghai, China; <sup>11</sup>The Chinese University of Hong Kong, Anatomical & Cellular Pathology, Hong Kong, Hong Kong S.A.R</italic>.</p><p><bold>Background/Objectives</bold>: TCF3‐PBX1 gene fusion happened in 3‐5% of childhood ALL. In a prospective multicenter trial of Chinese Children Leukemia Group (CCLG) 2008 Study, patients were treated with standard BFM‐based protocol. The outcome of this genetic subgroup was studied.</p><p><bold>Design/Methods</bold>: Newly diagnosed ALL patients were recruited from 10 hospitals in China from 04/2008 to 12/2012, 2231 patients were stratified into 3 risk groups according to age, WBC, genetic subtypes and 7‐day prednisone response. Two hospitals piloted MRD study by Flow and PCR with adjustment of treatment according to MRD response. TCF‐PBX1 group was assigned to intermediate risk (IR) at diagnosis.</p><p><bold>Results</bold>: There were 121 patients (5.4%) identified to be TCF3‐PBX1 positive by PCR and 41 also had t(1;19) on karyotyping. Mean age and WBC at diagnosis was 5.9 years and 42.2 x10<sup>9</sup>/L, male to female was 68:53. At diagnosis, 3 patients had CNS 3 and 3 with CNS 2 status. Compared with 604 of other IR patients, TCF3‐PBX1 group had higher good 7‐day prednisone response (91.5% vs 81.5%, p=0.007), less Day15 M3 (6.8% vs 15%, p=0.013), and better Day33 remission (99% vs 94.9%, p=0.047). Day33 MRD response was assessed in 286 IR patients, MRD negativity (<0.01%) was significantly higher in TCF3‐PBX1 group (63.3% (31/49) vs 26.6% (63/237) p<0.001〉〉. There were 11 relapses at BM but without any CNS relapse. Death occurred in 15 patients, 10 due to relapses and 5 due to infection. There was trend of better EFS for TCF3‐PBX1 group (87.1% vs 80.4%) but not significant (p=0.099).</p><p><bold>Conclusions</bold>: The incidence of TCF3‐PBX1 in Chinese children was 5.4% and CNS3 was only 2.5%, CNS relapse was not observed. The early response to treatment was better in TCF3‐PBX1 subset, and there was also trend of better survival.</p><p>Supported by grants from National Natural Science Foundation of China (Nos. 81200392 and 81170504)</p></sec><sec id="pbc26772-sec-2610"><label>PD-006</label><title>Functional Mitochondrial Apoptosis Signaling Indicates Anti‐Leukemia Activity of the BCL‐2‐Seletive Inhibitor ABT‐199 in BCP‐ALL</title><p><underline underline-style="single">F. Seyfried</underline><sup>1</sup>, S. Demir<sup>1</sup>, R. Hörl<sup>1</sup>, J. Ryan<sup>2</sup>, A. Scheffold<sup>3</sup>, M. Villalobos‐Ortiz<sup>2</sup>, S. Köhrer<sup>1</sup>, J. Zinngrebe<sup>1</sup>, S. Stilgenbauer<sup>3</sup>, A. Letai<sup>2</sup>, K.M. Debatin<sup>1</sup>, L.H. Meyer<sup>1</sup></p><p><italic><sup>1</sup>Ulm University Medical Center, Pediatrics and Adolescent Medicine, Ulm, Germany; <sup>2</sup>Dana‐Farber Cancer Institute, Medical Oncology, Boston, USA; <sup>3</sup>Ulm University Medical Center, Internal Medicine III, Ulm, Germany</italic></p><p><bold>Background/Objectives</bold>: In B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), deficient cell death pathways are associated with treatment failure. Anti‐apoptotic BCL‐2 family proteins regulate apoptosis, thereby serving as targets for novel, directed therapies. The BCL‐2 inhibitor ABT‐199 binds to BCL‐2, leading to release of pro‐death BCL‐2 family molecules and apoptosis induction. Here, we assessed the efficacy of ABT‐199 in BCP‐ALL and investigated factors mediating ABT‐199 susceptibility or resistance, indicative of anti‐leukemia activity.</p><p><bold>Design/Methods</bold>: ABT‐199 sensitivities were investigated in BCP‐ALL (cell lines and patient‐derived xenografts). Expression of apoptosis regulators was detected by western blot analysis. MCL‐1 deficient leukemias were generated by CRISPR/Cas9. Mitochondrial apoptosis signaling was assessed by BH3‐profiling. ABT‐199 anti‐leukemia activity was evaluated <italic>in vivo</italic>.</p><p><bold>Results</bold>: The vast majority of BCP‐ALL samples showed sensitivity to ABT‐199‐induced cell death in the nanomolar range. Interestingly, expression of the anti‐ and pro‐apoptotic regulators MCL‐1 and BCL‐2 were significantly associated with ABT‐199 effectivity and MCL‐1 knockout in ABT‐199‐resistant leukemias resulted in ABT‐199 sensitization, pointing to MCL‐1 as a mediator of ABT‐199 resistance. Next, we characterized the functional interplay of apoptosis regulators by BH3 profiling. Mitochondrial dependence on BCL‐2 was associated with ABT‐199 sensitivity, in contrast to low BCL‐2‐dependence and addiction to other regulators (BCL‐XL or MCL‐1) in ABT‐199‐resistant samples. Most importantly, in a preclinical <italic>in vivo</italic> setting in a xenograft mouse model, prolonged leukemia‐free survival upon <italic>in vivo</italic> ABT‐199‐therapy was indicated by high mitochondrial BCL‐2‐dependence, in contrast to low BCL‐2‐dependence in ABT‐199 insensitive leukemias.</p><p><bold>Conclusions</bold>: Taken together, most of BCP‐ALL show ABT‐199 sensitivity. However, ABT‐199 resistance occurs and is characterized by the level of the target molecule and counter‐players. Importantly, functional assessment of mitochondrial BCL‐2‐dependence (BH3‐profiles) is indicative of ABT‐199 sensitivity and anti‐leukemia activity <italic>in vivo</italic>, providing a marker for the upfront identification of patients who would benefit from novel effective ALL‐treatment strategies with BCL‐2 inhibitors.</p></sec></sec><sec id="pbc26772-sec-2620"><title>Haematology ‐ Myeloid Leukemias, Myelodysplastic and Myeloproliferative Syndromes</title><sec id="pbc26772-sec-2630"><label>PD-007</label><title>Molecular Findings of Infant Acute Myeloid Leukemia</title><p><underline underline-style="single">F. Gomes Andrade</underline><sup>1</sup>, I. Sardou Cezar<sup>1</sup>, F. Vicente dos Santos Bueno<sup>1</sup>, G. Dallapicola Brisson<sup>1</sup>, E. Pereira Noronha<sup>1</sup>, E. Terra‐Granado<sup>1</sup>, M.S. Pombo‐de‐Oliveira<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Câncer, Research Center, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: Initiating somatic mutations detected in dried neonatal blood spots and in cord blood samples of affected children with leukemia have been proved to be acquired prenatally. However, few epidemiological studies have been carried out exploring infant acute myeloid leukemia (i‐AML) that include infants and children under 24 months of age at the diagnosis. Our aim was to describe the molecular characterization of i‐AML cases and investigate the contribution of gene mutations in the probability overall survival (pOS).</p><p><bold>Design/Methods</bold>: One hundred and seventy‐eight non‐Down Syndrome cases with i‐AML were assessed throughout a multicentric network study. Mutations in hotspot regions of <italic>RAS</italic> pathway affecting genes (<italic>FLT3</italic>, <italic>NRAS</italic>, <italic>KRAS</italic>, <italic>PTPN11</italic>, and c‐<italic>KIT</italic>) were analyzed, as well as fusion genes [<italic>MLL/KMT2A</italic> and <italic>NUP98</italic> rearrangements (<italic>KMT2A</italic>‐r and <italic>NUP98</italic>‐r, respectively),<italic>MYST3‐CREBBP</italic>, <italic>RUNX1‐RUNX1T1</italic>, <italic>CBFβ‐MYH11</italic>, and <italic>PML‐RARα</italic>] associated with AML. The majority of patients was treated following the BFM‐AML2004, although out of clinical trials.</p><p><bold>Results</bold>: Eleven cases (6.2%) were congenital leukemia (≤1‐month‐old), 80 (44.9%) were aged between 2‐12 months old and 87 (48.9%) cases were aged ≥13 months old. The mostly morphological differentiation observed in blast cells was myelomonocytic (28.7%), monocytic (25.8%), and megakaryocytic (22.5%). All phenotypes presented with low white blood cell (WBC) count (≤50x10<sup>9</sup>/L) at diagnosis, other than acute myelomonocytic leukemia. Frequent molecular abnormalities were <italic>KMT2A‐</italic>r (34.6%), mainly <italic>KMT2A</italic>‐<italic>MLLT3</italic> and <italic>KMT2A</italic>‐<italic>AFF1</italic>, followed by <italic>NUP98</italic>‐r (7.4%) and <italic>RUNX1‐RUNX1T1</italic> (6.0%). <italic>RAS</italic> pathway gene mutations were observed in 30.1% of i‐AML, affecting mostly cases aged ≥13 months old and associated with <italic>KMT2A</italic>‐r (29.7%). The cumulative 5‐year pOS was 33.8±4.7%, with no statistical differences in survival rates among years or associated with molecular alterations.</p><p><bold>Conclusions</bold>: Despite presenting fewer genetic abnormalities than older pediatric AML, disease‐related death rate was high in i‐AML. Our data indicate that diagnosis and management of i‐AML raise questions that should be considered for further action.</p></sec><sec id="pbc26772-sec-2640"><label>PD-008</label><title>Molecular Characterization of Pediatric Acute Myeloid Leukemia: Results of a Diagnostic and National Multicentric Study in Brazil</title><p><underline underline-style="single">F. Gomes Andrade</underline><sup>1</sup>, E. Pereira Noronha<sup>1</sup>, F. Vicente dos Santos Bueno<sup>1</sup>, I. Sardou Cezar<sup>1</sup>, G. Dallapicola Brisson<sup>1</sup>, E. Terra‐Granado<sup>1</sup>, M.S. Pombo‐de‐Oliveira<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Câncer, Research Center, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: The biological characterization of childhood acute myeloid leukemia (c‐AML) is an important outcome predictor. In Brazil, little is known about the frequency of AML subgroups, although c‐AML accounts for about 18% of leukemias. <bold>Aim</bold>. To investigate the contribution of type I and II gene mutations in the probability overall survival (pOS) of c‐AML in Brazil.</p><p><bold>Design/Methods</bold>: Seven hundred and three <italic>de novo</italic> pediatric AML cases (2000‐2015) were assessed throughout a multicentric network study. Mutations in hotspot regions of <italic>FLT3</italic>, <italic>NRAS</italic>, <italic>KRAS</italic>, <italic>PTPN11</italic>, and c‐<italic>KIT</italic> genes were analyzed, as well as fusion genes (<italic>RUNX1</italic>‐<italic>RUNX1T1</italic>, <italic>MLL</italic>/<italic>KMT2A</italic>‐r, <italic>CBFβ</italic>‐<italic>MYH11</italic>, and <italic>PML</italic>‐<italic>RARα</italic>) associated with AML. Patients were treated out of the protocol, but the BFM‐AML2004 was followed since the year 2008. Acute promyelocytic leukemia (APL) was treated differently. AML with Down syndrome was excluded.</p><p><bold>Results</bold>: There were significant differences in gene mutations between age ranges (≤2 years‐old; >2‐10 years old and ≥11 years old) and the nonrandom association between type I/II mutations. Lower white blood cell count (≤50x10<sup>9</sup>/L) was associated with <italic>RUNX1</italic>‐<italic>RUNX1T1</italic> whereas higher WBC with <italic>CBFβ‐MYH11</italic> (p<0.05). The cumulative pOS in 5 years was 37.5±2.9% for total AMLs and 59.4±7.2% for APL (p=0.03). pOS differences were observed between Brazilian regions. The South‐Southeast regions had a better 5‐year pOS (47.6±4.7%) whereas the Northeast‐Midwest regions presented the poorest pOS (23.7±4.9%). <italic>PTPN11</italic> mutations conferred adverse prognosis, as an independent prognostic factor.</p><p><bold>Conclusions</bold>: The identification of genetic subgroups contributes to the molecular epidemiology and biology of AML worldwide, reflecting the profile of pediatric AML cases in Brazil. Survival data for the specific c‐AML subtype in Latin countries are found rarely in the literature. Inclusion of cytogenetic‐molecular markers in the characterization of AML are of great predictive value for OS.</p></sec><sec id="pbc26772-sec-2650"><label>PD-009</label><title>Prognostic Impact of Hyperdiploidy in Pediatric Acute Myeloid Leukemia Patients</title><p><underline underline-style="single">S. Salem</underline><sup>1</sup>, S. Mahmoud<sup>2</sup>, S. Soliman<sup>3</sup>, K. Shaaban<sup>4</sup>, M. Hammad<sup>5</sup>, N. Elguindy<sup>6</sup>, A. Haddad<sup>5</sup></p><p><italic><sup>1</sup>NCI ‐ Egypt and Children's Cancer Hospital Egypt, Cytogenetics, Cairo, Egypt; <sup>2</sup>NCI ‐ Egypt and Children's Cancer Hospital Egypt, Pediatric Oncology, Cairo, Egypt; <sup>3</sup>NCI ‐ Egypt and Children's Cancer Hospital Egypt, Hematolgy, Cairo, Egypt; <sup>4</sup>NCI ‐ Egypt and Children's Cancer Hospital Egypt, Immunolgy, Cairo, Egypt; <sup>5</sup>NCI ‐ Egypt and Children's Cancer Hospital Egypt, Pediatric Oncolgy, Cairo, Egypt; <sup>6</sup>Children Cancer Hospital Egpyt‐ 57357, Research, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Acute myeloid leukemia (AML) patients with hyperdiploid or triploid/tetraploid (TT) karyotype represent a relatively poorly understood entity. We aim to study the characteristics of this group as regards the karyotype, clinical and laboratory features and treatment outcome.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed data of 447 patients with de novo AML who were treated in Children Cancer Hospital Egypt, 57357 on AML0431 COG adopted protocol, from July 2007 to January 2014. Patients with Down syndrome and acute promyelocytic leukemia were excluded.</p><p><bold>Results</bold>: Thirty four patients had ≥49 chromosomes. Seven cases with core binding factor translocation were excluded from analysis. Out of the 27 hyperdiploid and TT cases, 9 cases (33%) were AML‐M7. Three cases had pure hyperdiploid karyotype.<italic>KMT2A</italic> gene rearrangement was found in 10 cases (37%), trisomy 8 in 11 cases (40.7%), gain of chromosome 21 in 16 cases (59%), and chromosome 5q abnormalities in 3 cases (11%). None of the patients had monosomy 7, t(6;9) or 17p/p53 deletion. Two patients died early in induction 1 and were excluded from further analysis. The two year overall survival was significantly lower (33%) compared to non‐hyperdiploid <italic>KMT2A</italic> rearrangement, normal karyotype and core binding factor AML; t(8;21) and inv(16)/t(16;16) 40.6%, 51%, 69.5% and 76%, respectively (P‐value=<0.05). The 2 year disease free survival for the hyperdiploid group was 35.5% while for non‐hyperdiploid <italic>KMT2A</italic> rearrangement, normal karyotype, t(8;21) and inv(16) was 61%, 70%, 88%, and 95.5%, respectively (P‐value=<0.05). Relapse occurred in 37.5% of patients with hyperdiploidy compared to 27%, 26%, 11.5% and 3% in non‐hyperdiploid <italic>KMT2A</italic> rearrangement, normal karyotype, t(8;21) and inv(16), respectively. The cumulative incidence of relapse in the hyperdiploid group is 48.2 with CI (27.7 to 66).</p><p><bold>Conclusions</bold>: Hyperdiploid and TT karyotype is a rare and adverse risk abnormality in pediatric AML compared to other genetic groups.</p></sec><sec id="pbc26772-sec-2660"><label>PD-010</label><title>Detection of Minimal Residual Disease in Down Syndrome‐AML by Error‐Corrected Sequencing: A Children's Oncology Group Study</title><p><underline underline-style="single">R.S. Tong</underline><sup>1</sup>, A.L. Young<sup>1</sup>, W.H. Wong<sup>1</sup>, J. Hitzler<sup>2</sup>, J.N. Berman<sup>3</sup>, T.E. Druley<sup>1</sup></p><p><italic><sup>1</sup>Washington University School of Medicine, Pediatrics, St.Louis‐ MO, USA; <sup>2</sup>The Hospital for Sick Children, Hematology/Oncology, Toronto‐ ON, Canada; <sup>3</sup>IWK Health Centre, Pediatrics, Halifax‐ NS, Canada</italic></p><p><bold>Background/Objectives</bold>: Down Syndrome (DS) neonates have a 10‐20‐fold higher incidence of acute myeloid leukemia (DS‐AML), which is characterized by mutations in exons 2 or 3 of <italic>GATA1</italic> (Xp11.23) (Alford KA et al. <italic>Blood</italic>, 2011). Given the unstable surface immunophenotypes in this leukemia, there has never been a bona fide method for detecting minimal residual disease (MRD) following chemotherapy. Next‐generation sequencing for <italic>GATA1</italic> mutations would provide such a platform, however, is limited by a high error‐rate (∼1:100). Error‐corrected sequencing (ECS) can circumvent this error‐rate and detect mutations with a limit of detection of 1:10,000 (Young AL et al. <italic>Leukemia</italic>, 2015). In collaboration with the Children's Oncology Group (COG), we are applying ECS in parallel with flow cytometry to improve MRD detection in DS‐AML.</p><p><bold>Design/Methods</bold>: Exons 2 and 3 of <italic>GATA1</italic> were amplified by high‐fidelity PCR. The resulting 300bp amplicons were ligated to an 8bp individual‐specific barcode to enable sample multiplexing as well as a random 16bp index to allow for error‐correction. ECS libraries were sequenced on the Illumina MiSeq and analyzed using published computational methods (Wong T et al. <italic>Nature</italic>, 2015).</p><p><bold>Results</bold>: To date, 51 samples from 30 DS‐AML patients enrolled on the COG AAML1531 study have been analyzed [diagnosis, n=29; End of Induction 1 (EOI1), n=22]. Nonsynonymous mutations were detected in 83% of diagnosis samples at an average variant allele frequency (VAF) of 0.1145 (range: 0.00101 ‐ 0.88847). MRD was detected in 53% of the paired EOI1 samples at an average VAF of 0.0016 (range: 0.00003 – 0.01405).</p><p><bold>Conclusions</bold>: ECS is capable of both detecting and monitoring MRD in DS‐AML. Interestingly, we detect MRD in 53% of the paired EOI1 samples, yet DS‐AML patients have exceptionally high event‐free survival rates (80‐100%). This suggests that secondary events in addition to <italic>GATA1</italic> mutations are involved in relapsed DS‐AML and are the focus of additional research.</p></sec><sec id="pbc26772-sec-2670"><label>PD-011</label><title>Therapy‐Related Acute Myeloid Leukemia/Myelodysplastic Syndrome Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India</title><p><underline underline-style="single">C. VYAS</underline><sup>1</sup>, S. Jain<sup>1</sup>, G. Kapoor<sup>1</sup></p><p><italic><sup>1</sup>Rajiv Gandhi Cancer Institute & Research centre‐ New Delhi‐ India, Department of Pediatric Haematology‐Oncology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Therapy‐related acute myeloid leukemia/myelodysplastic syndrome (t‐AML/MDS) is a devastating complication of cancer treatment. In view of paucity of literature from India, we report the incidence, risk factors t‐AML/MDS over a period of 20 years at our institute.</p><p><bold>Design/Methods</bold>: This is a retrospective analysis of patients (≤18 years of age) treated in the pediatric hematology‐oncology unit at our institute between January 1996 and December 2015. Amongst these, patients who developed t‐AML/MDS were identified. Information pertaining to primary malignancy, treatment details along with clinical, hematologic, cytogenetic features and outcome of t‐AML/MDS were obtained.</p><p><bold>Results</bold>: Amongst 1285 children, 8 patients developed t ‐AML/MDS (6 males and 2 females, median age of 15.5 years) with a median latency period of 24 months. The incidence of t‐AML/MDS was 0.62% [0.99% (4/402) for solid tumour and 0.45% (4/883) haematological malignancies respectively, P= 0.26] with 6390 person‐years of follow‐up. The primary malignancy was sarcoma [bone (2), soft tissue (2)], B‐non‐Hodgkin lymphoma (2) and acute lymphoblastic leukemia (2). The median cumulative equivalent doses of cyclophosphamide, doxorubicin and etoposide were 6.8gm/m<sup>2</sup> (range, 3‐28.3 gm/m<sup>2</sup>), 270 mg/ m<sup>2</sup> (range, 180‐375 mg/m<sup>2</sup>) and 2.5gm/ m<sup>2</sup> (range, 1‐4 gm/m<sup>2</sup>) respectively. Two patients received radiotherapy to the primary site. The dominant FAB morphology was M4/M5 (7/8) and cytogenetic abnormality was 11q23 translocation (4/8). Five patients opted for treatment and 4 achieved remission. Three patients died (2 toxic deaths and 1 relapse). Two patients are alive and disease free. The median survival was 5.5 months.</p><p><bold>Conclusions</bold>: We observed a high incidence of t‐AML/MDS in children with sarcoma compared to haematological malignancies. Shorter latency period and presence of 11q23 translocation implicates epipodophyllotoxin to be the probable causative agent. In view of poor outcome of t‐MDS/AML, strategies to identify host risk factors and to practise precision medicine need to be considered.</p></sec></sec><sec id="pbc26772-sec-2680"><title>Haematology ‐ Lymphomas</title><sec id="pbc26772-sec-2690"><label>PD-012</label><title>Outcome of Hodgkin Lymphoma in a Developing Country: The Children's Hospital Lahore Pakistan Experience</title><p><underline underline-style="single">A. Ahmad</underline><sup>1</sup>, N. Uddin<sup>1</sup>, F.S. Khan<sup>1</sup>, N. Asghar<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital and the Institute of Child Health Lahore, Haematology/ oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: The Children's Hospital Lahore is a tertiary government centre with 60 paediatric Oncology beds. It receives over 1000 new cancer patients per year. The purpose of this study was to analyze treatment and outcome of children with biopsy proven Hodgkin Lymphoma and discuss various factors causing poor outcome as compared to developed countries.</p><p><bold>Design/Methods</bold>: Retrospective review of 315 patients enrolled between January 2011 ‐ June 2016 was done. Data regarding age, stage, histopathology, treatment, outcome and impact of delayed presentation were analyzed. Patients were treated according to Euronet‐PHL‐C1 protocol receiving 4‐6 courses of OEPA/COPDAC.</p><p><bold>Results</bold>: Total 315 patients with age ranging from 2 to 15 (80% <10 yrs) were included. M: F Ratio was 5.7:1. 294/315(94%) presented with advanced stage and only 21(6%) had stage II at presentation. The histopathological examination showed Mixed Cellularity in 212/315(67%), Nodular Sclerosis in 62/315(20%), Lymphocytic Predominance in 8/315(3%) and Lymphocytic Depletion in 6/315(2%) cases, whereas 27 (8%) reports did not specify the subtype. Bone marrow/lung was involved in 110/315 (35%) patients. Total 251/315 (80%) have completed treatment, 22/315 (7%) left against medical advice (LAMA) and 28/315 (9%) expired due to sepsis and progressive disease. 5/315 relapsed and 9/315 had progressive disease (4%)</p><p><bold>Conclusions</bold>: Survival is good 251/315 (80%) for the whole group (70% in 2014 ISCAYAHL data) Mortality of 11% can be reduced by early diagnosis and aggressive infection control measures. In developing countries, late referrals are strongly associated with metastatic disease. The prognosis can significantly be improved by public awareness to seek early treatment and establishing safe and effective shared care oncology pathways, multidisciplinary team approach. By providing strong social support, intense psychosocial counseling and efficiently run Day Care Oncology can help increase patients compliance.</p></sec><sec id="pbc26772-sec-2700"><label>PD-013</label><title>Second Biopsy of Residual Mass in Pediatric Mature B‐Cell Non‐Hodgkin Lymphoma: Benefit Patients or Not?</title><p><underline underline-style="single">M. Cai</underline><sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center‐ Shanghai Jiao Tong University‐ School of Med, Pediatric Hematology & Oncology, ShangHai, China</italic></p><p><bold>Background/Objectives</bold>: The reliable assessment of residual masses remains a diagnostic problem in patients with non‐Hodgkin lymphoma (NHL). The objective of this study was to assess the impact of second‐look biopsy of residual mass during or after chemotherapy in pediatric mature B‐cell NHL.</p><p><bold>Design/Methods</bold>: Patients with mature B‐cell NHL who were suspicious of residual mass at mid or end of treatment and subjected to second biopsy were treated and followed at our medical center between 2001 and 2015. Their clinical characteristics, imagings, pathology, treatment and prognosis were reviewed retrospectively.</p><p><bold>Results</bold>: A total of 31 children were included. Twenty‐two with Burkitt lymphoma, 6 with Diffuse large B cell lymphoma and 3 with B‐cell lymphoma, unclassified. Median age at diagnosis was 6.1 years (2.5‐14 years). The median time from diagnosis to second biopsy was 3.15 months (2.3‐18 months). Biopsy confirmed the presence of viable tumor in 8 patients. The specificity and positive predictive value (PPV) of conventional imaging in detecting residual disease were poor, at 9% and 28.6%. Three of the histologic positive patients experienced progressive disease or relapse while the others achieved complete remission (CR) at the completion of therapy and 21 patients achieved long‐time CR at a median follow‐up of 3.2 years (1 year‐7 years). The median progression‐free survival (PFS) time was 28 months (5‐84 months) and 5‐year PFS rate was 90.0%. 5‐year PFS rate of negative‐biopsy group was 100% while that of positive‐biopsy group was 62.5%. (P=0.002<0.05)</p><p><bold>Conclusions</bold>: Residual mass is not uncommon in children with mature B‐cell NHL. An integrated tactics is important for the accurate determination of residual disease. Conventional imaging has low specificity and PPV. Second‐look biopsy is necessary to differentiate viable tumor from necrosis or fibrosis and is solid evidence‐based foundation of subsequent treatment. It also can help clinician to avoid overtreatment and to predict prognosis.</p></sec><sec id="pbc26772-sec-2710"><label>PD-014</label><title>AHOPCA LH 2004: Treatment of High Risk Hodgkin Lymphoma in LMIC: Drug Availability and Logn Term Outcomes</title><p><underline underline-style="single">S. Luna‐Fineman</underline><sup>1</sup>, M.E. Castellanos<sup>2</sup>, M. Metzger<sup>3</sup>, F. Baez<sup>4</sup>, Y. Gamboa<sup>5</sup>, A. Peña<sup>6</sup>, S. Alabi<sup>7</sup>, R. Nieves<sup>8</sup>, J. Blanco<sup>9</sup>, E. Rossi<sup>10</sup>, P. de Alarcon<sup>11</sup></p><p><italic><sup>1</sup>Stanford University, Pediatrics, Palo Alto, USA; <sup>2</sup>Unidad Nacional de Oncologia Pediatrica, Oncología Pediátrica, Guatemala, Guatemala; <sup>3</sup>St Jude Childrens Research Hospital, Oncology, Memphis, USA; <sup>4</sup>La Mascota Hospital, Oncologia Pediatrica, Managua, Nicaragua; <sup>5</sup>Hospital de Niños, Oncología Pediátrica, San Jose, Costa Rica; <sup>6</sup>Hospital Escuela Materno Infantil, Oncología Pediátrica, Tegucigalpa, Honduras; <sup>7</sup>Hospital de Niños Benjamin Bloom, Oncología Pediátrica, San Salvador, El Salvador; <sup>8</sup>Hospital Universitario, Oncología Pediátrica, Santo Domingo, Dominican Republic; <sup>9</sup>School of Medicine and Surgery‐ University of Milano‐Bicocca, Center of Biostatistics for Clinical Epidemiology, Milan, Italy; <sup>10</sup>School of Medicine and Surgery‐ University of Milano‐Bicocca, Biostatistics for Clinical Epidemiology, Milan, Israel; <sup>11</sup>University of Illinois College of Medicine and St Jude Midwest Affiliate, Department of Pediatrics, Peoria, USA</italic></p><p><bold>Background/Objectives</bold>: High risk Hodgkin lymphoma in children is curable with chemotherapy and radiation. Multiple chemotherapeutic drugs are often not available for purchase by low‐middle income countries (LMIC). AHOPCA implemented a modified treatment guideline with the aim to reduce abandonment while conserving survival.</p><p><bold>Design/Methods</bold>: 239 patients with high risk Hodgkin lymphoma (IIB, IIIB, IV) were diagnosed from August 2004‐September 2009 and followed‐up to March 2017. Costa Rica (n=20), El Salvador (n=30), Guatemala (n=87), Honduras (n=50), Nicaragua (n=39) and Dominican Republic (n=13) contributed to this report. All patients were staged with ultrasound or computer tomography. Chemotherapy regimen was a modified StanfordV, substituting cyclophosphamide for mechlorethamine. Response evaluation was performed after 12 weeks of chemotherapy All patients received either 2000cGy for a CR and 2500cGy for PR to involved‐field radiation therapy (IFRT).</p><p><bold>Results</bold>: 192 patients eligible and evaluable were enrolled. Median follow‐up time was 7.6 years; 152 were boys, median age was 9 years (2.6‐17.5 years), 47 were IIB, 88 IIIB and 57 IV; 106 finished therapy. 43 did not get IFRT due to death (n=7), abandonment (n=28, 14%) or progressive disease (PD, n=8); 28% (42/149) got IFRT later than 6 weeks after end of chemotherapy without affecting outcome. Overall, 34 patients had PD, 29 relapsed, 8 died and 28 abandoned. 8‐year abandonment‐sensitive EFS and OS for the whole cohort was 47%±3.7 (±SE) and 56%±3.8; 8‐year abandonment‐sensitive EFS was 68%±6.9, 53%±5.5 and 23%±5.6 in IIB, IIIB and IV stages.</p><p><bold>Conclusions</bold>: Treatment abandonment remains as an important failure (14% vs 12%, p=0.242). As previously described, substituting cyclophosphamide for mechlorethamine in StanfordV did not bring the expected results. The OS for earlier stages was better than stage IV. Substitution of drugs in LMIC, related to availability is dangerous and affects the outcome. A new regimen with available drugs is now implemented. Advocacy and compliance of drug availability are needed.</p></sec><sec id="pbc26772-sec-2720"><label>PD-015</label><title>Clinico‐Epidemiological Profile and Outcome of Pediatric Anaplastic Large Cell Lymphoma (ALCL): Single Center Experience from India</title><p><underline underline-style="single">N. Pradhan</underline><sup>1</sup>, D. Philip<sup>2</sup>, G. Narula<sup>1</sup>, M. Prasad<sup>1</sup>, G. Chinnaswamy<sup>1</sup>, T. Vora<sup>1</sup>, B. Arora<sup>1</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Centre, Pediatric Oncology, Mumbai, India; <sup>2</sup>Tata Memorial Centre, Medical Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: ALCL is a rare form of NHL in children. We evaluated the clinical, epidemiological profile and outcome of pediatric ALCL patients at Tata Memorial Center, Mumbai, India.</p><p><bold>Design/Methods</bold>: This is a retrospective study of 10 years data of ALCL patients, who were registered at our centre from 01/01/2005 to 31/12/2014. All patients who were treated at our centre received Vinblastin based MCP‐842 multi‐agent chemotherapy (Regimen‐A‐ Cyclophosphamide, Doxorubicin, Cytarabine, Vinblastin and Regimen‐B‐ Ifosfamide, Etoposide, Methotrexate, Vinblastin). Intensive phase consisted of alternating regimens of 8 cycles with 6 intrathecal Cytarabine and 8 intrathecal Methotrexate, followed by oral 6‐Mercaptopurine and Methotrexate maintenance therapy (Six months for stage 1 and 2 disease and one year for stage 3 and 4 disease).</p><p><bold>Results</bold>: We include 68 patients (<15 years) of ALCL. The male to female ratio was 3.5:1. Number of patients having Stage1,2,3 and 4 disease at diagnosis were 6(8.8%), 7(10.3%), 39(57.3%) and 16(23.5%) respectively. Forty‐three (63.2%) patients had B‐symptoms at presentation. The common sites of disease involvement were lymph nodes (85.3%), bone (29.4%), bone‐marrow (23.5%) and skin (19%). Fifty‐five (80.8%) patients had ALK‐positive disease on immunohistochemistry. For outcome analysis details of 4 patients were not available. Out remaining 64, complete remission (CR) was achieved in 55(85.9%), 4(6.2%) achieved partial response (PR) while 5(7.8%) had progressive disease. Six (9.3%) patients relapsed, of which 3 achieved second remission and are alive in CR at last follow‐up. Five (7.8%) patients died in remission. Thirteen (20.3%) died due to disease, all had advanced stage (3/4). Three‐year EFS and OS were 67.5% and 72.7% respectively at a median follow‐up 40 months (1‐132).</p><p><bold>Conclusions</bold>: Pediatric ALCL has reasonable outcome with Vinblastin based multi‐agent chemotherapy. Advanced stage disease is associated with higher risk of mortality, and requires innovative therapies.</p></sec><sec id="pbc26772-sec-2730"><label>PD-016</label><title>Impact of Secondary Chromosomal Abnormalities on Treatment Outcome in Pediatric Burkitt Leukemia</title><p><underline underline-style="single">S. Salem</underline><sup>1</sup>, H. Abdelrahman<sup>2</sup>, M. Tantawy<sup>3</sup>, S. Talaat<sup>2</sup>, R. Mohey<sup>4</sup></p><p><italic><sup>1</sup>NCI ‐ Egypt and Children's Cancer Hospital Egypt, Clinical Pathology, Cairo, Egypt; <sup>2</sup>NCI ‐ Egypt and Children's Cancer Hospital Egypt, Pediatric Oncology, Cairo, Egypt; <sup>3</sup>Children Cancer Hospital Egypt, Clinical Pathology, Cairo, Egypt; <sup>4</sup>Children Cancer Hospital Egypt, Research Department, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Burkitt leukemia (BL) is characterized by translocation of the <italic>MYC</italic> gene to one of the immunoglobulin genes. The clinical significance of secondary chromosomal abnormalities associated with this characteristic translocation remains unknown.</p><p>We aim to analyze the impact of secondary chromosomal abnormalities on treatment outcome in pediatric BL.</p><p><bold>Design/Methods</bold>: Patients with BL presenting to Children Cancer Hospital in Egypt‐57357 (CCHE) from July 2007 till March 2015, were reviewed for karyotyping and <italic>MYC</italic> status by FISH. These results were correlated with survival analysis.</p><p><bold>Results</bold>: Eighty‐eight patients with BL were diagnosed and treated according to the FAB/LMB 96 protocol. Majority were males (78%) and above 10 years of age at presentation (43%). Associated central nervous system involvement was diagnosed in 33% of the patients. Informative karyotype for 67 patients demonstrated translocation of the <italic>MYC</italic> and <italic>IGH</italic> genes in 85% of patients while translocation of the <italic>IGK</italic> and <italic>IGL</italic> were found in 3% and 12%, respectively. Secondary chromosomal abnormalities were detected in 60% of patients. Duplication of chromosome 1q was found in 17 patients, followed by chromosome 14q abnormalities (6 patients), chromosome 6q deletion (4 patients), and chromosome 13q deletion (3 patients). The five year OS was 57.5%, while the 5 year EFS was 51.6% of the whole group. After excluding 24 patients with treatment related mortality, relapse or tumor progression on chemotherapy was seen in 16 patients. The 3 years relapse free survival in patients with complex karyotype was 47.1%, while in patients having non‐complex karyotype it was 76.8% (p‐value=0.022).</p><p><bold>Conclusions</bold>: The frequency of secondary chromosomal abnormalities in our series is in concordance with other publications with duplication 1q being the most common, followed by deletion 6q, 13q, and 17p. Complex karyotype was significantly associated with higher incidence of relapse and poor outcome.</p></sec></sec><sec id="pbc26772-sec-2740"><title>Haematology ‐ Stem Cell Transplantation (Haematological Diseases/Technique and Supportive Care)</title><sec id="pbc26772-sec-2750"><label>PD-017</label><title>Effect of Activating KIR‐Ligand Match on the Outcome of Pediatric Allogeneic Hematopoietic Stem Cell Transplantation</title><p><underline underline-style="single">Y.B. Choi</underline><sup>1</sup>, L. Ji Won<sup>2</sup>, Y. Keon Hee<sup>2</sup>, K. Eun‐Suk<sup>3</sup>, S. Ki Woong<sup>2</sup>, K. Hong Hoe<sup>2</sup></p><p><italic><sup>1</sup>Chung‐Ang University Hospital, Pediatrics, Seoul, Republic of Korea; <sup>2</sup>Samsung Medical Center, Pediatrics, Seoul, Republic of Korea; <sup>3</sup>Samsung Medical Center, Laboratory Medicine and Genetics, Seoul, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Natural killer (NK) cells are precisely controlled by a network of activating and inhibiting signals through surface receptors. In this study, we evaluated the impact of KIR genotype on the outcome following allogeneic HSCT for malignant disease in children.</p><p><bold>Design/Methods</bold>: The donor's activating KIR and recipient's KIR ligand (KIR‐L match) were considered compatible if the donor had one or more activating receptors for which the cognate ligand was present in the recipient. KIR2DS1, KIR2DS2, KIR2DS4, and KIR3DS1 were deemed activating KIRs. The donors were classified as KIR haplotype A or B donors according to their gene content. Haplotype A donors were defined as individuals only possessing genes of the group A KIR haplotypes. All individuals possessing having one or more haplotype B‐specific genes were defined as haplotype B donors.</p><p><bold>Results</bold>: Fifty‐three patients received allogeneic HSCT from siblings (n = 11), unrelated donors (n = 20), or haploidentical donors (n = 22) between January 2011 and December 2014. The transplants were performed in patients with acute myeloid leukemia (n = 17), acute lymphoblastic leukemia (n = 14), neuroblastoma (n = 17), and other solid tumors (n = 5). Twenty‐eight donor‐recipient pairs had a KIR‐L match and the remaining twenty‐five donor‐recipient pairs had a KIR‐L mismatch. The 2‐year relapse‐free survival was 72.3 ± 9.0% in recipients with a KIR‐L match and 42.9 ± 10.1% in recipients with a KIR‐L mismatch (<italic>P</italic> = 0.043). Recipients who received HSCT from haplotype B donors had no survival benefit compared to those who received HSCT from haplotype A donors (60.6 ± 9.8% vs. 54.0% ± 10.3%, <italic>P</italic> = 0.558).</p><p><bold>Conclusions</bold>: This analysis revealed that allogeneic HSCT with activating KIR‐L match decreased relapse and improved relapse‐free survival. Therefore, for a successful HSCT outcome, KIR genotyping should be performed before selection of NK cell alloreactive donors.</p></sec></sec><sec id="pbc26772-sec-2760"><title>Solid Non Brain Tumours ‐ Neuroblastoma</title><sec id="pbc26772-sec-2770"><label>PD-018</label><title>Spinal Canal Invasion in Peripheral Neuroblastic Tumors ‐ A Siopen Prospective Study Registry</title><p><underline underline-style="single">S. Ash</underline><sup>1</sup>, R. Haupt<sup>2</sup>, K. Kraal<sup>3</sup>, D. Plantaz<sup>4</sup>, A. Wiecrorek<sup>5</sup>, D. Kachanov<sup>6</sup>, C. Owens<sup>7</sup>, C. Trager<sup>8</sup>, K. McHugh<sup>9</sup>, C. Gandolfo<sup>10</sup>, T. Trahair<sup>11</sup>, B. De Bernardi<sup>12</sup>, S. Sorrentino<sup>12</sup></p><p><italic><sup>1</sup>Schneider Children's Medical Center of Israel, Pediatric Hematology Oncology, Rosh Haain, Israel; <sup>2</sup>Istituto G. Gaslini‐, Epidemiology and Biostatistics Unit, Genova, Italy; <sup>3</sup>Princess Maxima Center PMC for Paediatric Oncology, Pediatric Oncology, Utrecht, The Netherlands; <sup>4</sup>Hôpital Albert Michallon‐CHU de Grenoble, Département de Pédiatrie, Grenoble, France; <sup>5</sup>University Children's Hospital of Krakow, Pediatric Oncology, Krakow, Poland; <sup>6</sup>Federal Scientific and Clinical Center of Pediatric Hematology‐, Department of Clinical Oncology, Moscow Russian Federation, Russia; <sup>7</sup>Our Lady Children's Hospital, Pediatric Oncology, Dublin, Ireland; <sup>8</sup>Astrid Lindgren`s Children Hospital, Childhood Cancer Research Unit, Stockholm, Sweden; <sup>9</sup>Great Ormond Street‐ Hospital for Children, Radiology Department‐, London, United Kingdom; <sup>10</sup>Istituto Giannina Gaslini, Neuroradiology Unit, Genova, Italy; <sup>11</sup>Sydney Children's Hospital‐Centre for Children's Cancer & Blood Disorders, Paediatric Haematologist & Oncologist, Sydney, Australia; <sup>12</sup>Istituto Giannina Gaslini, Department of Haematology‐Oncology, Genova, Italy</italic></p><p><bold>Background/Objectives</bold>: Spinal canal invasion (SCI) occurs in 10‐15% of children with peripheral neuroblastic tumors (PNTs). These patients have favorable clinical and biologic features and are cured more often than other patients, but are especially prone to develop late neurologic, functional and orthopedic sequelae. The question of their optimal treatment has not been solved yet. The prospective SIOPEN Study Registry aims to collect data on these patients with the aim 1) to increase the knowledge on natural history of PNTs presenting with SCI, 2) to evaluate the combined effects of different risk factors on their outcome and 3) to ultimately develop common treatment guidelines.</p><p><bold>Design/Methods</bold>: This SIOPEN Study intends to collect clinical, biological, therapeutic and follow‐up data on symptomatic and asymptomatic patients with PNT and SCI. A minimum of 150 patients are expected. Age adjusted, standardized tools for symptoms grading and functional impacts are the CTCAE, FLACC, pain scores and ASIA scales.</p><p><bold>Results</bold>: From June 2014 to February 2017, a total of 57 patients have been registered from 8 countries. Median age is 17 months, M/F ratio is 0.8. The most common histology is NB poorly differentiated. Three patients only had <italic>MYCN</italic> gene amplification. Twenty‐eight patients were symptomatic. Symptoms included motor deficit in 21, pain in 15 and bladder & bowel function in 2. Primary tumour site was located in the thorax in 18, in the thoraco/abdominal site in 11. The majority (63%) have L2 disease. Patients were treated according to SIOPEN/institutional protocols. Median follow‐up is 6 months. At 2 months from diagnosis, pain disappear in all patients presenting this symptom, while motor deficit persists in 5 of 17 patients available for response.</p><p><bold>Conclusions</bold>: This is the first cooperative study designed to collect data to evaluate the combined effects of different risk factors on neurologic, functional and orthopedic outcome of PNT's patients presenting with SCI.</p></sec><sec id="pbc26772-sec-2780"><label>PD-019</label><title>BRCA1 Hypomethylation Causes Chemoresistance in High‐Risk Neuroblastoma</title><p><underline underline-style="single">A. Hakkert</underline><sup>1</sup>, M. Ebus<sup>1</sup>, J. Koster<sup>2</sup>, F. Speleman<sup>3</sup>, R. Versteeg<sup>2</sup>, H. Heyn<sup>4</sup>, J. Molenaar<sup>1</sup></p><p><italic><sup>1</sup>Prinsess Máxima Center, TRST, Utrecht, The Netherlands; <sup>2</sup>Academisch Medisch Centrum, Oncogenomics, Amsterdam, The Netherlands; <sup>3</sup>Center for Medical Genetics‐ Ghent University, Paediatric oncogenomics, Ghent, Belgium; <sup>4</sup>Bellvitge Institute for Biomedical Research, Cancer Epigenetics and Biology Program, Barcelona, Spain</italic></p><p><bold>Background/Objectives</bold>: All induction treatment regimens for patients with neuroblastoma contain chemotherapeutics that cause double strand DNA breaks. BRCA1 is a tumor suppressor gene, and is involved in the repair of these double strand breaks in the DNA. Here we study the effects of BRCA1 expression on tumor progression and chemoresistance in neuroblastoma.</p><p><bold>Design/Methods</bold>: We performed an Illumina 450K methylation assay on 67 neuroblastoma tumor samples, and sought for differentially methylated CpGs between high risk and low risk tumors. MTT assays were performed to study the effect of target gene methylation on chemoresistance. And shRNA knock down was utilized to investigate the tumor driving effects of target gene expression.</p><p><bold>Results</bold>: BRCA1 was found to be the top hit with 15 significantly differentially methylated CpG between high risk and low risk neuroblastoma. This is surprising, since BRCA1 is known as a bonafide tumor suppressor gene. In neuroblastoma however, this gene seems to function as a tumor driver. Hypomethylation of BRCA1 is strongly correlated with high BRCA1 expression. shRNA knockdown of BRCA1 led to increased DNA damage and cell death in cell lines with high BRCA1 expression. We hypothesized that BRCA1 hypomethylation, would lead to resistance to chemotherapeutics since the induced double strand breaks would be efficiently repaired. Indeed, cell lines with BRCA1 hypomethylation show resistance against widely used chemotherapeutics.</p><p><bold>Conclusions</bold>: BRCA1 is hypomethylated in high risk neurblastoma tumors. Knockdown of BRCA1 leads to DNA damage and cell death in cell lines depending on BRCA1, suggesting that BRCA1 is essential for tumor progression in BRCA1 hypomethylated tumors. BRCA1 hypomethylation was shown to cause resistance to chemotherapeutics, indicating that BRCA1 hypomethylation might be involved in therapy resistance of patients with high risk neuroblastoma.</p></sec><sec id="pbc26772-sec-2790"><label>PD-020</label><title>MGMT Inhibitor O6‐Benzylguanine Enhanced the Activity of Temozolomide + Irinotecan against in Vitro and in Vivo Models of Progressive Disease High‐Risk Neuroblastoma</title><p><underline underline-style="single">A. Hindle</underline><sup>1</sup>, M. Makena<sup>1</sup>, B. Koneru<sup>1</sup>, T. Nguyen<sup>1</sup>, W.H. Chen<sup>1</sup>, C.P. Reynolds<sup>1</sup></p><p><italic><sup>1</sup>Texas Tech University Health Sciences Center, Cancer Center, Lubbock, USA</italic></p><p><bold>Background/Objectives</bold>: Patients with high‐risk neuroblastoma (NB) treated with DNA‐damaging chemotherapy often relapse with treatment‐refractory disease. Temozolomide (TMZ; DNA‐methylating agent) and irinotecan (IRN; topoisomerase I inhibitor) are well‐tolerated and have clinical activity in relapse/refractory NB. We hypothesized that DNA repair genes with increased expression in alkylator‐resistant NB models would provide potential therapeutic targets for enhancing chemotherapy.</p><p><bold>Design/Methods</bold>: TaqMan Low Density Arrays (TLDA) were used to analyze mRNA expression of 62 DNA repair genes in 9 alkylator‐resistant and 4 alkylator‐sensitive cell lines. Genes with differential expression were validated in an expanded NB cell line panel (n=26) by qRT‐PCR. <italic>In vitro</italic> cytotoxicity was assayed using the digital imaging microscopy scanning system (DIMSCAN). Double strand DNA breaks, apoptosis, and DNA fragmentation were assessed using phospo‐histone H2AX, cleaved caspase‐3, and TUNEL, respectively. <italic>In vitro</italic> testing used the SN38 active metabolite of IRN. Subcutaneous patient‐derived xenografts (PDXs) in nu/nu mice were treated with TMZ, IRN, and O6‐benzylguanine (O6BG) via oral gavage, tail vein injection, and intraperitoneal injection, respectively.</p><p><bold>Results</bold>: O6‐methylguanine‐DNA methyltransferase (<italic>MGMT</italic>) was upregulated in alkylator‐resistant relative to drug‐sensitive NB cell lines by TLDA and by qRT‐PCR (p<0.05). <italic>MGMT</italic> expression positively correlated with <italic>in vitro</italic> TMZ+SN38 IC50 (n=14, p<0.05). The MGMT inhibitor O6BG enhanced TMZ+SN38 <italic>in vitro</italic> cytotoxicity, H2AX phosphorylation, caspase‐3 cleavage, and apoptosis by TUNEL. TMZ+IRN+O6BG delayed tumor growth and increased median survival (p<0.05) relative to TMZ+IRN in COG‐N‐564x and COG‐N‐452x PDXs established at the time of death from progressive disease.</p><p><bold>Conclusions</bold>: High <italic>MGMT</italic> expression is associated with neuroblastoma multi‐drug resistance. The MGMT inhibitor 06BG synergistically enhanced the activity of TMZ+IRN both <italic>in vitro</italic> and <italic>in vivo</italic> with clinically achievable dosing. Further studies evaluating MGMT as a therapeutic target in recurrent high‐risk neuroblastoma are warranted.</p></sec><sec id="pbc26772-sec-2800"><label>PD-021</label><title>Exploring the relevance of Primary Tumour 123I‐MIBG Response to Induction Chemotherapy with Rapid COJEC in Children with High‐Risk Neuroblastoma</title><p><underline underline-style="single">E. Szychot</underline><sup>1</sup>, M. Chopra<sup>2</sup>, O. Arthurs<sup>2</sup>, N. Sebire<sup>3</sup>, P. Humphries<sup>2</sup>, <underline underline-style="single">L. Biassoni last author</underline><sup>2</sup>, <underline underline-style="single">D. Morgenstern last author</underline><sup>4</sup></p><p><italic><sup>1</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, Paediatric Oncology and Haematology, London, United Kingdom; <sup>2</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, Radiology, London, United Kingdom; <sup>3</sup>Great Ormond Street Hospital for Children NHS Foundation Trust, Pathology, London, United Kingdom; <sup>4</sup>Hospital for Sick Children, Paediatric Oncology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Assessment of metastatic response by <sup>123</sup>I‐mIBG scintigraphy is important for treatment decisions in management of patients with high‐risk neuroblastoma (HR‐NBL). However, the relevance of primary tumour mIBG response has not been explored. We aimed to compare clinical and histological (percentage of viable tumour) characteristics of primary mIBG‐avid tumours that became entirely mIBG‐non‐avid after induction chemotherapy (IC) (responders) with primary mIBG‐avid tumour that remained mIBG‐avid (non‐responders).</p><p><bold>Design/Methods</bold>: Retrospective review of patients with metastatic HR‐NBL (>18 months at diagnosis) treated at Great Ormond Street Hospital 2005‐2016. Patients received Rapid COJEC (multi‐agent IC as per SIOPEN HR‐NBL‐1). Patients who did not go on to have surgery after IC alone were excluded. Post‐surgical histopathology specimens were assessed for percentage of viable tumour. Primary tumour mIBG response was assessed qualitatively as positive, negative, or intermediate. mIBG uptake was assessed at diagnosis and after IC. Estimates of event‐free survival (EFS) using Kaplan‐Meier and comparisons by log‐rank test.</p><p><bold>Results</bold>: Seven of 68 (10.3%) patients had mIBG–negative tumours at diagnosis and were excluded. 16 of 61 patients showed complete primary tumour mIBG response, 20 partial response and 25 no response. There was no statistically significant difference between clinical demographics of responders and non‐responders. Primary tumour mIBG response did not correlate with extent of metastatic mIBG‐avid disease at diagnosis. Mean percentage viable tumour cells was significantly greater in mIBG‐non‐responders than responders (44.6% vs 20.6%; p=0.05). 5‐year EFS was significantly better in complete responders than non‐responders (43±15% vs 7±6%; p<0.005). 5‐year EFS was better in patients whose tumours showed <10% viable tumour after IC compared to those with ≥10% viable tissue (77±12% vs 25±10%, p= 0.007).</p><p><bold>Conclusions</bold>: Primary mIBG response correlates with tumour necrosis and patient outcome. However, it is not sufficient alone to be used to confirm complete necrosis and justify a decision not to resect these tumours.</p></sec><sec id="pbc26772-sec-2810"><label>PD-022</label><title>A Key Role for EMT Transcription Factor SNAI2 in Neuroblastoma Dissemination and Response to Retinoic Acid Therapy</title><p><underline underline-style="single">K. Vrenken</underline><sup>1</sup>, J. Middelbeek<sup>1</sup>, D. Van Ingen Schenau<sup>1</sup>, Y. Derks<sup>1</sup>, F. Van Leeuwen<sup>1</sup></p><p><italic><sup>1</sup>Radboudumc, Laboratory of Pediatric Oncology/ Pediatrics, nijmegen, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Despite intensive treatment close to 50% of patients with high‐risk neuroblastoma relapse. Recurrent disease is characterized by poorly differentiated, therapy resistant cells. Retinoic Acid (RA)‐induced differentiation improves event‐free survival, but many patients fail to respond. Hence, we aim to identify novel therapeutic targets that enhance the sensitivity to RA and promote neuroblastoma differentiation. The similarities between neural crest development and neuroblastoma progression provide an appealing starting point. During neural crest development the transcriptional program epithelial‐mesenchymal transition (EMT) drives cellular plasticity affecting migration, self‐renewal and pluripotency. We hypothesize that a similar mechanism maintains neuroblastoma cells in a poorly differentiated state. Therfore, targeting EMT may overcome therapy resistance.</p><p><bold>Design/Methods</bold>: By gene expression profiling we investigated the association of EMT transcription factors with neuroblastoma overall survival. Subsequently, we used a variety of different in vitro methods, including 3D spheroid invasion assays, to study the effects of CRISPR‐CAS9 mediated knockout of the EMT transcription factor SNAI2 on neuroblastoma differentiation and the response to RA. In addition, immuno‐compromised mice were used to identify the effect of SNAI2 knockout on in vivo colonization.</p><p><bold>Results</bold>: Expression of EMT transcription factors associate with neuroblastoma disease progression. Moreover, co‐regulation of genes that are directly controlled by SNAI2 is highly predictive of disease outcome in two independent neuroblastoma patient cohorts, supporting the idea that increased SNAI2 activity contributes to neuroblastoma progression. Consistently, knockout of SNAI2 promotes cellular differentiation, while reducing self renewal capacity, invasion into a 3D matrix and in vivo colonization. In addition, growth of SNAI2 knockout cells is strongly inhibited by RA treatment and accompanied by enhanced tumor cell differentiation.</p><p><bold>Conclusions</bold>: In summary, our results identify SNAI2 as a key player in regulating neuroblastoma differentiation and response to RA. Future research will focus on how EMT regulatory networks can be effectively targeted to enhance therapy response in patients with advanced neuroblastoma.</p></sec></sec><sec id="pbc26772-sec-2820"><title>Solid Non Brain Tumours ‐ Renal Tumours</title><sec id="pbc26772-sec-2830"><label>PD-023</label><title>Neoadjuvant Transcatheter Arterial Chemoembolization (TACE) and Systemic Chemotherapy for Treatment of Advanced Wilms Tumor</title><p><underline underline-style="single">M.J. LI</underline><sup>1</sup>, D.X. Tang<sup>2</sup>, S. Xu<sup>3</sup>, J.H. Wang<sup>4</sup>, C. Lai<sup>5</sup>, H.F. Tang<sup>6</sup>, Q. Shu<sup>4</sup></p><p><italic><sup>1</sup>Children's Hospital‐ Zhejiang University School of Medicine, Division of Surgical Oncology‐ Department of Pediatric Surgery, Hangzhou, China; <sup>2</sup>Children's Hospital‐ Zhejiang University School of Medicine, Division of Urology‐ Department of Pediatric Surgery‐, Hangzhou, China; <sup>3</sup>Children's Hospital‐ Zhejiang University School of Medicine, Division of Urology‐ Department of Pediatric Surgery, Hangzhou, China; <sup>4</sup>Children's Hospital‐ Zhejiang University School of Medicine, Division of Surgical Oncology‐ Department of Pediatric Surgery, Hangzhou, China; <sup>5</sup>Children's Hospital‐ Zhejiang University School of Medicine, Department of Radiology, Hangzhou, China; <sup>6</sup>Children's Hospital‐ Zhejiang University School of Medicine, Department of Pathology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: The aim of this study was to evaluate the clinical efficacy and safety of neoadjuvant transcatheter arterial chemoembolization (TACE) combined with systemic chemotherapy for treatment of advanced Wilms tumor.</p><p><bold>Design/Methods</bold>: From January 2003 to December 2013, 55 patients (median age 3.3 years; 29 males, 26 females) with advanced Wilms tumor were treated with preoperative TACE and systemic chemotherapy. Characteristics of patients were tumor diameter greater than 10 cm, involvement of periaortic lymph nodes, tumor thrombus in inferior vena cava/right atrium, distal metastasis, or diffuse anaplastic histology (AH). The chemoembolic emulsion for TACE consisted of pirarubicin, vindesine, cisplatin and iodized oil. Intravenous chemotherapy with vindesine, ifosfamide and actinomycin D or etoposide was administered 3 weeks after TACE. Nephrectomy was performed 2–3 weeks after preoperative therapy. Postoperative radiation therapy and chemotherapy were based on tumor histology and surgical stage.</p><p><bold>Results</bold>: No cardiotoxicity, renal and hepatic dysfunction after neoadjuvant therapy were found. Grade Ⅱ–Ⅲ marrow suppression developed in 12 (21.8%) patients. In terms of response evaluation criteria, PR in 34 (61.8%), SD in 19 (34.5%), and PD in 2 (3.6%) patients were observed. Distant metastasis disappeared in four of six cases. All patients underwent tumor resection after preoperative therapy. Complete surgical removal of the tumor was achieved in 50 (90.1%) patients. The 5‐year EFS and OS were 92.7% [95% CI: 85.8%–99.6%] and 94.5% (95% CI: 88.5%–100%) respectively with a median follow‐up of 8.4 years (range, 3.5‐14.0 years).</p><p><bold>Conclusions</bold>: Neoadjuvant TACE combined with systemic chemotherapy provide a promising choice for treatment of advanced Wilms tumor.</p></sec><sec id="pbc26772-sec-2840"><label>PD-024</label><title>Nephron‐Sparing Surgery for Bilateral Wilms Tumour: Risk Factors for Positive Resection Margins</title><p>A. Mantovani<sup>1</sup>, J. Brok<sup>2</sup>, L. Calciano<sup>3</sup>, C. Duncan<sup>2</sup>, T. Choudhury<sup>2</sup>, W. Mifsud<sup>4</sup>, N. Sebire<sup>4</sup>, O. Olsen<sup>5</sup>, K. McHugh<sup>5</sup>, T. Watson<sup>5</sup>, S. Marks<sup>6</sup>, R. Shroff<sup>6</sup>, M. Gaze<sup>2</sup>, A. Cherian<sup>1</sup>, I. Mushtaq<sup>1</sup>, K. Pritchard‐Jones<sup>2</sup>, <underline underline-style="single">N. Smeulders</underline><sup>1</sup></p><p><italic><sup>1</sup>Great Ormond Street Hospital, Paediatric Urology, London, United Kingdom; <sup>2</sup>Great Ormond Street Hospital, Paediatric Oncology, London, United Kingdom; <sup>3</sup>University of Verona, Epidemiology and Medical Statistics, Verona, Italy; <sup>4</sup>Great Ormond Street Hospital, Histopathology, London, United Kingdom; <sup>5</sup>Great Ormond Street Hospital, Radiology, London, United Kingdom; <sup>6</sup>Great Ormond Street Hospital, Paediatric Nephrology, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Nephron‐sparing surgery(NSS) for bilateral Wilms tumour(BWT) is a balance between complete tumour‐excision and maximal preservation of renal parenchyma. This study explores the risk factors for incomplete resection and its oncological impact.</p><p><bold>Design/Methods</bold>: Retrospective review of patients with BWT treated at Great Ormond Street Hospital (Aug’01‐Dec’16). Patient demographics, imaging, treatment, surgery, histology and clinical outcome were recorded. Lesions’ diameter, volume, number, location, distance from vessels, and type of NSS were assessed by multivariable logistic regression(Stata 14®) for their association with incomplete resection, and effect on mortality, relapse and treatment burden.</p><p><bold>Results</bold>: Fifty‐four patients, mean age 31(8‐129) months(m) at surgery, received 72 NSS (excising 108 lesions) and 45 total nephrectomies(TN). All but 2 patients had pre‐operative chemotherapy as per the SIOP‐2001 protocol. Follow‐up data were available for 52 patients: At mean of 68m (range 6‐182m) after surgery, 82% were disease‐free, 5(10%) had disease‐recurrences, 4(8%) died from disease‐progression. Renal outcomes at mean 45m(1‐190m) post‐surgery: 6(12%) patients were in end‐stage‐renal‐disease after 3 bilateral TN and 3 completion nephrectomy for 2 recurrences and 1infarction (3 dialysis, 2 renal transplant, 1 died‐metastatic progression), 5(10%) patients had hypertension and elevated creatinine, 4(8%) hypertension, 25(48%) elevated creatinine alone and 18(35%) patients had normal renal parameters. Positive margins (M+) occurred in 30%(16/35) patients for 35 lesions (10 TN (22%) and 25 NSS (35%) [9 partial nephrectomies, 16 tumorectomies; Histology: 11 regressive, 6 nephrogenic rest, 5 mixed, 1 anaplasia, 1 blastema, 1 epithelial]). Tumorectomy(Odds Ratio[OR] 7.68, 95%CI 1.48‐39.87) and increasing number of lesions/kidney unit(OR 1.68, 1.07‐2.64) were associated with M+. M+ significantly increased the risk of flank/abdominal radiotherapy(OR 5.29, 1.82‐15.32) and intensified 4‐drug chemotherapy(OR 3.45, 1.05‐11.3) but did not significantly increased risk of relapse or death.</p><p><bold>Conclusions</bold>: Multiple lesions and tumorectomy compared to partial nephrectomy were associated with M+ in patients with BWT. M+ increases treatment burden and risk of late effects.</p></sec></sec><sec id="pbc26772-sec-2850"><title>Solid Non Brain Tumours ‐ Bone Tumours</title><sec id="pbc26772-sec-2860"><label>PD-025</label><title>Mifamurtide and Tam‐Like Macrophages: Anti‐Proliferative Effect on Osteosarcoma Cells</title><p><underline underline-style="single">G. Bellini</underline><sup>1</sup>, I. Manzo<sup>1</sup>, D. Di Pinto<sup>2</sup>, E. Pota<sup>2</sup>, C. Tortora<sup>1</sup>, M. Di Martino<sup>2</sup>, S. Perrotta<sup>2</sup>, F. Casale<sup>2</sup>, F. Rossi<sup>2</sup></p><p><italic><sup>1</sup>University of Campania “Luigi Vanvitelli”, Experimental Medicine, Naples, Italy; <sup>2</sup>University of Campania “Luigi Vanvitelli”, Woman‐ Child‐ and General and Specialist Surgery, Naples, Italy</italic></p><p><bold>Background/Objectives</bold>: The process of osteoblast precursor dedifferentiation causes osteosarcoma, the most common tumor of the childhood. In contrast to most other tumor types, TAMs (tumor‐associated macrophages), that are M2 polarized macrophages, reduce metastasis and improve survival in high‐grade osteosarcoma patients.</p><p>The mifamurtide is an immunomodulatory drug given together with standard adjuvant chemotherapy in high‐grade osteosarcoma to improve outcome.</p><p>The aim of this study was to evaluate the role of mifamurtide in the macrophage polarization and in the modulation of the dedifferentiation of osteosarcoma cell line MG63.</p><p><bold>Design/Methods</bold>: Macrophages, obtained from peripheral blood mononucleated cells of healthy subjects, and activated or not with mifamurtide [100μM] were collected or co‐cultured with MG63 cells. By bio‐molecular (qPCR) and biochemical (Western blotting, ELISA) analyses, we evaluated the effects of mifamurtide on: M1 markers INOs, DMT1, IL‐1β and IL‐6; M2 markers CD206, IL‐4, IL‐10 and iron release; osteoblast markers RUNX2, OCN, OPG and RANKL; phosphorylation of STAT3.</p><p><bold>Results</bold>: Mifamurtide‐activated macrophages show a significant reduction of both the M1 polarization marker INOS and the M2 polarization marker CD206, and a significant increase of both pro‐inflammatory (IL‐1β, IL‐6) and anti‐inflammatory (IL‐4, IL‐10) cytokines. Moreover, they show a significant increase of the iron transporter DMT1, according to an increased iron uptake typical of the M1 phenotype, and a significant increase (more than 7 folds) of the iron release, according to a M2 polarization.</p><p>MG63 cells co‐cultured with mifamurtide‐activated macrophages show a significant increase of the osteoblast markers RUNX2 and OPG and a significant reduction of RANKL. Moreover, they show a significant reduction of the proliferation and of the STAT3 activation that several tumors, instead, constitutively activate.</p><p><bold>Conclusions</bold>: Collectively, these data suggest that mifamurtide, switching macrophage polarization towards a TAM‐like intermediate M1/M2 phenotype, and reducing STAT3 activation, inhibits the cellular proliferation and induces the tumor cell dedifferentiation.</p></sec><sec id="pbc26772-sec-2870"><label>PD-026</label><title>Impact of Neo‐Adjuvant Chemotherapy Dose Intensity on Outcomes of Children with Localized Osteosarcoma: Experience of Children's Cancer Hospital – 57357 Egypt (CCHE)</title><p><underline underline-style="single">M. Zamzam</underline><sup>1</sup>, A. Hassaan<sup>2</sup>, R. Soliman<sup>3</sup>, N. Kamal<sup>4</sup>, S. Ahmed<sup>1</sup></p><p><italic><sup>1</sup>Children's Cancer Hospital Egypt CCHE/National Cancer Institute‐ Cairo University, Pediatric Hematology/Oncology, Cairo, Egypt; <sup>2</sup>Children's Cancer Hospital Egypt CCHE, Pediatric Hematology/Oncology, Cairo, Egypt; <sup>3</sup>Children's cancer Hospital ‐ 57357 Egypt, Health Economics and Outcomes, Cairo, Egypt; <sup>4</sup>Children's Cancer Hospital Egypt CCHE, Research, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Neo‐adjuvant chemotherapy for osteosarcoma is the standard of care, but there is still confusion regarding the optimal dose intensity. This retrospective study aimed to determine the impact of neo‐adjuvant chemotherapy dose intensity on tumor necrosis and the outcomes of children with localized osteosarcoma at CCHE.</p><p><bold>Design/Methods</bold>: Dose intensity (DI) was determined by calculating the total dose of each drug (Methotrexate, Doxorubicin and Cisplatin) divided by the time duration in weeks. Relative dose intensity (RDI) was calculated by dividing the delivered DI by the standard DI as per CCHE Osteosarcoma protocol. The impact of chemotherapy RDI on histological response was determined using logistic regression. RDI was also correlated with the 5‐year relapse‐free survival (RFS) at a cut‐off point of 75% of the DI using log rank test. Cox regression was done for multi‐variate analysis.</p><p><bold>Results</bold>: One hundred and three patients (< 18 years old) with localized Osteosarcoma presented to 57357 hospital from 2009 until 2014 and were followed‐up until June 2016. Seventy‐two patients (70%) were poor responders, while thirty‐one patients (30%) showed good response. The histological response was affected by chemotherapy RDI (logistic regression, <italic>P</italic> = 0.03). Overall survival was 78%, while RFS was 62.7%. Patients who received the drugs in the neo‐adjuvant phase at RDI above 75% showed improved 5‐year RFS which was 80.7%, while those who received <75% showed RFS of 57.5% (<italic>P‐valu</italic>e = 0.04). Patients with good histological response showed RFS of 84.8%, while poor responders showed RFS of 52.8% (<italic>P‐value</italic>= 0.001). Upon multivariate analysis, histological response maintained significance (P = 0.007), while RDI lost significance (P = 0.129).</p><p><bold>Conclusions</bold>: The relative dose intensity is a good predictor of histologic response, which has a great impact on the relapse free survival. Therefore, it is recommended to deliver optimal dose intensity to achieve better outcomes.</p></sec><sec id="pbc26772-sec-2880"><label>PD-027</label><title>Long‐Term Outcome of Epiphyseal‐Preservation and Biological Reconstruction Using Tumor‐Bone Sterilized with Liquid Nitrogen for Childhood Osteosarcoma Around the Knee</title><p><underline underline-style="single">H. Tsuchiya</underline><sup>1</sup>, A. Takeuchi<sup>1</sup>, N. Yamamoto<sup>1</sup>, K. Hayashi<sup>1</sup>, T. Higuchi<sup>1</sup>, K. Abe<sup>1</sup>, Y. Taniguchi<sup>1</sup>, H. Aiba<sup>1</sup>, Y. Araki<sup>1</sup></p><p><italic><sup>1</sup>Kanazawa University Graduate School of Medical Sciences, Orthopaedic Surgery, Kanazawa, Japan</italic></p><p><bold>Background/Objectives</bold>: Various methods exist to reconstruct large bone defects after tumor excision such as tumor prostheses or biological reconstructions using allograft, autograft, or recycled tumor‐bearing bone. In 1999, we developed a reconstruction method using tumor‐bearing autograft treated by liquid nitrogen. The purpose of this study was to evaluate the clinical outcome of this technique for treating osteosarcoma around the knee in children after epiphyseal sparing tumor resections.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed 17 children (7 boys and 10 girls) with osteosarcoma around the knee with an average age of 12 years (range 6‐16). The mean follow‐up period was 49 months (range 19‐87). In 11 cases, the lesion was in the distal femur, while in 6 patients it was in the proximal tibia. Two distinct freezing techniques – resection and freezing (11 cases) and pedicle freezing (6 cases) – were used based on the location of the tumor. Complications and oncological outcomes were evaluated and graded using the Musculoskeletal Tumour Society (MSTS) scoring system.</p><p><bold>Results</bold>: The mean MSTS score was 95% (range 63‐100). Complications that required additional surgery were observed in 7 (41.2%) patients. The 7 complications consisted of 4 fractures, 2 local recurrences arising from the surrounding soft tissue, and one superficial infection managed by irrigation and IV antibiotics. Limb shortening (>3 cm) was observed in 6 patients; 2 of these patients underwent subsequent limb lengthening. One frozen‐autograft (5.9%) was surgically retrieved to manage the soft tissue recurrence. Clinically, 14 patients were able to run normally. Final oncological status was CDF in 13, NED in 3, and DOD in 1.</p><p><bold>Conclusions</bold>: The long‐term outcome of epiphyseal‐preservation surgery using tumor‐bone sterilized with liquid nitrogen for childhood osteosarcoma around the knee was satisfactory and promising. This procedure proved to be very beneficial for children with osteosarcoma.</p></sec></sec><sec id="pbc26772-sec-2890"><title>Solid Non Brain Tumours ‐ Soft Tissue Sarcomas</title><sec id="pbc26772-sec-2900"><label>PD-028</label><title>Desmoplastic Small Round Cell Tumor (DSRCT): Outcomes of Curative Intent Multimodality Treatment</title><p><underline underline-style="single">N. Khanna</underline><sup>1</sup>, A. Nayak<sup>1</sup>, G. Chinnaswamy<sup>2</sup>, T. Vora<sup>2</sup>, M. Prasad<sup>2</sup>, J. Bajpai<sup>2</sup>, A. Shah<sup>3</sup>, M. Ramadwar<sup>3</sup>, B. Rekhi<sup>3</sup>, S. Medhi<sup>4</sup>, S. Shah<sup>5</sup>, S. Qureshi<sup>6</sup>, A. Saklani<sup>6</sup>, S. Laskar<sup>1</sup></p><p><italic><sup>1</sup>Tata memorial hospital, Radiation Oncology, mumbai, India; <sup>2</sup>Tata Memorial Hospital, Medical Oncology, Mumbai, India; <sup>3</sup>Tata Memorial Hospital, Pathology, Mumbai, India; <sup>4</sup>Tata Memorial Hospital, Radiology, Mumbai, India; <sup>5</sup>Tata Memorial Hospital, Nuclear Medicine, Mumbai, India; <sup>6</sup>Tata Memorial Hospital, Surgical Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: DSRCT is a rare and aggressive mesenchymal neoplasm. We evaluated the clinic‐pathological profile, treatment response, patterns of failure and prognostic factors for patients with DSRCT treated at the Tata Memorial Hospital (TMH).</p><p><bold>Design/Methods</bold>: Between April 2006 & November 2016, 48 patients with histologically proven DSRCT in the age group of 6‐79 yrs (Median 27 yrs) were treated at TMH. Thirty eight (79%) were males. Majority (85%) had abdomino‐pelvic disease. Metastatic disease at presentation was seen in 50%. The commonest site being liver (71%). Curative treatment was offered to 24 (50%) patients. Local treatment was cytoreductive surgery (CRS) alone in 10 patients, CRS followed by adjuvant radiotherapy (RT) in 7 patients and 3 patients received RT alone. One patient underwent hyperthermic intraperitoneal chemotherapy (HIPEC) after CRS. Four patients progressed on induction chemotherapy and hence, did not undergo local treatment.</p><p><bold>Results</bold>: After a median follow‐up of 14 months, the progression free survival (PFS) and overall survival (OS) was 29% and 67% respectively. At last follow up, only 7 (29%) were alive and disease free. On univariate analysis, patients who were offered local treatment in the form of CRS with or without RT had improved OS (75% Vs 25%, p<0.05). Superior OS was seen in patients in whom complete cytoreduction was achieved (90% Vs 50%, p=0.04). At the time of relapse most patients had disseminated disease. Five patients developed severe treatment related toxicities.</p><p><bold>Conclusions</bold>: DSRCT is associated with poor outcome. Local treatment in the form of complete CRS or complete CRS followed by adjuvant RT confers best outcome.</p></sec><sec id="pbc26772-sec-2910"><label>PD-029</label><title>Mutation of Ras Pathway Should be a Target of Precision Medicine for Rhabdomyosarcoma</title><p><underline underline-style="single">N. nakagawa</underline><sup>1</sup>, K. Kikuchi<sup>1</sup>, K. Nakamura<sup>1</sup>, T. Tanaka<sup>2</sup>, S. Yagyu<sup>1</sup>, T. Iehara<sup>1</sup>, T. Tajiri<sup>2</sup>, T. Sakai<sup>3</sup>, H. Hosoi<sup>1</sup></p><p><italic><sup>1</sup>Kyoto Prefectural University of Medicine, Pediatrics, Kyoto, Japan; <sup>2</sup>Kyoto Prefectural University of Medicine, Pediatric Surgery, Kyoto, Japan; <sup>3</sup>Kyoto Prefectural University of Medicine, Molecular‐Targeting Cancer Prevention, Kyoto, Japan</italic></p><p><bold>Background/Objectives</bold>: One of the current strategies for adult malignant tumor is precision medicine based on individual gene mutation. Despite the advances in therapy, the outcome of recurrent or metastatic rhabdomyosarcoma (RMS) remains poor, and treatment related side effects are still a problem. Embryonal RMS (ERMS) is reported to be a heterogeneous tumor that displays various gene mutations. Investigations of the heterogeneity could contribute to the development of precision medicine for ERMS. CH5126766 is a potent and selective dual RAF/MEK inhibitor. In this study, we examined the activity of CH5126766 in RMS tumor cell lines with/without RAS mutation.</p><p><bold>Design/Methods</bold>: Human RMS cell lines, RD, CT‐TC, RH30, RH18, RH28, RH3, RH41, RMS‐YM, and SCMC‐RM2, were used in this study. RAS pathway mutations in the cell lines were identified by direct sequencing. Cell survival was evaluated by WST‐8 assay. The cell cycle was analyzed by flow cytometry, and apoptosis was detected using flow cytometry after appropriate staining with Annexin V. ERK phosphorylation and RB de‐phosphorylation were analyzed by immunoblotting.</p><p><bold>Results</bold>: CH5126766 inhibited growth of cells with RAS mutations and did not affect the cells that lacked RAS pathway mutations. Cell cycle arrest at the G1 phase was induced in RMS cell lines with RAS mutations within 24 h of exposure to pharmacological levels of CH5126766. In the immunoblotting analyses, the drug appeared to suppress ERK phosphorylation in all the cells, but it was found to induce RB de‐phosphorylation in RAS mutated cells.</p><p><bold>Conclusions</bold>: CH5126766 is a promising therapeutic option for molecular targeting of RAS mutated RMS. Our results suggest that the precision medicine approach targeting individual variability in genes could be an effective therapeutic strategy for RMS.</p></sec><sec id="pbc26772-sec-2920"><label>PD-030</label><title>Peritoneal Pleuropulmonary Blastoma: A New Manifestation of DICER1 Syndrome</title><p><underline underline-style="single">K.A. Schultz</underline><sup>1</sup>, M. Wilhelm<sup>1</sup>, G. Williams<sup>1</sup>, A. Field<sup>2</sup>, J. Jarzembowski<sup>3</sup>, P. Kreiger<sup>4</sup>, K. Conard<sup>5</sup>, T. Olson<sup>6</sup>, A. Bechtel<sup>7</sup>, Y. Messinger<sup>1</sup>, L. Dehner<sup>8</sup>, D.A. Hill<sup>2</sup></p><p><italic><sup>1</sup>Children's Minnesota, Cancer and Blood Disorders, Minneapolis‐ MN, USA; <sup>2</sup>Children's National Medical Center, Pathology, Washington DC, USA; <sup>3</sup>Children's Hospital of Wisconsin, Pathology, Milwaukee‐ WI, USA; <sup>4</sup>Children's Hospital of Philadelphia, Pathology, Philadelphia‐ PA, USA; <sup>5</sup>Nemours Children's Health System, Pathology, Jacksonville‐ FL, USA; <sup>6</sup>Children's Healthcare of Atlanta, Aflac Cancer and Blood Disorders Center, Atlanta‐ GA, USA; <sup>7</sup>University of Florida, College of Medicine, Jacksonville‐ FL, USA; <sup>8</sup>Washington University, Surgical Pathology, St. Louis‐ MO, USA</italic></p><p><bold>Background/Objectives: Background</bold>: Pleuropulmonary blastoma (PPB) is the most common primary malignant lung tumor of infancy and early childhood. Types I and Ir PPB are purely cystic whereas Types II and III PPB are mixed cystic/solid and entirely solid respectively. Types II and III PPB are multi‐patterned sarcomas often with rhabdomyosarcomatous and cartilaginous differentiation. PPB is linked to underlying germline and tumor specific mutations in <italic>DICER1</italic>.</p><p><bold>Design/Methods: Methods</bold>: Cases of primitive sarcoma resembling PPB but with primary site in the peritoneum were identified from pathology case files at Washington University Medical Center and Children's National Medical Center. <italic>DICER1</italic> sequencing was performed using standard techniques.</p><p><bold>Results</bold>: A total of five cases of peritoneal PPB were identified. The patients presented at an median age of 13 years. Primary site of origin was fallopian tube in 3 cases. One arose from the serosal surface of the colon and one from the pelvic sidewall. One case appeared analogous to Type Ir PPB; the other 4 were analogous to Type II or III PPB. All had <italic>DICER1</italic> mutations identified in germline and/or tumor DNA.</p><p><bold>Conclusions: Discussion</bold>: Peritoneal PPB represents a new manifestation of the <italic>DICER1</italic> syndrome whose pathologic features may be identical to Types II or III PPB as a multi‐patterned sarcoma with cartilaginous and rhabdomyosarcomatous differentiation. This pattern is also seen in <italic>DICER1</italic>‐related renal sarcoma and cervical embryonal rhabdomyosarcoma with cartilaginous features and Sertoli‐Leydig cell tumor with heterologous elements which may include rhabdomyosarcomatous and cartilaginous components. These newly recognized tumors are distinguished, however by their unusual origin in the peritoneal cavity. The differential diagnosis is malignant mixed müllerian tumor (carcinosarcoma) which is typically seen in women 40 years of age and older. Tumors arising in the abdomen/pelvis with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation should prompt consideration of germline and tumor <italic>DICER1</italic> testing.</p></sec><sec id="pbc26772-sec-2930"><label>PD-031</label><title>Prognostic Relevance of Early Radiologic Response to Induction Chemotherapy in Pediatric Rhabdomyosarcoma. A Report from the International Society of Pediatric Oncology MMT‐95 Study</title><p><underline underline-style="single">B. Vaarwerk</underline><sup>1</sup>, J.H. van der Lee<sup>2</sup>, W.B. Breunis<sup>1</sup>, D. Orbach<sup>3</sup>, J.C. Chisholm<sup>4</sup>, M. Jenney<sup>5</sup>, R.R. van Rijn<sup>6</sup>, K. McHugh<sup>7</sup>, S. Gallego<sup>8</sup>, H. Glosli<sup>9</sup>, C. Devalck<sup>10</sup>, M.N. Gaze<sup>11</sup>, A. Kelsey<sup>12</sup>, C. Bergeron<sup>13</sup>, M.C.G. Stevens<sup>14</sup>, O. Oberlin<sup>15</sup>, V. Minard‐Colin<sup>15</sup>, J.H.M. Merks<sup>1</sup></p><p><italic><sup>1</sup>Emma Children's Hospital ‐ Academic Medical Centre, Pediatric Oncology, Amsterdam, The Netherlands; <sup>2</sup>Emma Children's Hospital ‐ Academic Medical Centre, Pediatric Clinical Research Office, Amsterdam, The Netherlands; <sup>3</sup>Institut Curie, Pediatric adolescent and young adult department, Paris, France; <sup>4</sup>Royal Marsden Hospital, Children and Young People's Department, Sutton, United Kingdom; <sup>5</sup>Children's Hospital for Wales, Department of Pediatric Oncology, Cardiff, United Kingdom; <sup>6</sup>Emma Children's Hospital ‐ Academic Medical Centre, Pediatric Radiology, Amsterdam, The Netherlands; <sup>7</sup>Great Ormond Street Hospital for Children, Department of Radiology, London, United Kingdom; <sup>8</sup>University Hospital Vall d'Hebron, Pediatric Oncology, Barcelona, Spain; <sup>9</sup>Oslo University Hospital, Department of Pediatric and Adolescent Medicine, Oslo, Norway; <sup>10</sup>Hopital Universitaire des enfants, Pediatric Haematology Oncology Department, Brussels, Belgium; <sup>11</sup>University College London Hospitals NHS Foundation Trust, Department of Oncology, London, United Kingdom; <sup>12</sup>Royal Manchester Children's Hospital, Pathology Department, Manchester, United Kingdom; <sup>13</sup>Centre Léon Bérard, Department of Pediatric Oncology, Lyon, France; <sup>14</sup>Bristol Royal Hospital for Children, Department of Pediatric Oncology, Bristol, United Kingdom; <sup>15</sup>Gustave‐Roussy, Department of Pediatric and Adolescent Oncology, Villejuif, France</italic></p><p><bold>Background/Objectives</bold>: Early response to induction chemotherapy is used in current European guidelines to evaluate efficacy of chemotherapy and subsequently to adapt treatment in pediatric patients with rhabdomyosarcoma. However, existing literature on the predictive value of radiologic response on survival is contradictory. Therefore we retrospectively analysed the association of early response with survival from the data of the SIOP‐MMT‐95 study.</p><p><bold>Design/Methods</bold>: We studied432 IRS group III (macroscopic residual) patients enrolled in the SIOP‐MMT‐95 study with response assessment after 3 courses of chemotherapy (assessed 2‐dimensionally). Patients with progressive disease after 3 courses of chemotherapy were excluded (n=7). Failure‐free survival (FFS) and overall survival (OS), were assessed between three groups (complete/partial, objective and no response) with Cox proportional hazards.</p><p><bold>Results</bold>: After 3 courses of chemotherapy, 85.2% of the patients had complete/partial response, 8.6% had objective response, and 6.3% had no response. For all patients 5‐year FFS [95% CI] and OS [95% CI] was 60% [56%‐65%] and 74% [70%‐78]. Cox proportional hazards regression analysis revealed no significant difference in FFS and OS rate between response groups. The adjusted hazard ratios for objective response and no response were 1.09 [0.63 to 1.88] and 0.81 [0.39 to 1.67] for FFS and 0.91 [0.47‐1.76] and 1.27 [0.61‐2.64] for OS, respectively.</p><p><bold>Conclusions</bold>: These results provide further evidence that early radiologic response to chemotherapy is not predictive for survival in patients with rhabdomyosarcoma. Treatment adaptations based on early response (except for patients with progressive disease) should therefore not be incorporated in future studies.</p></sec><sec id="pbc26772-sec-2940"><label>PD-032</label><title>Is There A Role for Radiotherapy in Pediatric Patients with Locoregionally Recurrent Rhabdomyosarcoma? Toxicity and Clinical Outcomes in an Irradiated and Non‐Irradiated Multi‐Institutional Cohort</title><p><underline underline-style="single">D.V. Wakefield</underline><sup>1,2</sup>, J.T. Lucas Jr.<sup>1</sup>, B. Eaton<sup>3</sup>, C.Y. Hsu<sup>1</sup>, A. Pappo<sup>4</sup>, N. Eshiashvili<sup>3</sup>, A.M. Davidoff<sup>5</sup>, M. Krasin<sup>1</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Radiation Oncology, Memphis, USA; <sup>2</sup>University of Tennessee West Cancer Center, Radiation Oncology, Memphis, USA; <sup>3</sup>Emory University Winshop Cancer Institute, Radiation Oncology, Atlanta, USA; <sup>4</sup>St Jude Children's Research Hospital, Oncology, Memphis, USA; <sup>5</sup>St Jude Children's Research Hospital, Surgical Oncology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: A paucity of data exist detailing the role of local therapies (radiotherapy [RT], surgery) following locoregional recurrence (LR) in pediatric rhabdomyosarcoma (RMS). We evaluated outcomes and prognostic factors using a multi‐institutional cohort of patients with LR managed with or without repeat RT (ReRT).</p><p><bold>Design/Methods</bold>: 23 patients with LR RMS were treated from 1996 to 2012 were eligible for inclusion. Patient stage, risk, group, histology, translocation status, primary location, histology, surgical extent, RT dose and failure pattern were documented. Overall (OS), local, and distant failure free survival (LFFS, DFFS) were described using the Kaplan‐Meier estimator.</p><p><bold>Results</bold>: With a median follow‐up of 4.6 years from LR, 7 (30%) patients were alive and 5 (22%) had no evidence of disease. Salvage therapy included ReRT and surgery in 50% and 50% of cases. All patients received chemotherapy at LR. Median OS and PFS from LR were 19.3 and 16.9 months. Patients with low risk and favorable primary site had improved PFS and OS. LFFS and DFFS at 3 years following salvage therapy were 54%, and 56% respectively. The median LFFS and OS in the No ReRT vs. ReRT patients was 12.4 vs. 19.6 (p=0.1) and 18.8 vs. 26.1 mo (p=0.46). Patients with favorable site and group 3 disease, LR‐only failure, and embryonal histology had improved LFFS with ReRT. No patients experienced > grade 3 acute toxicity. Late toxicities included second malignancy, and chemotherapy induced end organ failure in 2 and 2 patients respectively. LR failure was a component of cancer related death in 60% vs. 40% in the No ReRT vs. ReRT group (p= 0.02).</p><p><bold>Conclusions</bold>: Salvage RT may reduce the risk of further LR in patients with favorable disease and relapse characteristics, although distant failure remains common. Acute toxicities were minimal while second malignancies and chemotherapy induced end organ failure were a cause of late mortality.</p></sec></sec><sec id="pbc26772-sec-2950"><title>Solid Non Brain Tumours ‐ Retinoblastoma</title><sec id="pbc26772-sec-2960"><label>PD-033</label><title>Impact of a Multi‐Faceted Retinoblastoma Program Model in a Tertiary Hospital in the Philippines</title><p><underline underline-style="single">A.P. Alcasabas</underline><sup>1</sup>, G. Mercado<sup>2</sup>, P. Fajardo<sup>1</sup>, M. Dolendo<sup>3</sup>, C. Rodriguez‐Galindo<sup>4</sup>, C. Lam<sup>4</sup>, J. Lecciones<sup>5</sup>, E. Domingo<sup>2</sup></p><p><italic><sup>1</sup>University of the Philippines ‐ Philippine General Hospital, Paediatrics, Manila, Philippines; <sup>2</sup>University of the Philippines ‐ Philippine General Hospital, Ophthalmology, Manila, Philippines; <sup>3</sup>Southern Philippines Medical Center, Pediatrics, Davao, Philippines; <sup>4</sup>St. Jude Children's Research Hospital, Global Pediatric Medicine, Memphis, USA; <sup>5</sup>Philippine Children's Medical Center, Pediatrics, Manila, Philippines</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma survival in the Philippines remains poor due to low detection rates, late referrals and incomplete treatment. Development of a retinoblastoma program involving stage‐based treatment protocols, on‐line tumor board meetings, patient navigation, data management and community‐based educational campaigns increased referrals and decreased extra‐ocular presentations in a public referral hospital in Mindanao. The same model was later implemented in three referral centers in Luzon. We review the program's impact on patient outcomes at Philippine General Hospital where baseline data (2008‐2012) showed census of 22/year, 54% extra‐ocular disease, 26% survival and 56% abandonment rates.</p><p><bold>Design/Methods</bold>: Prospective data collection of consecutive patients diagnosed January 1, 2014 to December 31, 2016. Study end‐point was March 1, 2017.</p><p><bold>Results</bold>: A total of 96 patients were diagnosed: unilateral 62; bilateral 32; and trilateral 2. Mean age was 24.6 months (2 – 108). M:F 1.5:1. Majority had extra‐ocular disease: International Retinoblastoma Staging System Stage 0: 1 (1%); Stage I: 38 (40%); Stage II: 2 (2%); Stage III: 31 (32%); Stage IV: 19 (20%); and unknown 5 (5%). Symptom‐to‐diagnosis lag time was 12 months (1 ‐ 45). At study end‐point, 43% (41) were alive, 28% (n=27) had died, 16% had refused (4%; n=4) or abandoned (12%; n=12) treatment; 7% (n=7) transferred care centers, and 5% (n=5) lost to follow‐up. The 1 and 2‐year overall survival was 69.7% and 55.3%, respectively, with survival highest for Stage I (100% and 97%, respectively) and lower for Stages III (63% and 40%, respectively) and IV (28% and 26%, respectively). The 1 and 2‐year abandonment‐sensitive overall survival was slightly lower (60.4% and 46%, respectively) and followed similar trends by stage as the overall survival.</p><p><bold>Conclusions</bold>: This multi‐faceted retinoblastoma outcome improvement model demonstrated increases in patient referrals, treatment adherence and survival, and provides data to support additional replication and extension efforts for a national protocol for retinoblastoma.</p></sec><sec id="pbc26772-sec-2970"><label>PD-034</label><title>Treatment Results In Extra‐Ocular Retinoblastoma with Invasion of the Optic Nerve at Presentation</title><p><underline underline-style="single">B. Chawla</underline><sup>1</sup>, F. Hasan<sup>1</sup>, R. Agarwal<sup>1</sup>, R. Seth<sup>2</sup>, S. Pathy<sup>3</sup>, S. Sharma<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, RP Centre for Ophthalmic Sciences, New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences, Paediatric Oncology Division‐ Department of Paediatrics, New Delhi, India; <sup>3</sup>All India Institute of Medical Sciences, Department of Radiation Oncology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Optic nerve invasion is a significant risk factor for metastasis in retinoblastoma. The purpose of this study was to evaluate the clinical outcome in retinoblastoma patients who had invasion of the optic nerve at the time of diagnosis and were treated with a uniform protocol consisting of multi‐modal therapy.</p><p><bold>Design/Methods</bold>: Patients of non‐metastatic extra‐ocular retinoblastoma with evidence of optic nerve invasion on contrast‐enhanced MRI scan of the orbits and brain were studied. Demographic and clinical details were recorded. The treatment protocol consisted of neo‐adjuvant chemotherapy, enucleation, orbital external beam radiotherapy and adjuvant chemotherapy. Systemic chemotherapy consisted of intravenous vincristine, etoposide and carboplatin for 12 cycles. Following neo‐adjuvant chemotherapy, the optic nerve status was re‐assessed on MRI scan. Outcome parameters were survival probability and cause of death.</p><p><bold>Results</bold>: Forty eight children were studied (66.7% unilateral, 60% boys). The median age at presentation was 30 months. The median follow up was 18.6 months. Of 48 children, 18 (38%) died. The Kaplan Meier survival probability was 79% and 59% at one year and four years respectively. The most common cause of death was CNS relapse (83%).</p><p><bold>Conclusions</bold>: Advanced cases of retinoblastoma with optic nerve invasion can be managed by a multi‐modal treatment protocol. Although short term results are encouraging, long term outcomes need further evaluation.</p></sec><sec id="pbc26772-sec-2980"><label>PD-035</label><title>Natural Killer Cell Therapy Against Retinoblastoma</title><p><underline underline-style="single">D.H. Jo</underline><sup>1</sup>, J.H. Kim<sup>2</sup>, H.O. Jun<sup>2</sup>, C.S. Cho<sup>2</sup>, E. Bak<sup>1</sup>, S. Lee<sup>3</sup>, S.R. Yoon<sup>3</sup>, Y.J. Park<sup>3</sup>, K.D. Park<sup>4</sup>, I. Choi<sup>3</sup>, J.H. Kim<sup>1</sup></p><p><italic><sup>1</sup>Seoul National University College of Medicine, Department of Ophthalmology, Seoul, Republic of Korea; <sup>2</sup>Seoul National University Hospital, Fight against Angiogenesis‐Related Blindness FARB Laboratory‐ Clinical Research Institute, Seoul, Republic of Korea; <sup>3</sup>Korea Research Institute of Bioscience and Biotechnology, Immunotherapy Research Center, Daejeon, Republic of Korea; <sup>4</sup>Seoul National University College of Medicine, Department of Pediatrics‐ Cancer Research Institute, Seoul, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: This study aims to investigate therapeutic potential of natural killer (NK) cell therapy against retinoblastoma, the most common intraocular malignant tumor in children. In patients with retinoblastoma, it is inevitable to perform enucleation, total removal of eyeball, if conventional treatment options fail. In this context, novel treatment options are desperately required to treat patients with retinoblastoma.</p><p><bold>Design/Methods</bold>: NK92 cells (commercially available cell line) and cord blood‐derived NK cells were prepared for <italic>in vitro</italic> cytotoxicity assays and <italic>in vivo</italic> intracardiac injection. <italic>In vitro</italic> cytotoxicity was evaluated by coculture of NK cells and retinoblastoma cells from 3 different retinoblastoma cell lines (Y79, WERI‐Rb1, and SNUOT‐Rb1) using calcein AM assay. For the evaluation of <italic>in vivo</italic> efficacy, retinoblastoma cells (2 × 10<sup>4</sup> cells) from 3 different retinoblastoma cell lines were injected into the vitreous cavity of Balb/c nude mice (<italic>n</italic> =12 per group). At 7 or 10 days after intravitreal injection of tumor cells, NK cells (1 or 5 × 10<sup>6</sup> cells) were administered via intracardiac route or carboplatin (50 mg/Kg) was administered through intraperitoneal route with 2 more administration on a weekly basis. <italic>In vivo</italic> cytotoxicity was evaluated using the visual grading system and histologic examination.</p><p><bold>Results</bold>: Both NK cells demonstrated considerable <italic>in vitro</italic> cytotoxicity against retinoblastoma cells. In addition, tumors were formed in a less severe manner in mice treated with NK cells than in ones treated with carboplatin or phosphate‐buffered saline (negative control). It is also remarkable that mice treated with combination of NK cells and carboplatin demonstrated minimal tumor formation in intraocular space compared to ones treated with only NK cells or carboplatin.</p><p><bold>Conclusions</bold>: Taken together, NK cells demonstrated <italic>in vitro</italic> and <italic>in vivo</italic> cytotoxicity against retinoblastoma. We expect that NK cell therapy might be involved in the treatment of retinoblastoma.</p></sec></sec><sec id="pbc26772-sec-2990"><title>Solid Non Brain Tumours ‐ Liver Tumours</title><sec id="pbc26772-sec-3000"><label>PD-036</label><title>CD146 Is a Potential Therapeutic Target in Hepatoblastoma</title><p><underline underline-style="single">M. Sonoda</underline><sup>1</sup>, K. Umeda<sup>2</sup>, S. Nodomi<sup>2</sup>, S. Obu<sup>2</sup>, S. Saida<sup>2</sup>, I. Kato<sup>2</sup>, H. Hiramatsu<sup>2</sup>, E. Ogawa<sup>1</sup>, A. Yoshizawa<sup>1</sup>, S. Okamoto<sup>1</sup>, K. Morita<sup>3</sup>, Y. Kamikubo<sup>3</sup>, S. Adachi<sup>3</sup>, T. Nakahata<sup>4</sup>, H. Okajima<sup>1</sup>, S. Uemoto<sup>1</sup>, T. Heike<sup>2</sup></p><p><italic><sup>1</sup>Kyoto University Graduate School of Medicine, Pediatric Surgery, Kyoto, Japan; <sup>2</sup>Kyoto University Graduate School of Medicine, Pediatrics, Kyoto, Japan; <sup>3</sup>Kyoto University Graduate School of Medicine, Human Health Science, Kyoto, Japan; <sup>4</sup>Kyoto University, Center for iPS Cell Research and Application, Kyoto, Japan</italic></p><p><bold>Background/Objectives</bold>: Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Recent progress in both surgical techniques and in neoadjuvant and adjuvant chemotherapy has markedly improved the prognosis for patients with HB: however, the survival rate of patients with metastatic and relapsed disease remains unsatisfactory. CD146 is an integral membrane glycoprotein that promotes tumor growth, angiogenesis and metastasis and is regarded as a promising candidate for immunotherapy against various CD146‐expressing malignancies.</p><p><bold>Design/Methods</bold>: The expression level of CD146 in two HB cell lines (HepG2 and Huh6) and clinical samples was examined by flow cytometric and immunohistochemical analyses. The anti‐tumor effect of blocking CD146 by rabbit anti‐CD146 polyclonal antibody or shRNA knockdown of CD146 was then evaluated both <italic>in vitro</italic> (by WST‐8 assay) and <italic>in vivo</italic> (by subcutaneous transplantation into immunodeficient mice).</p><p><bold>Results</bold>: CD146‐positive cells were detected in both HB cell lines and most of clinical samples. Knockdown of CD146 significantly inhibited <italic>in vitro</italic> tumor viability via induction of apoptosis, and markedly suppressed <italic>in vivo</italic> tumor formation in immunodeficient mice. Anti‐CD146 polyclonal antibody also showed effective <italic>in vivo</italic> anti‐tumor activity. Details of underlying mechanism are now under investigation.</p><p><bold>Conclusions</bold>: Notable anti‐tumor effect of blocking CD146 will facilitate a novel immunotherapy for HB.</p></sec><sec id="pbc26772-sec-3010"><label>PD-037</label><title>Impact of the Response to Chemotherapy on the Clinical Outcome of Hepatoblastoma after Liver Transplantation: A Single Institute Experience</title><p><underline underline-style="single">K. Umeda</underline><sup>1</sup>, H. Okajima<sup>2</sup>, K. Kawaguchi<sup>3</sup>, S. Nodomi<sup>1</sup>, S. Saida<sup>1</sup>, I. Kato<sup>1</sup>, H. Hiramatsu<sup>1</sup>, E. Ogawa<sup>2</sup>, A. Yoshizawa<sup>2</sup>, S. Okamoto<sup>2</sup>, S. Uemoto<sup>2</sup>, K. Watanabe<sup>3</sup>, S. Adachi<sup>2</sup></p><p><italic><sup>1</sup>Kyoto University Graduate School of Medicine, Pediatrics, Kyoto, Japan; <sup>2</sup>Kyoto University Graduate School of Medicine, Pediatric Surgery, Kyoto, Japan; <sup>3</sup>Shizuoka Children's Hospital, Hematology and Oncology, Shizuoka, Japan</italic></p><p><bold>Background/Objectives</bold>: Liver transplantation (LT), which was performed as a primary surgery (primary LT) or subsequently for recurrent tumor after a primary resection (rescue LT), has recently contributed to the elevation of cure rates for patients with unresectable hepatoblastoma (HB). The prognosis of patients with recurrent HB after LT was extremely dismal. However, there are many unresolved problems, including the risk factors for post‐LT relapse and treatment strategy for post‐LT relapse.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed the clinical outcome of 24 patients with HB who underwent LT between 1997 and 2015.</p><p><bold>Results</bold>: The 5‐yr OS rate of all patients was 69.6% ± 9.7%. Both serum AFP level at LT and decline in the serum AFP level at LT in comparison with that at diagnosis were significantly higher in the remission group than those in the relapse group. The 5‐yr OS rate of patients with a decline of AFP >95% (81.3% ± 9.8%) at LT was higher than that in patients with a decline of AFP ≤95% (42.9% ± 18.7%). The 5‐yr OS rate of patients undergoing rescue LT (72.7% ± 13.4%) was comparable to that of patients undergoing primary LT (69.2% ± 12.8%). In the primary LT group, six of ten patients with a decline of AFP >95% were alive in remission, whereas both patients with a decline of AFP ≤95% experienced post‐LT relapse. In the rescue LT group, all three patients with any decline of AFP to pre‐LT chemotherapy (range, 82.0–90.8%) were alive in remission, whereas three of six patients with no response to pre‐LT chemotherapy experienced post‐LT relapse.</p><p><bold>Conclusions</bold>: Response to chemotherapy might be a reliable marker for predicting post‐LT relapse, even for patients undergoing rescue LT.</p></sec></sec><sec id="pbc26772-sec-3020"><title>Solid Non Brain Tumours ‐ Germ Cell Tumours</title><sec id="pbc26772-sec-3030"><label>PD-038</label><title>Pediatric Testicular Germ Cell Tumors: The Associazione Italiana Ematologia Oncologia Pediatrica Study</title><p><underline underline-style="single">M. Terenziani</underline><sup>1</sup>, M. Conte<sup>2</sup>, M.D. De Pasquale<sup>3</sup>, F. Barretta<sup>4</sup>, D. Biasoni<sup>5</sup>, G. Bisogno<sup>6</sup>, R. Boldrini<sup>7</sup>, G. Cecchetto<sup>8</sup>, P. Collini<sup>9</sup>, D. Di Pinto<sup>10</sup>, A. Inserra<sup>11</sup>, F. Melchionda<sup>12</sup>, F. Siracusa<sup>13</sup>, F. Spreafico<sup>1</sup>, P. D'Angelo<sup>14</sup></p><p><italic><sup>1</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology, Milano, Italy; <sup>2</sup>Ospedale Pediatrico G. Gaslini, Pediatric Onco‐Hematology, Genova, Italy; <sup>3</sup>Ospedale Pediatrico Bambino Gesù‐IRCCS, Pediatric Onco‐Hematology, Roma, Italy; <sup>4</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Clinical Epidemiology and Trial Organization, Milano, Italy; <sup>5</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Surgery, Milano, Italy; <sup>6</sup>University Hospital‐ Padova, Pediatric Onco‐Hematology, Padova, Italy; <sup>7</sup>Ospedale Pediatrico Bambino Gesù‐IRCCS, Diagnostic Pathology and Laboratory Medicine, Roma, Italy; <sup>8</sup>University Hospital‐ Padova, Pediatric Surgery, Padova, Italy; <sup>9</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Diagnostic Pathology and Laboratory Medicine, Milano, Italy; <sup>10</sup>Seconda Università di Napoli, Pediatric Oncology, Napoli, Italy; <sup>11</sup>Ospedale Pediatrico Bambino Gesù‐IRCCS, Pediatric Surgery, Roma, Italy; <sup>12</sup>S.Orsola‐Malpighi University Hospital, Pediatric Oncology, Bologna, Italy; <sup>13</sup>Università degli studi di Palermo, Pediatric Surgery, Palermo, Italy; <sup>14</sup>ARNAS Civico Di Cristina, Pediatric Oncology, Palermo, Italy</italic></p><p><bold>Background/Objectives</bold>: We describe the results of a therapeutic approach with a pediatric BEP (bleomycin, etoposide, cisplatin) from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study on testicular germ cell tumors (TGCT).</p><p><bold>Design/Methods</bold>: From March 2004 to December 2016, males under 18 years were enrolled in the AIEOP study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk‐group assignment at diagnosis with consideration for stage. All patients underwent orchiectomy at diagnosis and those with stage I received no chemotherapy. Patients with stage II and III received three cycles for total doses of platinum 300 mg/m<sup>2</sup> plus etoposide 1200 mg/m<sup>2</sup> and bleomycin 45 mg/m<sup>2</sup> (BEP). Patients with stage IV received four cycles for a total doses of platinum 400 mg/m<sup>2</sup> plus etoposide 1,600 mg/m<sup>2</sup> and blemoycin 60 mg/m<sup>2</sup>. After chemotherapy, retroperitoneal and/or lung residual diseases were removed by surgery.</p><p><bold>Results</bold>: One hundred and thirteen patients were evaluable with a median age of 16 year old (range 6 months ‐ 17.10 years) staged as follows: 58 stage I, 9 stage II, 19 stage III and 27 stage IV. Overall survival (OS) and event‐free survival (EFS) at 5 years for the whole series were 97.8% (CI 96.3% ‐ 99.3%) and 75.1% (CI 70.7% ‐ 79.5%), for stage I 100% and 60.6% (CI 53.5% ‐ 67.7%), and for stages II‐IV 95.7% (CI 92.7% ‐ 98.5%)and 89.4% (CI 84.9% ‐ 93.9%), respectively. The median follow up was 42 months.</p><p><bold>Conclusions</bold>: We confirmed the excellent prognosis of TGCT in children and adolescents. Reduction of cumulative dose of etoposide did not seem to compromise survival outcomes for patients in stages II‐IV, but further investigations are needed to draw conclusions.</p></sec></sec><sec id="pbc26772-sec-3040"><title>Solid Non Brain Tumours ‐ Rare Tumours</title><sec id="pbc26772-sec-3050"><label>PD-039</label><title>Are Very Rare Tumors Correctly Recognized? A European Survey on Pleuropulmonary Blastoma</title><p>A. Tagarelli<sup>1</sup>, D. Orbach<sup>2</sup>, R. Lopez Almaraz<sup>3</sup>, A. Pourtsidis<sup>4</sup>, E. Bien<sup>5</sup>, G. Osterlundh<sup>6</sup>, A. Kolenova<sup>7</sup>, M. Cesen<sup>8</sup>, C. Devalck<sup>9</sup>, E. Koscielniak<sup>10</sup>, J. Rascon<sup>11</sup>, N.J. Farinha<sup>12</sup>, J. Roganovic<sup>13</sup>, S.S. Teresa<sup>14</sup>, Z. Jakab<sup>15</sup>, T. Ben Ami<sup>16</sup>, D. Kostantinov<sup>17</sup>, <underline underline-style="single">G. Bisogno</underline><sup>1</sup></p><p><italic><sup>1</sup>University of Padua, Department of Pediatric Hematology Oncology, Padua, Italy; <sup>2</sup>Institut Curie, Département d'oncologie pédiatrique, Paris, France; <sup>3</sup>Hospital Universitario Cruces, Pediatric Oncology and Hematology Unit, Bilbao, Spain; <sup>4</sup>P & A. Kyriakou Children's Hospital, Oncology Department, Athens, Greece; <sup>5</sup>Medical University of Gdansk, Department of Pediatrics‐ Hematology & Oncology, Gdansk, Poland; <sup>6</sup>Göteborg University, Department of Pediatrics, Göteborg, Sweden; <sup>7</sup>Comenius University Medical School and University Children's Hospital, Department of Pediatric Hematology and Oncology, Bratislava, Slovak Republic; <sup>8</sup>Jožef Stefan Institute, Department of Environmental Sciences, Ljubljana, Slovenia; <sup>9</sup>Hôpital Universitaire des Enfants Reine Fabiola, Department of Hemato‐Oncology, Brussels, Belgium; <sup>10</sup>Olga Hospital, Department of Pediatric Oncology, Stuttgart, Germany; <sup>11</sup>Children's Hospital‐ Vilnius University, Center of Pediatric Oncology and Hematology, Vilnius, Lithuania; <sup>12</sup>Centro Hospitalar de São João, Department of Pediatrics, Porto, Portugal; <sup>13</sup>Clinical Hospital Centre Rijeka, Department of Pediatrics‐ Division of Hematology and Oncology, Rijeka, Croatia; <sup>14</sup>Medical University of Gdansk, Department of Pediatric Oncology and Oncology, Gdańsk, Poland; <sup>15</sup>Semmelweis University, 2 nd Department of Pediatrics, Budapest, Hungary; <sup>16</sup>Hadassah Hebrew University Medical Center, Department of Pediatric Hematology Oncology and Bone Marrow Transplantation, Jerusalem, Israel; <sup>17</sup>University Hospital “Queen Johanna”, Children's Oncohaematology Clinic, Sofia, Bulgaria</italic></p><p><bold>Background/Objectives</bold>: Very rare tumors (VRT) in childhood represent a diagnostic and treatment challenge. In particular, Pleuropulmonary Blastoma (PPB), a rare and potentially aggressive intrathoracic neoplasm, can be confused with other tumors or malformative lesions. The correct diagnosis is the first step to establish the right treatment. The aim of the present study was to assess the ability of diagnosing patients with PPB for each European country, comparing the number of the expected PPB cases with the number of registered cases.</p><p><bold>Design/Methods</bold>: The expected number of PPB was calculated from 2000 to 2014 on the basis of pediatric epidemiological data (www.Eurostat.it) and the reported incidence of PPB. The number of observed patients with PPB has been obtained sending a questionnaire to the physicians identified as the national contact for VRT in 26 European countries.</p><p><bold>Results</bold>: Twenty countries provided data: overall 121 PPB cases have been observed, comparing to 109 expected cases. A low number of patients with PPB has been registered mainly in eastern countries, in particular: Bulgaria, Slovenia, Croatia, Bosnia and Lithuania did not observe any case. More patients than expected were diagnosed in Finland, Sweden, Israel and especially in France, Poland and Italy where national registries and cooperative groups dedicated to VRT exist. In addition the experience from these countries suggests that the incidence of PPB may be higher than previously reported.</p><p><bold>Conclusions</bold>: Our study demonstrates that differences in the number of observed/expected cases of PPB exist across European countries and suggest that this may be related to the presence of national VRT cooperative groups.</p></sec><sec id="pbc26772-sec-3060"><label>PD-040</label><title>Diagnosis and Treatment of Pancreatoblastoma in Children: A Retrospective Study in a Single Pediatric Center</title><p><underline underline-style="single">Z. Zhu</underline><sup>1</sup></p><p><italic><sup>1</sup>Beijing Children's Hospital Affiliated to Capital Medical University, Department of Surgical Oncology, Beijing, China</italic></p><p><bold>Background/Objectives</bold>: Pancreatoblastoma is a very rare malignant pancreatic tumor in children. A standardize management and therapy is still discussed. To summarize our experience in the management of pancreatoblastoma in children and adolescents.</p><p><bold>Design/Methods</bold>: This was a retrospective, observational study of primary pancreatoblastoma in patients< 18 years of age who were treated at Beijing children's hospital (BCH) between 2005 and 2015.</p><p><bold>Results</bold>: 21 patients with pancreatoblastoma were diagnosed at a median age of 4 years, 7 girls and 14 boys. The diagnosis of pancreatoblastoma was identified by the histology examination. The most common syndrome was abdominal mass(n=11), followed by abdominal pain(N=10), elevated serum AFP levels were noted in all cases, of 17 patients with disease initially unresectable at presentation, accepted neoadjuvant chemotherapy consisting of CDV, OPEC, PLADO, IEV, and AVCP. All patients underwent surgery, including pancreaticoduodenectomy(Whipple's procedure), the Pylorus‐preserving pancreaticoduodenectomy (traverse‐Longmire procedure), Spleen‐preserving distal pancreatectomy, and Distal pancreatectomy with en bloc splenectomy, Roux‐en‐Y end to end pancreatojejunostomy. In all, 13 children are disease free with a median follow‐up of 53 months (range, 11‐156 months).</p><p><bold>Conclusions</bold>: The pancreatoblastoma in children and adolescents is a curable malignant tumor. Complete resection combined with chemotherapy is associated with long‐term survival. For the unresectable tumor at diagnosis, preoperative chemotherapy (OPEC) were recommended to reduce tumor volume.</p></sec></sec><sec id="pbc26772-sec-3070"><title>Brain Tumours</title><sec id="pbc26772-sec-3080"><label>PD-041</label><title>Humanized Anti‐CD47 Antibody Combined with an Agonist ANTI‐CD40 Antibody is an Effective Treatment for DIPG Xenografts with Cranio‐Spinal Dissemination</title><p><underline underline-style="single">S. Gholamin</underline><sup>1</sup>, K. Suzana<sup>2</sup>, R. Esparza<sup>2</sup>, I. Weissman<sup>3</sup>, S. Mitra<sup>2</sup>, S. Cheshier<sup>4</sup></p><p><italic><sup>1</sup>California Institute of Technology Caltech, Biology and Biological Engineering, Pasadena, USA; <sup>2</sup>Stanford, Neurosurgery, Stanford, USA; <sup>3</sup>Stanford, Institute of Stem Cell Biology and Regenerative Medicine, Stanford, USA; <sup>4</sup>Stanford, Neurosurgery, Stanoford, USA</italic></p><p><bold>Background/Objectives</bold>: DIPG is the most common malignant brainstem tumor in children. The resistance of DIPG to standard treatments along with inoperability of this tumor because of the anatomical location leave DIPG patients with dismal prognosis. Multiple studies revealed that DIPG patients have only a few months of survival after detection of cranio‐spinal metastasis. Our previous work showed that a humanized anti‐CD47 antibody (anti‐huCD47 mAb), an immune‐modulatory drug that increases phagocytic activity of macrophages against cancer cells, has a therapeutic effect on DIPG xenografts. However, the efficacy of anti‐CD47 therapy was inversely correlated with tumor size and presence of metastasis at the onset of treatment. Therefore, we tested the synergistic effect of anti‐huCD47 mAb combined with anti‐msCD40 mAb, another immuno‐modulatory antibody that increases the recruitment of macrophages to the tumor site, on DIPG xenografts with cranio‐spinal dissemination.</p><p><bold>Design/Methods</bold>: Human‐derived DIPG cells were infected with GFP‐luciferase expressing virus and injected to the pons of NOD scid gamma mice. The engraftment was verified via bioluminescent (BLI) imaging. The mice with positive signal in forebrain and spine were randomized for treatment with anti‐huCD47 mAb alone, anti‐msCD40 Ab alone, anti‐huCD47 mAb coupled with anti‐msCD40 mAb, and control. The efficacy of treatment was measured using follow‐up BLI imaging and survival analysis.</p><p><bold>Results</bold>: Follow‐up BLI imaging revealed significant decline in the flux measures of mice receiving combined treatment (P< 0.05). BLI signals from the spinal and forebrain strongly diminished in the mice under combined treatment compared to the other groups. A significant extension in survival was seen in this group compared to the other three groups (P < 0.05).</p><p><bold>Conclusions</bold>: combinatorial treatment with anti‐CD47 Ab and anti‐CD40 Ab is effective in the removal of not only DIPG from a primary site but also a cranio‐spinal dissemination of the disease.</p></sec><sec id="pbc26772-sec-3090"><label>PD-042</label><title>Patient Derived Cell Lines to Study Alternative Lengthening of Telomeres (ALT) in Pediatric Brain Tumors</title><p><underline underline-style="single">H. Ijaz</underline><sup>1</sup>, R.L. Dilley<sup>2</sup>, M.H. Williams<sup>3</sup>, M.P. Koptyra<sup>3</sup>, J.L. Mason<sup>3</sup>, A.C. Resnick<sup>3</sup>, Y. Zhu<sup>3</sup>, B. Zhang<sup>3</sup>, A.J. Waanders<sup>1</sup>, R.A. Greenberg<sup>2</sup>, P. Raman<sup>3</sup>, K.A. Cole<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, USA; <sup>2</sup>University of Pennsylvania, Perelman School of Medicine, Philadelphia, USA; <sup>3</sup>The Children's Hospital of Philadelphia, Center for Data Driven Discovery in Biomedicine, Philadelphia, USA</italic></p><p><bold>Background/Objectives</bold>: All cancers acquire a mechanism of telomere maintenance (TMM) for unlimited replicative potential. Some cancers, including a subset of pediatric brain tumors, use the TMM of alternative lengthening of telomeres (ALT). However, there are few cancer cell lines with ALT, representing a mixture of histotypes. We aim to generate and characterize patient derived pediatric brain tumor cell lines with and without ALT.</p><p><bold>Design/Methods</bold>: The Children's Brain Tumor Tissue Consortium (CBTTC) database was queried for pediatric and adolescent brain tumor types likely to have ALT, and tumor in freezing media. Patient derived cell lines were generated as adherent and suspension lines. Corresponding primary tumor samples were analyzed for ALT by c‐circle assay (CCA) and genomic analysis for a targeted set of genes.</p><p><bold>Results</bold>: The CBTTC biorepository had 37 primary high‐grade glioma and PNET samples available for processing into patient derived cell lines, including 2 diagnosis‐relapse pairs. To date, 22/37 are growing well in various stages of development and validation. Analysis of the cell line's corresponding primary tumors revealed that 9/35 (25%) are ALT positive. H3F3A sequencing showed that 3/3 (100%) of G34R mutant, 2/8 (25%) of K27M mutant and 4/24 (17%) of H3F3A wild‐type tumors are ALT positive. As expected, ALT positive tumors are more likely to occur in older patients (16 <italic>vs</italic> 10 years old, p= 0.018) and to be hemispheric (6/9, 67%). WGS was available for 19 tumors, including 4 with ALT. The ALT positive tumors have damaging mutations in TP53 (4/4), ATRX (2/4), H3F3A (2/4) and IDH1 (1/4).</p><p><bold>Conclusions</bold>: The CBTTC makes it possible to generate patient derived cell lines from a well‐characterized set of pediatric primary brain tumors for collaborative science. The panel is representative of reported characteristics of ALT positive pediatric brain tumors with respect to associated mutations, frequency and location.</p></sec><sec id="pbc26772-sec-3100"><label>PD-043</label><title>Cutaneous Toxicities of BRAF and MEK Inhibitors in Children</title><p><underline underline-style="single">T. Loka</underline><sup>1</sup>, P. O'Hare<sup>1</sup>, C. Mahon<sup>2</sup>, D. Hargrave<sup>1</sup></p><p><italic><sup>1</sup>Great Ormond Street Hospital, Haematology & Oncology Clinical Trials Unit, London, United Kingdom; <sup>2</sup>Great Ormond Street Hospital, Dermatology, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: BRAF and MEK inhibitors are emerging therapies in childhood malignancy. The cutaneous side effects are well described in adult patients, but not in children. We undertook to document the spectrum of cutaneous side effects seen in children treated with these agents at our tertiary hospital, as well as the onset, duration and severity of the skin findings.</p><p><bold>Design/Methods</bold>: Retrospective chart review of children treated with either a BRAF (dabrafenib) or MEK inhibitor (trametinib). Basic demographic and clinical characteristics were collected from patient records and the skin findings assessed in collaborations with a paediatric dermatologist.</p><p><bold>Results</bold>: Twenty‐four children aged 1‐16 years (mean 8.4 years) treated with either a BRAF (11) or MEK inhibitor (13) for <italic>BRAF</italic>‐V600‐mutant refractory or relapsed intracranial malignancy (8), neurofibromatosis type 1 (NF1)‐associated optic glioma and neurofibroma (7), Langerhan cell histiocytosis (LCH) (3), or leptomeningeal melanocytosis/melanoma (3) were identified. One patient received combination BRAF/MEK inhibitor therapy. Mean treatment duration was 39 weeks (7‐92) for BRAF and 19 weeks (7‐37) for MEK inhibitor therapy.</p><p>Six (54%) children treated with dabrafenib developed new melanocytic naevi (7‐36 weeks), 5 of these also developed a persistent erythema nodsum‐like (EN) eruption (onset 1‐32 weeks) 2 diffuse alopecia, (onset 29 and 40 weeks) and single cases keratosis pilaris, an acneiform facial rash.</p><p>Six (46%) children on a MEK inhibitor developed paronychia (onset 4‐20 weeks), 5 of these also developing hair thinning (onset 4‐17 weeks) and generalised xerosis (onset 2‐8 weeks). Four patients (30%) developed acneiform eruptions. 1 child required dose reduction of therapy due to cutaneous side effects. Two patients discontinued treatment and one patient died because of disease progression.</p><p><bold>Conclusions</bold>: Cutaneous adverse effects of BRAF an MEK inhibitor therapy are common and well tolerated in paediatric patients. Our experience is that prophylactic management is beneficial.</p></sec><sec id="pbc26772-sec-3110"><label>PD-044</label><title>Quality of Life, Growth, and Hypothalamic Lesions in Childhood‐Onset Craniopharyngioma</title><p><underline underline-style="single">H.L. Müller</underline><sup>1</sup>, K. Tjaden<sup>1</sup>, S. Boekhoff<sup>1</sup>, A. Hoffmann<sup>1</sup>, M. Warmuth‐Metz<sup>2</sup>, M. Eveslage<sup>3</sup>, G. Calaminus<sup>4</sup></p><p><italic><sup>1</sup>Klinikum Oldenburg AöR‐ Medical Campus University Oldenburg, Department of Pediatrics and Pediatric Hematology / Oncology, Oldenburg, Germany; <sup>2</sup>University of Würzburg, Department of Neuroradiology, Würzburg, Germany; <sup>3</sup>University of Münster, Institute of Biostatistics and Clinical Research, Münster, Germany; <sup>4</sup>University of Bonn, Department of Pediatric Oncology and Hematology, Bonn, Germany</italic></p><p><bold>Background/Objectives</bold>: Quality of life (QoL) after childhood‐onset craniopharyngioma (CP) is frequently impaired by tumour and/or treatment‐related factors such as endocrine deficits and hypothalamic involvement (HI).</p><p><bold>Design/Methods</bold>: We prospectively analyzed parental and self‐assessment of CP patient QoL at 3 mo, 1 and 3 yrs after CP diagnosis related to growth hormone (GH) substitution and HI. Forty‐seven of 194 CP patients recruited 2007‐2015 fulfilled the inclusion criteria: 1.) histological CP diagnosis, 2.) age at diagnosis 6‐18 yrs; 3.) availability of QoL data one and three yrs after diagnosis. QoL was assessed using the Pediatric Quality of Life (PEDQOL) questionnaire.</p><p><bold>Results</bold>: Parents estimated QoL of their children worse than patients did themselves for the PEDQOL domains emotional stability, body image, physical function, and social function / friends and family. HI was associated with lower self‐assessed QoL 3 mo after diagnosis (body image, p<0.01; social function/friends, p<0.01). The negative impact of HI on QoL was greater for parental assessed QoL at all time points. GH substitution had no relevant effect on short‐term weight and height development. CP patients, GH‐treated at 3 yrs follow‐up, presented at baseline (1 yr after diagnosis, before GH substitution) with reduced self‐assessed QoL for the PEDQOL domains autonomy (p<0.05), cognition (p<0.01), physical function (p<0.05), and social function/friends (p<0.01), when compared with GH non‐treated CP patients. QoL stabilized during 1‐3 yrs of follow‐up in GH treated patients, whereas non GH‐treated patients experienced decreases in QoL for the PEDQOL domains physical function and social function/friends.</p><p><bold>Conclusions</bold>: Parents assess QoL in CP survivors worse than their children. As HI is a major risk factor for reduced QoL, treatment strategies in CP should aim at prevention of (further) hypothalamic damage. GH substitution should be considered as an effective option to ameliorate imminent impairments of QoL after CP.</p></sec><sec id="pbc26772-sec-3120"><label>PD-045</label><title>Prognostic Factors in Relapsed Medulloblastomas Treated with a Multimodal Therapy: A Report of the HIT’2000, HIT‐REZ‐97 and HIT‐REZ‐2005 Studies</title><p><underline underline-style="single">S. Tippelt</underline><sup>1</sup>, J. Buchholz<sup>2</sup>, R. Mikasch<sup>1</sup>, N. Siegler<sup>1</sup>, M. Warmuth‐Metz<sup>3</sup>, S. Rutkowski<sup>4</sup>, M. Mynarek<sup>4</sup>, B.O. Juhnke<sup>4</sup>, K. von Hoff<sup>4</sup>, T. Pietsch<sup>5</sup>, S. Pfister<sup>6</sup>, O. Witt<sup>6</sup>, R.D. Kortmann<sup>7</sup>, R. Kwiecien<sup>8</sup>, R. Faldum<sup>8</sup>, U. Bode<sup>9</sup>, G. Fleischhack<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Essen, Pediatric Oncology and Hematology, Essen, Germany; <sup>2</sup>Lukas Hospital Neuss, Children's Hospital, Neuss, Germany; <sup>3</sup>University of Würzburg, Neuroradiology, Würzburg, Germany; <sup>4</sup>University Medical Center Hamburg‐Eppendorf, Pediatric Hematology and Oncology, Hamburg, Germany; <sup>5</sup>University of Bonn, Institute of Neuropathology, Bonn, Germany; <sup>6</sup>University of Heidelberg, Pediatric Hematology and Oncology, Heidelberg, Germany; <sup>7</sup>University of Leipzig, Radiooncology, Leipzig, Germany; <sup>8</sup>University of Münster, Institute of Biostatistics and Clinical Research, Münster, Germany; <sup>9</sup>University of Bonn, Pediatric Hematology and Oncology, Bonn, Germany</italic></p><p><bold>Background/Objectives</bold>: Despite a multimodal relapse therapy the prognosis of patients with a recurrent medulloblastoma (MB) is poor. The aim of this analysis was to evaluate prognostic factors for progression‐free survival (PFS) and overall survival (OS) of patients with a 1<sup>st</sup> recurrence of MB enrolled in the German HIT’2000, HIT‐REZ‐97 and HIT‐REZ‐2005 studies.</p><p><bold>Design/Methods</bold>: Patients with a recurrent MB between July 1997 and August 2011 were included in this analysis. Data analyzed at relapse were age, gender, histological subgroup, metastases stage, relapse therapy, disease state at last follow up. Kaplan‐Meier analysis was used to estimate the PFS/OS after 1<sup>st</sup> recurrence. Possible prognostic factors for PFS/OS were investigated by performing univariate and multivariate analyses.</p><p><bold>Results</bold>: This analysis included 229 patients [71 female/158 male, median age at 1<sup>st</sup> recurrence 11.1 years (0.8–36.1), median PFS after primary diagnosis 2.0±0.1 years] suffering from a local or metastatic relapse (13.9%/86.1%). At first recurrence 90.4% of patients received chemotherapy (intravenously 56.3 %, orally 28.8%, intrathecally 45.4%, high‐dose 23.6%), 28.4% of patients underwent total to partial tumor resection, 31.4% of patients received radiotherapy. Median PFS after 1<sup>st</sup> recurrence was 1.0±0.1 years (0.1‐25.4), the median OS 1.8±0.2 years (0.1‐26.2). The 2‐, 5‐ and 10‐year‐PFS and ‐OS rates were 25.9%, 7.8%, 4.4% and 46.6%, 17.7%, 6.7%, respectively. In the multivariate analyses the metastatic relapse [Hazard ratio (HR) for PFS (1.9); OS (2.1)], the nonapplication of radiotherapy (HR 2.0;1.9), and the application of only an oral chemotherapy (HR 1.7;1.8) turned out to be poor prognostic parameters.</p><p><bold>Conclusions</bold>: Multimodal therapy led to long‐term OS in a few patients with recurrent MB. Local recurrent disease, re‐resection, re‐irradiation and systemic intravenous chemotherapy were associated with a prolonged PFS/OS. Future studies will identify the prognostic relevance of molecular subgroups and of new targeted or antiangiogenic therapies, therefore re‐biopsy is highly recommended.</p><p><italic>Supported by German Children's Cancer Foundation</italic></p></sec><sec id="pbc26772-sec-3130"><label>PD-046</label><title>Pseudoprogression After Irradiation in Pediatric Low Grade Glioma</title><p><underline underline-style="single">D.S. Tsang</underline><sup>1</sup>, E.S. Murphy<sup>2</sup>, J.T. Lucas Jr.<sup>1</sup>, P. Lagiou<sup>3,4</sup>, T.E. Merchant<sup>1</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Department of Radiation Oncology, Memphis, USA; <sup>2</sup>Cleveland Clinic, Department of Radiation Oncology, Cleveland, USA; <sup>3</sup>Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, USA; <sup>4</sup>School of Medicine‐ University of Athens NKUA, Department of Hygeine‐ Epidemiology and Medical Statistics, Athens, Greece</italic></p><p><bold>Background/Objectives</bold>: The goal of this study was to characterize the incidence of pseudoprogression after radiation therapy (RT) for pediatric low‐grade glioma (LGG).</p><p><bold>Design/Methods</bold>: Patients age ≤21 with intracranial pediatric LGG (WHO grade I‐II) treated with curative‐intent RT at a single institution were included in this retrospective review. Pseudoprogression was defined for this investigation as an increase in tumour size ≥10% in ≥2 dimensions between two MR imaging studies, or serial growth <10% in two dimensions over three studies, while accounting for competing risks of true progression or death. Event‐free survival (EFS) was defined as survival without true progression or secondary high‐grade glioma.</p><p><bold>Results</bold>: Sixty‐two of 221 patients (28%) developed pseudoprogression, with a 9‐year cumulative incidence of 29.0% (95% CI 23.0‐35.2). Median time to pseudoprogression was 6.1 months after RT (interquartile range [IQR] 3.5‐14.6, range 0.9‐105). Symptomatic pseudoprogression was managed with subtotal resection, shunt/Ommaya, and corticosteroids in 11 (18%), 7 (11%), and 2 patients (3%), respectively. The median time to pseudoprogression‐related procedure was 3.4 months after RT (IQR 1.8‐6.1). The remaining asymptomatic patients (68%) were observed; 30 (48%) had shrinkage and 11 (18%) stabilized. Median duration of pseudoprogression was 6.2 months (IQR 3.2‐11.7) among asymptomatic patients. Patients with pilocytic astrocytoma (PA) had increased odds of developing pseudoprogression relative to other histology (odds ratio 5.7, 95% CI 2.7‐12.0, p < 0.0001). Among patients with PA (n = 127), the 9‐year cumulative incidence of pseudoprogression was 42.9% (95% CI 33.8‐51.7) and in this group, pseudoprogression was associated with improved 10‐year EFS (84.5% vs. 58.5%, log‐rank p = 0.008) and overall survival (98.0% vs. 91.2%, log‐rank p = 0.030).</p><p><bold>Conclusions</bold>: Pseudoprogression after irradiation is common, especially in patients with pilocytic astrocytoma, and appears to be prognostic for survival. Knowledge of the incidence and temporal course of pseudoprogression may help avoid unnecessary salvage treatment.</p></sec></sec><sec id="pbc26772-sec-3140"><title>Treatment and Care ‐ New Drugs/Experimental Therapeutics</title><sec id="pbc26772-sec-3150"><label>PD-047</label><title>Development of a Small Molecule Inhibitor for SAMHD1 to Improve Outcome for Patients with Acute Myelogenous Leukaemia and Relapsed T‐Lymphoblastic Malignancies Treated with Nucleoside Analogues</title><p><underline underline-style="single">N. Herold</underline><sup>1</sup>, S. Rudd<sup>2</sup>, I. Hed Myrberg<sup>1</sup>, K. Sanjiv<sup>2</sup>, L. Ljungblad<sup>1</sup>, J. Kutzner<sup>3</sup>, D. Grandér<sup>4</sup>, P. Kogner<sup>1</sup>, G. Rassidakis<sup>4</sup>, T. Helleday<sup>2</sup>, J.I. Henter<sup>1</sup>, T. Schaller<sup>3</sup></p><p><italic><sup>1</sup>Karolinska Institutet, Women's and Children's Health, Stockholm, Sweden; <sup>2</sup>Karolinska Institutet, MBB, Stockholm, Sweden; <sup>3</sup>Heidelberg University Hospital, Department for Infectious Diseases, Heidelberg, Germany; <sup>4</sup>Karolinska Institutet, Onk‐Pat, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Acute myelogenous leukaemia (AML) accounts for approximately 5% of all childhood cancers, and despite highly toxic multidrug regimens more than 30% of patients cannot be cured. The deoxycytosine analogue cytarabine (ara‐C) together with anthracyclines constitutes the backbone of AML‐directed therapy. Treatment failure is frequently caused by resistance to ara‐C, more specifically, by the lack of intracellular accumulation of the triphosphorylated active metabolite ara‐CTP in leukemic blasts.</p><p>Nelarabine, a pro‐drug of ara‐G, has sparked hope to improve the dismal survival for children with relapsed T‐lymphoblastic leukaemia or lymphoma, but remission rates are only about 30% Just like ara‐C effects are mediated by ara‐CTP, nelarabine toxicity relies on its intracellular conversion to ara‐GTP.</p><p>We have previously shown that SAMHD1 hydrolyses ara‐CTP and ara‐GTP and confers resistance to ara‐C both in leukaemia mouse models. Retrospective analyses of 300 AML patients suggested a therapy‐limiting effect of SAMHD1.</p><p><bold>Design/Methods</bold>: Using a cell‐based phenotypic cell proliferation inhibition assay, we screened approximately 35,000 small molecule compounds to identify lead substances that synergise with ara‐C in wildtype SAMHD1, but not CRISPR/Cas9 SAMHD1‐knockout cells. SAMHD1 inhibition was confirmed using an <italic>in vitro</italic> activity assay with recombinant SAMHD1. Target engagement was assessed by cellular‐thermal shift assays (CETSA) and X‐ray crystallography.</p><p><bold>Results</bold>: We identified lower nanomolar small molecule inhibitors of SAMHD1 that sensitised wildtype SAMHD1 leukemic cells more than 100‐fold to ara‐C and nelarabine, i.e. completely abolished SAMHD1‐mediated resistance while leaving SAMHD1‐knockout cells unaffected. These results could be recapitulated <italic>in vivo</italic> using paediatric AML mouse models.</p><p><bold>Conclusions</bold>: We suggest that SAMHD1 might play a dual role for future leukaemia therapies: 1) a biomarker to guide dose adjustments with the aim to reduce toxicity for low expressers. 2) a target for drug candidates amenable for clinical trials based on our pre‐clinical SAMHD1 inhibitors to improve efficacy of ara‐C and nelarabine treatments for high expressers of SAMHD1.</p></sec><sec id="pbc26772-sec-3160"><label>PD-048</label><title>Reporting of Clinical Significance in Pediatric Oncology Randomized Control Trials: A Systematic Review</title><p><underline underline-style="single">F. Howard</underline><sup>1</sup>, K. Goddard<sup>2</sup>, O. Samargandi<sup>3</sup>, H. Hasan<sup>2</sup></p><p><italic><sup>1</sup>University of British Columbia, School of Nursing, Vancouver, Canada; <sup>2</sup>British Columbia Cancer Agency, Radiation Oncology, Vancouver, Canada; <sup>3</sup>QEII Health Sciences Centre, Division of Plastic Surgery, Halifax, Canada</italic></p><p><bold>Background/Objectives</bold>: Traditionally, the interpretation of randomized control trials (RCTs) have relied on statistical significance as opposed to clinical significance, including the use of minimally clinically important difference (MCID), which raises questions about study design rigor and utility of results. The degree to which clinical significance has been applied and reported in RCTs in pediatric cancer has not been determined.</p><p>The objective of this review was to systematically assess the reporting of clinical significance based on the delta value reported in the sample size calculation and to identify factors associated with clinical significance in RCTs in the pediatric oncology literature.</p><p><bold>Design/Methods</bold>: This systematic review involved a comprehensive search of MEDLINE, EMBASE and the Cochrane Childhood Cancer Group Specialized Register through CENTRAL from inception to July 2016. Eligible studies included RCTs of primary cancer treatments in pediatric patients diagnosed with cancer.</p><p><bold>Results</bold>: RCTs (101), representing 126 randomized questions were included. The minority (19.8%) of randomized questions reported conclusions based on clinical significance. Only 6.3% of randomized questions explicitly identified that the delta value in the sample size calculation was based on the MCID. The statistical significance of the primary outcome was based on a p‐value in 77.8% of randomized questions, while over half (63.5%) reported confidence intervals or standard error bars for the point estimate in question. The median publishing journal impact factor and planned sample size were larger for randomized questions that reported clinical significance as opposed to those that did not.</p><p><bold>Conclusions</bold>: A minority RCTs in the published pediatric oncology literature have reported methodological attributes related to clinical significance and have drawn study conclusions based on clinical significance. The integration of clinical significance into study design and subsequent reporting in future pediatric oncology trials will enhance evidence‐based decision making in clinical practice and policy.</p></sec><sec id="pbc26772-sec-3170"><label>PD-049</label><title>Comparing Arsenic Trioxide and Indigo Naturalis Formula in Pediatric Patients with Acute Promyeloid Leukemia: An Interim Report of Muticenter and Randomized Clinical Trial SCCLG‐APL</title><p><underline underline-style="single">X.Q. Luo</underline><sup>1</sup>, L.Z. Cao<sup>2</sup>, W.Q. Wan<sup>3</sup>, Y.D. Lin<sup>4</sup>, J.P. Fang<sup>5</sup>, L.H. Yang<sup>6</sup>, C.G. Li<sup>7</sup>, H.Q. Chen<sup>8</sup>, G.H. Chen<sup>9</sup>, X.Q. Feng<sup>10</sup>, R.Y. Liu<sup>11</sup></p><p><italic><sup>1</sup>The First Affiliated Hospital of Sun Yat‐sen University, Pediatrics, Guangzhou, China; <sup>2</sup>XiangYa Hospital Central South University, pediatrics, Changsha, China; <sup>3</sup>The Second XiangYa Hospital Central South University, pediatrics, Changsha, China; <sup>4</sup>Guangdong General Hospital, pediatrics, Guangzhou, China; <sup>5</sup>The Second Affiliated Hospital of Sun Yat‐Sen University, pediatrics, Guangzhou, China; <sup>6</sup>Zhujiang Hospital of Southern Medical University, pediatrics, guangzhou, China; <sup>7</sup>Shenzhen Children's Hospital, pediatrics, Shenzhen, China; <sup>8</sup>The Third Affiliated Hospital of Zhongshan University, pediatrics, Guangzhou, China; <sup>9</sup>The first people's Hospital of Huizhou, pediatrics, Huizhou, China; <sup>10</sup>Nanfang Hospital of Southern Medical University, pediatrics, Guangzhou, China; <sup>11</sup>Huizhou Central Hospital, pediatrics, Huizhou, China</italic></p><p><bold>Background/Objectives</bold>: Indigo naturalis formula (RIF) is a traditional Chinese medicine with tetraarsenic tetrasulfide, indirubin and tanshinone IIA as major active ingredients. RIF can be taken orally, which reduces hospital days. Event‐free survival (EFS) is about 90% in adult patients with acute promyelocytic leukemia (APL) treated on protocol containing RIF, all‐trans retinoic acid (ATRA) and chemotherapeutic agents (RIF+ATRA+chemotherapy), which is comparable to that of patients on arsenic trioxide (ATO)+ATRA+chemotherapy. However, the efficacy and safety of RIF in pediatric counterpart have not been evaluated, and it is unclear whether RIF can replace ATO.</p><p><bold>Design/Methods</bold>: SCCG (South China Children Leukemia Group)‐APL protocol was started in august 2011. Patients of age 0‐16 were enrolled except those having intracranial hemorrhage / central nervous system leukemia with coma, convulsion or nervous paralysis at diagnosis. Patients were randomized into ATO or RIF group and received “ATO/RIF+ATRA+low‐dose anthracycline” for induction and consolidation therapy followed by “ATO/RIF+ATRA+MTX+6MP” for 96 weeks of maintenance therapy. Those with high‐risk APL (WBC ≥ 10<sup>9</sup>/L at diagnosis) received additional Ara‐C in consolidation phase.</p><p><bold>Results</bold>: Among 84 patients diagnosed, 78 met the enrollment criteria and were willing to be randomized. Headache and vomit/nausea were the commonest treatment‐related adverse effects occurring in 18% and 12% of patients in each group during induction and consolidation therapy respectively. Significant treatment‐related infections including sepsis, pneumonia, cellulitis and etc. were observed in 13% and 8% of patients during induction, and 12% and 8% of patients during consolidation, in ATO and RIF groups, respectively (P>0.05). There were two drop‐out cases in ATO group, one abounded treatment and the other deviated from the protocol because of adverse effect. The 4‐year EFSs (median follow‐up of 2 years) of both groups were 100%.</p><p><bold>Conclusions</bold>: SCCG‐APL protocol containing arsenic (either ATO or RIF), ATRA and low‐intensive chemotherapy obtained a good outcome in childhood APL (including high‐risk).</p></sec><sec id="pbc26772-sec-3180"><label>PD-050</label><title>Development of GD2 and CD3 Targeted Bispecific T‐Cell Engaging Antibodies for Neuroblastoma</title><p>A. Patel<sup>1</sup>, C. Thevanesan<sup>1</sup>, J. Anderson<sup>1</sup>, M. Pule<sup>2</sup>, <underline underline-style="single">K. Straathof</underline><sup>1</sup></p><p><italic><sup>1</sup>UCL Great Ormond Street Institute of Child Health, Developmental Biology and Cancer Program‐ Cancer Section, London, United Kingdom; <sup>2</sup>UCL Cancer Institute, Haematology, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: New treatment strategies for high‐risk neuroblastoma are needed to improve outcome and reduce treatment‐related late effects. Using bi‐specific T‐cell engagers (BiTEs) to redirect the patient's own T‐cells to recognize and eliminate neuroblastoma tumour cells proves an attractive novel treatment option. Indeed, CD19/CD3 BiTE Blinatumumab has shown great promise in treatment of high‐risk leukemia. Here, we describe the selection of the optimal GD2/CD3 BiTE format for use in treatment of neuroblastoma.</p><p><bold>Design/Methods</bold>: Fourteen BiTE variants were constructed using single chain variable fragments (scFv) derived from three different humanized CD3‐specific antibodies and two different humanized GD2‐specific antibodies fused with three different size linkers. First, BiTEs were characterised by measuring thermal stability profiles using differential scanning fluorimetry, and antigen specificity and binding affinity to antigen‐positive and negative tumour cell lines using flow cytometry and Scatchard analysis. Then, functional comparisons were performed by determining antigen‐specific tumour cell lysis at a range of BiTE concentrations.</p><p><bold>Results</bold>: All BiTE formats tested demonstrated specificity for GD2 and CD3. BiTEs based on the GD2‐specific scFv with the highest binding affinity had the lowest IC50 values i.e. concentration that achieved half maximal cytolytic activity of GD2‐positive cells. In contrast, differences in CD3 binding affinities for scFv tested did not translate into significant differences in ability to redirect T‐cells to GD2‐positive cell lysis. BiTEs with medium and long linkers mediated T‐cell lysis of GD2‐positive cells at lower concentrations than BiTEs with shorter linkers.</p><p><bold>Conclusions</bold>: This study demonstrates that binding affinity of tumour‐specific scFv as well as linker length determine the potency of GD2/CD3 BiTEs. For selected BiTE formats detailed studies of anti‐tumour response including T‐cell proliferation and cytokine secretion profile are currently ongoing. This data set will inform the selection of the optimal GD2/CD3 BiTE format which will be taken forward for development into a novel clinical therapeutic for neuroblastoma.</p></sec><sec id="pbc26772-sec-3190"><label>PD-051</label><title>Complete Remissions Post Infusion of Multiple Tumor Antigen Specific T Cells for the Treatment of High Risk Leukemia and Lymphoma Patients After HCT</title><p><underline underline-style="single">K. Williams</underline><sup>1</sup>, M. Grant<sup>1</sup>, M. Ismail<sup>1</sup>, F. Hoq<sup>1</sup>, M. Martin Manso<sup>1</sup>, J. Hoover<sup>1</sup>, E. Mintz<sup>1</sup>, A. Namata<sup>1</sup>, E. Williams<sup>1</sup>, C. Barese<sup>1</sup>, S. Albihani<sup>1</sup>, R. Cruz<sup>1</sup>, H. Lang<sup>1</sup>, P. Hanley<sup>1</sup>, J. Barrett<sup>2</sup>, S. Gottchalk<sup>3</sup>, S. McCurdy<sup>4</sup>, R. Jones<sup>4</sup>, C. Bollard<sup>1</sup></p><p><italic><sup>1</sup>Children's National Medical Center, CETI, Washington DC, USA; <sup>2</sup>NIH, NHLBI, Bethesda, USA; <sup>3</sup>Texas Children's Hospital, BMT, Houston, USA; <sup>4</sup>Johns Hopkins School of Medicine, BMT, Baltimore, USA</italic></p><p><bold>Background/Objectives</bold>: Relapse of hematologic malignancies after hematopoietic cell transplantation (HCT) confers high mortality because of progressive disease and graft‐vs.‐host disease (GVHD). Hence, we hypothesized that tumor‐associated antigen‐specific lymphocytes (TAA‐L) would be specific, diminish immune escape, and could safely decrease cancer burden.</p><p><bold>Design/Methods</bold>: We expanded lymphocytes reactive to TAA: WT1, PRAME, Survivin, which are over‐expressed and immunogenic in hematologic malignancies. On a prospective study: NCT002203902, eligible patients received TAA‐L infusions at sequential dose levels: 0.5 to 4.0e7/m2 per dose.</p><p><bold>Results</bold>: Twenty‐five donor‐derived TAA‐L products were generated and lacked alloreactivity in vitro. TAA‐L products contained T cells were predominantly effector memory, with >30% expressing the activation markers, and <15% of T‐cells expressing exhaustion markers (PD1, TIM3, LAG3). Specificity of TAA‐L showed greatest response to PRAME by ELIspot. Ten HCT recipients (aged 9‐70 years) with relapsed Hodgkins disease (n=2), B‐ALL (n=3), or AML (n=5) received 1‐3 doses of TAA‐L. All patients had relapsed 2‐12 months after HCT (9 allo, 1 auto). Post infusion, there were no adverse events attributed to TAA‐L and no GVHD. One patient withdrew prior to study completion due to progressive disease in the setting of steroids for sepsis. Responses of evaluable patients (n=9) were: PD (n=2), PR (n=3), CR (n=4). Of the CR patients: 3 had AML (1 received adjunct vidaza after TAA‐L); 1 patient had Ph+‐ALL and achieved bcr‐abl negativity post TAA‐L for the first time post‐HSCT without additional therapy. Immunosequencing of T‐cell receptors detected multiple TCRs derived from the infused TAA‐L product 4‐5 weeks after infusion.</p><p><bold>Conclusions</bold>: This unique immunotherapeutic has been well tolerated without causing GVHD or life‐threatening cytokine release syndrome. Despite aggressive and multiply relapsed disease, 7/9 evaluable patients have demonstrated evidence of disease control after TAA‐L, with 44% complete response, suggesting that TAA‐L may have efficacy in relapsed high‐risk hematological malignancies after HCT.</p></sec><sec id="pbc26772-sec-3200"><label>PD-052</label><title>Mechanisms of Efficacy of the PAN‐FGFR Inhibitor AZD4547 in Pediatric Solid Tumor Models</title><p><underline underline-style="single">P. Zage</underline><sup>1</sup>, S. Hakim<sup>1</sup>, D. Subramonian<sup>1</sup>, J. Lesperance<sup>1</sup></p><p><italic><sup>1</sup>University of California ‐ San Diego ‐ Moores Cancer Center, Pediatrics, San Diego, USA</italic></p><p><bold>Background/Objectives</bold>: Children with aggressive pediatric solid tumors such as neuroblastoma, rhabdomyosaroma, and Ewing sarcoma have poor outcomes, and new therapies are needed. Aberrant expression and activity of growth factor receptors, including the Fibroblast Growth Factor Receptor (FGFR) family, are associated with many malignancies. Therefore, we hypothesized that inhibition of FGFR family members using the novel pan‐FGFR inhibitor AZD4547 would be effective against pediatric solid tumors.</p><p><bold>Design/Methods</bold>: We evaluated the effects of AZD4547 on the viability of neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma cells using continuous live cell imaging to measure cell confluence and caspase activity. We also evaluated the effects of AZD4547 on cell migration and invasion using scratch wound and matrigel chamber invasion assays and the effects of AZD4547 on intracellular signaling with western blotting and QT‐PCR.</p><p><bold>Results</bold>: AZD4547 treatment of pediatric solid tumor cells resulted in decreased cell confluence, with calculated IC50 values varying from 3.7mM to more than 20mM, and in the induction of apoptosis. AZD4547 treatment at sublethal concentrations inhibited migration and invasion <italic>in vitro</italic> in all tested cell lines compared to untreated cells. AZD4547 treatment also resulted in decreased phosphorylation of Akt and S6 in all tested cell lines. Sensitive cell lines demonstrated increased levels of phospho‐ERK and complete inhibition of ERK phosphorylation after treatment, while resistant cell lines demonstrated minimal inhibition of ERK phosphorylation. Sensitive cell lines further demonstrated increased levels of phospho‐STAT3 while resistant cell lines demonstrated decreased or unchanged levels of phospho‐STAT3, suggesting potential markers for AZD4547 response and mechanisms of resistance.</p><p><bold>Conclusions</bold>: AZD4547 is effective against pediatric solid tumors including neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma, and sensitivity to AZD4547 appears to be mediated by effects on the Ras/MAPK and JAK/STAT pathways. AZD4547 therefore represents a potential novel therapeutic agent for pediatric solid tumors, and further preclinical and clinical studies are warranted.</p></sec></sec><sec id="pbc26772-sec-3210"><title>Treatment and Care ‐ Supportive Care</title><sec id="pbc26772-sec-3220"><label>PD-053</label><title>Reducing Infection Related Morbidity and Mortality by Improving Time to Antibiotic Administration: A Quality Improvement Project in a Resource Limited Pediatric Oncology Unit</title><p><underline underline-style="single">M.C. dolendo</underline><sup>1</sup>, D. Aguilar<sup>1</sup>, E. Bacus<sup>1</sup>, C. Lam<sup>2</sup>, M.E. Concha<sup>3</sup></p><p><italic><sup>1</sup>Southern Philippines Medical Center, Pediatrics, Davao City, Philippines; <sup>2</sup>St Jude Children's Research Hospital, Global Pediatric Oncology Department, Memphis, USA; <sup>3</sup>Southern Philippines Medical Center, Family Medicine, Davao City, Philippines</italic></p><p><bold>Background/Objectives</bold>: Childhood cancer is an important health concern in the Philippines with an estimated 6,800 new cases annually. Although survival rates have improved, infection related morbidity and mortality continue to be a threat. Timely recognition of infection and immediate administration of antibiotics have been shown to improve survival. This project aims to improve time to antibiotic administration for children with cancer and concomitant infection at our institution through feedback to the different stakeholders about their performance.</p><p><bold>Design/Methods</bold>: A quality improvement cycle was implemented at the Southern Philippines Medical Center Pediatric Oncology Unit in Mindanao. Charts of admitted patients meeting the inclusion criteria were reviewed in terms of demographics, clinical profile, timeliness of antibiotic administration and outcomes for a 3‐month period as baseline data on performance. A group feedback was then given after which repeat data collection was done for three months.</p><p><bold>Results</bold>: A total of 103 charts were reviewed at the beginning of the quality improvement cycle and 79 charts were reviewed after group feedback was given. Antibiotic initiation was delayed at baseline in 80.27% of cases while this decreased to 44.08% on repeat measurement (<italic>p value < 0.001</italic>). There were 24.72% of patients who died at baseline data collection while 11.39% died on repeat measurement (<italic>p value 0.023</italic>). Length of hospital stay at baseline and repeat measurement was similar at around 17‐18 days.</p><p><bold>Conclusions</bold>: Group feedback significantly reduced delays in antibiotic administration. There were also lesser number of unimproved or expired patients probably due to reduction in delays. Continuous quality improvement initiatives and need for multifaceted interventions are necessary to improve and sustain improvements in improving time to antibiotic administration for children with cancer in order to improve outcomes and reduce morbidity and mortality.</p></sec><sec id="pbc26772-sec-3230"><label>PD-054</label><title>Olanzapine is an Inexpensive and Efficacious Agent for Breakthrough Chemotherapy Induced Acute Phase Vomiting Among Children Receiving Moderate or High Emetogenic Chemotherapy</title><p><underline underline-style="single">G. Kapoor</underline><sup>1</sup>, S. Koneru<sup>1</sup>, S. Jain<sup>1</sup></p><p><italic><sup>1</sup>Rajiv Gandhi Cancer Institute and Research Centre, Pediatric Hematology & Oncology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Chemotherapy induced vomiting remains one of the most distressing adverse effects of cancer therapy and negatively impacts compliance and nutrition. Antiemetic data related to Olanzepine, an approved antipsychotic drug is mainly restricted to adult and few retrospective pediatric studies. Its low cost, easy availability and oral preparation make it ideal for use in resource‐restricted settings.</p><p>The objectives of this study were to study the efficacy of olanzapine for breakthrough vomiting and assess its safety among children 2‐18 years of age receiving moderate or high emetogenic chemotherapy (MEC, HEC, respectively per POGO guidelines).</p><p><bold>Design/Methods</bold>: This observational study was done over 6 months from July‐December 2016, after obtaining ethical approval. Acute breakthrough emesis was defined as vomiting occurring within 24hours of last dose of chemotherapy, despite adequate prophylaxis that included 5‐HT3 receptor antagonist, dexamethasone and aprepitant (triple‐drug for HEC). The dose of olanzapine was 0.05‐0.1 mg/kg per oral once a day for 3 consecutive days. Patients on prior antiemetics or antipsychotics or with medical or surgical disorders likely to contribute to vomiting were excluded. Complete and partial responses were defined as no or 1‐2 emetic episode/s respectively and use of no other rescue medications. Adverse events were graded as per CTCAE version 4.03.</p><p><bold>Results</bold>: This study analyses 42 chemotherapy blocks among 31 children (median age 9 years, male 21/31) with various hematological and solid malignancies receiving MEC(18/42) or HEC(24/42). Complete and partial responses were observed among 83%(35) and 14%(6) blocks respectively, much better than reports with metoclopramide. No statistical difference in efficacy was observed by age, gender or emetogenic regimen (<italic>p</italic> 0.2). Side‐effects included somnolence (grade 1‐2, 11/42), orthostatic collapse(grade 3, 1/42) and transaminitis(grade 1, 1/42).</p><p><bold>Conclusions</bold>: Excellent efficacy and safety of an inexpensive agent like olanzapine make it a suitable option for breakthrough emesis for children in developing countries warranting large controlled prospective studies.</p></sec><sec id="pbc26772-sec-3240"><label>PD-055</label><title>Age, Sarcoma and Use of Tunneled Lines are Independently Associated with Requirement of Tissue Plaminogen Activator for Episodes of Central Venous Catheter Dysfunction</title><p>J. MacLean<sup>1</sup>, T. MacDonald<sup>1</sup>, C. Digout<sup>1</sup>, R. Krista<sup>1</sup>, <underline underline-style="single">K. Kulkarni</underline><sup>1</sup></p><p><italic><sup>1</sup>IWK Health Center, Pediatric Hematology Oncology‐ Department of Pediatrics, Halifax, Canada</italic></p><p><bold>Background/Objectives</bold>: Dysfunction (defined as inability to flush and/or draw blood) is a common complication associated with central venous catheters (CVC). Tissue plasminogen activator (tPA) is often instilled to reverse episodes of CVC dysfunction. However, data on risk‐factors associated with requirement of tPA are unclear. We hypothesized that clinic‐demographic and CVC related variables are associated with requirement of use of tPA for episodes of CVC dysfunction in pediatric oncology patients.</p><p><bold>Design/Methods</bold>: In this population based study, case records of all pediatric oncology patients from Maritimes, Canada managed by the Izaac Walton Killam Health Centre from January 2,000 to December 2,015 were reviewed after ethics approval. Clinico‐demographic data and characteristics of first CVC were pooled from: (i) Pediatric Oncology hospital database, (ii) Electronic medical records, (iii) Pharmacy database and (iv) Central line database. Patients with ≥1 episodes of CVC dysfunction of their first CVC requiring ≥1 dose of tPA were identified. Analysis was done using SPSS version 24.</p><p><bold>Results</bold>: At least 1 CVCs was required in 741 patients. One or more doses of tPA (mean: 2.04±2.0) were required by 20.1% (n=149) of the patients for episodes dysfunction related to first CVC. On univariate analysis, age>10 years (p=0.015), diagnosis (classified as leukemia, lymphoma, sarcoma, brain tumor and others) (p=0.001), and use of tunneled lines (p=0.006) were significantly associated with use of tPA while gender (p=0.098) was not. On multivariate analysis, age>10 years [p=0.016, OR: 1.6 (95% (confidence interval) (CI): 1.1‐2.3)], diagnosis of sarcoma [p=0.001, OR: 3.2 (95% CI:2‐5.3)] and use of tunneled lines [p=0.002, OR: 2.4 (95% CI:1.4‐4.1)] were independently associated with a requirement for tPA.</p><p><bold>Conclusions</bold>: The present study identified independent risk factors ascertained at diagnosis associated for use of tPA for episodes of dysfunction associated with first CVC. After validation, a predictive risk model ascertained at diagnosis could be developed to identify high risk patients.</p></sec><sec id="pbc26772-sec-3250"><label>PD-056</label><title>Effects of Combined Resistance and Endurance Training in Pediatric Cancer Patients during Intensive Treatment Phase: Design and First Insights into the MUCKI‐Study</title><p><underline underline-style="single">S. Stössel</underline><sup>1</sup>, M.A. Neu<sup>1</sup>, A. Wingerter<sup>1</sup>, F.T. Baumann<sup>2</sup>, P. Zimmer<sup>3</sup>, C. Paret<sup>1</sup>, K. El Malki<sup>1</sup>, H. Otto<sup>1</sup>, T. Abu Tair<sup>4</sup>, N. Henniger<sup>1</sup>, W. Bloch<sup>3</sup>, J. Faber<sup>1</sup></p><p><italic><sup>1</sup>University Medical Center, Center for Pediatric and Adolescent Medicine‐ Department of Pediatric Hematology/Oncology/Hemostaseology, Mainz, Germany; <sup>2</sup>University Hospital of Cologne, Department I of Internal Medicine‐ Center of Integrated Oncology Köln Bonn, Köln, Germany; <sup>3</sup>German Sport University Cologne, Institute of Cardiovascular Research and Sports Medicine‐ Department of Molecular and Cellular Sport Medicine, Köln, Germany; <sup>4</sup>University Medical Center, Center for Pediatric and Adolescent Medicine‐ Department of Pediatric Cardiology, Mainz, Germany</italic></p><p><bold>Background/Objectives</bold>: Due to various disease‐ and treatment‐related factors, skeletal muscle function in pediatric and adult cancer patients is impaired resulting in decreased muscular strength. Previous studies in adult cancer patients have shown that specific exercise interventions can increase muscular strength which was related to positive effects on whole‐body muscle mass, fatigue and quality of life. The purpose of the MUCKI study is to determine whether combined resistance and endurance training can improve muscle strength in pediatric cancer patients during intensive cancer treatment phase (ICT).</p><p><bold>Design/Methods</bold>: Based on a pilot experimental phase, a feasible exercise program was developed. A convenient study design was established aiming to enroll 40 childhood cancer patients aged between 4 and 18 years. As part of the randomized, controlled and interventional study design, individuals within the exercise group (EG) participate in supervised exercise training. Training takes place 3 to 5 times per week over a period of 6 to 8 weeks during ICT. Individuals of the control group (CG) obtain usual care. Before and after the intervention muscle strength of upper and lower limbs, aerobic performance, body composition, fatigue and quality of life are determined.</p><p><bold>Results</bold>: Recruitment started in November 2015. So far 18 patients have been included. 9 patients were randomized to the EG from whom 7 have already completed the exercise intervention. Comparing pre‐ and post‐intervention the knee flexor strength increased in the EG in average by 24.3% whereas it decreased by 7.6% in the CG (p<0.05). Further preliminary results regarding benefits from the exercise intervention on the above mentioned parameters show positive trends. In a post interventional interview patients reported that they enjoyed the exercise program and would recommend it to others.</p><p><bold>Conclusions</bold>: Early results of the MUCKI study support the feasibility of combined resistance and endurance training and evaluation of muscular strength during ICT.</p></sec><sec id="pbc26772-sec-3260"><label>PD-057</label><title>Polymorphisms in Immune Response Genes and Risk of Infection during Treatment of Pediatric Acute Leukemia</title><p>E. Zhukovskaya<sup>1</sup>, <underline underline-style="single">M. Avdonina</underline><sup>2</sup>, D. Fesenko<sup>3</sup>, T. Lisitsa<sup>1</sup>, T. Nasedkina<sup>2</sup>, A. Karelin<sup>1</sup></p><p><italic><sup>1</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Rehabilitation Centre “Russkoe Pole”, Moscow, Russia; <sup>2</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Genetic department, Moscow, Russia; <sup>3</sup>Engelhardt Institute of Molecular Biology‐ Russian Academy of Sciences‐ Moscow, Genetic department, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Advances in the treatment of children with leukemia are mostly determined by the use of intensive chemotherapy. However, the therapy results in the suppression of immunity, which is a risk factor for the development of serious infectious complications, significantly worsening the prognosis of the underlying disease. The study of polymorphism of the genes involved in the regulation of immune response is a prospective direction.</p><p><bold>Design/Methods</bold>: DNA was isolated from leukocytes of 109 children with leukemia: 53 children with severe infections (group 1) and 56 children without complications during treatment (group 2). A microarray was designed to determine 14 SNPs in the following genes: <italic>PTPN22, TLR1, TLR2, TLR4, IL‐4, IL‐10, IL‐12b, IL7R, NOD2, Dectin‐1</italic>. The genotyping procedure included polymerase chain reaction (PCR) with fluorescent labelling of DNA target followed by allele‐specific hybridization on microarray and image analysis. Two‐sided Fisher's exact test was used for statistical analysis.</p><p><bold>Results</bold>: The genotype and allele frequencies between two groups of patients were compared. It was found that the minor allele ‐589T of the IL‐4 gene (rs2243250) was less frequent in patients of the group (1) than in patients of the group (2), thus conferring a decreased risk of infection (odds ratio OR= 0.46, p=0,03, 96% CI=0.23‐0.92). The allele G of the IL7R gene (rs1494555) was more frequent in the group (1) regarding to the group (2) (OR = 2.02, p=0.02, 95% CI = 1.12‐3.64). The combination of allele G (rs1494555) with allele T in the IL7R gene (rs1494558) strengthened this association: the haplotype GT was much more frequent in the group (1) than in the group (2) (OR=4.3, р=0.002, 95% CI= 1.76‐10.4).</p><p><bold>Conclusions</bold>: Thus, polymorphisms rs2243250 in the IL‐4 gene, rs1494558 and rs1494555 in the IL7R gene were identified as genetic markers that may influence on risk of developing infectious complications during treatment of pediatric leukemia.</p></sec></sec><sec id="pbc26772-sec-3270"><title>Treatment and Care ‐ Psychosocial (PPO)</title><sec id="pbc26772-sec-3280"><label>PD-058</label><title>Emotional Adjustment in Siblings After a Child's Death From Cancer: The Role of Extrafamilial Relationships</title><p><underline underline-style="single">K. Balistreri</underline><sup>1</sup>, M. Hagan<sup>1</sup>, M. Barrera<sup>2</sup>, T. Foster Akard<sup>3</sup>, M.J. Gilmer<sup>3</sup>, B. Compas<sup>4</sup>, D. Fairclough<sup>5</sup>, T. Young‐Saleme<sup>6</sup>, C. Gerhardt<sup>1,7</sup>, K. Vannatta<sup>1,7</sup></p><p><italic><sup>1</sup>Nationwide Children's Hospital, Center for Biobehavioral Health, Columbus, USA; <sup>2</sup>The Hospital for Sick Children, Child Health Evaluative Sciences, Toronto, Canada; <sup>3</sup>Vanderbilt University, Nursing, Nashville, USA; <sup>4</sup>Vanderbilt University, Department of Psychology and Human Development, Nashville, USA; <sup>5</sup>University of Colorado Denver, Biostatistics and Informatics, Denver, USA; <sup>6</sup>Nationwide Children's Hospital, Department of Psychology, Columbus, USA; <sup>7</sup>The Ohio State University, Pediatrics, Columbus, USA</italic></p><p><bold>Background/Objectives</bold>: The death of a child from cancer is traumatic for families. Severe and prolonged parental grief may undermine family resources to meet the unique needs of surviving siblings. Therefore, extrafamilial social resources may assume particular importance. We examined whether relationships with peers and teachers mitigate risk for depression and internalizing symptoms for bereaved siblings.</p><p><bold>Design/Methods</bold>: Children (<italic>N</italic>=76, 58% female), aged 8‐18 (<italic>M</italic>age=12.47, SD=2.54) were recruited from three US/Canadian hospitals 3‐12 months after their sibling's death from cancer. Non‐bereaved comparison‐classmates (CC) were also recruited (<italic>N</italic>=73). At school, classmates rated how much they liked each other, yielding mean Peer Acceptance scores. At home visits, children completed the Social Support Scale for Children and Children's Depression Inventory (CDI) and parents completed the Child Behavior Checklist. Regression analyses tested variance in Depression/Internalizing symptoms accounted for by group, extrafamilial relationships, and their interactions.</p><p><bold>Results</bold>: Groups did not differ in perceptions of Peer, Teacher, and Friend support or Peer Acceptance. Peer and Friend Support were negatively associated with both Depressive/Internalizing Symptoms, and Teacher Support was negatively associated with Depressive Symptoms, regardless of group (<italic>B</italic>s=‐0.84‐ ‐0.38, <italic>SE</italic>s=0.12‐0.24, <italic>p</italic>s<0.05). Peer Acceptance was negatively associated with parent‐reported Internalizing Symptoms (<italic>B</italic>=‐2.27, <italic>SE</italic>=1.04, <italic>p</italic>=0.03). A significant interaction was found between Group and Peer Acceptance predicting Depressive Symptoms (<italic>B</italic>=2.18, <italic>SE</italic>=1.03, <italic>p</italic>=.035) in which bereaved siblings reported elevated CDI scores regardless of Peer Acceptance (<italic>p</italic>=.83), but a negative association was found for CC (<italic>B</italic>=‐2.34, <italic>SE</italic>=0.76, <italic>p</italic>=0.002).</p><p><bold>Conclusions</bold>: Bereaved siblings appear to maintain peer acceptance and support from peers, teachers, and friends, and extrafamilial support benefits bereaved siblings and non‐bereaved CC. In contrast, self‐reported depressive symptoms were elevated for bereaved siblings whether or not they were ‘well‐liked’ by classmates. Future research should seek to elucidate the directionality of these associations and identify factors that undermine perceptions as well as availability of extrafamilial support.</p></sec><sec id="pbc26772-sec-3290"><label>PD-059</label><title>Training and Education in Paediatric Oncology – Current Perspectives from the Literature</title><p><underline underline-style="single">C. Barton</underline><sup>1</sup></p><p><italic><sup>1</sup>Alder Hey Children's Hospital NHS Foundation Trust, Paediatric Oncology, Liverpool, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Clinical training and education programmes for trainees and fellows in paediatric oncology are variable between countries, and between centres within single nations. Standards are however established as far as possible to ensure that trainees acquire relatively uniform experience and knowledge. This study reported here describes current perspectives on the delivery and assessment of training in paediatric oncology as described in recent literature.</p><p><bold>Design/Methods</bold>: The NHS evidence portal was used to search PubMed, PsychINFO, Embase and CINHAL using clearly defined search terms. Where possible, these terms were match to the MESH/encyclopaedia of each database.</p><p><bold>Results</bold>: Of 172 results, 38 were included as directly relevant to the delivery and assessment of paediatric oncology education and training. Countries from all five continents were represented, but weighted significantly towards higher income countries. Problems that trainees experience in receiving their training include lack of time, focus on service provision, and heterogeneous case exposure relative to other trainees, difficulty gaining experience in centres with other tertiary and quaternary speciality services, and establishing and maintaining work‐life balance. Particular areas where there was an identified need for greater experience included the presentation of brain tumours, survivorship and late effects, and palliative care. Particular challenges in the assessment of paediatric oncology trainees include heterogeneous career paths (e.g. less than full time training, academic research, and maternity leave), a lack of validated patient/family assessment tools, communication, differences in the structure of training programs and lack of formal qualifications.</p><p><bold>Conclusions</bold>: The ability of paediatric oncologists to travel between countries and continents for research and employment is testament to the validity of professional certifications in the speciality despite a lack of formal assessment. Further research in the area should focus on common and successful themes in paediatric oncology programs.</p></sec><sec id="pbc26772-sec-3300"><label>PD-060</label><title>The Perceived Impact of Pediatric Cancer on Parental Couples’ Psychological Status and Relationship Satisfaction During the Survivorship Period</title><p><underline underline-style="single">W. Burns</underline><sup>1,2</sup>, K. Péloquin<sup>1</sup>, É. Rondeau<sup>2</sup>, S. Drouin<sup>2</sup>, L. Bertout<sup>2</sup>, M. Krajinovic<sup>3,4</sup>, C. Laverdière<sup>3,4</sup>, D. Sinnett<sup>3,4</sup>, S. Sultan<sup>1,2,3</sup></p><p><italic><sup>1</sup>Université de Montréal, Psychology, Montreal, Canada; <sup>2</sup>Sainte‐Justine University Health Center, Research center, Montréal, Canada; <sup>3</sup>Université de Montréal, Pediatrics, Montreal, Canada; <sup>4</sup>Sainte‐Justine University Health Center, Hematology‐Oncology, Montréal, Canada</italic></p><p><bold>Background/Objectives</bold>: Follow‐up studies suggest that the psychosocial impact of pediatric cancer on parents often extends beyond the end of their child's cancer treatments, and parents can continue to experience both individual and dyadic (couple‐based) effects. In a long‐term study of parents of children with acute lymphoblastic leukemia (ALL), we aimed to: 1) describe couples’ adjustment (psychological distress, relationship adjustment), 2) describe the perceived impact of cancer on couples’ relationships, and 3) identify to what extent the perceived impact of cancer on the couple is related to both parents’ long‐term adjustment.</p><p><bold>Design/Methods</bold>: Participants in this study were childhood ALL survivors and their parents, who were in ‘intact’ couples (i.e. together during the illness and at recall) (<italic>n</italic> =100). Survivors' medical information was collected from medical records and parents completed questionnaires (Brief Symptom Inventory‐18, abbreviated Dyadic Adjustment Scale, and Impact of Cancer on the Couple). Mothers and fathers’ scores were compared (e.g., repeated‐measures MANOVAs). Using the Actor‐Partner Interdependence Model (APIM), we examined the degree to which a parent's perceived changes in relationship dynamics were associated with their own adjustment (actor effects), and their partner's adjustment (partner effects).</p><p><bold>Results</bold>: Distress was normative in this sample of parents with frequencies ranging from 2‐20%. Generally, mothers and fathers agreed on their reported relationship satisfaction, and the perceived nature of relationship changes (positive, negative, or no change) following the illness. Findings from dyadic models indicate that while mothers’ adjustment was self‐related (relating to their perceived relationship changes), fathers’ adjustment was primarily other‐related (relating to their partner's perceptions).</p><p><bold>Conclusions</bold>: Given our findings, it appears that mothers may act as a bridge connecting illness experiences of survivors and fathers. This could explain why mothers’ perceptions of relationship changes influence their partners’ long‐term adjustment, but the reverse is not true for fathers.</p><p><bold>Acknowledgments</bold>: Cole Foundation (Montreal), CIHR, FRQs</p></sec><sec id="pbc26772-sec-3310"><label>PD-061</label><title>A Longitudinal Examination of Factors Associated with Friendships in Pediatric Brain Tumor Survivors</title><p><underline underline-style="single">L. Desjardins</underline><sup>1</sup>, U. Bartels<sup>1</sup>, D. Cataudella<sup>2</sup>, J. Chung<sup>3</sup>, D. Fairclough<sup>4</sup>, K. Hancock<sup>1</sup>, A. Saleh<sup>1</sup>, M. Barrera<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Psychology, Toronto, Canada; <sup>2</sup>London Health Sciences Center, Hematology‐Oncology, London, Canada; <sup>3</sup>British Columbia Children's Hospital, Psychology, Vancouver, Canada; <sup>4</sup>University of Colorado Denver, Biostatistics & Informatics, Denver, USA</italic></p><p><bold>Background/Objectives</bold>: Pediatric brain tumor survivors (PBTSs) experience impairments in social competence. Anxious and depressive symptoms, insult related variables (e.g., diagnosis, treatment), non‐insult related variables (e.g., age, gender), and social information processing (e.g., executive functions, social skills, emotional control) may be associated with social competence in PBTSs. The current study examined longitudinal associations between baseline variables and peer nominated friendships in PBTSs approximately one year later.</p><p><bold>Design/Methods</bold>: Caregivers of children (n = 32) ages 8‐16 (39% low grade glioma, 34% medulloblastoma, 28% other) completed ratings of child adjustment at baseline (T1) and PBTSs and classmates completed the Three Best Friends measure approximately 12 months later (T2). Preliminary descriptive statistics examined friendship nominations and reciprocated friendships of PBTSs. Bivariate analyses examined associations between baseline independent (anxious and depressive symptoms, emotional control, global executive composite, total social skills, diagnosis, treatment, age, gender) and T2 dependent variables (friendships).</p><p><bold>Results</bold>: On average, PBTSs were nominated as a best friend by two classmates (range: 0‐7). Of the PBTSs, 25% were not nominated by any classmates as a best friend. On average, PBTSs had one reciprocated best friend nomination (range: 0‐3). Of the PBTSs, 47% did not have any reciprocated best friend nominations. Greater depressive symptoms in PBTSs were associated with fewer peer nominations of friendship (<italic>r</italic> = ‐.41, <italic>p</italic> < .02) and a no reciprocal friendships (<italic>t =</italic> 2.30, <italic>p</italic> < .03). Fewer social skills were also associated with not having any reciprocated friendships (<italic>t =</italic> ‐2.36, <italic>p</italic> < .03).</p><p><bold>Conclusions</bold>: Depressive symptoms and social skills at baseline were associated with friendship in PBTSs a year later, within the context of a multifaceted model. This information contributes to further our understanding of social competence and could guide psychosocial interventions for these survivors.</p></sec><sec id="pbc26772-sec-3320"><label>PD-062</label><title>The Impact of School Climate on The Peer Relationships of Pediatric Brain Tumor Survivors</title><p><underline underline-style="single">M. Hagan</underline><sup>1</sup>, K. Balistreri<sup>1</sup>, E. Meadows<sup>2</sup>, E. Semmel<sup>3</sup>, C. Gerhardt<sup>1,4</sup>, M. Barrera<sup>5</sup>, A. Patenaude<sup>6</sup>, K. Vannatta<sup>1,4</sup></p><p><italic><sup>1</sup>Nationwide Children's Hospital, Center for Biobehavioral Health, Columbus, USA; <sup>2</sup>University of Toledo, Department of Psychology, Toledo, USA; <sup>3</sup>Georgia State University, Department of Psychology, Atlanta, USA; <sup>4</sup>The Ohio State University, Pediatrics, Columbus, USA; <sup>5</sup>Hospital for Sick Children, Child Health Evaluative Sciences, Toronto, Canada; <sup>6</sup>Dana‐Farber Cancer Institute at Harvard Medical Center, Divsion of Pediatric Oncology, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Pediatric brain tumor survivors (PBTS) are at risk for negative peer interactions, less acceptance, and fewer friends relative to healthy peers. Family influences on social competence have been explored, but relevant features of school climate (e.g., structure, safety, peer and teacher support) have not. Our aim was to investigate PBTS, comparison classmate (CC) and teacher perceptions of schools and explore whether school climate moderates the peer relationship problems for PBTS.</p><p><bold>Design/Methods</bold>: PBTS (N=85, 53% male), aged 8‐13 (M<sub>age</sub>=10.8, SD=1.65) at least 1 year post treatment (40% radiation, 51% chemotherapy, 78% neurosurgery), were recruited from three sites in the US and Canada. PBTS, classmates (87% participation) and teachers completed the Delaware School Climate Survey and sociometric measures of peer interactions (Revised Class Play), acceptance, and friendship. One CC, matched for gender, age, and race, was identified in each class. Dependent t‐tests compared school climate ratings for PBTS and CC, and correlations examined agreement of students and teachers.</p><p><bold>Results</bold>: PBTS did not view school climate more negatively than CC (0.08 < <italic>p</italic>’s < 0.83), and they had moderate agreement on student‐student relations, student engagement, and school safety subscales (<italic>r</italic>= 0.33 to 0.43, <italic>p</italic>’s < 0.01). Little agreement was found for teacher and student ratings of school climate. Further multivariate analyses will test if the difference between student and teacher perceptions of school climate moderate differences in peer interactions, acceptance, and friendship for PBTS and CC.</p><p><bold>Conclusions</bold>: Findings suggest that despite the negative peer experiences of PBTS, they do not perceive their school climate differently from CC. However, there is substantial disagreement between students and teachers, highlighting the importance of gathering information from students about school climate, rather than just teachers and administrators. Integrated perceptions of classmates may provide the most reliable estimates of school level variables that may mitigate social risk for PBTS.</p></sec><sec id="pbc26772-sec-3330"><label>PD-063</label><title>Prospective Family Influences on Neurocognitive Functioning in Pediatric Brain Tumor Survivors</title><p><underline underline-style="single">M. Hocking</underline><sup>1</sup>, Y. Li<sup>1</sup>, L. Quast<sup>1</sup>, J. Baran<sup>1</sup>, C. Brodsky<sup>1</sup>, A. Kazak<sup>2</sup>, P. Phillips<sup>1</sup>, L. Barakat<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital of Philadelphia, Oncology, Philadelphia, USA; <sup>2</sup>Nemours Children's Health System, Nemours Center for Healthcare Delivery Science, Wilmington‐ DE, USA</italic></p><p><bold>Background/Objectives</bold>: Pediatric brain tumor survivors (PBTS) are at risk for neurocognitive deficits. A theoretical model of childhood cancer survivorship suggests associations between family functioning and survivor neurocognitive outcomes over time. This prospective study tested the hypothesis that better family functioning at the end of tumor‐directed treatment would be associated with positive changes in survivor neurocognitive function 9 and 16 months later.</p><p><bold>Design/Methods</bold>: Fifty PBTS (ages 6‐16) completed brief neurocognitive assessments within four months of completing tumor‐directed therapy (T1) and again approximately nine (T2; n=35) and 16 (T3; n=30) months later. Parents completed measures of family functioning at T1. Neurocognitive domains assessed included working memory, processing speed, and long‐term auditory memory. Family functioning factors assessed included general family functioning, condition management difficulty, and perceived caregiver competence. Mixed‐effects models evaluated whether T1 family functioning variables predicted slopes of changes in survivor neurocognitive function over time.</p><p><bold>Results</bold>: Models predicting long‐term auditory memory were consistent with hypotheses. Better caregiver competence at T1, <italic>t</italic> (1, 54)=2.52, <italic>p</italic> < .05, and less condition management difficulty, <italic>t</italic> (1, 55)=‐2.54, <italic>p</italic> < .05, were associated with faster improvements in auditory memory over time. Models predicting working memory were in the opposite direction than hypothesized. Worse caregiver competence at T1, <italic>t</italic> (1, 48)=‐2.43, <italic>p</italic> < .05, and greater condition management difficulty at T1, <italic>t</italic> (1, 48)=3.32, <italic>p</italic> < .01, were associated with faster improvements in working memory over time. Models predicting processing speed were not significant.</p><p><bold>Conclusions</bold>: Family functioning variables at the end of tumor‐directed treatment may play a role in the trajectory of survivor neurocognitive function over time. The nature of the role and which aspects of family functioning should be considered need further study, particularly with longer follow‐up after the conclusion of tumor‐directed treatment. Family functioning is an important factor to monitor over time.</p></sec><sec id="pbc26772-sec-3340"><label>PD-064</label><title>Never Truth without Hope, Never Hope without Truth: Parents'views on the Disclosure of Prognosis in Paediatric Oncology</title><p><underline underline-style="single">A. Jankowska</underline><sup>1</sup>, I. Pałgan<sup>2</sup>, J. Skalska‐ Sadowska<sup>3</sup>, K. Sobieralska‐ Michalak<sup>4</sup>, M. Libura<sup>5</sup>, M. Wysocki<sup>6</sup></p><p><italic><sup>1</sup>Collegium Medicum Nicolaus Copernicus University, Pediatric Oncology and Hematology Deparment, Bydgoszcz, Poland; <sup>2</sup>J. Brudziński Voivodship Paediatric Hospital, Pediatrics‐ Oncology‐ Hematology and Rheumatology Department, Bydgoszcz, Poland; <sup>3</sup>University of Medical Sciences, Department of Pediatric Oncology‐ Hematology and Transplantology, Poznań, Poland; <sup>4</sup>Collegium Medicum Nicolaus Copernicus University, Department of Rehabilitation, Toruń, Poland; <sup>5</sup>Łazarski University, Institute for Interdisciplinary Studies, Warszawa, Poland; <sup>6</sup>Collegium Medicum Nicolaus Copernicus University, Pediatric Oncology and Hematology Department, Bydgoszcz, Poland</italic></p><p><bold>Background/Objectives</bold>: Identification of the needs and preferences for the process of prognostic discussion among parents in paediatric oncology</p><p><bold>Design/Methods</bold>: Parents of children treated in three oncological centers in Poland participated in one of six focus group discussions and completed a survey measuring their preferences for the manner of delivery of prognostic information.To develop survey items, key themes were abstracted from the published literature. Quantitative data were analyzed using descriptive statistics. Qualitative data were audiotaped and analyzed.</p><p><bold>Results</bold>: 116 (80%) of 144 parents invited onto the study participated.The majority of parents preferred detailed prognostic information, presented in an open and honest manner. Factors found to influence parents hope were physician willingness to answer questions and provide information offer the most up to date treatment and provide emotional support. Conversely, factors reported as potentially decreasing hope included pessimistic attitude, an impersonal context for the disclosure, the doctor appearing to be nervous or uncomfortable or using euphemisms. Parents preferred positive framing during the discussion about their child's prognosis. 112 (97%) of parents wanted their doctor to provide an opportunity to ask questions, and acknowledge them as an individual when discussing prognosis.</p><p><bold>Conclusions</bold>:
<list list-type="order" id="pbc26772-list-0020"><list-item><p>The majority of parents preferred an individualized realistic approach from the doctor.</p></list-item><list-item><p>Preferences may vary according to demographic, psychological and disease variables.</p></list-item><list-item><p>Study findings highlight the importance of training healthcare professionals in the content, timing, and potential biases associated with information delivery.</p></list-item></list></p></sec><sec id="pbc26772-sec-3350"><label>PD-065</label><title>A Survey to Assess Impact of an Innovative Educational Interventional Program on Attitudes Towards Education in Children Treated in a Large Tertiary Cancer Center</title><p><underline underline-style="single">S. Jatia</underline><sup>1</sup>, S. Imade<sup>1</sup>, J. Gupta<sup>1</sup>, U. Pandit<sup>1</sup>, M. Prasad<sup>2</sup>, G. Chinnaswamy<sup>2</sup>, T. Vora<sup>2</sup>, G. Narula<sup>2</sup>, S. Banavali<sup>2</sup></p><p><italic><sup>1</sup>Tata Memorial Center, ImPaCCT Foundation‐ Pediatric Oncology Division, Mumbai, India; <sup>2</sup>Tata Memorial Center, Pediatric Oncology Division, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Children undergoing treatment at our center‐ a large tertiary cancer hospital in India, come from all parts of the country with diverse socio‐economic backgrounds, educational status, religious‐beliefs, vernacular languages, and deep‐set family/community traditions. The diagnosis of cancer and its aftermath makes education their lowest priority. Since May‐2015, we instituted an innovative educational interventional program run by a professional teachers group, designed for out‐patient clinic waiting areas, largely through visual, auditory and skill‐based means reducing dependence on language and able to cater to wide age‐groups. A short survey was conducted to assess its impact on attitudes to education.</p><p><bold>Design/Methods</bold>: Children attending out‐patient clinics at the center for treatment or follow‐up, were issued a standard one‐page questionnaire over a two‐week period in Mar‐2017. Participation was voluntary. Background information, attendance status at the educational program and attitudes to further schooling, future ambition, and time taken/ intent to rejoin school were assessed.</p><p><bold>Results</bold>: Five‐hundred forms were distributed in the study‐period, 414 responded, of which 313 had attended the program, while 101 did not. Both groups were evenly‐matched for age (median‐8 years), sex‐ratio (1.8 vs 1.72), treatment status (72% and 78% on‐treatment), prior school attendance (84% and 78%), and medium of instruction (English‐ 37% and 35%; Hindi, Marathi, Bengali and others‐ 63% and 65%). More than 80% among those on follow‐up joined back school in both groups. In a question on future career, only 41% of non‐attendees responded, as compared to 85% attendees (p<0.05). Career choices were more diverse in attendees than non‐attendees (28 and 4 respectively), with Doctor being most popular in both. Attendees had more specific, specialized, niche‐area and exotic career preferences than non‐attendees.</p><p><bold>Conclusions</bold>: An innovative educational interventional program run in out‐patient waiting areas impacted preferences towards future education and career with attendees having more positive, open and diverse attitudes than non‐attendees.</p></sec><sec id="pbc26772-sec-3360"><label>PD-066</label><title>Feasibility of In‐Hospital Ambassador Classmates for Children with Cancer as Facilitators of Social, Physical, and Educational Rehabilitation (Respect)</title><p><underline underline-style="single">H.B. Larsen</underline><sup>1</sup>, A.S. Helms<sup>1</sup>, T. Thorsteinsson<sup>1</sup>, M.K.F. Nielsen<sup>1</sup>, M. Faber<sup>1</sup>, M.H. Nielsen<sup>1</sup>, C. Heilman<sup>2</sup>, K.V. Andersen<sup>2</sup>, P. Roland<sup>3</sup>, M. Madsen<sup>2</sup>, C. Johansen<sup>4</sup>, L. Stisen<sup>3</sup>, L.W. Gundersen<sup>5</sup>, H. Hasle<sup>6</sup>, K. Schmiegelow<sup>7</sup></p><p><italic><sup>1</sup>Rigshospitalet, Pediatric hematology oncology Bonkolab 5704, København Ø, Denmark; <sup>2</sup>Rigshospitalet, Pediatric hematology oncology 4072, København Ø, Denmark; <sup>3</sup>Rigshospitalet, Pediatric hematology oncology 5054, København Ø, Denmark; <sup>4</sup>Danish Cancer Society, Unit of Survivorship, København Ø, Denmark; <sup>5</sup>Rigshospitalet, HovedOrtoCentret‐ Clinic of ergotherapy and physical therapy, København Ø, Denmark; <sup>6</sup>Aarhus University Hospital, Departments of Pediatrics, Aarhus, Denmark; <sup>7</sup>Rigshospitalet, Pediatric hematology oncology‐ 4072, København Ø, Denmark</italic></p><p><bold>Background/Objectives</bold>: Background: Aiming at rehabilitating school‐aged children with cancer socially, academically, physically and diminish their treatment induced isolation and marginalization, the nationwide psychosocial intervention study RESPECT (<bold>Re</bold>habilitation including <bold>s</bold>ocial and <bold>p</bold>hysical activity and <bold>e</bold>ducation in <bold>c</bold>hildren and <bold>t</bold>eenagers with cancer) have included children since 2013.</p><p>Intervention: 1. A 60‐minutes educational presentation on cancer in the child´s school class, 2. Alternating in‐hospital co‐admission (9am‐3pm) of two ambassador classmates, 3. In‐hospital physical activity program.</p><p>Purpose: To examine the feasibility of the educational and ambassador intervention components of the ongoing RESPECT study.</p><p><bold>Design/Methods</bold>: Methods: Inclusion of the first 30 consecutive children (6‐18 years) newly diagnosed with cancer in the intervention group. Feasibility include: participation rate, acceptability, timeframe, frequency, duration and safety.</p><p><bold>Results</bold>: Results Of 31 children 30 consented to participate (97%). Median time from diagnosis to inclusion was six days. Within a median of 14 days the educational class presentation on cancer was conducted, with >90 % teacher's satisfaction with content, level and duration. A median of seven classmates applied for ambassadorship. Median time for ambassador assignments to all children was nine days. The median one‐way ambassador travel distance was 49 km. None of the patients or ambassadors discontinued study participation. None of the ambassadors experienced adverse emotional reactions or needed psychological intervention. The total number of ambassador co‐admissions was 422 and the median number of co‐admissions per child was 13.</p><p><bold>Conclusions</bold>: Conclusion: It is feasible, acceptable and safe to involve healthy classmates during intensive treatment of children with cancer. The intervention components are well suited for rehabilitation intervention in children with cancer and their school classes. Challenges are practical organization, travel distance, co‐admissions, parental language barriers, in‐hospital cultural acceptability and disease burden. The inclusion of classmates as psychosocial motivational supportive network during in‐hospital cancer treatment provides a novel approach to cancer rehabilitation of school‐aged children.</p></sec><sec id="pbc26772-sec-3370"><label>PD-067</label><title>Psychosocial Screening for Siblings of Children with Cancer: Development and Initial Testing of a New Sibling Screening Module</title><p><underline underline-style="single">K. Long</underline><sup>1</sup>, E. Pariseau<sup>1</sup>, A.C. Muriel<sup>2</sup>, A. Chu<sup>3</sup>, A. Kazak<sup>4,5</sup>, M. Alderfer<sup>4,5</sup></p><p><italic><sup>1</sup>Boston University, Psychological and Brain Sciences, Boston, USA; <sup>2</sup>Dana Farber Cancer Institute & Harvard Medical School, Pediatric Psychosocial Oncology, Boston, USA; <sup>3</sup>Boston University, School of Public Health, Boston, USA; <sup>4</sup>Nemours Children's Health System, Center for Healthcare Delivery Science, Wilmington, USA; <sup>5</sup>Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, USA</italic></p><p><bold>Background/Objectives</bold>: The absence of a standardized, sibling‐specific psychosocial screener limits healthcare providers’ ability to identify and pre‐emptively intervene with siblings who may have clinical levels of distress during or after a brother's/sister's cancer treatment. English and Spanish versions of a sibling module for the Psychosocial Assessment Tool (PAT), a well‐validated screener of family psychosocial risk, were developed. The project also examined associations between sibling risk factors and sibling and family adjustment.</p><p><bold>Design/Methods</bold>: English‐ and Spanish‐speaking families of children with cancer (29 parents, 17 siblings) participated in qualitative interviews to inform item content and provide in‐depth feedback on the wording and format of iterative versions of the new PAT Sibling Module. Purposive sampling ensured variability across sibling age (<italic>M(SD</italic>)=8.9(4.7) years), sibling gender (55% female), time since cancer diagnosis (<italic>M(SD</italic>)= 18.8(19.6) months), and parent primary language (34% Spanish/bilingual). Data collection continued until saturation was reached and the new screening modules were finalized. In Phase 2, parents of newly‐diagnosed children with cancer completed the PAT Sibling Module and measures of sibling, parent, and family functioning. To date, 38 families have completed Phase 2.</p><p><bold>Results</bold>: Sixteen distinct PAT Sibling Modules were developed based on timing (diagnosis, follow‐up), language (English, Spanish), and sibling age (0‐2, 3‐4, 5‐9, 10+ years). Higher scores on the PAT Sibling Module (i.e., greater sibling risk) are associated with poorer sibling psychosocial functioning as assessed by the Strengths and Difficulties Questionnaire Total Problem Scale (r=0.67, p=0.00), Emotion Symptoms Scale (r=0.40, p=0.05), Hyperactivity Scale (r=0.67, p=0.00), Peer Problems Scale (r=0.51, p=0.01), and Prosocial Scale (r= ‐0.56, p=0.01), and worse family functioning on the Family Assessment Device (r=0.63, p=0.00). Associations with parent mental health as assessed by the Brief Symptom Inventory were not significant.</p><p><bold>Conclusions</bold>: The new PAT Sibling Modules show promise as screeners of psychosocial risk among siblings of children with cancer.</p></sec><sec id="pbc26772-sec-3380"><label>PD-068</label><title>Is a Brief Parental Intake form Effective in Identifying Behavioral Adjustment Problems in Childhood Cancer Survivors?</title><p><underline underline-style="single">A. Michaud</underline><sup>1</sup>, C. Cadigan<sup>1</sup>, C. Mason<sup>2</sup>, C. Recklitis<sup>1</sup></p><p><italic><sup>1</sup>Dana Farber Cancer Institute, Perini Family Survivors' Center, Boston, USA; <sup>2</sup>Imperial College London, Neuroepidemiology and Ageing, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Childhood cancer survivors (CCS) are at elevated risk for behavioral adjustment problems. Screening is promoted as a means of identifying these problems, but practical and accurate screening methods for clinical settings are not well established. We developed a five‐item Brief Parental Intake Form (BPIF) and assessed its accuracy compared to parental report on the Brief Pediatric Symptom Checklist‐17 (BPSC‐17).</p><p><bold>Design/Methods</bold>: Parents of 291 CCS (ages 5‐17) completed the BPIF and BPSC‐17 at a survivorship visit. The BPIF asks parents to report on emotional, attention, behavioral, school and ‘other’ problems on a 4‐point likert scale. The BPSC‐17 includes 3 scales capturing depression/internalizing, attention, and externalizing problems. Based on normative data, BPSC‐17 scores were categorized into no significant elevation, moderate elevation, and significant elevation.</p><p><bold>Results</bold>: Parents reported 87 (29.9%) survivors had moderate or significant elevation on the BPSC‐17. Of those, 83 survivors were identified as having at least some behavioral problems on the BPIF. Using any reported problem v. no problem as a cut‐off on the BPIF showed high sensitivity (95.4%). For the 204 (70.1%) survivors whose parents did not report behavioral problems on the BPSC‐17, 93 did screen in on the BPIF, showing low specificity (54.4%).</p><p><bold>Conclusions</bold>: Parental report on the BPIF accurately identified symptomatic cancer survivors with high sensitivity compared to the BPSC‐17. The five‐item BPIF could lessen the burden for both patient and staff, while still identifying 95% of survivors with behavioral problems. Because of low specificity, the BPSC‐17 or another more detailed measure should be used as a second screener for survivors who screened in on the BPIF. Future studies should compare the BPIF with the Child Behavior Checklist (CBCL) and other measures, to see how accurately it identifies behavioral problems more broadly.</p></sec><sec id="pbc26772-sec-3390"><label>PD-069</label><title>Assessment of Information Needs and Intervention Preferences in Parents of Survivors with Neurocognitive Late Effects</title><p><underline underline-style="single">C. Peterson</underline><sup>1</sup>, N. Morris<sup>1</sup></p><p><italic><sup>1</sup>Eastern Michigan University, Psychology, Ypsilanti, USA</italic></p><p><bold>Background/Objectives</bold>: With approximately half of childhood cancer survivors (CCS) at risk for neurocognitive late effects (NCLE)<sup>1</sup>, parents report high need for information about learning and behavior, but in varying amounts and stages<sup>2</sup>. Understanding specific survivorship information needs, such as preferences for the amount, timing, type, and delivery of information needed, will inform intervention. This study assessed parent information needs and intervention preferences, associations with psychological functioning, and perceived utility of Internet‐based information interventions.</p><p><bold>Design/Methods</bold>: Ninety‐five parents of CCS completed measures of demographic/treatment information, child behavior and neurocognitive functioning, family burden, knowledge of NCLE, current and preferred sources of survivorship information, and interest in using Internet‐based resources.</p><p><bold>Results</bold>: Parents reported low information: 30% had never heard of NCLE, and 70.5% wanted “a lot” more information about NCLE. Only 26% reported receiving information at diagnosis; 34.7% reported finding information on their own or “never” receiving information. Parents wanted information immediately after diagnosis and before treatment consent, and again 1‐2 months before concluding treatment. Parents reported frequent reliance on other sources besides their medical team (e.g., internet, other parents) and need for repeated information at more frequent intervals in survivorship. Topics included: behavioral and school issues; fertility; long‐term follow‐up transitions; sibling issues; and communicating about late effects with their team. 93.7% of respondents would use an online program if available. Regression analyses indicated that greater survivorship information needs were associated with increased family burden and poorer child cognitive, behavioral, and emotional functioning. Family burden specific to NCLE significantly predicted information needs (<italic>B</italic> = .10, <italic>SE</italic> = .03, <italic>p =</italic> .001), beyond demographic and treatment variables.</p><p><bold>Conclusions</bold>: Families report high needs for information throughout survivorship, strongly predicted by the burden a parent experiences managing late effects. Results indicate targets for interventions for highly burdened parents that would be feasible, acceptable, and disseminable.</p></sec><sec id="pbc26772-sec-3400"><label>PD-070</label><title>Health‐Related Quality of Life and Psychological Distress in Adolescent and Young Adult Survivors of Childhood Cancer and Their Association with Treatment, Education and Demographic Factors</title><p><underline underline-style="single">J.F. Halvorsen</underline><sup>1</sup>, A.M. Sund<sup>2</sup>, L. Zeltzer<sup>3</sup>, M. Ådnanes<sup>4</sup>, H. Jensberg<sup>5</sup>, T.A. Eikemo<sup>6</sup>, B. Lund<sup>7</sup>, O. Hjemdal<sup>1</sup>, T. Reinfjell<sup>8</sup></p><p><italic><sup>1</sup>Norwegian University of Science and Technology NTNU, Department of Psychology, Trondheim, Norway; <sup>2</sup>Norwegian University of Science and Technology NTNU, Regional Centre for Child and Youth Mental Health and Child Welfare. St. Olav's University Hospital, Trondheim, Norway; <sup>3</sup>David Geffen School of Medicine at UCLA, Department of Pediatrics, Los Angeles, USA; <sup>4</sup>SINTEF Technology and Society, Dept. of Health Research, Trondheim, Norway; <sup>5</sup>Norwegian Directorate of Health, Division of Health Economics and Financing, Trondheim, Norway; <sup>6</sup>Norwegian University of Science and Technology NTNU, Department of Sociology and Political Science, Trondheim, Norway; <sup>7</sup>Norwegian University of Science and Technology NTNU, Department of Laboratory Medicine. St. Olav's University Hospital, Trondheim, Norway; <sup>8</sup>Norwegian University of Science and Technology NTNU, Department of Psychology. St. Olav's University Hospital, Trondheim, Norway</italic></p><p><bold>Background/Objectives</bold>: This study investigated the health‐related quality of life (HRQOL) and psychological distress of adolescent and young adult (AYA) survivors of childhood cancer and the association of these factors with treatment modalities, education and demographic factors ≥ 5 years post‐diagnosis.</p><p><bold>Design/Methods</bold>: Participants included cancer survivors (<italic>n</italic>=91) recruited through the Cancer Registry of Norway (CRN) and healthy controls (<italic>n</italic>=223) recruited from a student population. All participants completed self‐report questionnaires, and the Pediatric Quality of Life Inventory (PedsQL™) 4.0 and Hopkins Symptom Checklist‐10 (HSCL‐10) were used to measure HRQOL and distress, respectively.</p><p><bold>Results</bold>: Survivors reported the same mean levels of HRQOL as controls, with the exception of worse physical functioning. Compared with controls, survivors overall and female survivors in particular had higher odds of reporting psychological distress symptoms over the cut‐off, but survivors did not have higher mean levels of distress. Female survivors reported poorer physical health than female controls. Survivors reporting distress levels above the cut‐off had significantly poorer HRQOL regarding physical functioning and worse total PedsQL scores than controls scoring above the cut‐off. Age (for HRQOL only), female gender, low educational level and perceived low economic status significantly predicted HRQOL and distress.</p><p><bold>Conclusions</bold>: Survivors reported similar mean levels of HRQOL and distress as controls, except for physical functioning. For cancer survivors, demographic variables predicted HRQOL and distress. Some groups of survivors require closer follow‐up, and more attention should be paid to factors associated with poor HRQOL and psychological distress in survivors, including female gender, lower education level and lower income.</p><p><bold>Acknowledgements</bold>: This study was supported by grants from the Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU) as well as the Norwegian Cancer Organization.</p></sec><sec id="pbc26772-sec-3410"><label>PD-071</label><title>Anxiety Symptoms and Neurocognitive Functioning in Children with Leukemia and Brain Tumors: A Comparison of Symptomology across Multiple Informants</title><p><underline underline-style="single">C. Sharkey</underline><sup>1</sup>, A. Gioia<sup>2</sup>, T. Kennedy<sup>2</sup>, G. Dome<sup>2</sup>, K. Walsh<sup>2</sup>, K. Hardy<sup>2</sup></p><p><italic><sup>1</sup>Oklahoma State University, Psychology, Stillwater, USA; <sup>2</sup>Children's National Health System, Neurology, Washington‐ DC, USA</italic></p><p><bold>Background/Objectives</bold>: Children diagnosed with cancer may experience both psychological and neurocognitive difficulties, yet few studies have examined the relationship between these outcomes. However, adjustment difficulties, including anxiety, can contribute to poor cognitive performance. Thus, the present retrospective study aimed to compare the relationship between anxiety symptoms and neurocognitive functioning in children with leukemia or brain tumors (BT). Due to the importance of multiple informants, concordance across raters was also assessed.</p><p><bold>Design/Methods</bold>: Ninety‐seven children with leukemia (45.4% Female, <italic>M</italic><sub>age</sub>=11.61 years), and 121 children with brain tumor (48.8% Female, <italic>M</italic><sub>age</sub>=11.21 years) completed the Youth Self‐Report and an age‐appropriate Wechsler scale, as part of a clinical neuropsychological assessment. Parents (N=208) and teachers (N=157) completed Achenbach rating scales.</p><p><bold>Results</bold>: BT survivors had significantly lower processing speed than leukemia survivors (<italic>x2</italic>(177) =2.78, <italic>p</italic><.01). Although no differences existed in overall anxiety across survivorship groups, there were differences in rater agreement between leukemia and BT groups. Specifically, BT survivors’ self‐reported anxiety correlated with parent‐report (.001<<italic>p</italic><.01). Teacher‐report of Anxiety Problems only correlated with parent‐report (<italic>p</italic><.05). Contrastingly, among leukemia survivors, parent‐, teacher‐, and self‐report of anxiety were unrelated (<italic>p</italic>>.05). Among BT survivors, reports of anxiety were unrelated to cognitive performance (<italic>p</italic>>.05), whereas among leukemia survivors, parent‐ and self‐report of Anxious/Depressed symptoms were positively associated with working memory and IQ (.01<<italic>p</italic><.05), and parent‐report of Anxiety Problems was positively related to IQ (<italic>p</italic><.01). Teacher‐ and self‐report of Anxiety Problems were positively related to processing speed (<italic>p</italic><.01).</p><p><bold>Conclusions</bold>: The relationship between anxiety symptoms and cognitive performance, and the concordance between multiple informants of anxiety symptoms differs between BT and leukemia groups. Self‐report is associated with quantitative cognitive performance within leukemia, although in an unexpected direction, yet is more concordant with other‐reports in BT. Thus, multiple informants are essential and further investigation of this positive relationship between anxiety symptoms and neurocognitive functioning is warranted among leukemia survivors.</p></sec><sec id="pbc26772-sec-3420"><label>PD-072</label><title>A Pilot RCT Targeting Caregivers to Improve the Health Behaviors of Obese Pediatric Cancer Survivors</title><p><underline underline-style="single">M. Stern</underline><sup>1</sup>, J.B. Dr.<sup>1</sup>, E.D. MS<sup>2</sup>, C.L. Ms<sup>3</sup>, G.H. Dr<sup>4</sup>, L.E. Dr<sup>5</sup>, S.M. Prof<sup>6</sup></p><p><italic><sup>1</sup>University of South Florida, Child and Family Studies, Tampa, USA; <sup>2</sup>University of South Florida, psychology, Tampa, USA; <sup>3</sup>University of South Florida, School Psychology, Tampa, USA; <sup>4</sup>John Hopkins/All Children's Hospital, Pediatric Oncology, St Petersburg, USA; <sup>5</sup>University of Pittsburgh, Psychiatry‐ Psychology and Pediatrics, Pittsburgh, USA; <sup>6</sup>Virginia Commonwealth University, Psychology, Richmond, USA</italic></p><p><bold>Background/Objectives</bold>: Objective: Obesity rates in pediatric cancer survivors (PCS) are alarmingly high (40‐50%). Healthy lifestyle changes may prevent future health complications and improve quality of life in PCS. Few interventions have addressed the negative impact of cancer therapies on PCS health behaviors. This NIH funded RCT tests the efficacy of a parent‐focused intervention (NOURISH‐T) on improving caregiver and child bmi, dietary intake, and physical activity than caregivers in our control (EUC).</p><p><bold>Design/Methods</bold>: Methods: A total of 67 PCS from two sites were consented and 53 were enrolled (<italic>M</italic>=9.92yrs of age, 64.4% ALL or lymphoma diagnosis) at least 6 months off cancer treatment (<italic>M</italic>=1.96yrs off treatment), and BMI of 85th% percentile or greater (<italic>M</italic>=95.42 BMI percentile). Families were randomized to either a 6‐session intervention, NOURISH‐T, or one Enhanced Usual Care (EUC) session. Assessments were conducted at baseline, post‐6‐weeks intervention and 4‐month follow‐up (FU).</p><p><bold>Results</bold>: Results In comparison to EUC parents, NOURISH‐T parents showed significant decreases from pre to post to FU on BMI, waist‐hip ratio and total number of daily calories. NOURISH‐T parents also showed similar positive changes in their child feeding behaviors and perceptions of child vulnerability. Similar decreases on BMI %ile and waist‐hip ratio were found for PCS, but only from pre to post testing. NOURISH‐T PCS also showed significant increases in number of daily steps whereas EUC PCS decreased. Caregivers reported being very positive about NOURISH‐T sessions.</p><p><bold>Conclusions</bold>: Conclusions Results suggest that an intervention targeting parents can have a longer term effect on caregivers, but only shorter‐term impact on the PCS. Implications for intervention strategies are discussed. Whether length of time off treatment plays a moderating factor on treatment effects will be considered.</p></sec><sec id="pbc26772-sec-3430"><label>PD-073</label><title>Attitudes Towards Clinical Trials among Adolescents and Young Adults (AYA) with A History of Cancer: Psychosocial Maturity, Knowledge and Disease‐Related Correlates</title><p><underline underline-style="single">E. Stevens</underline><sup>1</sup>, B.M. Velázquez‐Martin<sup>1</sup>, L. Schwartz<sup>1,2</sup>, L.P. Barakat<sup>1,2</sup></p><p><italic><sup>1</sup>The Children's Hospital of Philadelphia, Pediatrics ‐ Division of Oncology, Philadelphia, USA; <sup>2</sup>The University of Pennsylvania, Perelman School of Medicine, Philadelphia, USA</italic></p><p><bold>Background/Objectives</bold>: Relative to younger cohorts, the progress in rate of survival has been slower for adolescents and young adults ages 15‐29 (AYA). Barriers to clinical trial enrollment may include limited knowledge of clinical trials, which may relate to limited engagement in the treatment decision‐making process, and difficulty of health care providers and caregivers to include them in shared decision‐making. This study sought to explore psychosocial maturity, knowledge and disease related correlates of attitudes towards clinical trials.</p><p><bold>Design/Methods</bold>: AYA completed measures of demographics, cancer diagnosis/treatment, knowledge of clinical trials, psychosocial maturity (consideration of future consequences), and attitudes (perceived benefits and barriers) towards clinical trial participation. Covariates included age, age at diagnosis, sex, cancer type (liquid, solid or brain) and treatment status (on/off treatment). Preliminary t‐tests, correlations and ANOVAs were conducted. Multivariable regressions and mediation/moderation analyses were used for hypothesis testing.</p><p><bold>Results</bold>: Ninety‐eight AYA (Mean age = 22.86, SD = 4.33; 55% Male, 86% non‐Hispanic White) had mean knowledge score of 80.77% correct (SD=13.84). Most frequent incorrect items included types of trials and voluntariness. Greater knowledge was significantly associated with more perceived benefits (b=0.69, p<0.001); this relationship was significantly moderated by cancer type. Knowledge mediated the relationship between consideration of future consequences and perceived benefits (Z=2.07, p=0.04). Cancer type was the only identified predictor of perceived barriers; AYA with brain tumors (Mean=46.42, SD=8.91) perceived significantly more barriers compared to those with liquid tumors (Mean=40.31, SD=10.32, p=0.04).</p><p><bold>Conclusions</bold>: AYA have moderate knowledge of cancer clinical trials with critical areas of misunderstanding. Informed consent processes should be tailored towards psychosocial maturity and address perceived benefits and barriers that may differ by diagnosis. Decision support tools may be effective resources to improve knowledge, enhance full understanding of clinical trials and their potential benefits, and increase AYA engagement in their treatment decisions.</p></sec><sec id="pbc26772-sec-3440"><label>PD-074</label><title>IMPACT of Family Density on Illness‐Related Parental Adjustment and Family Burden in Survivorship</title><p><underline underline-style="single">P. Weaver</underline><sup>1</sup>, C. Peterson<sup>1</sup></p><p><italic><sup>1</sup>Eastern Michigan University, Clinical Psychology, Ypsilanti, USA</italic></p><p><bold>Background/Objectives</bold>: Research has shown marital status and family size to be commonly endorsed psychosocial risk factors for families of children newly diagnosed with cancer.<sup>1</sup> However, for families of children with a chronic illness, research suggests that family density is a more objective indicator of the demands on parental resources as compared to single‐parent status.<sup>2</sup> Late effects in childhood cancer survivors (CCS), particularly neurocognitive late effects (NCLE), may present ongoing demands that burden parents.<sup>3</sup> Negative psychosocial outcomes for families of survivors may be exacerbated in high density families. The present study examined associations among illness‐related parental adjustment and family burden, moderated by family density, in parents of CCS.</p><p><bold>Design/Methods</bold>: Ninety‐three parents (96% mothers) of CCS completed measures assessing perceived emotional resources, parent guilt/worry, and family burden of NCLE, in addition to demographic and disease‐related variables. Density was defined as the household's total child‐adult ratio, with at‐risk identified as >2.<sup>4</sup> In the current study 26% of families were dense.</p><p><bold>Results</bold>: Regression analyses revealed that parents reporting more perceived emotional resources reported significantly less guilt/worry (B=‐0.89, <italic>p</italic><.001) and family burden (B=‐1.68, <italic>p</italic>=.002). Greater subjective experience of guilt/worry was associated with greater family burden (B=0.62, <italic>p</italic>=.005). Feelings of guilt/worry were associated with greater family burden for parents in higher density families (B=0.49, <italic>p</italic>=.037). However, despite family density, parents who perceived themselves as having sufficient emotional resources to manage the demands associated with their child's illness experienced less family burden. Findings were observed above and beyond the effects of socioeconomic status.</p><p><bold>Conclusions</bold>: Results highlight the buffering impact of perceived emotional resources in managing caregiver demands in CCS families, even within relatively higher density families. Interventions should focus on these high density families, as parents maybe at greater risk for experiencing feelings of guilt/worry that result in greater overall family burden.</p></sec><sec id="pbc26772-sec-3450"><label>PD-075</label><title>Pediatric Cancer Patients in Malawi Present to the Hospital with Poor Health‐Related Quality of Life as Measured by the Promis‐25 Questionnaire</title><p><underline underline-style="single">K. Westmoreland</underline><sup>1,2</sup>, A. Amuquandoh<sup>3</sup>, T. van der Gronde<sup>3</sup>, S. Itimu<sup>3</sup>, A. Salima<sup>3</sup>, O. Manthalu<sup>3</sup>, P. Ward<sup>3</sup>, A. Mpasa<sup>4</sup>, S. Wachepa<sup>4</sup>, I. Mtete<sup>4</sup>, M. Butia<sup>4</sup>, P. Wasswa<sup>4,5</sup>, N. El‐Mallawany Kim<sup>5</sup>, P. Kazembe<sup>6</sup>, B. Reeve<sup>7</sup>, S. Gopal<sup>8,9,10</sup></p><p><italic><sup>1</sup>UNC Project‐Malawi, Pediatric Hematology Oncology, Lilongwe, Malawi; <sup>2</sup>University of North Carolina, Pediatric Hematology Oncology, Chapel Hill, USA; <sup>3</sup>UNC Project‐Malawi, Oncology, Lilongwe, Malawi; <sup>4</sup>Baylor College of Medicine Children's Foundation Malawi, Oncology, Lilongwe, Malawi; <sup>5</sup>Texas Children's Hospital, Pediatric Hematology Oncology, Houston, USA; <sup>6</sup>Baylor College of Medicine Children's Foundation Malawi, Country Director, Lilongwe, Malawi; <sup>7</sup>University of North Carolina, Health Policy and Management, Chapel Hill, USA; <sup>8</sup>UNC Project‐Malawi, Cancer Program Director, Lilongwe, Malawi; <sup>9</sup>University of North Carolina, Oncology and Infectious Disease, Chapel Hill, USA; <sup>10</sup>University of Malawi School of Medicine, Oncology and Infectious Disease, Lilongwe, Malawi</italic></p><p><bold>Background/Objectives</bold>: Patient‐Reported Outcomes Measurement Information System 25‐item (PROMIS‐25) pediatric questionnaire was translated into Chichewa and validated for use in Malawi. This is among the first studies from sub‐Saharan Africa (SSA) to report health‐related quality of life (HRQoL) for pediatric cancer patients.</p><p><bold>Design/Methods</bold>: Thirty‐two pediatric lymphoma patients were interviewed at Kamuzu Central Hospital in Lilongwe, Malawi. The PROMIS‐25 questionnaire was administered to patients within three days of presentation before chemotherapy initiation. Participants reported on six HRQoL domains (mobility, anxiety, depression, fatigue, peer relationships, and pain interference) by answering four question items per domain using a 5‐point Likert scale. A single‐item pain intensity question was scored 0‐10. Each domain was transformed to a T‐score with a mean of 50 and standard deviation of 10 based on the original PROMIS reference sample. Median and interquartile range (IQR) for T‐scores was reported for each domain. A t‐test was used to compare our cohort to published T‐scores of 203 pediatric cancer patients in the United States.</p><p><bold>Results</bold>: Thirty‐two patients completed the baseline questionnaire. The median age was 9 years (IQR 6‐12). Children reported very low levels of mobility (median: 28, IQR: 23‐37), high anxiety (median: 63, IQR: 55‐71), high depressive symptoms (median: 62, IQR: 59‐66), high fatigue (median: 62, IQR: 54‐68), average satisfaction with peer relationships (median: 52, IQR: 44‐55), and high pain interference (median: 63, IQR: 55‐68). The highest score for pain intensity of 10 was given by 22/32 (68%) of patients. When compared to a United States pediatric cancer population, the Malawi cohort had statistically significant worse HRQoL in mobility, anxiety, depression, fatigue, and pain interference domains (<italic>p</italic><0.05).</p><p><bold>Conclusions</bold>: Baseline HRQoL for pediatric lymphoma patients in Malawi is poor for all HRQoL domains except peer relationships. This emphasizes an urgent need for clinical and research programs to specifically address HRQoL among children undergoing cancer treatment in SSA.</p></sec><sec id="pbc26772-sec-3460"><label>PD-076</label><title>Delirium: A Prospective Study within the Pediatric Hematology, Oncology, and Bone Marrow Transplant Population (PHO) at a Single Institution</title><p><underline underline-style="single">K. Winsnes</underline><sup>1</sup>, E. Shereck<sup>1</sup>, M. Recht<sup>1</sup>, C. Eriksson<sup>2</sup>, K. Johnson<sup>3</sup>, R. Loret De Mola<sup>1</sup>, L. Stork<sup>1</sup></p><p><italic><sup>1</sup>Oregon Health and Science University, Pediatric Hematology / Oncology, Portland, USA; <sup>2</sup>Oregon Health and Science University, Pediatric Critical Care, Portland, USA; <sup>3</sup>Oregon Health and Science University, Pediatric Psychiatry, Portland, USA</italic></p><p><bold>Background/Objectives</bold>: Delirium affects 10‐30% of patients in pediatric intensive care units (PICU) and causes increased length of stay, decreased attention in school, and post‐traumatic stress disorder. The Diagnostic and Statistical Manual of Mental Disorders (DSM V) defines delirium as a “disturbance of consciousness […] with reduced ability to focus, sustain or shift attention” due to an underlying medical condition. Hypothesizing that delirium is under recognized in the PHO population, we designed a prospective study using a validated screening tool to determine the frequency of delirium in hospitalized PHO patients and to identify associated clinical factors.</p><p><bold>Design/Methods</bold>: The baseline frequency of delirium diagnosis was determined using a data mining program of electronic medical records (EMR). PHO and PICU nurses have been trained to use the Richmond Assessment and Sedation Scale (RASS) and the Cornell Assessment for Pediatric Delirium. All PHO patients on the inpatient unit and in the PICU are screened for delirium once every 12‐hour shift and the scores are entered into the EMR. Additionally, specific variables are collected on each patient to help identify potential risk factors for delirium.</p><p><bold>Results</bold>: The frequency of delirium diagnosis in 2015 was 4.5%: 17/379 unique patients on the PHO unit and/or PICU. A 3‐month pre‐study feasibility phase identified 5 unique patients among 49 (10%) with a positive delirium screen, one which prompted psychiatric intervention. Two months into the year‐long prospective study, which began Jan 2017, 78 unique patients among 135 consecutive cases have enrolled; 7 pts (9%) had a positive delirium screening. Initial analysis will occur at six months.</p><p><bold>Conclusions</bold>: Delirium exists in the PHO population, however its frequency is yet to be determined. Routine delirium screening should improve our recognition and diagnosis of delirium and, thereby, allow us to promptly intervene or prevent delirium in order to avoid potential long term consequences.</p></sec><sec id="pbc26772-sec-3470"><label>PD-077</label><title>What Do Adolescents and Young Adults Want from Cancer Resources?</title><p><underline underline-style="single">B. Zebrack</underline><sup>1</sup>, C. Cheung<sup>2</sup></p><p><italic><sup>1</sup>University of Michigan, School of Social Work, Ann Arbor, USA; <sup>2</sup>University of California‐ Los Angeles, Department of Social Welfare, Los Angeles, USA</italic></p><p><bold>Background/Objectives</bold>: As clinicians are encouraged to provide personalized and patient‐centered care, inclusion of the patient's voice as a component of evidence generation is critical. The primary purpose of this study was to assess adolescent and young adult (AYA) cancer patients’ preferences for cancer information and support resources.</p><p><bold>Design/Methods</bold>: Utilizing a modified Delphi technique, AYA cancer patients identified barriers to optimal AYA cancer care, cancer resources that address their needs, and specific characteristics of cancer resources they find helpful. The Delphi panel consisted of a convenience sample of 21 patients aged 18‐39 years, who were diagnosed with cancer between ages 15‐39 years and were no more than eight years out from cancer treatment at the time of the study. Survey data were collected in three consecutive and iterative rounds over the course of six months in 2015.</p><p><bold>Results</bold>: Findings indicated that AYA patients prefer resources that reduce feelings of loneliness, create a sense of community or belonging, and provide opportunities to meet other AYA patients. Among the top barriers to optimal cancer care, AYAs identified a lack of cancer care providers specializing in AYA care, a lack of connection to an AYA patient community, and their own lack of ability to navigate the health system. Participants also described aspects of cancer information and supportive care resources that they believe address AYAs’ concerns.</p><p><bold>Conclusions</bold>: Information derived from this study will help developers of cancer information and support resources better reach their intended audience. From the point of view of AYA cancer patients, optimal cancer care and utilization of information and support resources requires that cancer support programs foster meaningful connections among AYA patients. Results also suggest that patient resources should equip AYAs with practical knowledge and skills necessary to navigate the health system and advocate for themselves.</p></sec></sec><sec id="pbc26772-sec-3480"><title>Treatment and Care ‐ Nursing</title><sec id="pbc26772-sec-3490"><label>PD-078</label><title>Memory AIDS: Assistive Tools for Pediatric Oncology Nurses in Patient Care Area from Indus Children Cancer Hospital, Pakistan</title><p><underline underline-style="single">S. Anwarali</underline><sup>1</sup>, R. Punjwani<sup>1</sup>, B. Ahmed<sup>1</sup></p><p><italic><sup>1</sup>Indus Children Cancer Hospital, Nursing Education Service, Karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Nurses are the pillar of any health care organization. They are the front line in providing care to patients. Many organizations seek to enhance the quality of patient care by improving nursing knowledge and competency. Pediatric oncology nurses working under pressure or novice nurses tend to miss small but valuable pieces of information which eventually can result in sentinel events. Thus, Indus Children Cancer Hospital Nursing Education Service in Karachi, Pakistan we created an essential memory aid– cue/flash cards– to help nurses as a reference guide.</p><p><bold>Design/Methods</bold>: An extensive literature review was conducted using key words ‘flash cards’, ‘memory aids’, ‘nurses’, ‘pediatric oncology’ and ‘patient care’ using Boolean (AND, OR) words, all suggestive of the effectiveness of flashcards. Selective flashcards were made and printed for personal usage to nurses in clinical areas. Project shall be evaluated by qualitative approach by asking nurses how and which flash cards were beneficial.</p><p><bold>Results</bold>: Evidence‐based nursing literature suggests that learning tools for nurses and other healthcare professionals are useful, effective and handy for referral to vital information. These memory aids have assisted novice nurses in learning and refreshing basic concepts and retaining knowledge and learnt skills. These aids have assisted nurses to perform better care with decreased number of sentinel events. Nurses benefit from memory aids for chemotherapy and medication calculation, vital signs, height and weight, basal surface area, pain assessment and management.</p><p><bold>Conclusions</bold>: Use of memory aids is an innovative way for ongoing learning in pediatric oncology clinical areas. The effectiveness of the flash cards will aid in referring to quick information required rather than making a mistake. The cards are used as a reference guide and precept pediatric oncology nurses and interns in clinical areas. The memory aids are expected to increase level of competency and confidence among pediatric oncology nurses to provide quality care.</p></sec><sec id="pbc26772-sec-3500"><label>PD-079</label><title>Pediatric Nurses Knowledge on Chemotherapy at Komfo Anokye Teaching Hospital</title><p><underline underline-style="single">R. Appiah</underline><sup>1</sup></p><p><italic><sup>1</sup>Staff Nurse at Komfo Anokye Teaching Hospital, Ghana</italic></p><p><bold>Background</bold>: Chemotherapy is one of the effective treatments of most oncological conditions with chemo (anti‐cancer drug)</p><p>This study was undertaken to evaluate the knowledge on staff nurses at pediatric wards at Komfo Anokye Teaching Hospital on chemotherapy.</p><p><bold>Methods</bold>: This study was a descriptive study structured questionnaire with both open and close ended questions were used. Systemic random sampling was used in selecting 100 respondents 40% of the respondent have knowledge on chemotherapy and the remaining 60% said they don't have knowledge on chemotherapy. Regarding the side effects, 45% have the knowledge and the remaining 55% said they don't have knowledge on it. For the specific chemo for treating specific types of oncological conditions 30% were able to give correct answer, 70% of the total respondent were not able to give correct answers.</p><p><bold>Results</bold>: At the end of the survey minority of the respondent have adequate knowledge on chemotherapy with a percentage of 40%, 45 % of the total respondents have adequate knowledge on side effect of chemotherapy and minority of the respondent have adequate knowledge on specific chemo for treating specific oncological condition/.</p><p><bold>Conclution</bold>: It is recommended that workshop and in‐dept. service training session on chemotherapy should be organized for nursing staffs of pediatric wards at Komfo Anokye Teaching Hospital.</p></sec><sec id="pbc26772-sec-3510"><label>PD-080</label><title>A Systematic Review of the Gut Microbiome, Treatment‐Related Symptoms and Targeted Interventions in Children with Cancer</title><p><underline underline-style="single">J. Bai</underline><sup>1</sup>, M. Behera<sup>2,3</sup>, D. Bruner<sup>1,3</sup></p><p><italic><sup>1</sup>Emory University, Nell Hodgson Woodruff School of Nursing, Atlanta, USA; <sup>2</sup>Emory University, School of Medicine, Atlanta, USA; <sup>3</sup>Emory University, Winship Cancer Institute, Atlanta, USA</italic></p><p><bold>Background/Objectives</bold>: With the development of high‐throughput DNA sequencing and bioinformatics technologies, a growing body of literature showed that the gut microbiome (GM) plays a critical role in maintaining children's health and in preventing and treating children's disease. Current application of the GM in childhood cancer is still unknown. This systematic review aimed at understanding the GM, its applications in gastrointestinal symptoms (GIS) and psychoneurological symptoms (PNS), and the efficacy of targeted interventions in children treated for cancer.</p><p><bold>Design/Methods</bold>: PubMed, EMBASE, the Cochrane Library, and the American Society of Clinical Oncology abstract were searched. Eligible studies included all study types in which the target population were children with cancer, the GM was studied as a primary or secondary outcome, and published in English. The Mixed Methods Assessment Tool was used to assess the methodological quality.</p><p><bold>Results</bold>: Seven studies met our eligibility criteria, including two case‐control studies, two cohort studies, and three randomized controlled trails. Our findings showed that children with cancer showed a significantly lower diversity in the GM (e.g., <italic>Bifidobacteria, Lactobacillus, Clostridium XIVa and IV</italic>) than the healthy controls. The total counts of healthy GM (e.g., <italic>Bacteroides and Bifidobacterium)</italic> decreased significantly pre‐ and post‐chemotherapy in children with cancer. Dysbiosis in the GM showed potential associations with GIS and PNS. Use of the probiotic (<italic>Bifidobacterium</italic> or <italic>Lactobacilli</italic>) and prebiotic supplementations (fructooligosaccharides) significantly improved dysbiosis of the GM, but did not significantly influence the adverse events (e.g., abdominal distention and diarrhea) in children treated for cancer.</p><p><bold>Conclusions</bold>: Children treated for cancer experienced dysbiosis of the GM, which can be improved by the prebiotic and probiotic supplementations. More studies are needed to investigate the relationships between the GM and GIS and PNS, and evaluate the effectiveness of prebiotic and probiotic interventions on dysbiosis of the GM in children with cancer.</p></sec><sec id="pbc26772-sec-3520"><label>PD-081</label><title>E‐Learning as a Tool for Continuing Education of Nurses in Hematopoietic Stem Cell Transplantation</title><p><underline underline-style="single">T. Bauters</underline><sup>1</sup>, J. De Munter<sup>2</sup>, S. Van Lancker<sup>1</sup>, T. Kerre<sup>2</sup>, G. Laureys<sup>1</sup>, A. Mannaerts<sup>1</sup>, L. Steendam<sup>1</sup>, C. Dhooge<sup>1</sup></p><p><italic><sup>1</sup>Ghent University Hospital, Pediatric Hematology‐ Oncology and Stem Cell Transplantation, Ghent, Belgium; <sup>2</sup>Ghent University Hospital, Hematology and Stem Cell Transplantation, Ghent, Belgium</italic></p><p><bold>Background/Objectives</bold>: The complexity of a Hematopoietic Stem Cell Transplantation (HSCT) with the common toxicities and side effects, necessitates specific and continuing education and training for nurses and care‐givers involved with HSCT.</p><p>The aim of this project was to develop a basic educational framework for nurses, medical students and paramedics involved in pediatric and adult HSCT recipients.</p><p><bold>Design/Methods</bold>: An educational course in a format that is easily accessible online has been created.</p><p><bold>Results</bold>: The theoretical part consists of different topics: aim of HSCT, indications, donor/stem cell sources, different types of HSCT, … each highlighting pediatric and adult issues. This is followed by a self‐evaluation test, which can be used for accreditation purposes. Upon completion, users will be able to understand the process of HSCT, have knowledge of different conditioning regimens and will be able to identify the common side effects or toxicities related to HSCT. In addition, they will have insight in supportive care concepts and preventive or treatment strategies, making sure that the course meets local needs.</p><p><bold>Conclusions</bold>: The e‐learning tool allows nurses and care‐givers involved in HSCT a more flexible learning, such as the option to choose the time and place to study, and provides electronic links to more detailed learning materials. Nurses who have completed the course will have a basic level of understanding of the principles of treatment and supportive care in HSCT patients. In the future, supplementary e‐lessons and an advanced level e‐learning tool will be developed.</p></sec><sec id="pbc26772-sec-3530"><label>PD-082</label><title>Risk Factors for Non‐Adherence to Treatment of Family Caregivers of Children with Cancer</title><p><underline underline-style="single">M. Cardenas</underline><sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional De Cancerologia, Cundinamarca, Bogota, Colombia</italic></p><p><bold>Background/Objectives</bold>: BACKGROUND: Two important factors (complete withdrawal and toxic deaths) associated with suboptimal service by health care providers, have been identified to explain the failure of treatments and differences in mortality among children with cancer in developed countries and the treaties in countries with economic limitations, one of them is the complete withdrawal of treatment.</p><p>OBJECTIVES: Determine the risk factors for non‐adherence to treatment of family caregivers of children with cancer at the National Cancer Institute.</p><p><bold>Design/Methods</bold>: Descriptive and transversal study, with quantitative approach, which participants are family caregivers of children with cancer. Implementation of two instruments, Survey characterization care dyad family caregiver – a person with a chronic disease of the National University of Colombia´s group of Chronic Care and the Instrument that evaluates the Factors that Influence the Adherence to the Pharmacological and Non‐Pharmacological Treatments in Patients, designed and validated by Nursing.</p><p><bold>Results</bold>: The risk factors for non‐adherence are identified such as, social and economic factors, related to the provider, the health system and equipment, related of therapy and / or treatment, related to the patient and related to the disease.</p><p><bold>Conclusions</bold>: The study pretends to intervene in a timely manner on the needs of families of children with cancer and in this way create lines of action in nursing to prevent non‐adherence to treatments.</p></sec><sec id="pbc26772-sec-3540"><label>PD-083</label><title>Changes of Nutritional Status and Associated Factors Among Chinese Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Patients</title><p><underline underline-style="single">B. Zhang</underline><sup>1</sup>, N. Shen<sup>2</sup>, M. He<sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center, Hematology and Oncology, Shanghai, China; <sup>2</sup>Shanghai Children's Medical Center, Nursing Department, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: Growing evidences suggested that hematological and oncological disease, chemo‐radiotherapy during conditioning of allogeneic hematopoietic stem cell transplantation (allo HSCT) and related complications could induce metabolic change in nutrition, which not only declined patients’ physical function but also predisposed them to nutrition‐related chronic illness. However, few studies have examined the changes of nutrition status and associated factors among Chinese pediatric allo HSCT patients.</p><p><bold>Design/Methods</bold>: This study was designed as a longitudinal study to determine the changes of nutritional status in 89 Chinese pediatric patients during pre‐transplant and post‐transplant periods (pre‐transplant day, day+18, day+30, day+60, and day+100). Data were collected using a questionnaire survey including demographic information, anthropometric measurements and body composition. A repeated measure ANOVA was used to analyze the change of nutritional status, and mixed linear model was used to evaluate the associations of potential related factors.</p><p><bold>Results</bold>: During the first 100 days after HSCT, the anthropometric measurements BMIz (Body Mass Index z), TSF (triceps skin fold thickness) decreased significantly for the first 30 days (<italic>p</italic><0.05)and then gradually increased (<italic>p</italic><0.01). WC(waist circumference) demonstrated a gradually upward trend from pre‐transplant day to day +100 (<italic>p</italic><0.01). The %BF(percent of body fat) increased significantly during the first 60 days after HSCT (<italic>p</italic><0.01), with summit in the day +60. The change of TSF was associated with time, diagnosis, source of stem cell, HLA matching, and BMIz before transplantation. The change of WC was associated with time, gender, source of stem cell, HLA matching, and BMIz before transplantation. The change of %BF was associated with time, gender, HLA matching, and BMIz before transplantation.</p><p><bold>Conclusions</bold>: Nutritional status of Chinese pediatric allo HSCT patients changed significantly, and was associated with time, gender, diagnosis, source of stem cell, HLA matching, and BMIz before transplantation. The transplantation period witnessed an accumulation of body fat, and central obesity, especially in girls.</p></sec><sec id="pbc26772-sec-3550"><label>PD-084</label><title>Predictors of the Posttraumatic Growth in Parents of Children with Leukemia</title><p><underline underline-style="single">S. Hong</underline><sup>1</sup>, H.R. Park<sup>2</sup>, S.H. Choi<sup>3</sup></p><p><italic><sup>1</sup>Kangwon National University‐ College of Health Science, Department of Nursing, Samcheok‐si, Republic of Korea; <sup>2</sup>The Catholic University of Korea, College of Nursing, Seoul, Republic of Korea; <sup>3</sup>Seoul St. Mary's Hospital‐ The Catholic University of Korea, BMT Center, Seoul, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Even though parenting a child with leukemia is a tremendous challenge that places struggle on caregivers, parents of children with leukemia experience positive outcomes. The purpose of this study was to identify predictors of posttraumatic growth in parents of children with leukemia.</p><p><bold>Design/Methods</bold>: Participants were 137 parents (117 mothers and 20 fathers) of children with leukemia recruited at C university hospital in Korea from May to August in 2016. Participants completed self‐report measures of posttraumatic growth, core belief, deliberate rumination, resilience, distress disclosure, social support, meaning in life and satisfaction with life.</p><p><bold>Results</bold>: All the variables except distress disclosure were positively correlated with posttraumatic growth. Resilience, core belief and social support were significant predictors related to posttraumatic growth in parents of children with leukemia and explained for 54% of the variance in posttraumatic growth.</p><p><bold>Conclusions</bold>: The results show that there are several factors affecting posttraumatic growth in parents of children with leukemia. Therefore, nursing intervention programs including strengthening resilience, revising core belief as well as utilizing social support system should be provide for this population in order to promote positive psychological change beyond parental traumatic events related to children with leukemia.</p></sec><sec id="pbc26772-sec-3560"><label>PD-085</label><title>Development of a Virtual Reality Distraction Intervention for Youths with Cancer Undergoing Subcutaneous Port Accesses: A Usability Testing Study</title><p><underline underline-style="single">L. Jibb</underline><sup>1</sup>, J. Stinson<sup>2</sup>, A. Oussama<sup>3</sup>, K. Positano<sup>4</sup>, K.A. Birnie<sup>5</sup>, V. Hum<sup>2</sup>, N. Juma<sup>6</sup>, P. Hroch<sup>7</sup></p><p><italic><sup>1</sup>The University of Ottawa, School of Nursing, Ottawa, Canada; <sup>2</sup>The Hospital for Sick Children, Child Health Evaluative Sciences, Toronto, Canada; <sup>3</sup>The Hospital for Sick Children, Oncology/ Haematology, Toronto, Canada; <sup>4</sup>The Hospital for Sick Children, Child Life, Toronto, Canada; <sup>5</sup>University of Toronto / Hospital for Sick Children, Lawrence S. Bloomberg Faculty of Nursing‐ University of Toronto / Child Health Evaluative Sciences, Toronto, Canada; <sup>6</sup>The Hospital for Sick Children, Nursing, Toronto, Canada; <sup>7</sup>McMaster University, Michael G. DeGroote School of Medicine, Hamilton, Canada</italic></p><p><bold>Background/Objectives</bold>: Subcutaneous port (SCP) accesses with needles are amongst the most painful and distressing treatment‐related experiences for youths with cancer. In response, we developed a virtual reality (VR) intervention with hardware (i.e., head‐mounted display, handheld controller) and software (underwater program where head movements allow exploration) to distract youths during SCP accesses. This study aimed to refine this intervention such that it was acceptable to youths, did not cause adverse events, and safely allowed communication between youths and healthcare providers during VR immersion.</p><p><bold>Design/Methods</bold>: Two iterative cycles of usability testing were used. Eleven youths (11±2.95 years; 27% female) with a variety of cancer diagnoses took part. Testing sessions were audio‐recorded and 1 observer took field notes. Youths used the intervention during SCP accesses while “thinking aloud” about their impressions. Youths answered open‐ended questions addressing the intervention and adverse events. The observer discussed the session and developed consensus on themes related to the study aims, referring to audio‐recordings as necessary.</p><p><bold>Results</bold>: Youths liked both the VR hardware and software and reported it was easy to use. No adverse events occurred. Cycle 1 revealed that full engagement with the VR environment (i.e., head movements) was limited by requirements to remain still during the procedure. Cycle 2 revealed needs for: (1) more distracting intervention components (e.g., games and music) and (2) optional notifications related to the status of the procedure. Software changes to rectify these issues were made.</p><p><bold>Conclusions</bold>: Next steps will include feasibility testing before examining the intervention's effect on pain and distress during SCP access in a randomized controlled trial. We expect that an acceptable and safe VR intervention will decrease pain and distress and improve the quality of care delivered to young cancer patients.</p><p>We would like to thank the patients who participated in the study. Funding was provided by the SickKids Garron Family Cancer Centre.</p></sec><sec id="pbc26772-sec-3570"><label>PD-086</label><title>Adolescent and Young Adult Cancer Survivors – Information and Support Regarding Sexual Concerns</title><p><underline underline-style="single">M. Olsson</underline><sup>1</sup>, M. Jarfelt<sup>1</sup></p><p><italic><sup>1</sup>Institute of Clinical Sciences‐ University of Gothenburg, Pediatrics, Göteborg, Sweden</italic></p><p><bold>Background/Objectives</bold>: In qualitative research, adolescent and young adult cancer patients express concerns on the lack of information on sexuality during treatment. The purpose of this study was to explore to what extent adolescent and young adult cancer survivors found information and support concerning sex.</p><p><bold>Design/Methods</bold>: A study specific questionnaire has been developed. The method used for question development includes expert validity from professionals and face‐to‐face validity from former cancer patients. The questionnaire contains several areas in an adolescent and young adult's life affected by cancer and this study focused on information and support regarding sexual issues. The web‐based questionnaire was sent to all adolescent and young adult cancer survivors treated during 2010 and 2011 in the North, South‐east and West Sweden.</p><p><bold>Results</bold>: Adolescent and young adult cancer survivors reported that health care professionals did not approach them on sexual issues during cancer treatment in 65% of the cases. Among adolescent and young adult cancer survivors 50 %, expressed not having any questions on sex during treatment. Of the adolescent and young adult cancer survivors who wanted information, 30 % were not satisfied with the information. They majority wanted information on sexual issues in person, from a physician or nurse and from written information, fewer wanted internet information and support. Almost half of the cancer survivors reported not having sex during treatment due to risk of infection.</p><p><bold>Conclusions</bold>: The result of this population‐based study encourage health care professionals caring for adolescent and young adult cancer patients to raise the question of sexual activity during treatment. To give an adolescent and young adult cancer patient general basic information on sexual issues along with individual recommendations may avoid misunderstandings regarding sexual activity during cancer treatment.</p></sec><sec id="pbc26772-sec-3580"><label>PD-087</label><title>Initiating a Quality Improvement Project on Self‐Care and Building Nurses’ Resiliency on a Haematology/Oncology Unit</title><p><underline underline-style="single">C. Wilson</underline><sup>1</sup>, A. Li<sup>1</sup>, C. Emmanuele<sup>1</sup>, T. Hiller<sup>2</sup>, B. O'Neil<sup>1</sup>, A. Chang<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Oncology/Haematology, Toronto, Canada; <sup>2</sup>The Hospital for Sick Children, Oncology/Haematology, Torono, Canada</italic></p><p><bold>Background/Objectives</bold>: A group of nurses within a paediatric Haematology/Oncology unit has witnessed a steady increase in, what they believe, burnout and emotional exhaustion from staff. This phenomenon has been evidenced through verbal expressions of concern among peers, as well as an increased staff turnover. Oncology nurses support the physical and emotional journeys of their patients while laughing, crying and celebrating with them (Rishel, 2015)</p><p>The ongoing stress of burnout is associated with nurse job dissatisfaction. (Potter et al., 2013). By being able to recognize signs and symptoms of burnout and compassion fatigue, as well as providing proper support to staff to incorporate wellness behaviours in their own life will help to increase job satisfaction and resiliency.</p><p><bold>Design/Methods</bold>: A Current State/Needs Assessment was done where nurses anonymously submitted “stressors” experienced on the identified unit. The next steps in this project are Focus Groups where five Focus Groups will be held with 6‐8 Registered Nurses from the Haematology/Oncology Inpatient Unit per session. A separate Focus Group will be held with RNs who have recently left the unit. Discussions will be recorded/transcribed and analyzed. A survey will be completed which will be developed based on findings from Focus Groups. The survey will provide richer data on stressors and potential interventions that would be helpful in self‐care and building resiliency. Based on the findings of the survey, current research, and benchmarking with similar institutions, a unit‐based program on self‐care and building resiliency will be developed and implemented and evaluated.</p><p><bold>Results</bold>: The Needs Assessment identified the stressors as: Lack of Breaks, The Number of New Initiatives and changes in Chemotherapy Protocols, Communication with the Interprofessional Team, Emotional Stress and Moral Distress leading to Burnout and The Increasing Workload Expectations.</p><p><bold>Conclusions</bold>: The conclusions that have been discovered this far are that there are stressors and that program development is needed.</p></sec></sec><sec id="pbc26772-sec-3590"><title>Treatment and Care ‐ Biology and Pathology</title><sec id="pbc26772-sec-3600"><label>PD-088</label><title>Cancer Predisposition in Childhood Cancer ‐The Duesseldorf Experience in Comprehensive Clinical Evaluation and Trio Whole Exome Sequencing of Families</title><p><underline underline-style="single">T. Brozou</underline><sup>1</sup>, M. Kuhlen<sup>1</sup>, A. Borkhardt<sup>1</sup>, J. Fremerey<sup>1</sup>, E. Velleuer<sup>1</sup>, D. Wieczorek<sup>2</sup>, M. Gombert<sup>1</sup>, C. Walter<sup>3</sup>, M. Dugas<sup>3</sup></p><p><italic><sup>1</sup>Heinrich Heine University Children' s Hospital‐ Dusseldorf, Pediatric Oncology‐ Hematology and Clinical Immunology, Dusseldorf, Germany; <sup>2</sup>Heinrich Heine University Hospital‐ Medical Faculty ‐ Dusseldorf, Insitutute of Human Genetics, Dusseldorf, Germany; <sup>3</sup>University of Muenster, Institute of Medical Informatics, Muenster, Germany</italic></p><p><bold>Background/Objectives</bold>: A considerable percentage of childhood cancers are due to cancer predisposition syndromes (CPS). The ratio of CPSs caused by inherited versus <italic>de novo</italic> germline mutations is unknown and, thus, recurrence risk in siblings. In addition, the attitude of affected parents towards genetic testing of themselves is unclear.</p><p><bold>Design/Methods</bold>: We initiated an ongoing prospective study performing whole‐exome sequencing (WES) of parent‐offspring trios to identify CPS and inheritance patterns in newly diagnosed cancer children</p><p><bold>Results</bold>: Between 01/2015 and 12/2016, 81 (85.3%) of 95 families participated, 14 (14.7%) refused to participate. Of 81 children, 5 (6.2%) presented with congenital malignancies, 4 (4.9%) with tumors with a high likelihood of an underlying CPS. Of 68 family pedigrees, in 3 (4.4%) malignancies were revealed in family members <18 years, relatives with cancer <45 years in 6 (8.8%), any cancer history in 26 (38.2%), and >1 relative with cancer in 14 (20.6%). In 10 (14.7%) families, one first‐ or second‐degree relative developed breast cancer, in 4 (5.9%) sarcoma and in 3 (4.4%) each lymphatic malignancies and colon cancer.</p><p>To date, 57 trios were analyzed (depth 250‐700x, median coverage >95%). A bioinformatic pipeline was established, the actual gene list comprises about 2,000 genes and is ongoing updated. Based on data of the St. Judes study group (Zhang et al., NEJM 2015) variants are classified in three pathogenic categories.</p><p>So far, 2 children with LFS and 1 child each with Dicer1 syndrome, CMMRD and APC associated polyposis were identified. Experimental analyses of various variants of unknown significance are in progress.</p><p><bold>Conclusions</bold>: Testing of an underlying CPS is of extraordinary interest to affected families. The vast majority opts for their right to know with particularly interest to recurrence risk in other offspring. Thus, trio sequencing should become common practice.</p></sec><sec id="pbc26772-sec-3610"><label>PD-089</label><title>Identifying Children at Increased Risk for a Cancer Predisposition Syndrome: The McGill Interactive Pediatric Oncogenetic Guidelines (MIPOGG)</title><p><underline underline-style="single">C. Goudie</underline><sup>1</sup>, N. Cullinan<sup>1</sup>, H. Coltin<sup>2</sup>, L. Witkowski<sup>3</sup>, A. Villani<sup>1</sup>, D. Malkin<sup>1</sup>, W. Foulkes<sup>4</sup></p><p><italic><sup>1</sup>Hospital for Sick Children, Pediatric Oncology, Toronto, Canada; <sup>2</sup>Children's Hospital of Eastern Ontario, Pediatric Oncology, Ottawa, Canada; <sup>3</sup>McGill University, Human Genetics, Montreal, Canada; <sup>4</sup>McGill University Health Center, Medical and Human Genetics, Montreal, Canada</italic></p><p><bold>Background/Objectives</bold>: An estimated 10‐29% of children with cancer have an underlying cancer predisposition syndrome (CPS); many are unrecognized. Identifying cancer susceptibility and appropriately referring to a genetics team is vital to optimize patient care by incorporating potential preventative measures, adapting therapies, improving surveillance and counselling around family risk. Many challenges limit the likelihood of a physician identifying CPSs and technological advances in cancer genetics/genomics are rapidly outpacing the knowledge of most clinicians. To address these issues, we are developing the MIPOGG, an electronic and educational application for smart devices that include tumor‐specific decisional algorithms designed to help identify those children with cancer at an increased risk of an underlying CPS.</p><p><bold>Design/Methods</bold>: For each pediatric cancer included in the International Classification of Childhood Cancers and the WHO classification of CNS tumors (2016 revision), an extensive literature review was undertaken to highlight clinical and/or molecular characteristics that increase the likelihood of a genetic predisposition. These characteristics were used to design simple algorithms following a binary tree structure with “yes / no” answers. Each algorithm ultimately advises one of two possible outcomes: ‘Referral Suggested’ or ‘No Referral Necessary’, linked with an educational module. All algorithms were critically reviewed by expert panels and validated through a multi‐institutional retrospective chart review to ensure sensitivity and positive predictive value.</p><p><bold>Results</bold>: Seventy‐five tumor‐specific algorithms will have been finalized and we will present examples including Osteosarcoma, Rhabdomyosarcoma and Wilms tumor, highlighting the performance of these algorithms in validation studies. We also outline the rationale for tumors requiring direct referral to a genetics service.</p><p><bold>Conclusions</bold>: The MIPOGG offers a clinically targeted approach, designed to easily identify patients at risk for a CPS, without the need for extensive or sophisticated investigations. As a clinical tool, it has potential to optimize management of children with cancer, across health care systems globally.</p></sec></sec><sec id="pbc26772-sec-3620"><title>Epidemiology ‐ Pathway of Care</title><sec id="pbc26772-sec-3630"><label>PD-090</label><title>Complementary and Alternative Medical Therapies in Pediatric Oncology Patients: A Single Center Experience in a Low‐Middle Income Country</title><p><underline underline-style="single">A. Farrag</underline><sup>1</sup>, F. Ali<sup>2</sup></p><p><italic><sup>1</sup>South Egypt Cancer Institute‐ Assiut University, Department of Pediatric Oncology, Assiut, Egypt; <sup>2</sup>Faculty of medicine‐ Assiut University, Department of Pediatrics, Assiut, Egypt</italic></p><p><bold>Background/Objectives</bold>: Many cultures have reported the usage of complementary and alternative medical therapies (CAMT) by cancer patients. Some patients waste time and money seeking advice for potentially harmful alternative medicine.</p><p><bold>Design/Methods</bold>: This study included pediatric oncology patients under all phases of therapy in South Egypt Cancer Institute. Personal interview with care givers (under consent) was done, focusing on their educational level, monthly income and residence. In addition to type, reason, experience and when they started CAMT, if used.</p><p><bold>Results</bold>: This study included 86 patients (54 males and 32 females), mean age was 7.7 (0.66‐19) years. Diagnoses included leukemia (44%) and other tumors (56%). Most patients were living in rural areas (83%), 29% of mothers were well educated. CAMT were reported by 52 patients (60.5%), causing delay in presentation (1‐2 weeks) in 6 patients (11.5%). Its purpose was complimentary in 37 cases (71%) and alternative to medical therapy in 15 cases (29%). CAMT types were herbal (63%), nutritional (33%), magical (29%), religious (19%), or massage (15%). Multiple CAMT were used in 25 patients. Advisers to use CAMT were mostly the family (62%), other therapists (21%), or other patients (15%). Reasons to use CAMT were either to treat complications (62%), cancer (21%), initial undiagnosed disease (10%), or pain (21%), or to increase immunity after chemotherapy (15%), or relaxation (10%). Most patients reported that CAMT was effective (65%) and is the same as or better than conventional medical therapy (38%), they started its use mostly in early phases of diagnosis and treatment (73%). Most patients denied that any physician asked them about using CAMT (98%). CAMT usage was more in relatively richer families (n=31, p=0.023). There was no detected relationship between the use of CAMT and patient's sex, diagnosis, residence, or maternal educational level.</p><p><bold>Conclusions</bold>: Full medical history including CAMT is essential in all pediatric oncology patients.</p></sec><sec id="pbc26772-sec-3640"><label>PD-091</label><title>Baseline Characteristics and Outcomes of Children with Cancer in the English‐Speaking Caribbean: A Multi‐National Retrospective Cohort</title><p>T. Gibson<sup>1</sup>, S. Beeput<sup>2</sup>, J. Gaspard<sup>3</sup>, C. George<sup>4</sup>, D. Gibson<sup>5</sup>, K. Glasgow<sup>6</sup>, V. Leandre‐Broome<sup>7</sup>, N. Palmer‐Mitchell<sup>8</sup>, C. Alexis<sup>7</sup>, J. Bird<sup>3</sup>, C. Bodkyn<sup>4</sup>, R. Boyle<sup>6</sup>, S. McLean<sup>2</sup>, M. Reece‐Mills<sup>8</sup>, C. SinQuee‐Brown<sup>5</sup>, U. Allen<sup>9</sup>, S. Weitzman<sup>10</sup>, V. Blanchette<sup>10</sup>, <underline underline-style="single">S. Gupta</underline><sup>10</sup></p><p><italic><sup>1</sup>The University of the West Indies, Pathology, Kingston, Jamaica; <sup>2</sup>Bustamante Children's Hospital, Oncology, Kingston, Jamaica; <sup>3</sup>Victoria Hospital, Oncology, Castries, St Lucia; <sup>4</sup>Eric Williams Medical Sciences Complex, Oncology, Port of Spain, Trinidad & Tobago; <sup>5</sup>Princess Margaret Hospital, Oncology, Nassau, Bahamas; <sup>6</sup>Milton Cato Memorial Hospital, Oncology, Kingstown, St Vincent and the Grenadines; <sup>7</sup>Queen Elizabeth Hospital, Oncology, Bridgetown, Barbados; <sup>8</sup>University Hospital of the West Indies, Oncology, Kingston, Jamaica; <sup>9</sup>The Hospital for Sick Children, Infectious Diseases, Toronto, Canada; <sup>10</sup>The Hospital for Sick Children, Haematology/Oncology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Children with cancer in the English‐speaking Caribbean (ESC) face unique challenges, including distribution across small populations at vast distances. ESC childhood cancer outcomes are unknown.</p><p><bold>Design/Methods</bold>: Through the SickKids‐Caribbean Initiative (SCI), we established a multi‐national childhood cancer outcomes database across seven centres in six countries (Bahamas, Barbados, Jamaica, St. Lucia, St. Vincent, and Trinidad and Tobago). Trained data managers at each site actively entered patient demographics, disease, treatment, and outcome data. Data collection commenced in 2013, with retrospective collection to 2011 and subsequent prospective collection; data for 2011‐2015 were analysed.</p><p><bold>Results</bold>: 367 children were diagnosed between 2011‐2015; median age was 5.7 years (interquartile range 2.9‐10.6 years). 124 (33.8%) patients were diagnosed with leukemia, 30 (8.2%) with lymphoma, and 149 (40.6%) with a solid tumour. A relative paucity of children with brain tumours was seen (N=48, 13.1%). Two‐year event free survival (EFS) for the entire cohort was 48.5%+/‐3.2%, while two‐year overall survival (OS) was 55.1%+/‐3.1%. Children with acute lymphoblastic leukemia (ALL) and Wilms tumour experienced better two‐year EFS (62.1%+/‐6.4% and 66.7%+/‐10.1%), while dismal outcomes were seen in children with acute myeloid leukemia (AML; 22.7+/‐9.6%), rhabdomyosarcoma (21.0%+/‐17.0%) and medulloblastoma (21.4%+/‐17.8%). Of 108 deaths with known cause, 58 (53.7%) were attributed to disease and 50 (46.3%) to treatment complications. Death within 60 days of diagnosis was relatively common in acute leukemia [13/98 (13.3%) ALL, 8/26 (30.8%) AML]. Despite this, traditional prognosticators adversely impacted outcome in ALL, including higher age, higher white blood cell count, and T‐cell lineage.</p><p><bold>Conclusions</bold>: ESC childhood cancer outcomes are superior to those in many other low‐ and middle‐income settings but are still significantly inferior to high‐income country outcomes. Based on these data, SCI interventions improving supportive care, diagnostics, and modifying leukemia treatment protocols are underway. Continued data collection will allow evaluation of these interventions and ensure maximal outcome improvements.</p></sec><sec id="pbc26772-sec-3650"><label>PD-092</label><title>Childhood Cancer: Survival in Argentina. Report from the National Pediatric Cancer Registry, ROHA NET, 2000‐2010</title><p><underline underline-style="single">F. Moreno</underline><sup>1</sup>, C. Cipolla<sup>1</sup>, G. Macias<sup>2</sup>, D. Loria<sup>1</sup>, G. Abriata<sup>3</sup>, ROHA Network<sup>1</sup></p><p><italic><sup>1</sup>Argentinian Oncopediatric Registry‐ National Cancer Institute‐, Ministry of Health, Ciudad Autonoma de Buenos Aire, Argentina; <sup>2</sup>National Cancer Institute, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina; <sup>3</sup>Survellance and Epidemiological Analysis ‐ National Cancer Institute‐, Ministry of Health, Ciudad Autonoma de Buenos Aire, Argentina</italic></p><p><bold>Background/Objectives</bold>: Information on the epidemiology of childhood cancer is mandatory for the planning of health‐care policies. The Argentine National Pediatric Cancer Registry (ROHA) is a hospital‐based registry with national coverage and has been active since 2000. The aim of the current study was to analyze the 5‐year overall survival (OS) of children diagnosed with cancer in Argentina during 2000‐2010 by major pediatric cancer subtypes.</p><p><bold>Design/Methods</bold>: Newly diagnosed pediatric cancer cases are registered in the ROHA (estimated coverage is 93% of the country´s cases). Five‐year OS was estimated using Kaplan‐Meier methods.</p><p><bold>Results</bold>: Between 2000 and 2010, a total of 14,239 new cancer diagnoses in children aged <15 years were reported to the registry. Five‐year OS for all cancers was 57.4% (95%CI: 56.5‐58.3). Specific 5‐year OS for the most common cancer subtypes was: leukemias 58.7% (95%CI: 57.3‐60.1), lymphomas and related neoplasms 73.1% (95%CI: 70.8‐75.3), brain neoplasms 41.1% (95%CI: 39.0‐43.2), soft‐tissue sarcomas 47.0% (95%CI: 43.3‐50.7), neuroblastomas 50.3% (95%CI: 46.4‐54.0), renal tumors 72.5% (95%CI: 68.6‐76.0), and malignant bone tumors 42.2% (95%CI: 38.2‐46.1).</p><p><bold>Conclusions</bold>: The 5‐year OS for children diagnosed with cancer in Argentina was 57%. Even though this percentage is lower than what is reported in high‐income countries the distribution of pediatric cancers by subtype were similar. Improving these results remains a challenge for our health‐care system.</p></sec><sec id="pbc26772-sec-3660"><label>PD-093</label><title>Adolescent and Young Adult (AYA) Cancer Care in Canada: Highlights from A Report on System Performance Metrics</title><p><underline underline-style="single">P. Rogers</underline><sup>1</sup>, C. Rae<sup>2</sup>, K. Marr<sup>1</sup>, S. Gupta<sup>3</sup>, D. Szwajcer<sup>4</sup>, C. Hammond<sup>5</sup>, J. Pole<sup>6</sup>, M. McBride<sup>7</sup>, C. D'cruz<sup>7</sup>, C. Digout<sup>8</sup>, A. Flanders<sup>9</sup>, A. Srikanthan<sup>10</sup>, M. Greenberg<sup>3</sup>, Y.S. Rho<sup>11</sup>, M. Palumbo<sup>11</sup>, P. Kavan<sup>11</sup>, T. Buckland<sup>12</sup>, P. Grundy<sup>13</sup>, B. Schacter<sup>4</sup>, R. Barr<sup>2</sup></p><p><italic><sup>1</sup>BC Children's Hospital, Pediatrics, Vancouver, Canada; <sup>2</sup>McMaster University, Pediatrics, Hamilton, Canada; <sup>3</sup>Hospital For Sick Children, Oncology, Toronto, Canada; <sup>4</sup>Cancercare Manitoba, Oncology, Winnipeg, Canada; <sup>5</sup>Canadian Hospice Palliative Care Association, Palliative care, Ottawa, Canada; <sup>6</sup>Pediatric Oncology Group of Ontario, Oncology, Toronto, Canada; <sup>7</sup>BC Cancer Agency, Cancer Control Research, Vancouver, Canada; <sup>8</sup>IWK Health Centre, APPHON, Halifax, Canada; <sup>9</sup>IWK Health Centre, Oncology, Halifax, Canada; <sup>10</sup>BC Cancer Agency, Oncology, Vancouver, Canada; <sup>11</sup>McGill University, Oncology, Montreal, Canada; <sup>12</sup>University of Alberta, Business, Edmonton, Canada; <sup>13</sup>University of Alberta, Pediatrics, Edmonton, Canada</italic></p><p><bold>Background/Objectives</bold>: Health care needs for AYAs with cancer are different from those in older and younger patients. Reporting of indicators is essential to evaluate projects and system changes being undertaken to improve care for this population. The goal of this project was to report on indicators to assess the current state of AYA cancer care in Canada.</p><p><bold>Design/Methods</bold>: Measures of health system performance were selected from consensus‐based indicators. Data were obtained from administrative databases and national surveys. Areas of focus included: epidemiology, active care, palliation, psychosocial issues, survivorship and research.</p><p><bold>Results</bold>: <italic>Epidemiology</italic>: Over the last 20 years there has been an 18.2% relative increase in new cancer cases in 15‐29 year olds. Five‐year relative survival was 86.3%, an absolute increase of 6.2% from the early 1990s. <italic>Active care</italic>: Among 20–29 year olds, 26.6% began treatment ≥57 days after diagnosis for breast cancer; approximately 20% of other age groups waited a similar period. 54% of AYAs with breast and colon cancer were treated at teaching hospitals as compared to 47.8% of older adults. <italic>Palliation</italic>: Most AYA cancer deaths in 2012 occurred in hospital (73%). <italic>Psychosocial issues</italic>: Emotional support was rated negatively by both AYA males (24.1%) and females (26.2%). <italic>Survivorship</italic>: Cancer survivors and the general population shared similar achievement rates of post‐secondary education; cancer survivors reported higher unemployment. <italic>Research</italic>: Average annual investment in AYA‐specific cancer research between 2005 and 2013 was $1.8 million, 0.4% of total cancer research investments in Canada. As of June 2016, 128 of therapeutic cancer clinical trials (32.9%) were for a cancer prevalent among AYAs.</p><p><bold>Conclusions</bold>: Opportunities for improving care for AYAs with cancer were identified, as was a gap in research investment. Challenges to reporting on AYA indicators were identified e.g. lack of age‐specific data; inability to analyze by type of cancer and age. The report is available through systemperformance.ca.</p></sec><sec id="pbc26772-sec-3670"><label>PD-094</label><title>Hispanic Ethnicity is Associated with Methotrexate‐Related Neurotoxicity in Children Receiving Acute Lymphoblastic Leukemia Treatment</title><p><underline underline-style="single">O. Taylor</underline><sup>1</sup>, A. Brown<sup>1</sup>, J. Brackett<sup>1</sup>, I. Moore<sup>2</sup>, C. Hooke<sup>3</sup>, R. Luna‐Gierke<sup>1</sup>, M. Hockenberry<sup>4</sup>, P. Lupo<sup>1</sup>, M. Scheurer<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics‐ Hematology‐Oncology Section, Houston, USA; <sup>2</sup>University of Arizona, School of Nursing, Tucson, USA; <sup>3</sup>University of Minnesota, School of Nursing, Minneapolis, USA; <sup>4</sup>Duke University, School of Nursing, Durham, USA</italic></p><p><bold>Background/Objectives</bold>: Methotrexate (MTX) is a critically important chemotherapeutic agent in acute lymphoblastic leukemia (ALL) therapy. However, MTX‐induced neurotoxicity (NT) can lead to treatment modifications, which may jeopardize long‐term survival in affected patients. The objective of this study is to evaluate demographic and clinical factors associated with incidence of acute MTX NT among pediatric patients with ALL.</p><p><bold>Design/Methods</bold>: Pediatric ALL patients (n=216) undergoing therapy at three major childhood cancer treatment centers in the United States (Texas Children's Cancer Center; University of Arizona; Children's Minnesota) between 2012 and 2017 were enrolled on a prospective study of treatment‐related toxicity. MTX NT was defined as any neurologic event (e.g., aphasia, seizure) following intrathecal (IT) and/or intravenous (IV) MTX that resulted in modifications in IT and/or IV MTX therapy. Logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (CI) for the impact of demographic and treatment features on MTX NT.</p><p><bold>Results</bold>: Thirty‐four patients (16%) experienced acute MTX NT. Of the patients who experienced NT, 77% (n=26) were Hispanic compared to 41% (n=75) of those without MTX NT (n=182). Median age at diagnosis was significantly higher (p<0.001) in MTX NT group: 12.4 years vs. 6.3 years, respectively. Hispanics were 4 times (OR=4.60, 95% CI: 1.76‐11.98, p=0.002) more likely to experience MTX NT than non‐Hispanics after adjusting for sex, age at diagnosis, and ALL risk stratification. Independent of Hispanic ethnicity, only ALL risk stratification remained a statistically significant predictor of MTX NT.</p><p><bold>Conclusions</bold>: In this large multi‐ethnic cohort, we found that Hispanic ethnicity was strongly associated with increased risk of MTX NT. This adds to the growing body of evidence indicating that Hispanic patients with ALL encounter significant disparities in treatment outcomes. Understanding the mechanisms and predictors of these disparities is critical to improving the outcomes and survival for these patients.</p></sec></sec><sec id="pbc26772-sec-3680"><title>Late Effects</title><sec id="pbc26772-sec-3690"><label>PD-095</label><title>Long‐Term Cardioprotective Efficacy of Dexrazoxane and Liposomal Doxorubicin Evaluated in a Murine Model of Early Doxorubicin Treatment</title><p>T. Andrews<sup>1</sup>, <underline underline-style="single">G. Aune</underline><sup>1</sup></p><p><italic><sup>1</sup>Greehey Children's Cancer Research Institute/University of Texas Health Science, Pediatrics‐ Division of Hematology‐Oncology, San Antonio, USA</italic></p><p><bold>Background/Objectives</bold>: Exposure to anthracyclines such as doxorubicin (DOX) during childhood cancer treatment is unequivocally linked to the development of cardiovascular disease. Clinical strategies to mitigate long‐term cardiac morbidity in childhood cancer survivors include pretreatment with the iron chelator dexrazoxane (DEX) and the use of liposomal doxorubicin (L‐DOX). Both strategies decrease acute cardiac toxicity. However, due to the long latent period between exposure and development of cardiac disease, the long‐term cardiac outcome of survivors treated using these strategies is mostly unknown. Thus, their use has not yet been widely adopted in clinical practice. Here we report the evaluation of DEX and L‐DOX in a clinically relevant murine model of early anthracycline exposure followed by the monitoring of cardiac function and survival throughout lifespan into aged adult mice.</p><p><bold>Design/Methods</bold>: Beginning at 2 weeks of age, C57BL6/J mice (n = 6 per group, equal numbers of males and females) were treated with weekly intraperitoneal injections as follows: saline control, 5 mg/kg DOX, 50 mg/kg DEX:5 mg/kg DOX, and 5 mg/kg L‐DOX. Following completion of therapy, mice were monitored under normal laboratory conditions. Physical parameters including body weight, survival, and cardiac function using standard echocardiography were evaluated every three months up to 22 months of age (aged adult mouse).</p><p><bold>Results</bold>: Compared to controls, mice treated with DOX exhibited significantly reduced body weight (26% decrease), survival (50% decrease), and cardiac function (12% decrease in ejection fraction‐ E.F.) In contrast, mice treated with DEX + DOX or L‐DOX exhibited normal body weight (no decrease), enhanced survival (100%), and normal cardiac function (normal E.F.) compared to DOX‐treated animals.</p><p><bold>Conclusions</bold>: These studies performed in mice indicate that both dexrazoxane and L‐DOX significantly mitigate cardiac damage induced by early anthracycline exposure, throughout the lifespan and into old age. Clinical practice should incorporate widespread use of these cardioprotective strategies.</p></sec><sec id="pbc26772-sec-3700"><label>PD-096</label><title>Neurocognitive Change Following Treatment for Pediatric Brain Tumors with Proton Beam Radiotherapy Versus Surgery Only</title><p><underline underline-style="single">L. Kahalley</underline><sup>1</sup>, M.D. Ris<sup>1</sup>, A. Mahajan<sup>2</sup>, M.F. Okcu<sup>1</sup>, M. Chintagumpala<sup>1</sup>, W. Whitehead<sup>3</sup>, A. Paulino<sup>4</sup>, J. Orobio<sup>1</sup>, H. Stancel<sup>1</sup>, C. Minard<sup>5</sup>, D. Grosshans<sup>4</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>2</sup>Mayo Clinic, Radiation Oncology, Rochester, USA; <sup>3</sup>Baylor College of Medicine, Neurosurgery, Houston, USA; <sup>4</sup>The University of Texas MD Anderson Cancer Center, Radiation Oncology, Houston, USA; <sup>5</sup>Baylor College of Medicine, Dan L. Duncan Institute for Clinical and Translational Research, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Cranial radiotherapy is associated with neurocognitive toxicity. Proton beam radiotherapy (PBRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes. We examined change in neurocognitive scores over time in pediatric brain tumor patients treated with craniospinal PBRT (P‐CSI), focal PBRT (P‐Focal), and Surgery Only (SO).</p><p><bold>Design/Methods</bold>: Patients received annual neurocognitive evaluations for up to 5 years. We examined Full Scale IQ (FSIQ), Working Memory Index (WMI), and Processing Speed Index (PSI) scores. Separate general linear mixed models examined change in scores over time by treatment group.</p><p><bold>Results</bold>: Scores were available for 69 patients (16 P‐CSI, 21 P‐Focal, 32 SO). Groups did not differ on demographic or clinical variables (47.8% male, 37.7% infratentorial tumor, mean age‐at‐treatment=9.8 years, mean follow‐up interval=2.3 years). Tumor types included: 55.1% glioma, 17.4% medulloblastoma, 7.2% ependymoma, 7.2% germ cell, 5.8% craniopharyngioma, and 7.2% other. Median RT dose was 54.0 Gy for P‐CSI and 50.4 Gy for P‐Focal. FSIQ, WMI, and PSI scores remained stable over time in all treatment groups (all<italic>p</italic>>0.05). Means for all three groups were within normal limits across scores and available time points. Even though FSIQ did not decline significantly in any group, the FSIQ slope of the P‐CSI group differed significantly from the slopes of the P‐Focal and SO groups (both <italic>p</italic>=0.03).</p><p><bold>Conclusions</bold>: Within early survivorship, PBRT was not associated with significant cognitive decline. Outcomes were similar whether patients received PBRT (CSI or focal) or no radiotherapy. Not only was global IQ within normal limits for age, but processing speed and working memory (domains known to be particularly radiosensitive) were also consistent with age‐expectations across groups. CSI emerged as a cognitive risk factor, consistent with photon outcomes research. While findings are hopeful, replication with a larger sample and later outcomes is needed and underway.</p></sec><sec id="pbc26772-sec-3710"><label>PD-097</label><title>Risk Factors for Preterm Delivery Among Early Onset Cancer Survivors – A Register‐Based Study</title><p>J. Melin<sup>1</sup>, S. Heinävaara<sup>1</sup>, N. Malila<sup>1</sup>, A. Tiitinen<sup>2</sup>, M. Gissler<sup>3</sup>, <underline underline-style="single">L. Madanat‐Harjuoja</underline><sup>1</sup></p><p><italic><sup>1</sup>Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; <sup>2</sup>University of Helsinki‐ Helsinki University Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland; <sup>3</sup>National Institute for Health and Welfare, National Institute for Health and Welfare, Helsinki, Finland</italic></p><p><bold>Background/Objectives</bold>: Previous studies have shown an elevated risk for preterm delivery among female cancer survivors. Our aim was to assess pregnancy related conditions possibly underlying the elevated risk for preterm labor in cancer survivors.</p><p><bold>Design/Methods</bold>: Nationwide cancer and birth registries were merged to identify 1,831 first deliveries of cancer survivors (diagnosed below 40 years of age) and 5,281 first deliveries of matched female controls between January 1991 and December 2013. Multiple unconditional logistic regression models were used to estimate the risk for pregnancy related conditions adjusting for maternal age, year of delivery, gestational age and smoking.</p><p><bold>Results</bold>: We found a significantly elevated risk for hospitalization due to threatened preterm labor (OR 1.42, 95% CI 1.03‐1.95), fear of childbirth (OR 1.99, 95% CI 1.30‐3.05) and mental disorders and diseases of the nervous system (OR 3.99, 95% CI 2.13‐7.48) among survivors compared to controls. An increased risk for overall hospitalization (OR 1.47, 95% CI 1.28‐1.68) and hospital stays exceeding 7 days (OR 1.23, 95% CI 1.04‐1.46) was also found.</p><p>The risk for premature rupture of the membrane, vaginal bleeding, pre‐eclampsia or gestational diabetes was not increased.</p><p>The highest risk for hospitalization due to threatened preterm labor was seen among survivors delivering 0‐5 years after cancer treatment and survivors diagnosed as young adults (age 25‐39 years).</p><p><bold>Conclusions</bold>: Cancer survivors have an increased risk for preterm delivery possibly explained by spontaneous preterm labor due to premature contractions and cervical shortening. Health professionals treating these women should be aware of these risks. In general, however, our results are reassuring when it comes to pregnancies among cancer survivors.</p></sec><sec id="pbc26772-sec-3720"><label>PD-098</label><title>An Exploratory Analysis of Physical Activity on Modifiable Aging‐Related Risk Factors Among Survivors of Childhood Cancer</title><p>N. Sloof<sup>1</sup>, E. Hendershot<sup>2</sup>, M. Griffin<sup>3</sup>, L. Anderson<sup>2</sup>, <underline underline-style="single">S. Marjerrison</underline><sup>2,4</sup></p><p><italic><sup>1</sup>McMaster University, Kinesiology, Hamilton, Canada; <sup>2</sup>McMaster Children's Hospital, Pediatric Hematology/Oncology, Hamilton, Canada; <sup>3</sup>McMaster University, Health‐ Aging & Society, Hamilton, Canada; <sup>4</sup>McMaster University, Pediatrics, Hamilton, Canada</italic></p><p><bold>Background/Objectives</bold>: By age 45, more than 80% of survivors of cancer in childhood (SCC) have serious chronic health conditions. The literature remains unclear whether lifestyle factors, including physical activity (PA), are related to long‐term health outcomes. The objective of this study was to examine the relationship between PA and established late effects of treatment in adult survivors of childhood cancer.</p><p><bold>Design/Methods</bold>: A retrospective chart review including all adult SCC currently enrolled in the McMaster Aftercare program was performed. Information on diagnosis, treatment, PA and other lifestyle behaviours, as well as physiologic measures was abstracted. Predictors of established late effects of cancer therapy were examined using logistic regression on multivariable models built with known risk factors determined <italic>a priori</italic>, and significant predictors from univariate analyses.</p><p><bold>Results</bold>: Of the 262 patients included, only 42% reported behaviour that met PA recommendations, and 27% indicated no PA participation. In multivariable analysis, significant independent associations were shown between normal left ventricular ejection fraction (LVEF) and adequate PA (P=0.03), as well as female sex (P=0.04), while accounting for doxorubicin (P=0.21), chest radiation (P=0.08), as well as other factors. Low bone mineral density (BMD) was associated with no PA (P=0.03) and ideal body mass index (BMI) (P=0.02). Body fat percentage was associated with cranial radiation (P<0.01) and female sex (P<0.01). High BMI was associated with no PA (P=0.01) and normal BMD (P<0.01). BMI was the only modifiable risk factor associated with any lipid levels in univariate analysis.</p><p><bold>Conclusions</bold>: Despite ongoing healthy active living counselling, only 42% of SCC in our clinic meet PA guidelines. We identified novel independent associations between PA and LVEF, BMD, and BMI in SCC, shown to be more strongly associated with these markers of health than many established predictive treatment and lifestyle‐related factors. PA is an important predictor of healthy aging among SCC.</p></sec><sec id="pbc26772-sec-3730"><label>PD-099</label><title>Neurological Outcomes in Pediatric Low Grade Glioma by Tumor Site and Timing of Diagnosis</title><p><underline underline-style="single">Z. Sadighi</underline><sup>1</sup>, E. Curtis<sup>1</sup>, J. Zabrowski<sup>2</sup>, C. Billups<sup>3</sup>, R. Khan<sup>1</sup>, I. Qaddoumi<sup>4</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Neurology, Memphis, USA; <sup>2</sup>, Neurology, Memphis, USA; <sup>3</sup>St. Jude Children's Research Hospital, Biostatistics, Memphis, USA; <sup>4</sup>St. Jude Children's Research Hospital, Oncology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Characterization of neurological outcomes by site of tumor and duration of presenting symptoms in patients with pediatric low grade glioma (LGG) has not been assessed until now.</p><p><bold>Design/Methods</bold>: An institutional review board‐approved retrospective study was conducted for patients diagnosed with LGG at St. Jude Children's Research Hospital between 1995 and 2005. Neurological impairments (severity defined by Common Terminology Criteria for Adverse Events version 4.03) were compared at first and last visit by tumor location and pre‐diagnosis symptom interval (PSI) (≥ 3months or < 3 months) using Kruskal‐Wallis test, Wilcoxon rank sum test, and Fisher's exact test.</p><p><bold>Results</bold>: 246 patients with LGG (106 spinal cord, posterior fossa (PF), and brainstem; 88 optic pathway and midline; and 52 cerebral hemisphere) were included; median age of diagnosis 7.1 (range, 0.1 – 20.7) years, median PSI 2.1 (<1–131.1) months, and median time to last follow‐up 11.6 (0.1‐21.4) years. Cerebral hemisphere had fewest median neurological impairments (2) compared to other locations (4) at baseline (p<0.001); and at last follow‐up (3) compared to other locations (5) (p=0.004). In all patients, PSI ≥ 3 months had higher incidence of ataxia and dysmetria (41.6%) (p=0.003). PSI ≥ 3 months had overall worse motor weakness in cerebral hemisphere; dysmetria in optic pathway and midline; and dysmetria and ear and vestibular disturbances in spinal cord, PF, and brainstem (p≤0.05). PSI < 3 months) in spinal cord, PF, and brainstem had worsening vagal nerve deficit (p=0.026).</p><p><bold>Conclusions</bold>: Neurological outcomes in pediatric LGG vary by location and delayed diagnosis minimally affects neurological outcomes.</p></sec></sec><sec id="pbc26772-sec-3740"><title>IPSO Poster Discussion</title><sec id="pbc26772-sec-3750"><label>PD-100</label><title>Bronchial Blockers in Pediatric Thoracic Surgical Oncology</title><p><underline underline-style="single">L. Martynov</underline><sup>1</sup>, N. Matinyan<sup>1</sup>, V. Gruzdev<sup>2</sup>, A. Sotnikov<sup>1</sup>, P. Kerimov<sup>3</sup>, A. Kazantsev<sup>3</sup></p><p><italic><sup>1</sup>Pediatric Oncology and Hematology Institute‐ Blokhin Russian Oncological Research Center, Anesthesiology department, Moscow, Russia; <sup>2</sup>Blokhin Russian Oncological Research Center, Anesthesiology department, Moscow, Russia; <sup>3</sup>Pediatric Oncology and Hematology Institute‐ Blokhin Russian Oncological Research Center, Oncology department, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: In pediatric oncology lungs are the most frequent target of metastasis, so diagnostic and therapeutic surgeries are required. To guarantee optimal conditions for surgery, collapse of operated lung is required, thus one lung ventilation (OLV) should be performed. Novel devices for OLV, such as Cohen, EZ‐Blocker and Arndt bronchial blockers (BB) allow to achieve OLV avoiding traumatisation of trachea and other complications.</p><p><bold>Design/Methods</bold>: During September'14 ‐ March'17, 57 surgeries in patients 10‐17 years old were performed. OLV was maintained using BB. BB was introduced through the lumen of video endotracheal tube and was placed into bronchus under video control. Installation of Arndt BB was conducted under endoscopic control. In 24 cases (43%) right main bronchus, in 33 cases (57%) ‐ left main bronchus were blocked. Time of BB installation, lung collapse score after installation of thoracoscopic ports, hemodynamic profile during surgery, frequency of postoperative complications such as sore throat and aphonia were evaluated.</p><p><bold>Results</bold>: Mean time of intubation and BB installation was 187 +/‐ 42 seconds. In all cases it was possible to achieve satisfactory lung collapse, but in 16 cases aspiration of air through the channel of BB had to be performed. Collapsing the right lung presents some difficulties due to the anatomical features as higher embranchement of right upper lobe bronchus. In this case use of EZ‐Blocker BB is preferable as it is designed to be securely fixed over carina, making it less likely to displace during surgery. In surgeries on the left lung Cohen BB is more preferable.</p><p><bold>Conclusions</bold>: The use of BB requires expensive high‐tech equipment for video or endoscopic control, and well trained staff with skills of BB installation and maintaining OLV. BB is a promising technique to achieve the effective collapse of the lung with minimal traumatisation, fewer complications postoperatively and rapid rehabilitation of patients after surgery.</p></sec><sec id="pbc26772-sec-3760"><label>PD-101</label><title>Curcumin in Rhabdomyosarcoma: Influences on Photodynamic and Cytotoxic Effects in Vitro</title><p><underline underline-style="single">C. Sorg</underline><sup>1</sup>, E. Schmid<sup>1</sup>, J. Fuchs<sup>1</sup>, V. Ellerkamp<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Tübingen, Pediatric Surgery and Pediatric Urology, Tübingen, Germany</italic></p><p><bold>Background/Objectives</bold>: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children. The outcome for children with advanced tumor disease is still poor. Curcumin, a naturally occuring phenol, is investigated in complementary oncology research for its phytochemical and antiproliferative effects.</p><p><bold>Design/Methods</bold>: Alveolar (RH30, ZF) and embryonal (RD, SRH) RMS cell lines were treated with curcumin alone (2‐11μg/ml), combination of curcumin and vincristine (curcumin: 4‐7μg/ml; vincristine: 0,0005, 0,00075, 0,004μg/ml) and combination of curcumin and photodynamic therapy (curcumin: 0,5‐1μg/ml; light with 488nm for 5sec.). The human skeletal muscle cell line SKMC served as control. Cell viability was assessed with MTT assays. The apoptosis rate was evaluated via FACS analysis. Migration was investigated with a wound healing assay. Clonogenic survival of RMS cells was detected by Colony forming assay.</p><p><bold>Results</bold>: Combination of curcumin and vincristine led to dose‐depending effects on all cell lines: that appears in a decrease in cell proliferation and migration potential as well as an increase in apoptosis rate. The combination therapy with photodynamic therapy resulted in a highly significant decrease of cell viability in RMS cell lines even with very low concentrations of curcumin (1μg/ml). The results also show that curcumin inhibits the cloning efficiency of RMS cells.</p><p><bold>Conclusions</bold>: In summary, this study provides first evidence that curcumin, especially in combination with standard chemotherapy or photodynamic therapy is a promising agent in the treatment of RMS. Further <italic>in vivo</italic> studies are pending.</p></sec><sec id="pbc26772-sec-3770"><label>PD-102</label><title>The Risk of Adrenal Insufficiency in Neuroblastoma Surgery</title><p><underline underline-style="single">C.H. Chui</underline><sup>1</sup></p><p><italic><sup>1</sup>Surgery Centre for Children Pte Ltd, Surgical Oncology, Singapore, Singapore</italic></p><p><bold>Background/Objectives</bold>: More than 40% of neuroblastoma arise from the adrenal gland. Adrenalectomy has been the treatment of choice. However, the contralateral adrenal gland is often also at risk leading to the development of postoperative adrenal insufficiency (AI). We reviewed the risk of AI in our patients who underwent neuroblastoma surgery.</p><p><bold>Design/Methods</bold>: Retrospective analysis of 165 patients with neuroblastoma in the “suprarenal region”, defined as retroperitoneal zone superior to the renal veins and arteries. AI was defined as chronic or transient. Patients were categorized based on loco‐regional disease distribution: (A) right adrenal disease only, (B) left adrenal disease only, (C) right adrenal and left peri‐adrenal disease, (D) left adrenal and right peri‐adrenal disease, (E) bilateral adrenal disease, and (F) non‐adrenal paravertebral disease. Demographic data, surgical records and postoperative charts were reviewed.</p><p><bold>Results</bold>: 18(10.9%) out of 165 patient developed AI, of which 3 were chronic and 15 were transient. None of unilateral adrenal‐diseased patients in Groups A(n=21) and B(n=28) developed AI. Half(50%) of 8 bilateral adrenal‐diseased patients in Group E developed AI. 2(7.4%) of 27 patients in Group F developed AI. When unilateral adrenal disease was coupled with contralateral peri‐adrenal disease, 9(33.3%) of 27 patients in Group C compared to 3(5.6%) of 54 patients in Group D developed AI (<italic>p=0.0009</italic>) suggesting that the left adrenal gland was more vulnerable to surgical damage. The right adrenal gland was more likely to be preserved due to the shorter course of right adrenal vein.</p><p><bold>Conclusions</bold>: Preserving adrenal function should be considered in neuroblastoma surgery. Due caution should be rendered to left adrenal gland after right adrenalectomy because of its vulnerable vasculature. Early hydrocortisone replacement should be instituted when AI is suspected.</p></sec><sec id="pbc26772-sec-3780"><label>PD-103</label><title>Radiotherapy Omitted in the Treatment of Positive Surgical Margins after Nephron‐Sparing Surgery for Wilms Tumor</title><p><underline underline-style="single">D. Cozzi</underline><sup>1</sup>, S. Ceccanti<sup>1</sup>, S. frediani<sup>1</sup>, I. Falconi<sup>1</sup>, A. Boscarelli<sup>1</sup>, F. Cozzi<sup>1</sup></p><p><italic><sup>1</sup>Sapienza University of Rome, Pediatric Surgery Unit, Rome, Italy</italic></p><p><bold>Background/Objectives</bold>: Current treatment of microscopic residual disease with negative lymph nodes after nephron‐sparing surgery (NSS) for Wilms tumor includes radiotherapy and multi‐drugs chemotherapy. The aim of present study is to test the hypothesis that some children with positive margins after NSS may be successfully treated without radiotherapy.</p><p><bold>Design/Methods</bold>: Between 1992 and 2016, 50 children with renal tumor underwent surgery at our institution. Eight patients with unilateral Wilms tumor and 1 with unilateral renal oncocytoma underwent partial nephrectomy. In addition, 6 children with unilateral Wilms tumor and 1 with bilateral Wilms tumor underwent one or multiple enucleation. Two children after partial nephrectomy and 2 after enucleation presented positive surgical margins without lymph nodes involvement and were treated with chemotherapy without radiotherapy.</p><p><bold>Results</bold>: The child with bilateral Wilms tumor underwent second‐look operation consisting in new enucleations followed by post‐operative chemotherapy without radiotherapy. This patient is alive and well at the age of 7 years. The other 3 children with positive margins treated without radiotherapy are alive and well at the age of 24,23, and 6 years. All patients had an eGFR within the range of two‐kidney renal function, no hypertension and albuminuria.</p><p><bold>Conclusions</bold>: Some children with positive surgical margins after NSS for Wilms tumor may be successfully treated without radiotherapy. Larger numbers of patients are needed to determine whether this approach is generally applicable.</p></sec><sec id="pbc26772-sec-3790"><label>PD-104</label><title>Lack of Renal Artery Inspection is Associated with Low Resectability at the Renal Hilus in Relapsed High‐Risk Neuroblastoma</title><p><underline underline-style="single">G. Cernaianu</underline><sup>1</sup>, T. Simon<sup>2</sup>, B. Hero<sup>2</sup>, M. Dübbers<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Cologne, Pediatric Surgery, Köln, Germany; <sup>2</sup>University Hospital Cologne, Pediatric Oncology and Hematology, Köln, Germany</italic></p><p><bold>Background/Objectives</bold>: The renal hilus is the main lymphatic drainage route of the adrenal medulla. Inspection and preparation of the renal artery during debulking of tumor tissue at the renal hilus constitutes a surgical challenge in high‐risk neuroblastoma. However, the association of renal artery exposure with resectability of high risk neuroblastoma during first line resecting abdominal surgery (S1) at the renal hilus is not clearly defined.</p><p><bold>Design/Methods</bold>: Fourty patients with relapse or progression of high‐risk neuroblastoma (R‐HR‐NB) after first line surgery enrolled in the German neuroblastoma trials between 2000‐2010 were evaluated. We analyzed the frequency of renal artery exposure and the resectability at the renal hilus by means of surgical reports for S1.</p><p><bold>Results</bold>: The tumor involved the renal vessels in 28/40 (70%) of patients on the right (R) and left (L) side. Inspection of the artery during operation was documented on the right side in 9/28 (32%), and on the left side in 6/28 (21%) patients. Exposure of the renal artery was associated with a higher resection rate at the renal hilus as compared to cases without exposure (R: 8/9 (88%) vs. 3/19 (16%), <italic>P</italic>=.000; L: 5/6 (83%) vs. 9/22 (41%), <italic>P</italic>=.006).</p><p><bold>Conclusions</bold>: The surgical analysis of R‐HR‐NB revealed a high frequency of tumors at the renal hilus but a low rate of renal artery inspection. Renal artery inspection was associated with a higher resection rate of tumors at the renal hilus. The results of our study emphasize the importance of renal artery inspection as instrument of surgical quality during first resection of abdominal high risk neuroblastoma at the renal hilus. Vice versa inspection of the renal arteries might also be an indication of an operation technique more likely to achieve complete tumor resection.</p></sec><sec id="pbc26772-sec-3800"><label>PD-105</label><title>The Role of Radiology Versus Clinical Follow Up for Identification of Solid Tumour Relapse</title><p><underline underline-style="single">M. Collin</underline><sup>1</sup>, K. Schultz<sup>2</sup>, D. McDowell<sup>1,2</sup>, B. Goh<sup>1</sup>, J. Karpelowsky<sup>3,4</sup></p><p><italic><sup>1</sup>The Children's Hospital at Westmead, Paediatric Surgery, Westmead, Australia; <sup>2</sup>University of Sydney, Sydney Medical School, Sydney, Australia; <sup>3</sup>The Children's Hospital at Westmead, Paediatric Oncology and Thoracic Surgery, Westmead, Australia; <sup>4</sup>University of Sydney, Children's Cancer Research Unit, Sydney, Australia</italic></p><p><bold>Background/Objectives</bold>: The clinical and radiological follow up of paediatric solid tumour patients aims to include early identification of relapse. Standardised three monthly (or more frequent) imaging is often employed, however surveillance imaging has not been well studied. The risks of the high cumulative doses of radiation in these protocols include the potential for secondary malignancies. Our study aims to identify the role imaging plays in establishing relapse in the solid tumour population.</p><p><bold>Design/Methods</bold>: This study involves a retrospective audit of patients who were managed at our hospital in a sixteen‐year period (2000‐2015) who presented with common solid tumours (osteosarcoma, rhabdoyosarcomas, Ewing sarcoma, neuroblastoma, Wilms tumour, non‐rhabdomyosarcoma soft‐tissue sarcoma or hepatoblastoma). Data was collected from the oncology and radiology databases, as well as medical records.</p><p><bold>Results</bold>: We identified 528 patients from the oncology databases, of which 131 failed to meet inclusion criteria of achieving radiological remission or had incomplete records throughout the follow up period and were excluded. This left 397 included patients of which 72 patients had relapse. In those cases with relapse 35 were identified clinically, PET, 1 with combined CT/MRI) and 19 cases with other imaging forms (5 with PET alone, 3 with bone scan, 3 with MIBG alone, 2 with CXR, 3 with MRI alone and 3 with ultrasound). There were 4 cases of secondary malignancies identified in the follow up period. The total number of CT scans performed in the follow up period was 1,953, resulting in a mean number of CT studies per patient of 4.9 and equating to one episode of CT identified relapse per 108.5 CT scans.</p><p><bold>Conclusions</bold>: We conclude that while radiological investigations play a role alongside clinical history and examination in establishing relapse, further studies are required to minimise the radiation exposure in these protocols, while maximising the clinical benefit.</p></sec><sec id="pbc26772-sec-3810"><label>PD-106</label><title>The Violations of The Surgical Guidelines for Wilms Tumour Nephrectomy</title><p><underline underline-style="single">J. Godzinski</underline><sup>1,2</sup>, G. Audry<sup>3</sup>, G. Cecchetto<sup>4</sup>, J. Fuchs<sup>5</sup>, S. Irtan<sup>3</sup>, B. Okoye<sup>6</sup>, M. Powis<sup>7</sup>, D. von Schweinitiz<sup>8</sup>, S. Warmann<sup>5</sup>, K.P. van de Veen<sup>9</sup>, M. Lopez<sup>10</sup>, N. Graf<sup>11</sup></p><p><italic><sup>1</sup>Marciniak Hospital, Paediatric Surgery, Wroclaw, Poland; <sup>2</sup>Medical University, Paediatric Traumatology and Emergency Medicine, Wroclaw, Poland; <sup>3</sup>Hospital Trousseau, Chirurgie Pediatrique, Paris, France; <sup>4</sup>University Hospital of Padua, Pediatric Surgery Unit‐Women's and Children Health Department, Padoua, Italy; <sup>5</sup>University of Tuebingen, Paediatric Surgery, Tuebingen, Germany; <sup>6</sup>St Georges University Hospital, Paediatric Surgery, London, United Kingdom; <sup>7</sup>LEEDS TEACHING HOSPITALS NHS TRUST, Paediatric Surgery, Leeds, United Kingdom; <sup>8</sup>University of Munich, Department of Pediatric Surgery‐, Munich, Germany; <sup>9</sup>Princess Maxima, Paediatric Surgery, Utrecht, The Netherlands; <sup>10</sup>NKI, NKI, Amsterdam, The Netherlands</italic></p><p><italic><sup>11</sup>Saarland University, Department of Pediatric Oncology and Hematology, Homburg, Germany</italic></p><p><bold>Background/Objectives</bold>: Surgery plays important role in the treatment of nephroblastoma. The major multicentre studies precisely recommend the guidelines for the surgical treatment. <bold>Aim of the study was</bold> to evaluate the rates and types of potentially most important violations and iatrogenic failures of the SIOP2001 surgical guidelines.</p><p><bold>Design/Methods</bold>: The retrospective review of 2429 records of patients aged > 6 months with unilateral nephroblastoma registered in the SIOP2001. The candidate violations/iatrogenic failures were (1) preoperative open biopsy, (2) intraoperative tumour rupture and (3) sampling less than 6 regional lymph nodes. Factors 1 and 2 result in staging patient 3, longer chemotherapy and radiotherapy. Factor 3 (not representative sampling) may lead to incorrect lower staging and, in consequence, insufficient aggressiveness and duration of the postoperative treatment.</p><p><bold>Results</bold>: The preoperative open biopsies were performed in 7% of all patients and were the main reason for staging III in 24% of stage III patients. The intra operative tumour ruptures were reported in 1.45% of patients. Not adequate sampling (less than 6 lymph nodes) of the regional lymph nodes was reported in 88.2 % of patients. In 13.8% lymph nodes were not sampled at all. This factor was the only reason for staging 3 in 15% of cases, however the underestimation of the rate of lymph nodes involvement seems probable.</p><p><bold>Conclusions</bold>: Surgical guidelines are correctly followed in majority of patients, main problem considers incorrect sampling of the lymph nodes what results in possible downstaging of patients, less aggressive postoperative treatment and higher risk of relapse. The iatrogenic upstaging the patients due to pre‐treatment open biopsy and the intraoperative tumour rupture were less frequent, however majority of such events were possible to avoid.</p></sec><sec id="pbc26772-sec-3820"><label>PD-107</label><title>Follow‐Up of Benign Ovarian Tumours: Should We Change UK Practice?</title><p><underline underline-style="single">S. Arul</underline><sup>1</sup>, K. Best<sup>1</sup>, A. Choudhary<sup>1</sup>, M. Pachl<sup>1</sup>, I. Jester<sup>1</sup></p><p><italic><sup>1</sup>Birmignham Children's Hospital NHS Foundation Trust, Dept. of Surgery, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Established UK practice, following complete resection of unilateral benign ovarian tumour, was that the risk of developing a metachronous tumour in the contralateral ovary was very low and therefore, did not require follow up. However this was challenged by a 2014 paper which showed a 23% rate of metachronous tumours in the contralateral ovary.<sup>1</sup> We wished to establish exactly what our follow up arrangements were and whether there had been any cases of metachronous tumours in our group of patients which could help to shape future UK guidelines.</p><p><bold>Design/Methods</bold>: A retrospective study of girls with ovarian teratomas presenting to us between 2006 and 2016 were identified from the histology database. Clinical data on age of diagnosis, biochemical tumour markers, histology, follow‐up appointments and radiology were collected from hospital records and analysed.</p><p><bold>Results</bold>: 41 girls underwent surgery for an ovarian teratoma between 2006 and 2016 (median age 11.9 years (range 4.5 ‐ 16.1 yr)). Patients all presented with abdominal pain or asymptomatic lower abdominal swelling. Four had raised tumour markers.</p><p>Histology revealed 34 mature teratomas, 4 immature teratomas and two were unclassified. Eleven patients had evidence of torsion.</p><p>Radiological follow up with ultrasound occurred in 19 patients (median 6 months, range 1 month to 5 years). In this time there was not a single case of radiological recurrence. In addition there were no cases in the remaining 22 patients that presented with clinical signs of a ovarian tumour.</p><p><bold>Conclusions</bold>: In our series there was not a single case of a metachronous ovarian tumour to suggest a need for a change in our practice. However, a prospective study of UK patients would be required to definitively establish the rate of recurrence.</p><p><sup>1</sup>Metachronous benign ovarian tumors are not uncommon in children Taskinen a, et al, 2014, Journal Paediatric Surgery:49;43‐545</p></sec><sec id="pbc26772-sec-3830"><label>PD-108</label><title>Surgical Challenges and Lessons Learnt in Paediatric Large Cervicofacial Teratomas</title><p><underline underline-style="single">K. Khanna</underline><sup>1</sup>, V. Khanna<sup>2</sup>, N. Sugandhi<sup>3</sup>, D. Bagga<sup>3</sup>, M. Bajpai<sup>4</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Pediatric Surgery, New Delhi, India; <sup>2</sup>Lady Hardinge Medical College & Associated Kalawati Saran Children's Hospital, Paediatric Surgery, New Delhi, India; <sup>3</sup>Safdarjung Hospital, Paediatric Surgery, Delhi, India; <sup>4</sup>All India Institute of Medical Sciences, Paediatric Surgery, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: The incidence of mature congenital teratomas at all sites is 1 in 4000 live births. Of these, <2% are cervicofacial. We highlight the challenges involved in the perioperative and intraoperative management of large cervicofacial teratomas in infants.</p><p><bold>Design/Methods</bold>: Four infants operated for large cervicofacial teratomas between June 2015 till February 2017 were included.</p><p><bold>Results</bold>: Four infants, age ranging from 12 days to 88 days, presented with huge cervicofacial teratomas. The average tumor size ranged from 7×8×4cm to 22×18×12cm. Two neonates presented with epignathus teratomas with cleft palate and intranasal extension but no intra cranial extension on CT scan. The other two presented with giant cervicofacial teratomas with compression and flattening of underlying skull bone but no intracranial extension. Preoperative αFP levels were normal for age in all. Two required 15 days of nasogastric (NG) feeds preoperatively. Intubation was a challenge to the anaesthetist and was aided by fiberoptic bronchoscopy and naso‐tracheal intubation in 2 cases. Average blood loss was 53.5ml and the mean operating time was 92 ± 11minutes. All underwent complete excision and histopathology confirmed the diagnosis of mature teratoma in all.</p><p><bold>Conclusions</bold>: Large congenital cervicofacial teratomas in infants are usually benign but they may pose a surgical emergency if airway is compromised. Detailed imaging is required to delineate the extent of lesion and plan surgery. Good preoperative nutritional status guides the timing of surgery. Naso‐tracheal intubation/ flexometallic endotracheal tubes may be required. Large tumor size, distortion of the normal anatomy and increased vascularity pose a surgical risk. Harmonic scalpel aids excision. Early institution of postoperative NG feeds and physiotherapy helped in speedy recovery, return of function and normalization of appearance.</p></sec><sec id="pbc26772-sec-3840"><label>PD-109</label><title>Ablation Techniques as Adjuvant Therapy for Pediatric Malignancies</title><p><underline underline-style="single">J. Daley</underline><sup>1</sup>, R. Bhuta<sup>2</sup>, D. Tessier<sup>3</sup>, A. Chawla<sup>2</sup>, B. DeNardo<sup>2</sup></p><p><italic><sup>1</sup>Rhode Island Hospital, Department of Pediatrics, Providence, USA; <sup>2</sup>Rhode Island Hospital, Division of Pediatric Hematology‐Oncology, Providence, USA; <sup>3</sup>Rhode Island Hospital, Department of Radiology, Providence, USA</italic></p><p><bold>Background/Objectives</bold>: Image‐guided ablation techniques, including thermal and chemical ablation, are commonly used therapeutic options for the treatment of malignant lesions in adults. Ablation may be used with curative intent incorporated into a multimodal treatment regimen or as palliative treatment for painful lesions. Although well established in adult malignancies, there is little data regarding the use of such techniques in pediatric oncology patients. This study retrospectively analyzes the use of image‐guided ablation as adjuvant therapy for a pediatric oncology population at our institution.</p><p><bold>Design/Methods</bold>: A retrospective chart review identified 11 pediatric patients with 21 malignant lesions treated with 36 ablations. Clinical information and treatment details regarding each ablation procedure were collected with institutional review board approval.</p><p><bold>Results</bold>: The 11 patients treated with ablation at our institution were 2‐22 years of age. Five of the patients were diagnosed with osteosarcoma; the 6 additional patients each had a solid tumor of varying histology. The majority of patients had diffusely metastatic or relapsed disease. Of 17 ablation sessions, 13 were performed for palliative purposes, while 4 were performed with curative intent. Microwave, radiofrequency and cryoablation were used to ablate lesions ranging in size from 1‐7 cm. Common sites of ablation included the lung, liver, and soft tissues. All 36 ablations were reported with technical success with limited complications including 1 pneumothorax. All symptomatic patients achieved pain relief. Local progression occurred in 10% of previously treated lesions and 10 of 11 patients have died of disease.</p><p><bold>Conclusions</bold>: Ablation can be performed safely and effectively in children with limited toxicity. Ablation may provide effective local disease control in addition to palliation for appropriately selected pediatric patients and tumor sites. Differential considerations must be acknowledged between adults and children. Ablation represents a minimally invasive treatment approach that should be considered in the treatment course of children with metastatic solid tumors.</p></sec><sec id="pbc26772-sec-3850"><label>PD-110</label><title>Posterior Retroperitoneoscopic Adrenalectomy for Pediatric Adrenal Tumors</title><p><underline underline-style="single">Y.T. Lee</underline><sup>1</sup>, C.P.C. Ong<sup>1</sup>, P.H. Tang<sup>2</sup>, B.L.K. Lim<sup>3</sup>, H. Samsudin<sup>4</sup>, H.P.A. Loh<sup>1</sup></p><p><italic><sup>1</sup>KK Women's and Children's Hospital, Department of Paediatric Surgery, Singapore, Singapore; <sup>2</sup>KK Women's and Children's Hospital, Department of Diagnostic & Interventional Imaging, Singapore, Singapore; <sup>3</sup>KK Women's and Children's Hospital, Department of Orthopaedic Surgery, Singapore, Singapore; <sup>4</sup>KK Women's and Children's Hospital, Operating Theatre, Singapore, Singapore</italic></p><p><bold>Background/Objectives</bold>: Posterior retroperitoneoscoic adrenalectomy has been reported as an option for adrenal tumor resection, but is not commonly performed in children due to the extreme semi‐kneeling position advocated to flatten the lumbar lordosis in order to achieve adequate retroperitoneal space. As children have smaller lordosis angles, flattening of the lordosis and creation of optimal retroperitoneal space may be achieved with less hip flexion. We used pediatric lumbar lordosis measurements to develop a modified prone jackknife position, and report our experiences with this setup for posterior retroperitoneoscopic adrenalectomy for adrenal tumors.</p><p><bold>Design/Methods</bold>: Lordosis angles were measured on sagittal computed tomography (CT) and magnetic resonance imaging (MRI) studies of pediatric patients with adrenal tumors and compared to normal references. The data was used to develop our modified prone jackknife position. Selected patients with adrenal tumors underwent posterior retroperitoneoscopic adrenalectomy in this position. Patient demographics, diagnoses, operative time, complications, post‐op analgesia requirements, and length of hospitalization were analyzed.</p><p><bold>Results</bold>: CT and MRI studies were analyzed for 20 patients with adrenal tumors diagnosed in our institution from 2012‐2017; median lordosis angle was 25.85°(range: 24.32°‐37.41°). Four patients underwent retroperitoneoscopic adrenalectomy between June and December 2016. Histological diagnoses were neuroblastoma, adrenal hyperplasia, pheochromocytoma, and adrenal angiomatoid fibrous histiocytoma. Median age was 5.5 years [range: 3–11 years]. Median operating time was 150.5 minutes [range: 111–181 minutes]. No conversions to open surgery were required. One patient had intra‐operative bleeding from the adrenal vein. Only 1 patient required postoperative opioids for analgesia. Median length of hospitalization after surgery was 2 days (range: 2‐3 days).</p><p><bold>Conclusions</bold>: Pediatric patients can achieve flattening of lumbar lordosis with less extreme positioning. Posterior retroperitoneoscopic adrenalectomy in a modified prone jackknife position is a feasible operation for pediatric patients with small adrenal tumors, with advantages of short operative time, minimal requirements for opioid analgesia and short lengths of hospitalization.</p></sec><sec id="pbc26772-sec-3860"><label>PD-111</label><title>Incidence, Treatment, and Outcomes of Non‐Wilms Renal Tumors in Children: A Single Institution Experience</title><p><underline underline-style="single">S. Qureshi</underline><sup>1</sup>, S. Kembhavi<sup>2</sup>, M. Ramadwar‐<sup>3</sup>, G. Chinnaswamy<sup>4</sup>, T. Vora<sup>4</sup>, M. Prasad<sup>4</sup>, N. Khanna<sup>5</sup>, S. Laskar<sup>5</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Pediatric Surgical Oncology, Mumbai, India; <sup>2</sup>Tata Memorial Hospital, Radiology, Mumbai, India; <sup>3</sup>Tata Memorial Hospital, Pathology, Mumbai, India; <sup>4</sup>Tata Memorial Hospital, Medical Oncology, Mumbai, India; <sup>5</sup>Tata Memorial Hospital, Radiation Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Although Wilms tumour is the most common paediatric renal tumour, the non‐Wilms renal tumour encountered occasionally may pose a diagnostic and therapeutic challenge. The aim of this study is to determine the incidence and analyze the treatment and overall outcome of non‐Wilms tumours in children.</p><p><bold>Design/Methods: Materials and methods</bold>: Of the 264 patients with primary renal tumours treated between January 2004 to December 2016, 229 (87%) with Wilms and 35(13%) patients with non‐Wilms tumour were identified from the prospectively maintained database. Patients presenting with recurrent disease were excluded from treatment and outcome analysis.</p><p><bold>Results</bold>: The non‐Wilms tumour included renal cell carcinoma (n=9), clear cell sarcoma (n=7), Ewing's sarcoma (n=5), malignant rhabdoid tumour (n=3), congenital mesoblastic nephroma (n=3), synovial sarcoma (n=2), and metanephric adenoma (n=1). All patients underwent nephroureterectomy either upfront (n= 22) or after preoperative chemotherapy (n= 8). Adjuvant therapy was offered based on the histology to 16 patients. Disease relapse was seen in nine patients, of whom eight have died of disease, including all the three patients with malignant rhabdoid tumour. The median survival range from seven months to 11 years and the projected 5 years overall and event‐free survival for all patients is 65.2% and 63% respectively.</p><p><bold>Conclusions</bold>: Non‐Wilms tumour constitutes less than 15% of all renal tumours. The treatment depends on the specific histology and the survival range from a few months to several years. Accurate diagnosis is essential to select and decide the intensity of the treatment.</p></sec><sec id="pbc26772-sec-3870"><label>PD-112</label><title>Multidisciplinary Approach to Malignant Solid Tumors in Neonates and Infants Younger Than 1 Year</title><p><underline underline-style="single">T. Sharoev</underline><sup>1</sup>, N. Ivanova<sup>1</sup>, J. Nesterova<sup>1</sup>, O. Polushkina<sup>1</sup>, A. Korneeva<sup>1</sup>, K. Savlaev<sup>1</sup>, D. Nishonov<sup>1</sup>, J. Ishutina<sup>2</sup>, A. Kotlovsky<sup>3</sup>, A. Prityko<sup>4</sup></p><p><italic><sup>1</sup>St Luka's Clinical Research Centre for Children‐ Moscow‐ Russia, Oncology, Moscow, Russia; <sup>2</sup>St Luka's Clinical Research Centre for Children‐ Moscow‐ Russia, Neonatology, Moscow, Russia; <sup>3</sup>St Luka's Clinical Research Centre for Children‐ Moscow‐ Russia, Pediatric Surgery, Moscow, Russia; <sup>4</sup>St Luka's Clinical Research Centre for Children‐ Moscow‐ Russia, Administration, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Despite advances in pediatric oncology, the management of neonates and infants younger than 1 year with malignant solid tumors poses a challenge. Aiming to achieve the optimal outcome for these patients we apply the multidisciplinary approach to the comprehensive care. The objective of this review is to demonstrate the usefulness of the multidisciplinary team for this particular group of patients.</p><p><bold>Design/Methods</bold>: From 2011 to 2017, all neonates and infants aged under 1 year, with malignant solid tumors, managed under the care of the multidisciplinary team in our center were included in the review. The patient data was prospectively collected and then analyzed.</p><p><bold>Results</bold>: In total there were 108 patients aged between 3 days and 1 year (mean 6.8 months). Diagnoses were as follows: neurogenic tumor n=42 (38.3%), brain tumor n=19 (17.5%), nephroblastoma n=18 (16.6%), retinoblastoma n=8 (7.4%), soft tissue sarcoma n=7 (6.4%), hepatic tumor n=7 (6.4%), germ cells tumor n=5 (4.6%), others n=2 (1.8%). In four cases tumors were detected intranatally on the fetal ultrasound scan. In all other cases, the time for making the accurate diagnoses took from 3 to 5 days following the patient presentation. According to internationally accepted guidelines and protocols all patients underwent combined modality therapy including surgical resection of the tumor and metastases. The treatment was completed in 71 patients (65.7%). The overall survival rate was 77% at follow up ranging from 1 to 60 months. 34 patients (31.4%) continue receiving chemotherapy.</p><p><bold>Conclusions</bold>: In our experience the implementation of multidisciplinary team care for neonates and infants younger than 1 year with malignant solid tumors is a very practical approach to making a timely diagnosis and initiating promptly the appropriate treatment thus allowing achievement of the high survival rate. Further study at longer follow up is warranted to evaluate the overall effectiveness of this approach.</p></sec><sec id="pbc26772-sec-3880"><label>PD-113</label><title>Disease Patterns of Malignant Tumors in Adolescents</title><p><underline underline-style="single">S. Bhatnagar</underline><sup>1</sup></p><p><italic><sup>1</sup>B.J.Wadia Hospital for Children‐ Bombay Hospital, Pediatric Surgery, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: According to Indian demographic profile, pediatric and adolescent population represents 45.7% of the entire population. While most of pediatric malignancies are much researched, little is known about the malignant tumors in adolescents. This population poised between children and adults, has been called the “lost tribe.” An attempt is made here to study the demographics, disease patterns and overall outcomes vis‐à‐vis pediatric malignant solid tumors.</p><p><bold>Design/Methods</bold>: Patients aged 15‐19 years with the diagnosis of malignant tumors, registered with two tertiary care hospitals in Mumbai, India from January 2012 to December 2016 were included. Basic demographic information, clinical, diagnostic details, histology grouping, treatment, outcome and survival were retrospectively studied.</p><p><bold>Results</bold>: Of 36 patients, 20F, 16M, various types of tumors were encountered. In young girls (n=20), ovarian tumors (n=11), Ewing's sarcoma (n=4), ganglioneuroblastoma (n=2), Osteosarcoma (n=2), Papillary pseudotumor of the pancreas (n=1). Adolescent boys (n=16) showed, Rhabdomyosarcoma (n=6), Ewing's sarcoma/PNET (n= 4), testicular malignant Germ cell tumor (n=3), Osteosarcoma (n=2), Carcinosarcoma of abdomen (n=1). Pretherapy staging of the tumors revealed that 22/36 (61%) of the tumors were found to be stage 4, the metastatic nodules being present in the lungs (n=10), abdomen (n= 8), bone/bone marrow (n= 8). Upfront chemotherapy was given to all patients except 4/36. R0 resection of the primary could be achieved in 13/36 patients. Radiotherapy was utilized as adjuvant therapy in 19/36, including primary and metastatic sites. Metastatectomy was performed in 12/22 patients post‐chemotherapy. Overall survival was 86%, even though all of them were not tumor free.</p><p><bold>Conclusions</bold>: High incidence of advanced malignancies is seen in adolescent age in both boys and girls. The tumors which are encountered in this age group differ in type, biologic behaviour as well as response to therapy. An attempt at early detection and treatment is of vital importance to prevent the presentation at advanced age.</p></sec></sec><sec id="pbc26772-sec-3890"><title>Haematology ‐ Acute Lymphoblastic Leukaemia</title><sec id="pbc26772-sec-3900"><label>P-001</label><title>Prevalence of Tuberculosis Infection in Children with Acute Leukemia</title><p><underline underline-style="single">A. Ahad</underline><sup>1</sup>, R. Seth<sup>1</sup>, S. Kabra<sup>1</sup>, S. Vishnu<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences‐ New Delhi, Pediatrics, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Children with acute leukemia are at an increased risk of infections. There are opposing views regarding tuberculosis as an etiology in these patients. The aim of our study was to determine the prevalence of tuberculosis infection in children with acute leukemia, to determine the Mantoux conversion rate during chemotherapy and to determine the disease rate and treatment outcome of tuberculosis.</p><p><bold>Design/Methods</bold>: It was a prospective cohort study at All India Institute of Medical Sciences, New Delhi. A Mantoux test (5.0 tuberculin units) was given prior to chemotherapy to determine the prevalence of tuberculosis infection. Children were monitored for development of tuberculosis disease over one year by doing a repeat Mantoux test at 6 and 12 months of follow up while on chemotherapy or when they developed symptoms of tuberculosis. Risk factors such as BCG vaccination, family history, age, socioeconomic status and malnutrition were assessed.</p><p><bold>Results</bold>: One hundred twenty‐five children (93 acute lymphoblastic leukemia and 32 acute myeloid leukemia) aged one to fourteen years (average 6.3 years) were studied. Four percent had tuberculosis infection at diagnosis before chemotherapy. Among the Mantoux negative children, 3.3% became Mantoux positive during chemotherapy. Isoniazid was given for 6 months to all the infected children and none developed tuberculosis during follow up. Mantoux positivity was more in children older than 5 years of age; however, none of the other risk factors had a statistically significant association with tuberculosis infection.</p><p><bold>Conclusions</bold>: Mantoux positivity increases with increasing age and a low prevalence of tuberculosis infection was attributed to a younger population in the study. None of the children who received isoniazid developed disease, emphasizing its efficacy for chemoprophylaxis. The antitubercular effect of chemotherapy like 6‐mercaptopurine and antimicrobials like quinolones used in febrile neutropenia may play a role.</p></sec><sec id="pbc26772-sec-3910"><label>P-002</label><title>DNA Index and Triple Trisomy at Diagnosis, and Pattern of Relapse in Children with Acute LYMMPHOBLASTIC Leukemia (A.L.L) – Reporting Results from a Single Institution</title><p><underline underline-style="single">S. al‐sweedan</underline><sup>1</sup>, R. Jaffri<sup>1</sup>, A. Alseraihy<sup>1</sup>, A. alahmari<sup>1</sup>, I. Ghemlaz<sup>1</sup>, K. Siddiqui<sup>1</sup></p><p><italic><sup>1</sup>King Faisal Specialist Hospital & Research Center, pediatric hematology/oncology, Riyadh, Saudi Arabia</italic></p><p><bold>Background/Objectives</bold>: Relapse rate of 10‐20% in children with A.L.L., is a major hindrance in achieving excellent overall survival rates.To assess the role of Triple trisomy and DNA Index at diagnosis in timing and pattern of site of relapse.</p><p><bold>Design/Methods</bold>: Retrospective review of 455 pediatric (≤14 years at diagnosis) A.L.L patients’ medical charts, diagnosed and treated at our institute from 2005 to 2014.</p><p><bold>Results</bold>: 108 (28.7%) from 376 patients with available DNA Index data were hyperdiploid (HDALL, DNA Index>1.16) while remaining 268 (71.3%) were non‐HDALL. 12(22.6%) patients in HDALL group relapsed at a median of 2.3 years (1.1 month – 8.3 years) from first complete remission (CR‐1). 9 (75%) were isolated hematopoietic (BM), 2(16.7%) extramedullary testis, and 1 (8.3%) CNS. For the non‐HDALL group, 41(77.45) relapsed; 24 (58.5%) were isolated hematopoietic, 2(4.9%) CNS, 1 (2.4%) testis and remaining 14(34.1%) were combined Hematopoietic (BM) with CNS or testis. Relapses in HDALL group frequently involved isolated hematopoietic site unlike in non‐HDALL group (P‐Value: 0.022). Any of Trisomy (+4,+10, +17) or triple trisomy (+4,+10, +17) did not exhibit significant role in providing protection from relapse. Relapses in HDALL group were occurring early (median: 2.4 years) compared to non‐HDALL group, but the trend was not statistically significant (P‐Value: 0.572). Five‐year overall survival for HDALL group (0.952±0.024) was not statistically significantly better in non‐HDALL group (0.878±0.031, P‐Value: 0.116). Triple trisomy (+4,+10,+17) or any trisomy (+4,+10,+17) was significantly associated with HDALL (P‐Value<0.001).</p><p><bold>Conclusions</bold>: Significantly different pattern of relapse sites exist between the HDALL and Non‐HDALL groups but not the timings of relapse in our cohort of pediatric patients.</p></sec><sec id="pbc26772-sec-3920"><label>P-003</label><title>Allergic Reaction to Asparaginase in Pediatric Acute Lymphoblastic Leukemia (A.L.L.) – Does It Have Any Prognostic Value?</title><p><underline underline-style="single">S. al‐sweedan</underline><sup>1</sup>, J. RAFAT<sup>1</sup>, A. ali<sup>1</sup>, A. amal<sup>1</sup>, G. ibrahim<sup>1</sup>, A. hawazen<sup>1</sup>, K. Siddiqui<sup>1</sup></p><p><italic><sup>1</sup>King Faisal Specialist Hospital & Research Center, pediatric hematology/oncology, Riyadh, Saudi Arabia</italic></p><p><bold>Background/Objectives</bold>: We conducted this retrospective study to assess the incidence of allergic reactions to Asparaginase in pediatric A.L.L. patients and to determine if it is of any prognostic significance.</p><p><bold>Design/Methods</bold>: Medical charts of pediatric non‐infantile patients diagnosed with A.L.L. registered at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, from 2005 to 2014 were reviewed in retrospective fashion and the outcome data were analyzed in the backdrop of incidence of allergic reaction to Asparaginase.</p><p><bold>Results</bold>: Five hundred and four (504) patients were enrolled in this study. Median age at diagnosis was 4.8 years (Min‐Max: 1.0‐14.8), with 41.3%(208) girls. Clinical allergic reactions to Asparaginase identified by continual measurement of activity levels, were observed in 95(18.8%) patients. 69.5%(66) of these occurred during consolidation phase. 15.8%(15) were categorized as severe and 42.2%(40) as moderate and mild, each. It was significantly more common in High Risk group than Standard Risk (21.9% vs. 10.2%, P‐Value: 0.004), and in CNS‐II (29.6%) than in CNS‐I and CNS‐III (17.4% and 7.1%, P‐Value: 0.033). Rate of first relapse was 14.1%(71). Incidence of first relapse was higher in those who did not experience any allergic reaction (14.4%,59 vs. 12.6%,12) but, this protective effect did not achieve statistical significance (P‐Value: 0.745). Among High Risk patients (374), mortality rate was significantly lower in patients with recorded allergic reaction to Asparaginase (4.9%,4 of 82) than others (15.1%,44 of 292) with P‐value of 0.014. However, no significance difference was observed in probability of five year Event Free Survival (EFS) between the former and the later (0.854±0.039 vs. 0.797±0.021, P‐Value: 0.085) for the whole cohort.</p><p><bold>Conclusions</bold>: Early switch to erwinia type after reaction to asperginase improve survival and decrease relapse in patients with ALL</p></sec><sec id="pbc26772-sec-3930"><label>P-004</label><title>MicroRNA Expression Profiles in Brazilian Childhood T‐Cell Acute Lymphoblastic Leukemia (T‐ALL)</title><p><underline underline-style="single">R.S.</underline><underline underline-style="single">Almeida</underline><sup>1</sup>, F.S. Araújo<sup>2</sup>, L.L. Coutinho<sup>3</sup>, E.A. Donadi<sup>4</sup>, N. Lucena‐Silva<sup>5</sup></p><p><italic><sup>1</sup>Centro de Pesquisas Aggeu Magalhães/FIOCRUZ‐PE, Departamento de Imunologia, Recife, Brazil; <sup>2</sup>Universidade Federal de Pernambuco and Centro de Pesquisas Aggeu Magalhães/FIOCRUZ‐PE, Departamento de Imunologia, Recife, Brazil; <sup>3</sup>ESALQ/Universidade de São Paulo, Departamento de Biotecnologia Animal, Piracicaba, Brazil; <sup>4</sup>Faculdade de Medicina de Ribeirão Preto/Universidade de São Paulo, Divisão de Imunologia Clínica, Ribeirão Preto, Brazil; <sup>5</sup>Oncologia Pediátrica/Instituto de Medicina Integral Professor Fernando Figueira and Centro de Pesquisas Aggeu Magalhães/FIOCRUZ‐PE, Departamento de Imunologia, Recife, Brazil</italic></p><p><bold>Background/Objectives</bold>: T‐cell acute lymphoblastic leukemia (T‐ALL) is a hematologic malignancy that accounts for 15% of childhood ALL, and can affect distinct maturation stages of T cell. MicroRNAs (miRNAs) are small non‐coding RNAs with an essential role in gene expression regulation and normal hematopoiesis. In this study, we aimed to investigate differential miRNA expression between bone marrow (BM) mononuclear cells from patients with childhood T‐ALL and blood CD8+ T cell from healthy adult and neonatal individuals (control group – CG).</p><p><bold>Design/Methods</bold>: Patients with T‐ALL (7 males, 1 female; median age= 11,5 years) were referred to Instituto de Medicina Integral Professor Fernando Figueira in Recife, Northeast Brazil, where BM was collected. CG data (adult, n=3; neonatal, n=3) were retrieved from Gene Expression Omnibus (GEO) database (GSM1627014, GSM1627015, GSM1627016, GSM1627017, GSM1627018 and GSM1627019). Total RNA was extracted with TRizol and used for library construction (Illumina Small RNA Kit). MiRNAs were sequenced in HiSeq plataform (Illumina) and data analyzed by bioinformatics (FastQC – quality control, Cutadapt – removing adapters, miRDeep2 – miRNA identification, and edgeR – differential expression (DE)) using miRBase v21 data and hg38 human reference genome. A False Discovery Rate (FDR) ≤ 0.05 was considered in DE analysis, and miRNA target prediction was performed by miRWalk 2.0. DAVID v6.8 tools were applied to functional annotation (FA) of miRNA targets.</p><p><bold>Results</bold>: Forty‐nine miRNAs DE were identified between the two groups, with 33 up‐ and 16 down‐regulated in T‐ALL. Fourteen thousand, three hundred and eighty‐one gene targets were predicted, and FA revealed 120 enriched Kegg Pathways (corrected <italic>P</italic> ≤ 0.05), including Metabolic pathways, Pathways in cancer, PI3K‐Akt signaling pathway, Endocytosis, MAPK signaling pathway and others related to immune system, cancer and cell function.</p><p><bold>Conclusions</bold>: MiRNAs play a role in biological pathways related to cancer development and immune system regulation. Acknowledgements: Supported by FIOCRUZ‐PE, CAPES‐PROCAD2013, FACEPE‐APQ‐0040‐4.00/13, and FACEPE‐APQ‐1044‐4.01/15.</p></sec><sec id="pbc26772-sec-3940"><label>P-005</label><title>Demographics and Disease Response Evaluation in Pediatric High Risk Acute Lymphoblastic Leukemia (ALL) Patients at a Tertiary Care Centre</title><p><underline underline-style="single">S. Anwar</underline><sup>1</sup>, M. Faizan<sup>2</sup></p><p><italic><sup>1</sup>The Children's Hospital &ICH, Paediatric Hematology/Oncology, Lahore, Pakistan; <sup>2</sup>The Children's Hospital &ICH, Paediatric Haematology Oncology, Lahore, Pakistan</italic></p><p><bold>Background / Objectives: Background</bold>: Acute Lymphoblastic leukemia (ALL) is commonest malignancy among children.Different Protocols are being used in different part of world to treat ALL.</p><p><bold>Objective</bold>: The main objective of the study is to discuss presentation and outcome of children with acute lymphoblastic leukemia (ALL).</p><p><bold>Design / Methods: STUDY DESIGN</bold>: We present a retrospective study, looking at demographics and outcome of children with ALL presented to the hematology and oncology department of the children's hospital Lahore between January 2009 and December 2009.</p><p><bold>MATERIALS AND METHODS</bold>: Children with Bone Marrow biopsy proven ALL were included and data regarding age, gender, risk categorization and outcome were recorded and analyzed. Children were stratified as high risk who were <2 and >9 years of age, BFM‐risk factor 1.2 or above, CNS disease and mediastinal mass on presentation. Lahore Group Protocol for acute lymphoblastic Leukemia LALL01(BFM and UKALLXI based ) was used for treatment.</p><p><bold>Results</bold>: A total of 198 patients were included. Seventy percent were males. Majority 141(66.6%) were between 2‐8.9 years of age while 44(22.2%) patients were of 9 years and above. One hundred and sixteen (60%) had high risk disease and only 55(27%) with standard risk. Initial WBC was >100,000/mm3 in 35 (17.6%), 50,000‐100,000/mm3 in 14 (7%) and 47 (23.7%) had 10,000‐50,000/mm3. BFM risk factor was 1.2 and above in 66 (33.3%), 14(7%) patients had CNS disease and 5% mediastinal mass on presentation. Seventy eight (40%) patients had completed treatment, 44(22.2%) left against medical advice and 38(19.1%) died. Twenty nine (14.6%) had relapse and among them 76% relapsed while on treatment.</p><p><bold>Conclusions</bold>: High risk disease is the most common presentation of ALL in children at our centre with initial High WBC count, massive organomegaly and male predominance. Abandonment is another major factor affecting the overall survival rate. However overall survival is almost 50% in our treated patients.</p></sec><sec id="pbc26772-sec-3950"><label>P-006</label><title>Severe Vincristine Toxicity in Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">R. Bhuta</underline><sup>1</sup>, B. DeNardo<sup>1</sup>, P. Cole<sup>2</sup>, K. Matook<sup>1</sup>, J. Welch<sup>1</sup></p><p><italic><sup>1</sup>Rhode Island Hospital, Pediatric Hematology/Oncology, Providence, USA; <sup>2</sup>Montefiore Medical Center, Pediatric Hematolgoy/Oncology, New York City, USA</italic></p><p><bold>Background/Objectives</bold>: An integral part of standard treatment for patients with acute lymphoblastic leukemia (ALL) includes the use of vincristine. While significant side effects from vincristine are rare, severe neurotoxicity can occur and result in omission of this chemotherapeutic agent from treatment. This study specifically looked at patients with ALL who had vincristine removed from their therapy plan to assess severity of side effects and disease response.</p><p><bold>Design/Methods</bold>: A retrospective chart review identified 4 patients from 2 institutions with ALL and severe polyneuropathy requiring discontinuation of vincristine. Demographic information and details about individual treatment course in relation to vincristine administration were collected with institutional review board approval.</p><p><bold>Results</bold>: The four children were 3 to 12 years old and were diagnosed with B‐cell ALL. They received treatment on or as per Dana Farber Cancer Institute Protocols 05‐001 or 11‐001. The first patient developed severe visual loss secondary to optic nerve atrophy, vocal cord dysfunction, and inability to ambulate due to severe peripheral neuropathy prompting discontinuation of vincristine after 5 doses. The second patient developed severe constipation and inability to ambulate secondary to peripheral neuropathy, with discontinuation of vincristine after 6 doses; genetic testing revealed Charcot Marie Tooth type 2D. The 3rd and 4th patients developed inability to ambulate due to significant motor neuropathy, and vincristine was discontinued after 11 doses and 21 doses, respectively. All four children had improvement in their symptoms after discontinuation of vincristine and are currently 2‐36 months off therapy and remain in remission.</p><p><bold>Conclusions</bold>: Severe vincristine toxicity can result in vision loss (optic nerve atrophy), vocal cord dysfunction, constipation, and inability to ambulate (peripheral and motor neuropathy) requiring removal of this agent from standard treatment plans. Discontinuation of vincristine within the first year of treatment in our subset of patients resulted in improvement of symptoms and continued ALL remission.</p></sec><sec id="pbc26772-sec-3960"><label>P-007</label><title>Expression of CD10 on Residual Cells in Children with B‐Cell Precursor Acute Leukemia</title><p><underline underline-style="single">K. Bukowska‐Strakova</underline><sup>1</sup>, K. Pawińska‐Wąsikowska<sup>2</sup>, M. Marta<sup>3</sup>, K. Anna<sup>1</sup>, B. Walentyna<sup>2</sup>, S. Maciej<sup>1</sup></p><p><italic><sup>1</sup>Jagiellonian University Medical College ‐ Polish‐American Institute of Pediatric, Department of Clinical Immunology, Krakow, Poland; <sup>2</sup>Jagiellonian University Medical College ‐ Polish‐American Institute of Pediatric, Department of Oncology and Hematology‐, Krakow, Poland; <sup>3</sup>University Children's Hospital of Cracow, Clinical Immunology, Krakow, Poland</italic></p><p><bold>Background/Objectives</bold>: The most common childhood malignancy is acute lymphoblastic leukemia (ALL), particularly B‐cell precursor ALL (BCP‐ALL). Leukemic cells remaining in the bone marrow are the major cause of relapse, therefore state of minimal residual disease monitoring (MRD) during the induction therapy is consider a strong predicting factor of treatment outcome. Multicolor flow cytometry (MFC) is commonly used technique for monitoring MRD.</p><p><bold>Design/Methods</bold>: MRD was assessed by MFC in patients with BCP‐ALL diagnosed between 2007‐2016 (200 patients). Children were treated according to ALL IC‐BFM‐2002 (between 2007‐2012) or according to ALL IC‐BFM‐2009 (between 2013‐2016) in Oncology and Hematology Department, Children's University Hospital in Krakow. The level of residual leukemic cells and the quality of antigen expression (mean fluorescence intensity ‐ MFI) was assessed on leukemic cell on diagnosis day, 15th and 33th day of induction chemotherapy. To achieve expected sensitivity of the method (10<sup>‐4</sup>), at least 300.000 of nucleated cells were collected. The sample quality was assessed based on percentage of erythroblasts (<2% poor quality, >2% good quality).</p><p><bold>Results</bold>: The correlation between surface antigen expression and response to prednisone therapy was found. The CD10 MFI was down‐regulated in patients with good prednisone, yet in patients with poor prednisone, CD10 MFI on leukemic blasts was not altered, suggesting insensitivity to chemotherapy.</p><p>The most frequent antigenic shifts were seen in CD10, CD34 and CD20 expression, whereas CD19, CD45, CD38, CD58 and CD66c were more stable. The percentage of leukemic cells in BCP‐ALL at 15<sup>th</sup> and 33th day of therapy were negatively correlated with early clinical outcome.</p><p><bold>Conclusions</bold>: Our study shows that not only the quantitative MRD results are important, but also qualitative changes of immunophenotype of residual leukemic cells might give additional clinical information, especially, in poor quality samples, with admixture of peripheral blood.</p></sec><sec id="pbc26772-sec-3970"><label>P-008</label><title>Transfusion‐Related Iron Overload (TRIO) in Children with Leukemia/Lymphoma</title><p><underline underline-style="single">C. Cacciotti</underline><sup>1</sup>, U. Athale<sup>1</sup>, S. Millson<sup>1</sup></p><p><italic><sup>1</sup>McMaster Children's Hospital, Department of Pediatrics, Hamilton, Canada</italic></p><p><bold>Background/Objectives</bold>: Children with cancer commonly receive red blood cell (RBC) transfusions. Transfusion‐related iron overload (TRIO) is a common complication and a significant iron burden is documented after only 10 RBC transfusions. Despite heavy transfusions, few studies have evaluated TRIO in children with cancer and no guidelines for screening exist.</p><p><bold>Design/Methods</bold>: A retrospective chart review, observational study was performed to evaluate the screening practices for TRIO in children (<18 years) with leukemia/lymphoma. In addition to demographic data, ferritin values, and number of RBC transfusions were extracted.</p><p><bold>Results</bold>: The study cohort included 155 eligible patients, 91 (59%) had standard risk (SR) ALL, 52 (33%) high risk (HR) ALL, and 12 (8%) AML. The mean age at diagnosis was 6 years (range 5 months‐ 18 years). Overall 34% of patients received > 10RBC transfusions; SR‐ALL median 6 (range 0‐92), HR‐ALL median 12 (range 4‐63) and AML median 23 (range 8‐56) transfusions. Patients with HR‐ALL and AML were more likely to receive >10 transfusions (58% and 92% respectively) in comparison to those with SR‐ALL (14%). Ferritin levels were measured in 105 patients (68%); and were elevated (>1,000mcg/L) in 22 (14%). Evaluation of iron overload with Ferriscan was performed in 4 patients (2%).</p><p><bold>Conclusions</bold>: The iron burden was not routinely evaluated, despite high number RBC transfusions. Screening for TRIO should be incorporated into routine practice in children with leukemia/lymphoma.</p></sec><sec id="pbc26772-sec-3980"><label>P-009</label><title>Enhancer Role of rMnSOD in Apoptosis Triggering by Daunorubicin of Pediatric B‐All Cells</title><p><underline underline-style="single">F. Casale</underline><sup>1</sup>, V. D'Angelo<sup>1</sup>, A. Pica<sup>2</sup>, A. Iannotta<sup>1</sup>, M. Ramaglia<sup>1</sup>, L. Di Massa<sup>1</sup>, M.L. Pollio<sup>2</sup>, R. Manca<sup>2</sup>, M. Di Martino<sup>1</sup>, M. Oreste<sup>1</sup>, A. Mancini<sup>3</sup>, A. Borrelli<sup>3</sup>, P. Indolfi<sup>1</sup></p><p><italic><sup>1</sup>Università della Campania “L.Vanvitelli” SUN, Department of Women‐Children and General and Specialistic Surgery, Naples, Italy; <sup>2</sup>Federico II University Naples, Department of Biology, Naples, Italy; <sup>3</sup>National Cancer Institute “Fondazione Pascale”, Exp. Oncology, Naples, Italy</italic></p><p><bold>Background/Objectives</bold>: Leukemic cells produce higher amounts of ROS than healthy cells and express low levels of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). Recently, it was demonstrated that rMnSOD, a recombinant new isoform of MnSOD, recently isolated from human liposarcoma cell line, is able to trigger apoptosis of human T‐ALL cells (99%) without toxic effects on healthy cells. The present study was aimed to verify if rMnSOD is able to induce apoptosis and to stop in G0/G1 stage of the cell cycle in pediatric patients with B‐cell acute lymphoblastic leukaemia (ALL) and if it displays synergic action with daunorubicin.</p><p><bold>Design/Methods</bold>: Cells were collected from three patients diagnosed for B‐cell ALL at the Pediatric Oncology of University “Luigi Vanvitelli”. Cell viability, apoptosis and cell cycle of lymphoblasts and SUP‐B15 cell line (ATCC) were analyzed through “ Muse Kit” after rMnSOD treatment. ROS analysis was detected with NAC. Apoptotic fragmentations of SUP‐B15 were demonstrated by confocal imaging.</p><p><bold>Results</bold>: We observed that low concentrations of rMnSOD are able to trigger apoptosis of SUP‐B15 cell line and B‐ALL cells from pediatric patients. In detail, we observed an apoptosis rate from 30% to 46% in B‐ALL pediatric patient cells and of 45% in SUP‐B15 cell line. Instead, cell cycle analysis showed a cell fraction decrease in G0/G1 phase. Moreover, the synergic activity of rMnSOD and Daunorubicin induces apoptosis in 92% of cells, by comparing the treatment with the single substances, rMnSOD (64,7%) and Daunorubicin (23,9%). Confocal microscopy analysis revealed internalization of rMnSOD in SUP‐B15 cells and evident apoptotic alterations, such as nuclear fragmentations and apoptotic‐bodies.</p><p><bold>Conclusions</bold>: In conclusion, rMnSOD exerts toxic activity only against cancer cells, by enhancing drug effect, thus allowing to utilize lower concentration of standard chemotherapy to increase the apoptosis level.</p></sec><sec id="pbc26772-sec-3990"><label>P-010</label><title>MIR‐125 as Biomarkers in Chemo Resistant Leukemic Cells</title><p><underline underline-style="single">F. Casale</underline><sup>1</sup>, M. Ramaglia<sup>1</sup>, A. Iannotta<sup>1</sup>, A. Lombardi<sup>2</sup>, C. Ferri<sup>2</sup>, H. Kawasaki<sup>2</sup>, M. Caraglia<sup>2</sup>, P. Indolfi<sup>1</sup>, S. Perrotta<sup>1</sup>, F. Rossi<sup>1</sup>, D. Di Pinto<sup>1</sup>, E. Pota<sup>1</sup>, V. D'Angelo<sup>1</sup></p><p><italic><sup>1</sup>Università della Campania “L.Vanvitelli” SUN, Department of Women‐ Children and General and Specialized Surgery, Naples, Italy; <sup>2</sup>Università della Campania “L.Vanvitelli” SUN, Department of Biochemistry‐ Biophysics‐and General Pathology, Naples, Italy</italic></p><p><bold>Background/Objectives</bold>: The microRNAs (MiRNA) are involved in the differentiation process of various hematopoietic lineages. Their dysregulation has now clearly been linked to cancer and particularly to leukemia and to drug resistant process MiRNA miR‐125b is the ortholog of lin‐4 in Caenorhaditis elegans. As lin‐4 is implicated in several developmental processes and miR‐125b negatively regulates many proteins in the p53 pathway, the deregulation of miR‐125b expression would impair human and mouse hematopoiesis. Recently, miR‐125b and its homolog miR‐125a are analyzed and resulted highly expressed in hematopoietic stem cells. In these studies, miR‐125b was found to regulate stem‐cell pool size and to confer a competitive advantage to engrafting hematopoietic cells. MiRNA 125b can function dually as both an oncogene and tumor‐suppressor gene depending on the cancer type and cellular context. Aim of our study was to analyze the expression and correlation with biologic profile of these MiRna in patients with ALL B‐cell or T‐cell.</p><p><bold>Design/Methods</bold>: We examined expression levels of miR‐125b in 57 children (37 of ALL B‐cell and 20 of ALL T‐cell) diagnosed and treated to the Pediatric Oncology of the University “Luigi Vanvitelli”, and in two cell lines, SUP‐B15 and Jurkat. Mononuclear cells were isolated from bone marrow samples whereas the biologic fluids (serum and spit) were collected from ALL children. We tested the expression levels of miR‐125b by quantitative RT‐PCR at diagnosis and after complete remission (to 33° and 78° day).</p><p><bold>Results</bold>: Preliminary data showed that miR‐125b expression in ALL B‐cell samples were upregulated (27/37, 73%), whereas the expression in T‐cell samples were downregulated (18/20 samples, 90%). Interestingly, the 29% (8/27) of overexpressed B‐ALL samples resulted high risk.</p><p><bold>Conclusions</bold>: These data support the hypothesis that aberrant expression of miR‐125b might contribute to leukemogenesis and the overexpression is important in the biologic profile of high risk leukemic patients.</p></sec><sec id="pbc26772-sec-4000"><label>P-011</label><title>Adverse Events in Children with Acute Lymphoblastic Leukaemia Treated from 1994‐2011. Single‐Centre Retrospective Study in Poland</title><p>A. Szłapińska<sup>1</sup>, K. Adamczewska<sup>2</sup>, K. Molenda<sup>2</sup>, P. Marciniak‐Stępak<sup>1</sup>, J. Wachowiak<sup>1</sup>, <underline underline-style="single">K. Derwich</underline><sup>1</sup></p><p><italic><sup>1</sup>Poznan University of Medical Sciences, Pediatric Oncology‐ Hematology and Transplantology, Poznan, Poland; <sup>2</sup>Poznan University of Medical Sciences, Pediatric Oncology‐ Hematology and Transplantology‐ Students Paediatric Society, Poznan, Poland</italic></p><p><bold>Background/Objectives</bold>: The aim of this study was a retrospective analysis of adverse events in children with acute lymphoblastic leukaemia (ALL) treated between 1994‐2011 at Department of Pediatric Oncology, Haematology and Transplantology in Poznan, Poland.</p><p><bold>Design/Methods</bold>: Between 1994‐2001, 103 children with ALL (48 [46.6%] girls, 55 [53.4%] boys) aged 1‐17 (med 5 yrs) were stratified into SRG:69 [67%], HRG:34 [33%] and treated with the ALL BFM‐90 and the New York (NY) protocols, respectively.</p><p>According to ALL IC BFM 2002 criteria 196 pts (90 [46%] girls, 106 [54%] boys) aged 1‐18 (med 5.04 yrs) were classified to SRG‐53 (27%), IRG‐74 (37%), HRG‐69 (35%).</p><p><bold>Results</bold>: Among children treated with ALL BFM‐90 and NY protocol, CR1 was achieved in SR: 94.2% and HR: 87.9% pts. Treatment failures were due to: therapy complications 2/102(2%) in HR only. Relapses occurred in 13/102 (12.7%) pts: 6/69 (8.7%) in SR (BM‐5/6[83.3%], BM‐CNS‐1/6[16.7%]); and 7/33 (21.2%) in HR (BM‐5/7 [71.4%]; BM‐testicular‐1/7 [14.3%]; CNS‐1/7 [14.3%]).</p><p>Among children treated with ALL IC BFM 2002 CR1 was achieved by 190 (97%) pts. Among adverse events 29 (14.8%) relapses were observed (1.1‐79 months from diagnosis; med 29.5 months): 14 (48.3%) in BM (SR:4, IR:4, HR:5), 4(13.7%) in CNS (SR:1, IR:1 HR:2), 1(3.4%): testis (HR), 1(3.4%): mediastinum (HR) and 9(31%) mixed relapses: 6 BM‐CNS (SR:1, IR:3, HR:2), 1 CNS‐testicular (IR), 1 BM‐testicular (IR) and 1 BM‐CNS‐abdominal (SR). There were 27 (13.8%) deaths due to: early because of sepsis (1; 0,5%); treatment complications (14; 7,1%; 9 in CR1 [IR:2, HR:7]), relapse/progression (16; 8.2%; [SR:3, IR:5, HR:8]), car accident (1; 0.5%).</p><p><bold>Conclusions</bold>: BM relapses were most frequent in children regardless of the protocol.</p><p>Patients treated with ALL IC BFM 2002 suffered from isolated CNS and mixed relapses more often, than those with ALL BFM‐90.</p><p>There were no deaths due to treatment complications in SR group.</p></sec><sec id="pbc26772-sec-4010"><label>P-012</label><title>Results of Treatment with Nelarabine in Relapsed T‐Cell Acute Lymphoblastic Leukemia (T‐ALL) in Children ‐ Report of Polish Paediatric Leukemia/Lymphoma Study Group (PPLLSG)</title><p>P. Marciniak‐Stepak<sup>1</sup>, <underline underline-style="single">K. Derwich</underline><sup>1</sup>, J. Owoc‐Lempach<sup>2</sup>, M. Mielcarek‐Siedziuk<sup>2</sup>, W. Balwierz<sup>3</sup>, M. Krawczuk‐Rybak<sup>4</sup>, T. Szczepanski<sup>5</sup>, J. Wachowiak<sup>1</sup>, E. Gorczynska<sup>2</sup></p><p><italic><sup>1</sup>Poznan University of Medical Sciences, Pediatric Oncology‐ Hematology and Transplantology, Poznan, Poland; <sup>2</sup>Wroclaw Medical University, Department of Paediatric Transplantology‐ Oncology and Haematology, Wroclaw, Poland; <sup>3</sup>Jagiellonian University‐ Medical College, Department of Paediatric Oncology and Haematology, Cracow, Poland; <sup>4</sup>Medical University of Bialystok, Department of Paediatric Oncology and Haematology, Bialystok, Poland; <sup>5</sup>Medical University of Silesia, Department of Paediatrics‐ Haematology and Oncology, Katowice, Poland</italic></p><p><bold>Background/Objectives</bold>: Although good prognosis in children with ALL, there is still 20% risk of relapse. Current protocols for relapse treatment are not highly effective in breaking resistance of T‐ALL, therefore there is a need for an alternative therapies. Nelarabine (Ara‐G) may cause significant benefit in patients with T‐ALL leading to long‐term second remission (CR2).</p><p>The aim was a retrospective analysis of results achieved in relapsed T‐ALL patients treated with Ara‐G prepared by PPLLSG.</p><p><bold>Design/Methods</bold>: Between 2009‐2015 in 5 Polish centers of pediatric oncology in 8 patients (8 boys) with T‐ALL, diagnosed at age 1.7‐13.4 years (median 3.8 years), relapse was treated according to ALL‐REZ 2002 (1 patient) or IntReAll2010‐HR (7 patients). Due to resistance and no CR2, protocol with Ara‐G was introduced.</p><p><bold>Results</bold>: Relapse was seen 6.7‐45.6 months (median 15.85 mths) after diagnosis (during first line [6 pts] or after completing treatment [2 pts; 2.7 and 36.9 mths]). There were 4 isolated bone marrow (BM) and 4 mixed relapses (1 BM‐lymph nodes, 1 BM‐mediastinum, 1 BM‐central nervous system, 1 BM‐testis). Due to failure of previous treatment (5 pts: no CR2 after second line treatment; 2 pts: relapse after alloHSCT; 1 pt: multiple relapses) Ara‐G was introduced as a single drug (1 pt) or NECTAR (Ara‐G/VP‐Cy)(7 pts). In 4 pts: 1, 2 pts: 2 and 2 pts: 3 cycles with Ara‐G were given. No significant adverse effects and toxicities were observed. Among 8 pts CR2 was achieved in 6 pts (75%); in 5 pts alloHSCT was performed, 1 had another relapse. In 2 pts (25%) there was a progression of ALL. Currently 3/8 pts (37.5%) in CR2 are alive, while 5/8 pts died (62.5%) due to: progression (2), infection (2), toxicity after alloHSCT (1).</p><p><bold>Conclusions</bold>: Ara‐G is an effective alternative drug in patients with relapsed T‐ALL not combined with significant toxicities.</p></sec><sec id="pbc26772-sec-4020"><label>P-013</label><title>A Cost‐Effective, High Sensitivity 10‐Color Single Tube Flow‐Cytometry (FC) Based B‐Cell Precursor Acute Lymphoblastic Leukemia (BCPALL) Minimal Residual Disease (MRD) Assay</title><p><underline underline-style="single">D. Dhaliwal</underline><sup>1</sup>, G. Chatterjee<sup>1</sup>, P. Subramanian<sup>1</sup>, S. Kedia<sup>1</sup>, P. Rodrigues<sup>1</sup>, M. Sanyal<sup>1</sup>, S. Ghogale<sup>1</sup>, N. Deshpande<sup>1</sup>, Y. Badrinath<sup>1</sup>, A. Kumar<sup>1</sup>, G. Narula<sup>2</sup>, B. Aurora<sup>2</sup>, S. Gujral<sup>1</sup>, S. Banavali<sup>2</sup>, P. Tembhare<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Hematopathology, Mumbai, India; <sup>2</sup>Tata Memorial Hospital, Pediatric Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Minimal residual disease (MRD) is widely used for monitoring treatment‐effectiveness, risk‐stratification and even for treatment modification. Hence, methodology for MRD assessment needs to be accurate, fast, sensitive and affordable. Previous studies have shown that flow‐cytometry based MRD (FC‐MRD) cannot reach beyond “1 in 10<sup>4</sup>” sensitivity. We are presenting a study of high sensitivity, cost effective 10‐color BCPALL‐FC‐MRD assay.</p><p><bold>Design/Methods</bold>: We studied 234 cases of pediatric (<15 years) BCPALL registered under ICICLE‐treatment protocol (modified BFM‐protocol). MRD was monitored in 284 bone‐marrow (BM) samples at post‐induction(PI), post‐consolidation (PC) and subsequent follow‐up time‐points (SFU) using 10‐color single tube FC‐MRD assay. MRD was defined as cluster 20 events with minimum two immunophenotypic abnormalities.</p><p><bold>Results</bold>: We studied 234 pediatric (<15 year) BCPALL cases for high sensitivity FC‐MRD monitoring. High number of events were acquired for MRD‐assay (median‐events, 4561000; range, 1507860‐5106540). Of 284 MRD samples, PI‐MRD were 234 (82.3%), PC‐MRD were 40 (14%) and SFU were 10 (6.1%). Of 284 samples, MRD was positive in 121(42.6%) (median MRD level, 0.028%; range, 0.0002% to 48.3%). We categorized positive MRD results into samples with MRD <0.001%, 0.001‐ <0.01%, 0.01‐ <0.1%, 0.1‐<1.0%, 1.0‐ <10% and >10% and they were 13%, 24%, 27.7%, 24%, 9.3% and 1.9% respectively. Furthermore, in 29 samples with MRD‐levels ≤0.01% and >1.5 million acquired‐events, the results were compared between time‐gated initial 500000‐events, and 1000000 events versus all events acquired. Of them, eighteen samples turned MRD‐negative in initial 500000‐events and eleven in initial 1000000‐events (since MRD‐events were <20) highlighting the importance of acquisition of >1.5 million cells to increase the sensitivity of FC‐MRD assay.</p><p><bold>Conclusions</bold>: We established a cost‐effective 10‐color single tube FC‐MRD assay with high sensitivity of 1 in 10<sup>5</sup> and applicability in >97% MRD samples. Our study showed that acquisition of events ≤1 million cells can reduce the sensitivity of FC‐MRD assay significantly.</p></sec><sec id="pbc26772-sec-4030"><label>P-014</label><title>Treating Adolescents with Acute Lymphoblastic Leukemia in a Resource‐Poor Setting: A Challenging Proposition</title><p><underline underline-style="single">N. Dhingra</underline><sup>1</sup>, N. Gupta<sup>1</sup>, P. Mishra<sup>1</sup>, T. Seth<sup>1</sup>, S. Tyagi<sup>1</sup>, H.P. Pati<sup>1</sup>, R. Saxena<sup>1</sup>, M. Mahapatra<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Hematology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Adolescents with acute lymphoblastic leukemia (ALL) are distinct from their pediatric counterparts in terms of disease biology and outcomes. The high success rates of pediatric ALL have thus far eluded this cohort of patients. We describe our experience of managing adolescent patients with ALL in a developing nation.</p><p><bold>Design/Methods</bold>: Medical records of adolescents (age 11 ‐ 18 years) with ALL treated as per a uniform augmented BFM protocol between 2011 and 2016 were retrospectively reviewed.</p><p><bold>Results</bold>: Seventy‐four patients met the inclusion criteria of which 64 were evaluable. The median age was 15 years, male‐female ratio was 9.6:1. Forty‐four patients (68.75%) had B‐ALL and 20 (31.25%) had T ALL. The median presenting WBC count was 41630/mm<sup>3</sup> (range 600‐800000/mm3). 20 patients (31.25%) had a presenting WBC count of >1, 00,000/mm3. Adverse cytogenetics were seen in 5 patients while 3 had favourable cytogenetics, the remainder being normal. Of 61 patients whose baseline CNS status was available, 55 were CNS 1, 3 were CNS 2, 2 were CNS 3 and 4 had a traumatic tap without blasts. Early treatment response, assessed by day 7 bone marrow, was performed in 55 patients of which 30 (54.5%) were M1, 7 (12.7%) were M2 and 18 (32.7 %) were M3. Nine patients died during induction and 2 had refractory disease. Therapy omissions due to infectious or drug‐related complications were observed in 34.38%. Remission rates were 82.8% at end of induction. Relapses were documented in 17 (26.56%) patients (8 CNS, 8 medullary, 1 combined). Kaplan‐meier estimates for 2 year event‐free survival were 44.74 % (CI 29.6 to 60.05 %).</p><p><bold>Conclusions</bold>: Adolescents in this study had poor outcomes. An Increased prevalence of high‐risk features such as male preponderance, T‐cell phenotype, elevated presenting WBC count and poor therapy responses on day 7 were identified.</p></sec><sec id="pbc26772-sec-4040"><label>P-015</label><title>Target for Minimal Residual Disease Detection in Pediatric Patients with PHI‐ALL: IG/TCR Rearrangements or BCR‐ABL1 Transcript?</title><p><underline underline-style="single">J.A.</underline><underline underline-style="single">Digiorge</underline><sup>1</sup>, P. Rubio<sup>1</sup>, E. Sajaroff<sup>2</sup>, A. Medina<sup>1</sup>, E. Baialardo<sup>3</sup>, J. Rossi<sup>2</sup>, M. Guitter<sup>1</sup>, M.S. Felice<sup>1</sup>, C.N. Alonso<sup>1</sup></p><p><italic><sup>1</sup>Hospital de Pediatría Prof. Dr. J.P. Garrahan, Hematology and Oncology, Ciudad Autónoma de Buenos Aires, Argentina; <sup>2</sup>Hospital de Pediatría Prof. Dr. J.P. Garrahan, Immunology and Rheumatology, Ciudad Autónoma de Buenos Aires, Argentina; <sup>3</sup>Hospital de Pediatría Prof. Dr. J.P. Garrahan, Cytogenetics, Ciudad Autónoma de Buenos Aires, Argentina</italic></p><p><bold>Background/Objectives</bold>: Minimal residual disease (MRD) is useful for risk‐group stratification in pediatric ALL‐protocols. Detection of patient‐specific Immunoglobulin/T‐cell‐receptor (Ig/TCR) rearrangements by quantitative‐PCR (q‐PCR) is a reliable tool for MRD detection. In Phi‐ALL cases, q‐RT‐PCR quantification of<italic>BCR‐ABL1</italic> transcript can be used as additional target.</p><p>Aims: 1‐To compare MRD results detected by both methodologies. 2‐To evaluate the predictive value of both targets as prognostic factors.</p><p><bold>Design/Methods</bold>: A total of 212 follow‐up samples from 16 Phi‐ALL patients were analyzed. MRD for Ig/TCR was performed following standardized EuroMRD recommendations. <italic>BCR‐ABL1</italic> minor/major transcripts quantification was performed as described in EAC program.</p><p><bold>Results</bold>: <italic>BCR‐ABL1</italic> was quantified in 201 and Ig/TCR in 164 samples. One‐hundred‐fifty‐six samples were available for analysis by both techniques, correlation coefficient: 0.5725(p<0.00001). Concordant results by both methods were observed in 15(9.6%) positive and 51(32.7%) negative samples. However, 90(57.7%) samples showed MRD positivity only by <italic>BCR‐ABL1</italic>, with a median of 0.036; [r:0.001‐77.9]%. Of them, 40(44.4%) were ≥0.1%. No cases were positive only by Ig/TCR. From the 15 samples positive by both methods, 2 samples showed >1 log‐difference between <italic>BCR‐ABL1</italic> and Ig/TCR values, median log‐difference: 0.21 [r:‐0.59‐1.49]. Outcome: Fourteen patients achieved complete remission (CR). Two patients died in CR, 3 relapsed and 11 remain in CR (median follow‐up:32 months). MRD≥0.1% was observed in 2/3 relapsed patients by both targets. In the group of 11 CCR patients, MRD≥0.1% was found in 4 patients by Ig/TCR (4 day‐33; 0 week‐12) and 9 by <italic>BCR‐ABL1</italic> (any time point). MRD‐Ig/TCR<0.1% at week‐12 correlated with better outcome (p<0.00001).</p><p><bold>Conclusions</bold>: No correlation was observed between both MRD methods, with almost 60% of samples being positive by <italic>BCR‐ABL1</italic> while negative by Ig/TCR. Regarding the prognostic value of MRD targets, Ig/TCR<0.1% at week‐12 showed a significant correlation with outcome, while both measurements of Ig/TCR on day‐33 and <italic>BCR‐ABL1</italic> at any follow‐up time were not significantly associated with outcome.</p></sec><sec id="pbc26772-sec-4050"><label>P-016</label><title>Reducing Hospital Length of Stay for Patients Newly Diagnosed with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">A. DiNofia</underline><sup>1</sup>, J. Wilkes<sup>2</sup>, T. Flaherty<sup>3</sup>, R. English<sup>3</sup>, J. Sullivan<sup>1</sup>, K. Oranges<sup>1</sup>, E. Dwyer<sup>1</sup>, S. Powell<sup>1</sup>, S. Rheingold<sup>1</sup>, S.P. Hunger<sup>1</sup>, A. Reilly<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital of Philadelphia, Department of Pediatrics‐ Division of Oncology, Philadelphia, USA; <sup>2</sup>Seattle Children's Hospital, Department of Pediatrics‐ Cancer and Blood Disorders Center, Seattle, USA; <sup>3</sup>Children's Hospital of Philadelphia, Office of Clinical Quality Improvement, Philadelphia, USA</italic></p><p><bold>Background/Objectives</bold>: Most patients with newly diagnosed acute lymphoblastic leukemia (ALL) at the Children's Hospital of Philadelphia (CHOP) were discharged after day 8 of chemotherapy and many stayed 2‐3 weeks into their first month of therapy, called Induction. The goal of this quality improvement project was to reduce the length of stay (LOS) for patients newly diagnosed with ALL to less than 5 days after the start of chemotherapy.</p><p><bold>Design/Methods</bold>: Clinicians, nurses, and administrators were educated on the data regarding the safety of earlier discharge from the hospital and the plan for implementation of an earlier discharge goal at CHOP. Family education, planned procedures, and chemotherapy side effect surveillance and management that usually take place in the inpatient setting were transitioned to the outpatient clinic. LOS following administration of first chemotherapy was measured. In addition, the average number of emergency department (ED) visits, inpatient and intensive care unit (ICU) admissions, telephone calls from parents, and sick visits into oncology clinic within the Induction course were collected to ensure these metrics did not rise following implementation of this new practice.</p><p><bold>Results</bold>: The mean LOS following administration of the first dose of chemotherapy was reduced by 78.5% from 20 days in the months prior to the intervention was implemented to 4.3 days 11 months after the intervention was introduced. There was no change in average number of ED visits, inpatient and ICU admissions, telephone calls from parents, or sick visits into oncology clinic during Induction following patients’ initial discharge.</p><p><bold>Conclusions</bold>: It is feasible and safe to discharge newly diagnosed patients with ALL from the hospital within 5 days of initiation of treatment.</p></sec><sec id="pbc26772-sec-4060"><label>P-017</label><title>Cost‐Analysis of Treatment of Childhood Acute Lymphoblastic Leukemia Based on UKALL Protocol</title><p><underline underline-style="single">M. Ehsani</underline><sup>1</sup>, H. Hayati<sup>2</sup>, E. Shahgholi<sup>1</sup>, A. KebriaeeZadeh<sup>2</sup>, S. Nikfar<sup>2</sup>, M. Tashvighi<sup>3</sup>, A. Mehrvar<sup>3</sup></p><p><italic><sup>1</sup>Tehran University of Medical Sciences, Pediatric Hematology and Oncology, Tehran, Iran; <sup>2</sup>Tehran University of Medical Sciences, PediatrPharmacoeconomics and Pharmaceutical Administrationic Hematology and Oncology, Tehran, Iran; <sup>3</sup>MAHAK Charity Hospital, Pediatric Oncology, Tehran, Iran</italic></p><p><bold>Background/Objectives</bold>: Health systems have adopted financing to enhance access to care for patients with cancer. the cost of ALL treatment is a blurred image for hospitals and third party payers. The cost of each component of the care should be analyzed to differentiate justifiable cost and to act on waste full practices.</p><p><bold>This</bold> study on the direct and indirect costs of ALL based on the United Kingdom protocol (UK‐ALL), in pediatrics ALL management in Iran.</p><p><bold>Design/Methods</bold>: A retrospective study design was used to study children with ALL managed with UKALL protocol in specialized pediatric hospitals from 2010‐2015. The data was collected from patients’ medical records. MsoNormal style='tab‐stops:252.75pt;border:none; Health systems have adopted financing to enhance access to care for patients with cancer. the cost of ALL treatment is a blurred image for hospitals and third party payers. The cost of each component of the care should be analyzed to differentiate justifiable cost and to act on waste full practices.</p><p><bold>Aims</bold>: a study on the direct and indirect costs of ALL based on the United Kingdom protocol (UK‐ALL), in pediatrics ALL management in Iran.</p><p><bold>Results</bold>: The total direct medical cost per patient was 8282 US dollars. Most of costs were from inpatient beds (3338±1110 USD) and drug expenditures (2157±1035 USD). The direct non‐medical cost incurred by study participants was 1286.4 USD, The total indirect cost of due to productivity loss was 769.9.</p><p><bold>Conclusions</bold>: Treatment of pediatrics ALL is less costly in Iran comparing other countries. So, physicians and policy makers and health care system administrators should devise an appropriate strategy to reduce the direct medical costs which have more economic burden special for hospitalization days and chemotherapy costs based on the findings.</p></sec><sec id="pbc26772-sec-4070"><label>P-018</label><title>Cost‐Effectiveness of Pediatric‐Inspired vs Hyper‐CVAD Protocols for First‐Line Treatment of Adolescent and Young Adult (AYA) Patients with Philadelphia‐Negative Acute Lymphoblastic Leukemia (ALL)</title><p>E. Hooper<sup>1</sup>, <underline underline-style="single">X. Xingdi Hu</underline><sup>2</sup>, P. Lin<sup>3</sup></p><p><italic><sup>1</sup>Shire, Medical Director‐ Oncology, Cambridge, USA; <sup>2</sup>Shire, Analytics and Statistics Lead‐ GHEORE, Cambridge, USA; <sup>3</sup>Shire, Global HEOR Lead‐ Oncology, Cambridge, USA</italic></p><p><bold>Background/Objectives</bold>: Various protocols exist for first‐line treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA; aged 16‐39 years). Evidence suggests pediatric‐inspired protocols for ALL that include asparaginase as part of a multi‐therapy chemotherapy regimen are associated with better outcomes than conventional adult regimens, such as Hyper‐CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone).<sup>1</sup> Evidence regarding the cost‐effectiveness of pediatric‐inspired protocols versus Hyper‐CVAD in AYA patients is limited. The objective of this study was to estimate the cost‐effectiveness of a pediatric‐inspired protocol (CALG‐10403) versus Hyper‐CVAD for first‐line treatment of AYA patients with Philadelphia‐negative (Ph‐) ALL from a US payer perspective.</p><p><bold>Design/Methods</bold>: A 6‐state Markov model was developed to estimate overall survival, treatment‐related costs, and quality‐adjusted life years (QALYs) over a lifetime horizon. The modeled health states were: no first complete remission, first complete remission, first relapse, second complete remission, second relapse, and death. Model inputs for survival, adverse events, health utility, and costs were obtained from published sources. Cost‐effectiveness was measured by the incremental cost‐effectiveness ratio (ICER; incremental costs/QALY gained). Deterministic and probabilistic sensitivity analyses were performed to evaluate uncertainty around model input values.</p><p><bold>Results</bold>: The base‐case analysis suggested that the pediatric‐inspired protocol resulted in increased QALYs and reduced costs (QALYs gained, 2.05; cost savings, $41,685) compared with the Hyper‐CVAD protocol. Sensitivity analysis indicated that the probability of receiving stem cell transplantation at second complete remission was the key driver of cost‐effectiveness. At a willingness‐to‐pay threshold of $50,000/QALY, the probability of the pediatric‐inspired protocol being cost‐effective relative to Hyper‐CVAD was ∼92%.</p><p><bold>Conclusions</bold>: The pediatric‐inspired protocol (CALG‐10403) is cost‐effective compared to Hyper‐CVAD for first‐line treatment of AYA patients with Ph‐ ALL. Cost should not be a barrier to the use of a pediatric‐inspired protocol in AYA patients.</p><p><bold>Reference</bold>: 1. Ram R., et al. Am J Hematol 2012.</p></sec><sec id="pbc26772-sec-4080"><label>P-019</label><title>Systematic Literature Review and Meta‐Analysis of Event Free Survival and Overall Survival Rates for Pegaspargase in Pediatric Patients with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">E. Hopper</underline><sup>1</sup>, A. Wijatyk<sup>2</sup>, D. Bollag<sup>3</sup></p><p><italic><sup>1</sup>Shire, Medical Director‐ Oncology, Cambridge, USA; <sup>2</sup>Shire, Global Clinical Development Lead at Shire, Cambridge, USA; <sup>3</sup>Shire, Global Franchise Medical Lead Hematologic Tumors, Zählerweg, Switzerland</italic></p><p><bold>Background/Objectives</bold>: PEGylated L‐asparaginase (pegaspargase, PEG‐ASP) is a foundational component of combination therapy for acute lymphoblastic leukemia (ALL) that, when compared to native asparaginase (native‐ASP), offers sustained asparaginase activity with less frequent dosing and reduced immunogenicity. The objective of this assessment was to compare the clinical benefit of PEG‐ASP vs native‐ASP in newly diagnosed pediatric ALL patients with regard to event free survival (EFS) and overall survival (OS).</p><p><bold>Design/Methods</bold>: A systematic literature review was undertaken to identify all available evidence for newly diagnosed patients treated in pediatric ALL protocols using PEG‐ASP or native ASP. Randomized and observational studies were included. Outcomes were EFS and OS. Safety/immunogenicity was also examined. Asparaginase‐specific pooled estimates were calculated by patient risk level.</p><p><bold>Results</bold>: A total of 39 studies met criteria for abstraction; 13 used PEG‐ASP and 27 used native ASP. For standard‐risk patients treated with native ASP, 5‐year EFS was 82% (95% Confidence Interval (CI) 75‐88) vs 89% (95% CI 85‐93) with PEG‐ASP, and OS was 81% (95% CI 67‐96) vs 85% (95% CI 64‐100) in favor of PEG‐ASP. For high‐risk patients, 5‐year EFS was 71% (95% CI 67‐76) vs 80% (95% CI 75‐86), and OS was 73% (95% CI 59‐86) vs 80% (95% CI 73‐87) for native ASP and PEG‐ASP, respectively. Safety was consistent with the product class for both asparaginases.</p><p><bold>Conclusions</bold>: The results of this assessment support a favorable efficacy profile for PEG‐ASP vs. native ASP in treatment of newly diagnosed pediatric patients with ALL, with the benefits of less frequent administration. Safety was consistent with the known class profile.</p></sec><sec id="pbc26772-sec-4090"><label>P-020</label><title>MIR‐3117 and MIR‐3689D2 in MAPK Signaling Pathway: Implication in Childhood Acute Lymphoblastic Leukemia Susceptibility</title><p>A. Gutierrez‐camino<sup>1</sup>, I. Martin‐guerrero<sup>1</sup>, N. Garcia De Andoin<sup>2</sup>, A. Navajas<sup>3</sup>, A. Sastre<sup>4</sup>, A. Carbone‐baneres<sup>5</sup>, <underline underline-style="single">M. Garcia‐ariza</underline><sup>6</sup>, I. Astigarraga<sup>6</sup>, A. Garcia‐orad<sup>1</sup></p><p><italic><sup>1</sup>University of the Basque Country UPV/EHU, Genetics‐ Physic Anthropology and Animal Physiology, Leioa, Spain; <sup>2</sup>University Hospital Donostia, Pediatrics, Donostia, Spain; <sup>3</sup>BioCruces Health Research Institute, Pediatrics, Barakaldo, Spain; <sup>4</sup>University Hospital La Paz, Oncohaematology, Madrid, Spain; <sup>5</sup>University Hospital Miguel Servet, Pediatrics, Zaragoza, Spain; <sup>6</sup>University Hospital Cruces, Pediatrics, Barakaldo, Spain</italic></p><p><bold>Background/Objectives</bold>: Recently, several Genome wide associations studies (GWAS) have found genetic variants associated with pediatric acute lymphoblastic leukemia (ALL) risk. These studies were mainly focused in coding regions. Nowadays, it is known that more than 40% of significant variants associated with cancer risk are situated in non‐coding regions, where non‐coding RNAs are located. MicroRNAs (miRNAs) are non‐coding RNA molecules dysregulated in ALL, suggesting a role in ALL risk. Despite miRNA SNPs interfere with miRNA levels or function, only 3 studies in ALL susceptibility were done, showing significant results. Therefore, variants in miRNAs could contribute to childhood B‐ALL predisposition. Nowadays, a large number of new miRNAS were annotated. Therefore, the aim of this study was to determine if any of SNPs in these new miRNAs are involved in B‐ALL susceptibility.</p><p><bold>Design/Methods</bold>: Blood samples of 217 pediatric patients with B‐cell ALL in complete remission and 330 healthy controls of Spanish origin were analyzed. We selected all the SNPs described in pre‐miRNAs with a MAF>1% (213 SNPs in 206 miRNAs). VeraCode GoldenGate platform was used. MirWalk, RNAFold web server and Consensus Path Databases were used to performed bioinformatic analysis.</p><p><bold>Results</bold>: The SNPs rs12402181 in mir3117 and rs62571442 in mir3689d2 were associated with B‐ALL risk possibly through its effect on MAPK signaling pathway.</p><p><bold>Conclusions</bold>: Therefore, in this study we found rs12402181 in mir3117 and rs62571442 in mir3689 associated with B‐ALL risk. These SNPs could be novel markers for B‐ALL susceptibility.</p><p>This project was supported by UPV/EHU (UFI 11/35) and Basque Government (IT989‐16).</p></sec><sec id="pbc26772-sec-4100"><label>P-021</label><title>Experience with Clofarabine use in Refractory/Relapsed Acute Leukemia Pediatric Patients at the Instituto Nacional De Enfermedades Neoplasicas (INEN), LIMA ‐ PERU</title><p><underline underline-style="single">J.L. Garcia</underline><sup>1</sup></p><p><italic><sup>1</sup>Institutoi Nacional de Enfermedades Neoplásicas, Pediatric Oncology, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: To know the usefulness of Clofarabine regimens in refractory/relapsed Leukemia patients at our setting and find the best scenario for it's use.</p><p><bold>Design/Methods</bold>: Retrospective review of medical charts of pediatric patients below 15 years old with refractory/relapsed acute leukemia between 2009 and 2017, clinical data, laboratory results and bone marrow results with Minimal Residual Disease (MRD) by flow cytometry study were recorded.</p><p><bold>Results</bold>: Thirty three courses of Clofarabine regimens were administrated in 27 patients with refractory/relapsed acute leukemia, 24 had Acute Lymphoblastic Leukemia (ALL), Clofarabine, Cyclofosfamide and Etoposide (CCE) combination was used in 22 patients, only one patient was in first relapse, he achieved complete remission (CR) with negative MRD, 6 patients were in second relapse, 2 of the evaluable patients had CR, one with negative MRD, in the other the test was not done. Four patients were in third relapse, none had CR. One patient was in fourth relapse, he had CR with positive MRD. Seven patients had refractory disease, only one had CR but with positive MRD. Of the 19 relapsed patients, CR was achieved in 29.4% of them, only one with negative MRD. CCE regimen was used in 8 patients with MRD positive disease, negative MRD was achieved in 75% of them, all of these patients went to bone marrow transplant (BMT) therapy. Severe hematologic toxicity was seen in 87.8% of the courses given, followed by febrile neutropenia in 72.7% and hepatic toxicity in 51.5%, there were 3 patients dead during chemotherapy.</p><p><bold>Conclusions</bold>: CCE regimen was very useful in MRD positive disease, achieving a good rate of negativization of disease, giving the option for BMT therapy.</p></sec><sec id="pbc26772-sec-4110"><label>P-022</label><title>Efficacy and Toxicity of Inotuzumab in a Patient with Relapsed/ Refractory Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">G. Giagnuolo</underline><sup>1</sup>, F. Petruzziello<sup>1</sup>, G. Maisto<sup>1</sup>, M.R. D'Amico<sup>1</sup>, M. Ripaldi<sup>1</sup>, G. Loffredo<sup>1</sup>, S. Buffardi<sup>1</sup>, G. Menna<sup>1</sup>, R. Parasole<sup>1</sup></p><p><italic><sup>1</sup>Santobono‐Pausilipon Hospital, Pediatric Hemato‐oncology, Napoli, Italy</italic></p><p><bold>Background/Objectives</bold>: The outcome of relapsed/refractory acute lymphoblastic leukemia (ALL) in childhood is still poor; current chemotherapies’ regimen are associated with significant toxicities and scanty responses. Recently, physicians’ attention has been directed toward alternative drugs with different mechanism of action compared to standard chemotherapy. Inotuzumab ozogamicin is an anti‐CD22 monoclonal antibody conjugated to the toxin, calecheamicin. The complex Inotuzumab‐CD22 receptor is rapidly internalized with intracellular calicheamicin release. Calicheamicin binds to the DNA, inducing double‐strand cleavage and apoptosis. Herein we describe the case of a young girl with hypodiploid ALL relapsed for the second time after allogeneic bone marrow transplantation (BMT). Since the patient had an early relapse ( 5 months after BMT) and was resistant to previous chemotherapy, we opted for immunotherapy with Inotuzumab as bridge to a second allogenic BMT.</p><p><bold>Design/Methods</bold>: The drug was administered in monotherapy at the dosage of 1.8 mg/mq/course, given weekly for 3 times, every 29 days. The patient obtained hematological remission after the first course and minimal residual disease (MRD) negativity after the second; a third course was administered before haploidentical transplant.</p><p><bold>Results</bold>: Treatment with inotuzumab was well tolerated; the patient showed grade IV hematological toxicities after the first course and grade I‐II hepatotoxicities in the subsequent cycles. During transplant VOD prophylaxis with defibrotide was administered. During transplant no toxicity was reported; the engraftment occurred at day +13 and MRD negativity was documented at day +35. Unfortunately, 5 months after the second transplant, the patient relapsed again.</p><p><bold>Conclusions</bold>: The good toxicity profile and the efficacy on MRD suggests a larger using of inotuzumab, possibly in combinations with chemotherapy or other biological drugs before BMT; this association could allow long‐lasting disease‐free survival in patients with relapsed/refractory ALL. Further study are needed to evaluate the optimal use of Inotuzumab to improve cure rates in these patients.</p></sec><sec id="pbc26772-sec-4120"><label>P-023</label><title>Parvovirus B19 Induced Cytopenias in Children on Maintenance Phase of Acute Lymphoblastic Leukemia (ALL) Chemotherapy Lead to Prolonged Chemotherapy Interruptions</title><p><underline underline-style="single">B. Gupta</underline><sup>1</sup>, A. kumar<sup>1</sup>, N. verma<sup>1</sup>, G. pant<sup>1</sup>, A. sharma<sup>1</sup></p><p><italic><sup>1</sup>King Georges Medical University, Pediatrics, Lucknow, India</italic></p><p><bold>Background/Objectives</bold>: Chemotherapy interruptions during maintenance phase of ALL may lead to relapses and hence are avoidable.In the present study role of parvovirus B19 infection in causing these chemotherapy interruptions was evaluated.</p><p><bold>Design/Methods</bold>: A cohort of 90 children with ALL during the maintenance phase chemotherapy of ALL were evaluated for 840 cycles (3 months each,2520 months).IgM,IgG,PCR were done for Parvovirus B19 infection during episodes of cytopenias requiring chemotherapy interruption.</p><p><bold>Results</bold>: Of total 90 patients( 42 new entrants during study period,48 already in various phases),30(33.3%) patients were found to be parvovirus B19 Positive by PCR at various phases of maintenance chemotherapy which was tested on grounds on clinical suspicion.</p><p>Out of 30 parvovirus B19 positive patients 24 (80%) required multiple blood tranfusions whereas amongst the 60 Parvovirus B19 negative patients only 23(38%) required multiple tranfusions(p<.0.00).</p><p>During maintenance phase chemotherapy,18 patients had more than 2 episodes of neutropenia and 11 out of 18(61%) patients were parvovirus B19.</p><p>One twenty two cycles of maintenance phase were observed to be delayed by more than 7 days and parvovirus B19 was found positive in 85 out of 122(69.6%) cycles(p<0.000).</p><p><bold>Conclusions</bold>: Parvovirus B19 infection emerges to be an important cause of cytopenias leading to chemotherapy interruptions in maintenance phase of ALL Chemotherapy. So Screening of ALL patients by PCR in cases of unexplained cytopenias is recommended.</p></sec><sec id="pbc26772-sec-4130"><label>P-024</label><title>Impact of Invasive Fungal Infections in Children and Adolescents with Acute Lymphoblastic Leukemia in a Resource Poor Setting</title><p><underline underline-style="single">N. Gupta</underline><sup>1</sup>, N. Dhingra<sup>1</sup>, P. Mishra<sup>1</sup>, T. Seth<sup>1</sup>, S. Tyagi<sup>1</sup>, H.P. Pati<sup>1</sup>, R. Saxena<sup>1</sup>, M. Mahapatra<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Hematology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Infectious morbidity and mortality is a major concern in patients with hematological malignancies. Invasive fungal infections (IFI) during induction chemotherapy in acute lymphoblastic leukemia (ALL) can adversely impact outcomes. Experience with fungal infections in children and adolescents during ALL induction from a tertiary care centre in north India is discussed here.</p><p><bold>Design/Methods</bold>: Records of 120 patients (age < 18 years), who underwent ALL induction at our institution between 1/1/2011 and 31/12/2016, were retrospectively reviewed. All patients were on primary prophylaxis with fluconazole. Incidence and characteristics of IFI were identified. We assessed therapy delays and interruptions in this group and the impact of IFI on outcomes.</p><p><bold>Results</bold>: Thirty‐one patients (25.8%) out of 120 had evidence of IFI at baseline or during induction chemotherapy. As per standard definitions, 16 (51.6%), 12 (38.7%) and 3 (9.6%) patients had possible, probable and proven fungal infections respectively. Positive galactomannan antigen was documented in 12 (38.7%). Aspergillus species was isolated in all 3 proven cases. The most common site of infection was lungs (83.8%), followed by sino‐rhinal (6.4%), 2 patients (6.4%) had multi‐organ involvement while 1(3.2%) had cutaneous aspergillosis. Therapy omissions and interruptions during induction occurred in 16 cases (51.6%). Induction mortality attributable to progressive fungal infections was 16.1% (5 cases). Median duration of follow up of 26 patients who achieved remission was 9 months (range 1‐54 months). Six patients (23%) out of these had early relapses, of which 5 died.</p><p><bold>Conclusions</bold>: A high incidence of fungal infections, particularly invasive aspergillosis, was observed. Invasive fungal infections during induction lead to morbidity and mortality in patients with ALL and contribute to therapy interruptions, which would influence long term outcomes.</p></sec><sec id="pbc26772-sec-4140"><label>P-025</label><title>Subclavian Vein Access to Long Term Catheter Placed in the ARM: A New Surgical Strategy in Pediatric Oncology</title><p><underline underline-style="single">R. Vianna</underline><sup>1</sup>, J.T.D.S.D. Oliveira<sup>1</sup>, S. Coelho<sup>1</sup>, M.F. Grabois<sup>1</sup>, V.D.N. Santos<sup>1</sup>, E.C. Lopes<sup>1</sup>, C.S.D. Santos<sup>1</sup>, R.H. Junior<sup>1</sup>, A.L.D.M. Guaraldi<sup>1</sup>, F.F. Lima<sup>1</sup>, C.A.S. Martins<sup>1</sup>, F.N. Gutierrez<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Câncer, Pediatric Surgery, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: To evaluate the follow up and complications of long term catheters implanted in pediatric oncology patients with a subclavian vein puncture and an arm port/tunneled catheter insertion technique</p><p><bold>Design/Methods</bold>: Since 1994, about 140 long term central venous catheters/ year were inserted in the pediatric oncology patients, and the arm was the first choice as site of insertion. Dissection of basilica, brachial and axillar veins were the venous access. Since 2014, puncture of subclavian vein has been used as the first option to venous access in some cases, utilizing the reservoir/tunneled catheter positioned in the arm.</p><p>A retrospective review of the long‐term catheters implanted in pediatric oncology patients from 2014 to 2017, in children ranging from 2 months to 16 years old (median 5 years old) Complications as infections, thrombosis, and rupture were compared in all techniques.</p><p><bold>Results</bold>: 447 long term catheters were inserted, 267 totally implanted and 174 tunneled catheters (in 6 cases weren´t identified), 294 dissection of arm veins, 115 Subclavian punctions, 6 Jugular punctions (in 26 cases weren't identified). Causes of catheter removal were: infection, thrombosis, obstruction, rupture, exteriorization and others. Infection rates were 15% in port catheters: 12,7% dissection technique and 2,2% (6/267 subclavian puncture) and 24% (42/174) in tunneled catheters: 19% dissection technique, 4% subclavian puncture and 1,1% Jugular puncture. Trombosis rates were 1 in port catheters (100% dissection technique) and 2 in tunneled catheters (100% dissection technique).</p><p><bold>Conclusions</bold>: The use of the arm to place the reservoir/tunneled catheter was widely used since 1994, providing a safe, comfortable and a good quality of life during oncologic treatment in children. The use of subclavian vein puncture as venous access to arm reservoir/tunneled catheter insertion has shown a good choice without major complications with literature comparing results.</p></sec><sec id="pbc26772-sec-4150"><label>P-026</label><title>Single Dose of Folinic Acid Rescue after High‐Dose Methotrexate is not Associated with Neurotoxicity in Children with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">A. Harila‐Saari</underline><sup>1</sup>, J. Banerjee<sup>2</sup>, P. Riikonen<sup>3</sup>, T. Pokka<sup>4</sup>, R. Niinimaki<sup>5</sup></p><p><italic><sup>1</sup>Astrid Lindgren Children's Hospital‐ Karolinska, Pediatric Oncology, Stockholm, Sweden; <sup>2</sup>Helsinki University Hospital, Paediatric oncology, Helsinki, Finland; <sup>3</sup>Kuopio University Hospital, Paediatric oncology, Kuopio, Finland; <sup>4</sup>Oulu University Hospital, Paediatrics and Adolescents, Oulu, Finland; <sup>5</sup>Oulu University Hospital and University of Oulu, PEDEGO Research Unit and Department of paediatrics and adolescents, Oulu, Finland</italic></p><p><bold>Background/Objectives</bold>: Folinic acid (FA) is needed after administration of high‐dose methotrexate (HD‐MTX) in order to rescue normal cells from toxicity. Low FA doses have been associated with increased toxicity, including neurotoxicity, whereas high doses may be related to decreased antileukemic effect. NOPHO‐ALL2000 protocol used in Finland included 15 mg/m² FA given every 6 hours from 42 hours after HDMTX (5 g/m²) and continued until serum MTX concentration was < 0.20 μmol/L. Extended alkalinization and prehydration (> 12 hours) was used. Only one or two doses were given in patients with rapid clearance of MTX. We studied here the association between low doses of FA after HD‐MTX and severe clinical toxicity, especially neurotoxicy.</p><p><bold>Design/Methods</bold>: Patient files of 44 children (27 males; mean age at diagnosis 5.7 years) with standard or intermediate risk acute lymphoblastic leukaemia (ALL) treated with NOPHO‐ALL2000 protocol in two Finnish centers were reviewed. Data on HD‐MTX clearance, FA dosing and clinical toxicity with special focus on neurotoxicity were collected and analysed.</p><p><bold>Results</bold>: Patients had received a total of 351 HD‐MTX courses. After 181 courses (51.6%, CI 46.2–56.9) only one or two doses of FA were administered. Single dose was given after 55 courses (15.7%, CI 12.0–19.9). None of the patients had clinical neurotoxicity. Magnetic resonance imaging of the brain was performed at the end of treatment in 22 patients and no leukoencephalopathy was detected. Small (3 mm) bilateral high signal intensity lesions in the frontal area were detected in one patient. Low FA doses were not associated with other severe clinical toxicity, steady state MTX concentration, age or gender of the patients.</p><p><bold>Conclusions</bold>: Single dose of FA after HDMTX seems to be sufficient to prevent neurotoxicity in children with ALL who have received extended alkalinization and prehydration and have rapid clearance of MTX.</p></sec><sec id="pbc26772-sec-4160"><label>P-027</label><title>XRCC1 Gene Polymorphism and the Risk of Childhood Acute Lymphoblastic Leukemia: A Case Control Study</title><p><underline underline-style="single">T. Hassan</underline><sup>1</sup>, N. Khalifa<sup>1</sup>, A. Baraka<sup>2</sup>, M. Abdel Alim<sup>2</sup></p><p><italic><sup>1</sup>Faculty of medicine‐ Zagazig university‐Egypt, Pediatrics, Zagazig, Egypt; <sup>2</sup>Faculty of medicine‐ Zagazig university‐Egypt, Clinical Pathology, Zagazig, Egypt</italic></p><p><bold>Background/Objectives</bold>: DNA repair systems have a crucial role in maintaining genome integrity and stability. Defects in repair pathways may promote development of cancer, including leukemia. Currently, research activities have focused on polymorphisms in DNA repair genes as an important component of susceptibility to cancer. Among them, XRCC1 (X‐ray repair cross‐complementing groups 1) gene polymorphisms were reported to induce defective functional capacity of the DNA Polymerase β, PARP, and ligase III enzyme, resulting in defective DNA repair. We aimed to assess whether XRCC1 gene polymorphisms contribute to development of childhood ALL or not, and to evaluate their prognostic significance as regards to induction of remission and relationship to well‐known pretreatment risk factors.</p><p><bold>Design/Methods</bold>: A case control study was carried out at clinical pathology and pediatric oncology departments, Zagazig University, Egypt, during period from March 2016 to February 2017. Ninety subjects were included ;45 children with de‐novo ALL and 45 age and sex matched healthy children as a control group.Patients were subjected to complete history taking, thorough clinical examination and routine laboratory investigations according to our local standards. Genotyping of XRCC1 gene polymorphisms was performed for all study participants using polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP).</p><p><bold>Results</bold>: There was no significant difference between patients and controls as regards to different XRCC1 genotypes. Apart from the significant association between Arg 399 Gln and Gln 399 Gln genotypes and common ALL immunophenotype, there was no significant difference among XRCC1 genotypes in relation to any of the demographic,clinical and laboratory data of patients as well as remission rates.</p><p><bold>Conclusions</bold>: There is no relation between XRCC1 gene polymorphism and risk of developing ALL in children. Apart from the significant association between certain XRCC1 genotypes and common ALL immunophenotype, XRCC1 gene polymorphism has no prognostic significance in childhood ALL. Larger studies are still needed to support our findings.</p></sec><sec id="pbc26772-sec-4170"><label>P-028</label><title>Differences Between Urban and Rural Areas of Castilla‐Leon in the Incidence and Survival of Childhood Leukemias (SPAIN)</title><p>R. Garrote Molpeceres<sup>1</sup>, <underline underline-style="single">R.</underline><underline underline-style="single">Herraiz</underline><underline underline-style="single">Cristobal</underline><sup>2</sup>, E. Urbaneja Rodríguez<sup>3</sup>, M.A. Pino Vázquez<sup>4</sup>, P. Gutiérrez Meléndez<sup>5</sup>, F.J. Álvarez Guisasola<sup>6</sup>, H. González García<sup>2</sup></p><p><italic><sup>1</sup>Hospital Clínico Universitario Valladolid, Servicio de Pediatría, Valladolid, Spain; <sup>2</sup>Hospital Clínico Universitario Valladolid, Sección de Oncohematología Pediátrica, Valladolid, Spain; <sup>3</sup>Hospital Clínico Universitario Valladolid, Sección de Inmunología Pediátrica, Valladolid, Spain; <sup>4</sup>Hospital Clínico Universitario Valladolid, Jefe Servicio de Cuidados Intensivos Pediátricos, Valladolid, Spain; <sup>5</sup>Dirección General de Salud Pública Junta de Castilla y León, Servicio de Salud Pública, Valladolid, Spain; <sup>6</sup>Hospital Clínico Universitario Valladolid, Jefe de Servicio y Catedrático de Pediatría, Valladolid, Spain</italic></p><p><bold>Background/Objectives</bold>: To analyze the differences between urban and rural children population in incidence and survival of children under 15 years old diagnosed with leukemia in the region of Castilla‐León (Spain) during the period 2003‐2014.</p><p><bold>Design/Methods</bold>: Leukemia cases were extracted from the registry of childhood tumors of population base of Castilla‐León, with an annual mean of childhood population of 296,776 children under 15 years old. Cases were classified by age and sex. Leukemia incidence was adjusted by age to world population (ASRw, 95%CI) and their differences through standardized rate. For three‐year survival analysis, we included cases with follow‐up until 31/12/2013. Survival rates were calculated by Kaplan‐Meier analysis and their comparisons with log‐rank test. Rural population was considered to be one with ≤ 20,000 habitants.</p><p><bold>Results</bold>: From 155 leukemias diagnosed, we could identify the rural/urban population in 145(93.55%), 79(54.48%) rural and 66(45.52%) urban. Leukemia incidence was significantly greater in rural areas [ASRw: 51.08(40.31‐64.02) vs 33.65(25.93‐43.07)], p=0.018. Incidence analysis by age showed greater significantly rural leukemia incidence in 0‐4 years old children [ASRw: 59.23(39.96‐84.56) vs 36.18(22.93‐54.28)], p<0.0001. Global survival was of 83%(76.1‐88), with a mean follow‐up of 7.25 years (Quartiles: 3.77‐9.5). Urban leukemia survival was significantly less than rural [76%(64.5‐84.2) vs 91%(82.9‐95.4)], p=0.005. There were no survival differences by sex in 0‐4 years old children between rural and urban populations. In the 5‐9 years old group, female survival was greater in rural areas (p=0,006) and in the 10‐14 years old group, survival was greater in males from rural areas (p=0.018).</p><p><bold>Conclusions</bold>: We found higher incidence of childhood leukemia in rural areas due to an increase of incidence in 0‐4 years old children. Survival was greater in rural areas in children older than 5 years at diagnosis. These differences in incidence and survival could help to investigate epigenetic or environmental factors of childhood leukemia.</p></sec><sec id="pbc26772-sec-4180"><label>P-029</label><title>IDH1 and KRAS Mutations are Involved in Acute Lymphoblastic Leukemia in Maffucci Syndrome</title><p><underline underline-style="single">S. Hirabayashi</underline><sup>1</sup>, M. Seki<sup>2</sup>, D. Hasegawa<sup>1</sup>, M. Kato<sup>3</sup>, N. Hyakuna<sup>4</sup>, T. Shuo<sup>5</sup>, S. Kimura<sup>2</sup>, K. Yoshida<sup>6</sup>, K. Kataoka<sup>6</sup>, Y. Fujii<sup>6</sup>, Y. Shiraishi<sup>7</sup>, K. Chiba<sup>7</sup>, H. Tanaka<sup>7</sup>, N. Kiyokawa<sup>8</sup>, S. Miyano<sup>7</sup>, S. Ogawa<sup>6</sup>, J. Takita<sup>2</sup>, A. Manabe<sup>1</sup></p><p><italic><sup>1</sup>St. Luke's International Hospital, Department of Pediatrics, Tokyo, Japan; <sup>2</sup>University of Tokyo, Department of Pediatrics, Tokyo, Japan; <sup>3</sup>National Center for Child Health and Development, Children's Cancer Center, Tokyo, Japan; <sup>4</sup>Hospital of University of the Ryukyu, Center of Bone Marrow Transplantation, Okinawa, Japan; <sup>5</sup>St. Luke's International University, Institute for Medical Innovation, Tokyo, Japan; <sup>6</sup>Graduate School of Medicine‐ Kyoto University, Department of Pathology and Tumor Biology, Kyoto, Japan; <sup>7</sup>Institute of Medical Science‐ University of Tokyo, Laboratory of DNA Information Analysis‐ Human Genome Center, Tokyo, Japan; <sup>8</sup>National Center for Child Health and Development, Department of Pediatric Hematology and Oncology Research, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: Somatic mosaic mutations of the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1, IDH2) cause Maffucci syndrome, rare nonhereditary disorders in which patients develop multiple enchondromas combined with hemangiomas. Although malignant transformation of enchondromas to chondrosarcomas and secondary neoplasms, such as brain tumors or acute myeloid leukemia, are serious complications, reports of acute lymphoblastic leukemia (ALL) as a secondary neoplasm are limited.</p><p><bold>Design/Methods</bold>: In this study, we present a 15‐year‐old girl with Maffucci syndrome who developed B‐cell precursor (BCP)‐ALL as a secondary neoplasm. <italic>IDH1</italic> and <italic>IDH2</italic> mutations in leukemic cells at relapse and hemanigoma were screened by Sanger sequencing. Additionally, whole exome sequencing and SNP array were done in leukemic cells at relapse.</p><p><bold>Results</bold>: The girl was diagnosed Maffucci syndrome because of shortness of right arm and hemangioma at infant. At the age of 12 years, she had fever, anemia and severe pain on her systemic body. Bone marrow examination revealed necrotic bone marrow and chondromatosis. She had severe anemia 6 months later, and was diagnosed with B‐precursor ALL. She received chemotherapy, however, she relapsed at the age of 15 years 4 months after cessation of maintenance therapy. Mutational analysis of <italic>IDH1</italic> revealed p.R132C in leukemic cells at relapse. A somatic mutation in <italic>IDH1</italic> c.394C>T (encoding p.R132C) was detected in her hemangioma and leukemic cells, and the <italic>KRAS</italic> mutation c.38G>A (encoding p.G13D) and deletion of<italic>IKZF1</italic> were detected in her leukemic cells.</p><p><bold>Conclusions</bold>: Patients with Maffucci syndrome might be at risk of BCP‐ALL associated with secondary genetic events that affect lymphocyte differentiation. Our observations suggest that secondary mutations may account for the development of ALL in patients with Maffucci syndrome. Prospective registration of any patient suspected of genetic predisposition is mandatory to identify the mechanism of leukemogenesis and variation of penetrance of ALL.</p></sec><sec id="pbc26772-sec-4190"><label>P-030</label><title>Isolation of Pathogenic Bacteria and Their Antibiotic Sensitivity Profiles in Hospitalized Febrile Neutropenic Children with Acute Lymphoblastic Leukaemia</title><p><underline underline-style="single">C.Y. Jamal</underline><sup>1</sup>, M.B. Yeamin<sup>1</sup></p><p><italic><sup>1</sup>Bangabandhu Sheikh Mujib Medical University, Paediatric Haematology and Oncology, Dhaka, Bangladesh</italic></p><p><bold>Background/Objectives</bold>: Acute lymphoblastic leukemia (ALL) is the commonest malignancies in childhood. Common obstacle in the treatment of ALL is febrile neutropenia and its complications. To identify bacteria causing infection, their isolation rate and antibacterial sensitivity pattern in hospitalized febrile neutropenic children with ALL in different cycle of chemotherapy.</p><p><bold>Design/Methods</bold>: This cross sectional study conducted in 2014 ‐ 2015 in the department of paediatric haematology/ oncology, BSMMU, Dhaka BANGLADESH. Sixty febrile neutropenic episodes from 52 diagnosed cases of ALL aged 0 to18 years were included. Complete blood count, blood culture, urine microscopy and culture, serum alanine aminotransferase, serum creatinine were done in every patient. X‐ray chest, stool microscopy and culture, pus, wound, throat and aural swab for culture & sensitivity were done in selective patient.</p><p><bold>Results</bold>: Bacterial infection was confirmed by culture in 15 (25%) episodes from 60 febrile neutropenic episodes. Fifteen (25%) organisms were isolated from the study subjects from sample of blood (60%), pus (13.3%), aural swab (13.3%), wound swab (6.7%) and throat swab (6.7%) respectively. All isolates were gram negative. The organism isolated were <italic>Klebsiella</italic> spp 5 (33.31%), <italic>E. coli</italic> 4 (26.7%),<italic>Acinetobacter</italic> 3 (20%), <italic>Pseudomonas</italic> 2 (13.3%) and only one (6.7%) <italic>Enterobacter</italic> species. All the isolates of the <italic>Klebsiella</italic> spp., <italic>E.coli</italic> and <italic>Acinetobacter</italic> spp. were resistant to amoxicillin. All isolated <italic>E.coli</italic> were resistant to cotrimoxazole, ceftazidime, ceftriaxone, cefotaxime and ciprofloxacin, <italic>Acinetobacter</italic> spp. Isolated were100% sensitive to imipenem, colistin sulphate & piperacillin‐tazobactam and resistant to cotrimoxazole and cephradine. All <italic>Pseudomonas</italic> spp. showed 100% sensivity to imipenem, amikacin, ciprofloxacin & colistin and resistantance to ceftazidime,</p><p><bold>Conclusions</bold>: The species of <italic>Klebsiella</italic> were the predominant causative bacterial agent followed by <italic>Escherichia coli, Acinetobacter</italic> spp, <italic>pseudomonas</italic> spp. and <italic>enterobacter</italic> spp.’They showed resistance to commonly prescribed antibiotics ceftazidime, gentamicin, ceftriaxone & ciprofloxacin and sensitive to imipenem, colistin‐sulphate & piperacillin‐tazobactam.</p></sec><sec id="pbc26772-sec-4200"><label>P-031</label><title>Bone Disease in Childhood Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">K. Katsibardi</underline><sup>1</sup>, K. Roka<sup>1</sup>, G. Avgerinou<sup>1</sup>, N. Tourkantoni<sup>1</sup>, M. Filippidou<sup>1</sup>, H. Tsipou<sup>1</sup>, N. Krallis<sup>2</sup>, A. Kattamis<sup>1</sup></p><p><italic><sup>1</sup>Aghia Sophia Children's Hospital, Pediatric Hematology Oncology, Athens, Greece; <sup>2</sup>Aghia Sophia Children's Hospital, Orthopaedic Unit, Athens, Greece</italic></p><p><bold>Background/Objectives</bold>: Bone abnormalities, such as low bone mineral density, osteoporosis and non‐traumatic bone fractures, frequently occur in children under chemotherapy for acute lymphoblastic leukemia (ALL). Their pathogenesis seems to be multifactorial, due to chemotherapeutic agents and the leukemic process.</p><p><bold>Design/Methods</bold>: Children diagnosed with ALL were evaluated in regards to the occurrence of bone abnormalities within a 4‐year period (January 2013‐ December 2016). Severe bone abnormalities were defined as: significant bone pain associated with activity restrictions, and significant loss of bone mineral resulting in objective osteoporosis or/and non‐traumatic bone fractures.</p><p><bold>Results</bold>: During this period, 70 children were diagnosed with ALL (N=35, 50% girls), of median age 4.42 years (range: 1.02‐ 16.91 years). Among them twelve (17%) experienced bone abnormalities.</p><p>Bone pain with activity restriction and gait disturbances was observed in eight patients, half at diagnosis and during maintenance. Four patients experienced bone fractures (two at diagnosis, one during reinduction and one during maintenance). Osteoporosis was documented in two patients, at maintenance. Four patients (3 girls / 1 boy, of six, ten, thirteen and fifteen years old) developed aseptic necrosis of femoral head with severe limping. Most patients were treated conservatively. Arthroplasty was performed in 1/4 patients after maintenance completion. Four children received Zoledronic acid, with median number of 6 doses, for 13.2 months (median duration). Symptoms improved slowly and had resolved by the end of treatment. Bone mineral density measured at the dual energy x‐ray absorptiometry (DEXA) return to age‐appropriate levels by a median period of seven months.</p><p><bold>Conclusions</bold>: We documented a high incidence of bone disease in children with ALL. Bisphosphonate therapy with Zoledronic acid seems to decrease skeletal pain and increase bone density. Early recognition of patients at risk and timely application of adequate preventive and therapeutic measures are essential to prevent this debilitating complication in ALL patients.</p></sec><sec id="pbc26772-sec-4210"><label>P-032</label><title>Prevalence and Clinical Correlation of TPMT, ITPA and NUDT15 Gene Polymorphisms in Children with Acute Lymphoblastic Leukaemia in North India</title><p><underline underline-style="single">S. Khera</underline><sup>1</sup>, A. Trehan<sup>1</sup>, P. Bhatia<sup>1</sup>, M. Singh<sup>2</sup>, D. Bansal<sup>1</sup>, N. Varma<sup>3</sup></p><p><italic><sup>1</sup>PGIMER, Pediatrics, Chandigarh, India; <sup>2</sup>PGIMER, Lab Hematology, Chandigarh, India; <sup>3</sup>PGIMER, Hematology, Chandigarh, India</italic></p><p><bold>Background/Objectives</bold>: Toxicity of 6‐Mercaptopurine (6‐MP) is related to single nucleotide polymorphism (SNP) in genes coding for metabolizing enzymes; with thiopurine S‐methyltransferase (TPMT) analysis being recommended prior to maintenance therapy in Acute Lymphoblastic Leukemia (ALL). However, inosine triphosphate pyrophosphatase (ITPA) and nucleoside diphophate–X‐type motif 15 (NUDT15) SNP's appear more important in the Asian population.</p><p><bold>Design/Methods</bold>: In this prospective Mendelian randomisation study consecutive patients with ALL ( Jan 2016 to Jun 2016), entering maintenance phase were evaluated for TPMT, ITPA and NUDT15 by PCR RFLP. Haematological and hepatic toxicities were monitored for 9 months.The two groups with and without SNP's mutation (Mut+ and Mut‐) were compared.</p><p><bold>Results</bold>: Sixty three patients of ALL [5.3 years (4.61‐ 6.06)] underwent molecular analysis. Fifty eight were followed for 9 months. Eighteen (28.6%) patients had SNP mutations. ITPA, NUDT, TPMT*3C mutations: 11(17.5%),6(9.5%) and 2(3.1%).One patient had TPMT3*C and ITPA. All mutations except 1 ITPA were heterozygous. Mean cumulative dose of 6MP was lower 10927 mg/m<sup>2</sup> in Mut+ compared to 12533 mg/m<sup>2</sup> in Mut‐ group (P=0.009). Neutropenic events were greater in Mut+ (P=0.03), Weeks of full dose of 6 MP were lower in Mut + (21 versus 30; P=0.0009). Risk of Neutropenia>2 weeks was pronounced (OR=4.41; 95%CI 1.21‐16; P=0.024) and the weeks off chemotherapy were greater in Mut + group (5 versus 2.8; P=0.019). The ITPA and NUDT SNP subgroups had similar cumulative 6MP doses and chemotherapy interruptions. There was no difference in average cumulative dose of Methotrexate in 2 groups. Malnourishment did not correlate with doses. No significant hepatotoxicity was noted.</p><p><bold>Conclusions</bold>: Polymorphisms in 6MP metabolizing enzymes are notably related to ethnic ancestry. TPMT (3.1%) SNP's do not appear to have a significant role in our population. ITPA (17.5%) and NUDT (9.5%) polymorphisms appear to be the important SNP's in the north Indian population for optimizing chemotherapy doses.</p></sec><sec id="pbc26772-sec-4220"><label>P-033</label><title>Dual Inhibition of Beta‐Catenin and RAS by Targeting AXIN‐RGS Domain (KYA1797K*) in Acute Leukemia</title><p><underline underline-style="single">M.K. Kim</underline><sup>1</sup>, M.R. Lee<sup>1</sup>, J. Lim<sup>1</sup>, S.M. Hahn<sup>1</sup>, J.W. Han<sup>1</sup>, C.J. Lyu<sup>1</sup></p><p><italic><sup>1</sup>Yonsei Cancer Center‐ Yonsei University Health System, Department of Pediatrics, SEOUL, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Signaling pathways in acute leukemia are aberrantly activated to cause leukemogenesis and relapse after treatment. Upregulation of WNT/beta‐catenin pathway is common and hyperactive RAS is strongly associated with treatment resistance in leukemia. Small molecule therapy opened a new window for cancer treatment but targeting one subject may have limitations. KYA1797K binds directly to RGS domain of axin and enhances the beta‐catenin destruction complex which activates GSK3beta and results in degradation of beta‐catenin and RAS. In the current study, the effects of KYA1797K on acute leukemia were studied in leukemic cell mono‐culture and in co‐culturing with human BM‐derived MSC (hBMSC).</p><p><bold>Design/Methods</bold>: Leukemic cells (MOLT‐4, Jurka, KG‐1, THP‐1) were cultured in RPMI1640 media under various concentration (0.2‐10 microM) of KYA1797K and with Erlotinib (1 microM) for comparison. Cell proliferation assay on KYA1797K was done and Immunoblotting for beta‐catenin, GSK3beta, Pan‐RAS was checked and compared between monoculture and co‐culture with hBMSC. Downstream targets of WNT pathway (c‐Myc, CD44, LEF1, Met, TCF1/TCF7) were studied by Immunoblotting in mono‐culture.</p><p><bold>Results</bold>: Suppression of leukemic cells by KYA1797K was evident starting from the concentration of 5 microM. Beta‐catenin was downregulated in all cell lines by KYA1797K. Pan‐RAS was downregulated in MOLT‐4 and THP‐1. All the downstream targets evaluated were downregulated by KYA1797K in MOLT‐4 monoculture which was evident at the concentration of 5microM. Co‐culture of MOLT‐4 with hBMSC showed similar pattern with monoculture for beta‐catenin and Pan‐RAS. Pan‐RAS of hBMSC was not affected.</p><p><bold>Conclusions</bold>: This preclinical study suggest that KYA1797K may be an option for patients with acute leukemia especially who experience relapse. KYA1797K effectively destabilized beta‐catenin and RAS in acute leukemia. Difference in effective concentration may mean the need of further study in each leukemia cell line. The effect of KYA1797K on leukemia‐MSC crosstalk needs further research.</p><p>* KYA1797K (Nat Chem Biol 2016, 12:593) kindly provided by Kang‐Yell Choi.</p></sec><sec id="pbc26772-sec-4230"><label>P-034</label><title>In Vivo Effect of Interferon‐Gamma Primed Mesenchymal Stem Cells on the Growth of Acute Lymphoblastic Leukemia Cells</title><p><underline underline-style="single">H.H. Koo</underline><sup>1</sup>, Y.T. Lim<sup>2</sup>, Y.J. Park<sup>1</sup>, H.J. Park<sup>1</sup>, M.W. Lee<sup>1</sup>, D.S. Kim<sup>1</sup>, K.W. Sung<sup>1</sup>, K.H. Yoo<sup>1</sup></p><p><italic><sup>1</sup>Samsung Medical Center, Pediatrics, Seoul, Republic of Korea; <sup>2</sup>Pusan National University College of Medicine, Pediatrics, Busan, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Although many studies have been tried to clarify cellular interactions between human mesenchymal stem cells (MSCs) and cancer cells <italic>in vitro</italic> models, the role of MSCs in the growth of tumor cells <italic>in vivo</italic> is still not fully understood. In this study, we examined the effect of naive MSCs or interferon (IFN)‐γ‐primed MSCs on the growth of acute lymphoblastic leukemia (ALL) cells in an <italic>in vivo</italic> model.</p><p><bold>Design/Methods</bold>: We established four distinct stable cell lines expressing firefly luciferase (fLuci) gene by infection of lentivirus in Jurkat, CCRF‐CEM, Sup‐T1 and CCRF‐HSB2 ALL cells. We measured luciferase activity using an IVIS optical imaging technique to determine the effects of MSCs on leukemic mass formation.</p><p><bold>Results</bold>: 10<sup>5</sup> ALL/fLuci cells together with 10<sup>6</sup> MSCs were inoculated into NOD/SCID mice by intraperitoneal (IP) injection.Much higher luciferase activity was observed when ALL/fLuci cells were co‐injected with MSCs as compared to that when ALL/fLuci cells were inoculated alone. In addition, we co‐inoculated 10<sup>5</sup> ALL/fLuci cells with different numbers of MSCs (1:1, 1:5 or 1:10 ratio) into mice. Although the bioluminescent intensity gradually increased in all groups, the mice that were co‐injected with 10<sup>6</sup> MSCs showed higher bioluminescent intensity than those co‐injected with lower number of MSC, indicating the possibility that MSCs play an important role in stimulating a leukemic proliferation. To determine the effects of IFN‐γ priming on the growth of leukemic cells by MSCs, ALL/fLuci cells together with IFN‐γ‐primed MSCs were inoculated into NOD/SCID mice via IP injection. Lower luciferase activity was observed when ALL/fLuci cells were co‐injected with IFN‐γ‐primed MSCs as compared to that when ALL/fLuci cells were co‐inoculated with naive MSCs.</p><p><bold>Conclusions</bold>: Our results suggest that IFN‐γ priming may activate MSC's potential anti‐cancer effects. Further studies are needed to elucidate the precise roles of IFN‐γ‐primed MSCs on the microenvironment of leukemia cells.</p></sec><sec id="pbc26772-sec-4240"><label>P-035</label><title>Demographics and Outcome of Philadelphia Chromosome Positive ALL in Pediatric Population in a Resource Constraint Setting – A Single Centre Experience</title><p><underline underline-style="single">A. Kumar</underline><sup>1</sup>, G. Pant<sup>1</sup>, N. Verma<sup>1</sup>, B. Gupta<sup>1</sup>, A. Sharma<sup>1</sup></p><p><italic><sup>1</sup>King George Medical University, Pediatric Oncology, Lucknow, India</italic></p><p><bold>Background/Objectives</bold>: Children with Philadelphia chromosome positive (Ph+) Acute Lymphoblastic Leukemia (ALL) are considered to have a poor prognosis with high risk features. This study was conducted to evaluate the frequency, demographics and outcome of induction chemotherapy in such patients in a resource constraint setting.</p><p><bold>Design/Methods</bold>: Among children with ALL registered from January 2014 to June 2016, in whom flowcytometry and translocations could be done, the demographic data of Ph+ patients were compared with Ph‐ patients. The outcome of Ph+ patients was compared with Ph‐ B and T cell ALL on similar high risk treatment protocols). Ph+ patients additionally received imatinib mesylate as soon as diagnosis was confirmed. Statistical analysis was done by Fischer exact test and outcome by Kaplan Meyer curves for survival analysis.</p><p><bold>Results</bold>: Of 207 patients with ALL, 15(7.28%) were Ph+. No difference was demonstrated between age and sex in Ph+ and Ph‐ ALL (median age 6 years in both and males ‐73.3% and 74% respectively). Median TLC at presentation was significantly higher in Ph+ as compared to Phnegative patients (2,16,000/mm<sup>3</sup> vs 21,000/ mm<sup>3</sup> respectively, p<0.0001). A significantly higher proportion of Ph+ patients 4/15 (26.6%) had CNS leukemia as compared to 1/131 (0.76%) Phnegative patients (p = <0.0004). Though induction deaths were higher 6/15 (40%) in Ph+ patients as compared with Ph‐ high risk patients 10/63(15.8%) this did not reach statistical significance (p = 0.069, OR=3.533 (1.028 to 12.25). Post induction D35 bone‐marrow showed remission in 73.3% Ph+ as compared to 100% of Ph‐ high risk patients.</p><p><bold>Conclusions</bold>: Children with Ph+ ALL (7.28%), had significantly higher TLC and CNS disease at presentation as compared to Ph‐ ALL patients. Induction deaths and failure to reach remission after induction was higher in Ph+ ALL as compared to Ph‐ high risk ALL, despite similar treatment protocol and addition of Imatinib mesylate.</p></sec><sec id="pbc26772-sec-4250"><label>P-036</label><title>CD44 Expression in T Cell Acute Lymphoblastic Leukemia and ITS Association with RAS and NOTCH1 Pathways</title><p><underline underline-style="single">L.V.C. Marques</underline><sup>1</sup>, E. P. Noronha<sup>1</sup>, F. G. Andrade<sup>1</sup>, E. T. G. Pina<sup>1</sup>, M. S. Pombo‐de‐Oliveira<sup>1</sup></p><p><italic><sup>1</sup>INCA, PHOP Programa de Hematologia Oncologia Pediatrica, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: CD44 is an adhesion glycoprotein widely expressend in hematopoietic cells. In murine T‐cell acute lymphoblastic leukemia (T‐ALL) models, CD44 expression was associated with organ infiltration and influencing survival. <italic>CD44</italic> was also identified as a direct NOTCH1 transcriptional target, as well as a target of the RAS pathway, which promotes its alternative splicing, throughout a positive feedback loop. We have investigated whether the cellular expression of CD44 in different maturational subtypes of pediatric T‐ALL could predict <italic>RAS</italic> and <italic>NOTCH1</italic> mutations.</p><p><bold>Design/Methods</bold>: We tested a series of 140 patients with childhood leukemia, being 110 T‐ALL and 30 Acute myeloid leukemia (AML) with less than 18 years of age; evaluated for the immunophenotypic profile by multiparameter flow cytometry and used Sanger sequencing to detect mutation in codons 12 and 13 of <italic>N/KRAS</italic>, 9 and 10 of <italic>FBXW7</italic> and 26, 27 and 34 of <italic>NOTCH1</italic>. CD44 expression was evaluated by median fluorescence intensity (MFI) in leukemic blast cells of patients and 75th percentile MFI value was used as a cutoff between high or low CD44 expression T‐ALL.</p><p><bold>Results</bold>: There was no association between high expression of CD44 and organomegaly in T‐ALL; and between the expression of CD44 among T‐ALL subtypes. AML cases have a higher expression of CD44 (MFI:18890[1019‐44720]) than T‐ALL (MFI:1211[68‐8325]) (p<0.0001). There was no significant difference in CD44 expression between <italic>NOTCH1/FBXW7</italic><sup>mut</sup> cases (MFI:2689[194‐19150]) and <italic>NOTCH1/FBXW7</italic> Wild Type (WT) (MFI:2773[156‐12750]); and between <italic>N/KRAS</italic><sup>mut</sup> cases (MFI:1715[365‐8325]) and <italic>N/KRAS</italic><sup>WT</sup> (MFI:1179[68‐5544]) in T‐ALL, whereas in AML, <italic>N/KRAS</italic><sup>mut</sup> cases had a lower CD44 expression (MFI:10979[7650‐18810]) than <italic>N/KRAS</italic><sup>WT</sup> cases (MFI:21720[1019‐44720]) (p=0.032).</p><p><bold>Conclusions</bold>: CD44 cellular status was not relevant for T‐ALL tumoral profile and its expression was not associated with T‐ALL subtype. CD44 is under expressed in T‐ALL when compared with AML. <italic>N/KRAS</italic> and <italic>NOTCH1/FBXW7</italic> mutations do not seem be associated with different expression of CD44 in pediatric T‐ALL and AML.</p></sec><sec id="pbc26772-sec-4260"><label>P-037</label><title>Dyslipidemia and Glucose Metabolism at Time of Diagnosis in Children with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">P. Mogensen</underline><sup>1</sup></p><p><italic><sup>1</sup>University hospital of Copenhagen, Dept. of Metabolism and Diabetes & Dept. Pediatric Oncology Research, Copehagen Ø, Denmark</italic></p><p><bold>Background / Objectives: Background</bold>: Survivors of childhood acute lymphoblastic leukemia (ALL) have a threefold risk of developing type 2 diabetes, probably caused by intensive chemotherapy including corticosteroids. However, it is unknown if the ALL <italic>per se</italic> contributes to early dysmetabolic manifestations. This study undertook to determine the glycemic and lipid profiles at time of ALL diagnosis before the onset of ALL therapy.</p><p><bold>Design / Methods: Material and methods</bold>: All patients (Median age 4 years (range 1‐17 years) 70 males) were diagnosed with ALL at University Hospital Rigshospitalet, Denmark since 2008.</p><p>122 fasting blood samples were collected at time of diagnosis before onset of therapy. Lipid analyses were performed retrospectively on blood samples collected since 2008. HbA1c, fasting plasma glucose and fasting plasma insulin were measured prospectively in a subgroup (N=24). Insulin resistance was calculated by the HOMA‐IR based on fasting glucose and insulin.</p><p><bold>Results: Preliminary Results</bold>: Preliminary data at baseline showed median (25<sup>th</sup>‐75<sup>th</sup> quartiles) values of BMI 16.3 kg/m<sup>2</sup> (15.4‐18.0), cholesterol 3.2 mmol/L (2.0‐5.1), HDL 0.42 mmol/L (0.08‐1.43), LDL 1.7 mmol/L (0.4‐3.3), triglycerides 2.8 mmol/L (0.6‐6.7) and a triglyceride/HDL‐ratio at 6.8. Median fasting glucose and insulin were 4.9pmol/L (4.4‐5.3) and 24 mmol/L (9‐46) and HbA1c are 6.8 mmol/L (6.5‐7.4). Insulin resistance (HOMA‐IR) was 0.84 (0.20‐1.55).</p><p><bold>Conclusions</bold>: ALL seems to influence metabolic parameters including the lipid profile before start of anti‐leukaemic therapy. Currently, correlation analysis is ongoing in order to understand the mechanisms behind these findings.</p></sec><sec id="pbc26772-sec-4270"><label>P-038</label><title>Survival Analysis of Pediatric Patients with Acute Leukemia and Down Syndrome at the Instituto Nacional De Enfermedades Neoplasicas (LIMA‐PERU)</title><p><underline underline-style="single">J.E. Montoya Vasquez</underline><sup>1</sup></p><p><italic><sup>1</sup>Institutoi Nacional de Enfermedades Neoplásicas, Paediatric Oncology, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Children with Down syndrome (DS) have an increased risk of developing acute leukemia than children without this syndrome. Usually, this type of patients develop more chemotherapy‐related toxicity, severe infectious and toxic deaths. The aim of the study is to examine the overall survival (OS) and the disease‐free survival (DFS) at 5 years of children with DS and acute lymphoblastic leukemia (ALL).</p><p><bold>Design/Methods</bold>: From January 2000 to December 2016, 45 infants and children younger than 14 years with DS who was diagnosed and treated as ALL at the Instituto Nacional de enfermedades Neoplásicas (INEN) were retrospectively reviewed. Medical charts were evaluated for socio‐ demographical, clinical characteristics and treatment outcomes. All descriptive data, OS and DFS was analyzed using Stata 14.0 statistical software. We estimated survival rates with the Kaplan‐Meier method and analyzed the results with log‐rank test and Cox proportional hazard model.</p><p><bold>Results</bold>: With a median follow up time of 50.4 months (range, 1‐192), 5‐year OS and DFS were 38.4% (Standard error, SE 9.4%) and 27.2 (SE 7.8%), respectively. In univariate analysis, younger age (<3 years) and risk group were significantly associated with lower OS and DFS rates. The multivariate analysis showed that younger age was an independent predicting factor for both OS (HR=12.0, p=0.003) and DFS (HR=7.8, p=0.004). High‐risk group patients had worse outcome in terms of DFS (HR=2.5, p=0.007)</p><p><bold>Conclusions</bold>: In this study, younger age and high‐risk ALL children with DS had poor treatment outcomes. Efforts are needed to improve survival in these patients.</p></sec><sec id="pbc26772-sec-4280"><label>P-039</label><title>Epidemiology of Cancers in Infancy</title><p><underline underline-style="single">S. Mudaliar</underline><sup>1</sup>, A. Swami<sup>1</sup>, B. Agarwal<sup>1</sup></p><p><italic><sup>1</sup>B J Wadia Hospital, Pediatric Hemato‐Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Incidence and histological distribution of malignancies in Infants are much different than older children.</p><p>This study was done to establish the incidence and types of malignancies in infants referred in tertiary care centre and to report changes observed over the last three decades.</p><p><bold>Design/Methods</bold>: Data retrieved from referral records maintained in Oncology Department (for 1985‐2015) was analysed and compared to assess incidences and types of malignancies presenting in infants.</p><p><bold>Results</bold>: During the period, a total of 2,307 children were referred. Of them 285 (12%) were infants including 28 (1.2%) Neonates. The sample had 175 male and 110 female (1.5:1). Neuroblastoma, Sacrococcygeal Teratoma, Hepatoblastoma, Wilm tumor and leukaemia were 5 major referrals. In span of 10 years, the representation was –</p><p>1. Percentage of Infant: 61/553 (11%) in first, 108/806 (13.3%) in second and 116 /955 (12.1%) in the third decade.</p><p>2. Major cases: Sacrococygeal tumours (18%), Neuroblastoma (18%) and Leukaemias (25%) respectively were commonest referrals in the three decades.</p><p>3. Ratio of solid to leukaemias was 3:1, 2.6:1 and 1.2:1 respectively in the three decades.</p><p>Other cases referred were hemangioendothelioma, fibrosarcoma, hamartoma, infantile myofibromatosis, mesoblastic nephroma, retinoblastoma, medulloblastoma and ATRT. Very rare malignancies in infants like CML and pancreatoblastoma, 1 case each were diagnosed during 1996‐2005; adrenocortical cancer and ovarian granulose cell tumor during 2006‐2015.</p><p><bold>Conclusions</bold>: Over the three decades, there has been progressive increase in the number of cases referred for malignancies in children.</p><p>The proportion of infants to childhood and adolescents malignancies remained same in last 3 decades.</p><p>Embryonal tumors like neuroblastoma, nephroblastoma, retinoblastoma, hepatoblastoma were more prevalent in infancy. Their early onset and predominantly embryonal nature suggest pre‐natal origin and possibilities of genetic factors. In last two decades, incidence of leukaemias showed increase in infancy as compared to solid tumours (may be due to increased awareness/early referral).</p></sec><sec id="pbc26772-sec-4290"><label>P-040</label><title>Clinico‐Epidemiological Profile and Outcome Predicted by Minimal Residual Disease (MRD) in Children with Mixed Phenotype Acute Leukemia (MPAL)</title><p><underline underline-style="single">H.H. Myint</underline><sup>1</sup>, S. Tandon<sup>1</sup>, G. Narula<sup>1</sup>, M. Prasad<sup>1</sup>, P. Subramanian<sup>2</sup>, P. Tembhare<sup>2</sup>, S. Gujral<sup>2</sup>, B. Arora<sup>1</sup>, S.D. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital‐ Tata Memorial Centre, Pediatric Oncology, Mumbai, India; <sup>2</sup>Tata Memorial Centre, Pathology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Mixed Phenotype Acute Leukemia (MPAL) accounts for 3–5% of acute leukemia of all age groups and has poor prognosis with currently available treatment modalities. Our study evaluated the clinico‐epidemiological profile and outcome of this rare subset of Pediatric leukemia.</p><p><bold>Design/Methods</bold>: Records of the children with acute leukemia from Jan‐2010 to Dec‐2016 were reviewed by 2008 WHO criteria for MPAL. Patients were treated uniformly by modified MCP‐841 protocol, which included high‐dose cytarabine 24gm/m<sup>2</sup> in below 3‐years age, 16gm/m<sup>2</sup> and cranial radiation for 3 or more‐years age. Data collected was subjected to descriptive analysis tools.</p><p><bold>Results</bold>: Among 3,830 children with acute leukemia, 26(0.68%) had MPAL. Median age at diagnosis was 9 years (range:2‐14) with M:F ratio 2.3:1. Median WBC was 13.4×10<sup>9</sup>/L (range:1.5‐364.4). LDH was elevated in 22 cases (median 433U/L, range:173‐4880), while 23% had bulky disease. B/Myeloid was the commonest in 14(53%) cases, followed by T/Myeloid 9(35%) and B/T lymphoid 3(12%). Abnormal cytogenetics was detected in some B/Myeloid cases (2‐AML/ETO, 1‐BCR/ABL, 1‐MLL rearrangement, 1‐Monosomy 7 and 1‐hypodiploidy). Nineteen patients were evaluated for outcome, as 5 were treated elsewhere, 1 refused treatment and 1 opted for oral palliative chemotherapy. Seventeen underwent post‐induction bone marrow of which 14(82%) achieved morphological remission. Fourteen patients had post‐induction MRD status available, 5 were negative, and of the remaining, another 5 became negative post‐consolidation. Remarkably, 80% of 10 MRD‐negative cases were in sustained remission at last follow‐up. None underwent bone marrow transplant. Projected three‐year overall survival was 45% and progression free survival was 40% with median follow‐up of 22 months (range:4‐49).</p><p><bold>Conclusions</bold>: MPAL represented less than 1% of childhood acute leukemia with B/Myeloid being the commonest. Outcome remains poor without transplant for relapse/refractory disease. ALL‐type chemotherapy incorporating high‐dose cytarabine block was effective in achieving MRD‐negativity defined response rate of 71% in evaluated patients, which correlated with better outcome.</p></sec><sec id="pbc26772-sec-4300"><label>P-041</label><title>A Rare Demon: Dengue Fever in Febrile Neutropenia of Pediatric Malignancy</title><p><underline underline-style="single">M. Naseer</underline><sup>1</sup>, P. Ankit<sup>1</sup>, K. Purva<sup>1</sup>, C. Shraddha<sup>1</sup>, V. Krishnan<sup>1</sup>, M. Sangeeta<sup>1</sup>, S. Archana<sup>1</sup>, D. Mukesh<sup>1</sup>, S. Nitin<sup>1</sup>, A. Bharat<sup>1</sup></p><p><italic><sup>1</sup>Bai Jerbai Wadia Hospital for Children, Department of Pediatric Hemato‐Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Febrile neutropenia (FN) is a pediatric oncological emergency where most common organisms are bacteria and fungus, very rarely a virus. In tropical country like India particularly in rainy season lethal dengue virus can be a common organism complicating FN. As management of Dengue Fever (DF) with FN is different from conventional management, early diagnosis is warranted. Clinical profile and outcome of patients with FN with DF in pediatric malignancies at a tertiary care center is analyzed.</p><p><bold>Design/Methods</bold>: All cases of FN in children with leukemia admitted in a tertiary care center between August 2016 till December 2016 were analyzed. Diagnosis DF or Severe DF with FN was based on WHO guidelines. Clinical profile and outcome of patients analyzed.</p><p><bold>Results</bold>: Of 80 patients with FN in unit, 23 had DF or Severe DF. Fever was present in all with febrile seizure in one patient. Typical rash was present in 21%, with third space fluid accumulation in 8% of patients. Average duration of hospital stay was 3.5 days more as compared to other FN patients. Two patients required PICU stay for ionotrope support. All recovered with no mortality. Thrombocytopenia was present in 14 patients with a mean platelet count of 56,000. Abnormal liver function was seen 21%. Dengue NS1 Ag was positive in all with a mean duration of diagnosis of 2.6 days. Dengue IgM ELISA was positive in 30% of patients.</p><p><bold>Conclusions</bold>: Early diagnosis of DF in FN is important as treatment focuses more on fluid resuscitation and monitoring rather than on antibiotics. It reduces the mean duration of hospital stay. Hence, high index of suspicion of DF is required in FN patients to avoid life threatening complications. Strategies by WHO for prevention of mosquito bite needs to be implemented to reduce morbidity associated with DF in children with FN in endemic areas</p></sec><sec id="pbc26772-sec-4310"><label>P-042</label><title>Detection of Minimal Residual Disease in Children with Acute Lymphoblastic Leukemia Treated According to the ALL IC‐BFM‐2002 and ALL IC‐BFM 2009 Protocols</title><p><underline underline-style="single">K. Pawińska‐Wąsikowska</underline><sup>1</sup>, K. Bukowska‐Strakova<sup>2</sup>, M. Surman<sup>2</sup>, W. Balwierz<sup>1</sup></p><p><italic><sup>1</sup>Institute of Pediatrics Jagiellonian University Medical College, Department of Oncology and Hematology, KRAKOW, Poland; <sup>2</sup>Institute of Pediatrics Jagiellonian University Medical College, Department of Clinical Immunology and Transplantology, KRAKOW, Poland</italic></p><p><bold>Background/Objectives</bold>: Monitoring of minimal residual disease (MRD) during the induction treatment is currently recognized the most important prognostic factor in acute lymphoblastic leukemia (ALL). Achievement of MRD below 0.1% on day 15 of induction assessed by multicolor flow cytometry (MFC) is an powerful predictor of survival in ALL patients. Assessment of MRD in other time points can be also crucial, however identification of low amounts residual cells is usually disturbed by excessive regeneration of bone marrow, or by its hypoplasia.</p><p>The main goal of the study was to verify usefulness of monoclonal antibodies’ panel applied in ALL IC‐BFM studies, by 4‐ and 6 and 10‐color flow cytometry to define aberrant phenotypic profiles in ALL blasts.</p><p><bold>Design/Methods</bold>: In this prospective study, we used 4‐color flow cytometry since 2007 to 2009 and 6 –color since 2010 to 2015, and 10‐color flow cytometry since 2016 to detect MRD. Two hundred forty one children with ALL (200 common/preB‐ALL, 9 proB‐ALL, 32 T‐ALL; 140 boys, 101 girls) treated according to ALL IC‐BFM protocols 2002 and 2009: 137 and 104 patients, respectively, were enrolled in this study. Analysis of MRD was performed at day 0 and day 15 and 33 induction of chemotherapy, before consolidation (day 78), as well at the end of therapy. Sensitivity of detection at all time points was at least 1/10 000 cells.</p><p><bold>Results</bold>: In patients with common/preB‐ALL (CD20/CD10/CD34/CD19) and (CD58/CD34/CD45/CD10/CD19/CD20) were most suitable for assessment of leukemic blasts, suggesting that these are the most efficient for MRD detection. Two weeks after ending maintenance chemotherapy is the optimal time for reliable assessment of MRD.</p><p><bold>Conclusions</bold>: Our results shows that even limited panel of antibodies used in the study allows defining leukemic phenotypes and monitoring levels of MRD at set time points despite of changes in expression of antigens during the treatment.</p></sec><sec id="pbc26772-sec-4320"><label>P-043</label><title>Role of Endocannabinoid/Endovanilloid System in T‐CELL LLA</title><p><underline underline-style="single">F. Punzo</underline><sup>1</sup>, C. Tortora<sup>2</sup>, E. Pota<sup>1</sup>, I. Manzo<sup>2</sup>, V. D' Angelo<sup>1</sup>, E. Boccieri<sup>1</sup>, M. Oreste<sup>1</sup>, F. Casale<sup>1</sup>, F. Rossi<sup>1</sup></p><p><italic><sup>1</sup>Università degli Studi della Campania “Luigi Vanvitelli”, Department of Woman‐ Child and General and Specialist Surgery, Napoli, Italy; <sup>2</sup>Università degli Studi della Campania “Luigi Vanvitelli”, Department of Experimental Medicine‐ Division of Pharmacology, Napoli, Italy</italic></p><p><bold>Background/Objectives</bold>: The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G‐Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells.</p><p>We investigated the role of the EC/EV system in T‐Cell Acute Lymphoblastic Leukemia (T‐Cell ALL).</p><p><bold>Design/Methods</bold>: We cultured primary lymphoblasts from 7 children with T‐Cell ALL and Jurkatt cell line, and treated them with a selective CB2 agonist (JWH‐133) and a TRPV1 agonist (RTX). We measured the Apoptosis before and after treatment with JWH‐133 (100nM, 1uM, 5uM) and RTX (2,5uM and 5uM), at 6, 12 and 24 hours, performing a citofluorimetric Annexin V Assay and we evaluated the expression level of 2 target genes (Caspase 3 and p53) by Real‐Time PCR and Western Blotting.</p><p><bold>Results</bold>: We observed a dose‐response effect after JWH‐133 treatment, while stimulating the Vanilloid receptors caused a non‐dose dependent increase in apoptosis. The effect is more striking at 6 hours after treatment and it decreases with time. Moreover Caspase‐3 and p53 mRNA and protein levels where increased 12 hours after exposure to JWH‐133 at the concentration of 100nM, both in primary lymphoblast cell cultures as in Jurkatt cell line.</p><p><bold>Conclusions</bold>: In conclusion we observed a pro‐apoptotic effect induced by EC/EV compounds, by up‐regulating 2 target genes (Caspase‐3 and p53) both in primary lymphoblasts obtained from patients with T‐Cell ALL and in Jurkatt cell line. Our results show that both CB2 stimulation and TRPV1 activation, can increase the Apoptosis in vitro, indicating that a new therapeutic approach to T‐cell ALL might be possible by modulating the Endocannabinoid/Endovanilloid system.</p></sec><sec id="pbc26772-sec-4330"><label>P-044</label><title>Monosomy/Total Loss of Chromosome 7 in Pediatric Acute Leukemia: Report from a Single Institution in Argentina</title><p><underline underline-style="single">C.D. Quispe</underline><sup>1</sup>, E. Baialardo<sup>2</sup>, M. Guitter<sup>1</sup>, J. Rossi<sup>3</sup>, C. Alonso<sup>1</sup>, E. Alfaro<sup>1</sup>, C. Sanchez La Rosa<sup>1</sup>, N. Millan<sup>1</sup>, P. Zubizzareta<sup>1</sup>, M. Felice<sup>1</sup></p><p><italic><sup>1</sup>Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Hematology and Oncology, Buenos Aires, Argentina; <sup>2</sup>Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Genetic, Buenos Aires, Argentina; <sup>3</sup>Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Immunology and Rheumatology, Buenos Aires, Argentina</italic></p><p><bold>Background/Objectives</bold>: Chromosome‐7 abnormalities are frequent acute myeloid leukemia (AML) and myelodysplasia. However, they are not usually detected in acute lymphoblastic leukemia (ALL). Monosomy/total loss‐chrosome‐7 has been associated with adverse outcome in AML and its prognostic significance in ALL is not clearly defined.</p><p>1‐To analyze clinical/biological characteristics and outcome of patients with monosomy/loss‐chromosome‐7. 2‐To compare prognostic value in AML and ALL.</p><p><bold>Design/Methods</bold>: From January‐1990 to January‐2017, 447 AML and 1531 ALL patients were admitted. Monosomy/loss‐chromosome‐7 was detected in 21 (4.5%) AML and 26 (1.7%) ALL patients. We evaluated clinical/biological features and outcome. The pEFS was estimated by Kaplan‐Meier and compared with log‐rank‐test.</p><p><bold>Results</bold>: No differences were observed in age and WBC count when comparing AML vs. ALL. Monosomy/loss‐chromosome‐7 as unique abnormality was detected in 11 AML and 3 ALL cases. We divided ALL with loss‐chromosome‐7 in 2 groups: <45 (n=15) or >45 chromosomes (n=11). Complete remission (CR) was achieved in 14/21 (66%) AML cases, 3 died early and 4 presented null response. Of the 14 who achieved CR, 8 relapsed, 3 died in CR and 3 remain in CR. Regarding ALL, 23 (88%) achieved CR, 2 died early and 1 patient presented null response. Of the 23 patients who achieved CR, 3 relapsed, 2 died in CR and 18 remain in CR. The pEFS for AML with monosomy/loss‐chromosome‐7 was 12(10)% vs. 50(3)% for AML without this abnormality (p=0.0113). For ALL cases with loss‐chromosome‐7, pEFS(SE) was 61(11)% and 70(1)% for ALL without this abnormality (p=0.3925). The pEFS(SE) for ALL patients with monosomy‐7 alone was 33(27)%. If we compare cases <45 chromosomes vs. >45 chromosomes pEFS(SE) was 38(15)% and 100% respectively (p=0.0067).</p><p><bold>Conclusions</bold>: Monosomy/loss‐chromosome‐7 conferred significant inferior outcome to AML patients. In ALL, monosomy‐7 did not influence survival probabilities. However, ALL patients with monosomy‐7 and non‐hypodiploid achieved a significant better survival rates than hypodiploid plus loss‐chromosome‐7 cases.</p></sec><sec id="pbc26772-sec-4340"><label>P-045</label><title>Cytomegalovirus Retinitis in Children with Acute Lymphoblastic Leukemia During Maintenance Phase Chemotherapy</title><p><underline underline-style="single">A.A. Rahman</underline><sup>1</sup>, F. Begum<sup>2</sup>, M. Begum<sup>1</sup>, C.S.H. Kibria<sup>1</sup>, A. Islam<sup>1</sup>, C.Y. Jamal<sup>1</sup>, S. Fateha Noor<sup>3</sup></p><p><italic><sup>1</sup>Bangabandhu Sheikh Mujib Medical University, Pediatric Hematology and Oncology, Dhaka, Bangladesh; <sup>2</sup>National Institute of Cancer Research and Hospital, Paediatric Oncology, Dhaka, Bangladesh; <sup>3</sup>Bangabandhu Sheikh Mujib Medical University, department of dermatology, Dhaka, Bangladesh</italic></p><p><bold>Background/Objectives</bold>: Viral infections are an under recognized problem in children on standard chemotherapy for acute lymphoblastic leukemia (ALL). Cytomegalovirus (CMV) is an important cause of morbidity and mortality in immunocompromised individuals. But data regarding the incidence and manifestations of CMV disease in pediatric ALL patients are scanty. Cytomegalovirus retinitis (CMVR) is rarely reported in children with ALL who did not receive hematopoietic stem cell transplantations (HSCT) and quite rare during maintenance phase therapy. Herein, we report cases of bilateral cytomegalovirus retinitis in children with ALL during maintenance phase therapy; highlighting the importance of eye examination and care in patients diagnosed with acute lymphoblastic leukemia.</p><p><bold>Design/Methods</bold>: During the period from January to December’ 2016, we found three cases of CMV retinitis in children with ALL at our department who were referred to ophthalmologist for reduced vision. CMVR was diagnosed by the presence of characteristic lesion on fundoscopy in immunocompromised state as confirmed by ophthalmologist and positive CMV DNA in blood sample.</p><p><bold>Results</bold>: We identified total three male children of CMVR during one year period with age range 3.8 to 6 yr. The underlying causes of immunocompromise were chemotherapy for leukemia ; identified as having CMVR during maintenance phase therapy. All the three children were neutropenic for a period of days to months before ; were getting treatment for febrile neutropenia. Cytomegalovirus retinitis was bilateral in all three children. Discontinuation of immunosuppressive medications and administration of anticytomegalovirus drugs led to regression of active retinitis . later 2/3 children died within 1 to 5 months of being diagnosed with cytomegalovirus retinitis. The remaining one child is alive, with improvement of vision.</p><p><bold>Conclusions</bold>: The present cases suggests that pediatric patients with ALL in the maintenance phase may be immunosuppressed and immediate ophthalmologic examination and CMV testing is warranted in cases with disturbances of visual acuity.</p></sec><sec id="pbc26772-sec-4350"><label>P-046</label><title>Acute Lymphoblastic Leukaemia; Are We Missing Early Diagnosis In Children?</title><p><underline underline-style="single">J. Ranasinghe</underline><sup>1</sup>, W. Rathnayaka<sup>2</sup>, I. Dharshika<sup>1</sup>, S. Liyanarachchi<sup>1</sup>, L. Samaranayaka<sup>1</sup>, K. Premachandra<sup>1</sup></p><p><italic><sup>1</sup>Lady Ridgeway Hospital for Children, General Paediatrics, Colombo 08, Sri Lanka; <sup>2</sup>National Cancer Institute, Pediatric Clinical Oncology, Maharagama, Sri Lanka</italic></p><p><bold>Background/Objectives</bold>: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy accounting for one‐fourths of all childhood cancers and three‐fourths of all newly diagnosed patients with acute leukemia. The incidence varied from 03 to 04 / 100,000 children with a male predominance. The objective was to evaluate the presenting features and time duration to diagnose ALL in children presenting to National Cancer Institute (NCI), Sri Lanka.</p><p><bold>Design/Methods</bold>: This retrospective cross sectional study was carried out at Paediatric unit‐A of NCI. All patients were less than 15 years and confirmed with ALL. Data was collected using an interviewer administered questionnaire and from health records.</p><p><bold>Results</bold>: A total of 85 children included with 58 (68.2%) were males. Age ranged from 08 months to 11 years. Majority (n=66,77.6%) were “B”‐immunophenotype. CD 10 surface antigen was detected in 31 (36%) and in 33 (38.8%) none were detected. Others were CD 05(n=01), 13(n=03), 19(n=01), 20(n=02) & 117(n=01). Only 39 patients (47.6%) were diagnosed within first 14 days. Three patients took 4 months. The longest time taken was 15 months who have had steroid treatments frequently. The most common symptom was “intermittent fever” complained by 52 patients (67%). Other common symptoms were neck lump (n=14,16%), joint pain (n=11,13%), myalgia (n=7,8%), loss of appetite (n=05,05.8%), lethargy (n=05,05.8%), respiratory tract infection (n=04,04.7%), rash (n=04,04.7%), acute gastroenteritis, abdominal mass, ecchymosis, limping, investigated for anaemia, headache, generalized lymphadenopathy and chest pain etc. Only 13 patients had white cell count <04.0x10<sup>3</sup>/ml<sup>3</sup> and 43%(n=36) had leucocytosis. Only 74.7%(n=56) had platelet count <150x10<sup>3</sup>/ml<sup>3</sup> and 01.3%(n=2) thrombocytosis and 72%(n=54) had haemoglobin <10g/dl. However these findings were not statistically significant.</p><p><bold>Conclusions</bold>: Only 39(47.6%) patients were diagnosed within the first 14 days. The most common symptom was “intermittent fever” and this was the complaint in 52 (67%) patients.</p></sec><sec id="pbc26772-sec-4360"><label>P-047</label><title>Effects of Ubiquitin Ligase HUWE1 on Metabolic Imbalances in Leukemic Cells</title><p><underline underline-style="single">M. Ruckert</underline><sup>1</sup>, A. Brouwers‐Vos<sup>2</sup>, L.G. Tone<sup>3</sup>, J.J. Schuringa<sup>2</sup>, V.S. Silveira<sup>1</sup></p><p><italic><sup>1</sup>University of São Paulo, Department of Genetics, Ribeirão Preto, Brazil; <sup>2</sup>University Medical Center Groningen, Experimental Hematology, Groningen, The Netherlands; <sup>3</sup>University of São Paulo, Department of Pediatrics, Ribeirão Preto, Brazil</italic></p><p><bold>Background/Objectives</bold>: Acute lymphoid leukemia (ALL) is the most common childhood malignancy. Philadelphia chromosome (Ph) is present in 5% of childhood cases. Ph positive leukemias express the tyrosine kinase BCR‐ABL, that is responsible for constitutive activation of RAS pathway and mediates leukemic cells proliferation. Even with high cure rates, a lot of patients develop resistance to treatment and relapse. Previously published data suggests association between hyperactivation of RAS pathway and favorable treatment outcome, pointing to a new research approach. HUWE1 participates in negative feedback mechanism controlling Shoc2 activity in activation of ERK1/2. Thus, it can be assumed that loss of HUWE1 would lead to increased activation of ERK1/2 and, therefore, hyperactivation of RAS pathway.</p><p><bold>Objectives</bold>: To evaluate the impact of <italic>HUWE1</italic> knockdown in leukemic cell lines.</p><p><bold>Design/Methods</bold>: ALL, chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) cell lines were transduced with miR‐E lentiviral particles for gene knockdown. Flow cytometry, qPCR, Western Blot and apoptosis assay were performed.</p><p><bold>Results</bold>: <italic>HUWE1</italic> knockdown cells showed decreased proliferation in Nalm‐6, K562 and THP‐1, but not HL‐60. Nalm‐6 showed increased apoptosis levels, which correlate with significant <italic>p21</italic> upregulation (P<0.05), however, p‐ERK1/2 increase was not seen. K562 showed no changes in apoptosis or <italic>p21</italic> expression despite the increase in p‐ERK1/2. Regarding AML cells, THP‐1 showed increase in p‐ERK1/2 and <italic>p21</italic> expression (P<0.05). Besides having no disadvantage in growth, HL‐60 showed downregulation of <italic>p21</italic> when p‐ERK1/2 was increased, suggesting that hyperactivation of RAS pathway might have protective effect on them. This opposite behavior between THP‐1 and HL‐60 reveals an interesting path involving <italic>HUWE1</italic> because these cell lines have opposite metabolic patterns: THP‐1 relies on oxidative phosphorylation while HL‐60 are glycolytic cells.</p><p><bold>Conclusions</bold>: These results suggest that <italic>HUWE1</italic> might play a role in metabolic imbalances in leukemic cells. Further studies are necessary to investigate this correlation.</p><p>Financial Support: FAPESP (Process 2015/12146‐5)</p></sec><sec id="pbc26772-sec-4370"><label>P-048</label><title>Detection of IKZF1 Deletions by a Very Simplified and Low‐Cost Reverse Transcription Polymerase Chain Reaction (RT‐PCR) Technique and ITS Impact on Childhood All Prognosis</title><p>L.B.P. Moreira<sup>1</sup>, R.D.P. Queiróz<sup>1</sup>, E. Perna<sup>1</sup>, V.K. Suazo<sup>1</sup>, L.G. Tone<sup>1</sup>, <underline underline-style="single">C.A. Scrideli</underline><sup>1</sup></p><p><italic><sup>1</sup>Ribeirão Preto School of Medicine ‐ University of São Paulo, Pediatrics, Ribeirão Preto, Brazil</italic></p><p><bold>Background/Objectives</bold>: <italic>IKZF1</italic> gene deletion has been associated with worse prognosis in children with acute lymphoblastic leukemia (ALL). Its detection has been made by laborious and expensive techniques, making it difficult to perform at most treatment centers, especially in developing countries. This study analyzed the presence of deletions of the <italic>IKZF1</italic> gene in children with ALL by a very simplified and low‐cost RT‐PCR technique and evaluated its association with prognosis</p><p><bold>Design/Methods</bold>: It were analyzed 48 consecutive BM samples obtained from children with ALL (41 pre‐B and 7 T‐ALL) treated according to the Brazilian Treatment Protocol, with a median follow‐up of 120 months. The same cDNA used to the routine translocation studies were amplified by RT‐PCR using only a pair of primers that flanks the exons 1 to 8 of the <italic>IKZF1</italic> gene. The product obtained was electrophoresed in 2% agarose gel. Association between <italic>IKZF1</italic> deletion and event‐free survival (EFS) was assessed by Kaplan Meier curves and multivariate analysis by Cox Regression Model</p><p><bold>Results</bold>: Deletion in the<italic>IKZF1</italic> gene was observed in 6/41 (14.6%) samples of B‐derived ALL and in none of the T‐ALL. Ten years EFS was 70.1 ± 7.3% versus 16.7 ± 15.2 (P = 0.017), for the groups with and without <italic>IKZF1</italic> deletion respectively, with a relative risk of unfavorable event of 3.27 (95% CI: 1.15‐9.32) for the presence of the deletion. Multivariate analysis showed that IKZF1 deletion was an independent prognostic factor (P = 0.028) when analyzed in association with age and number of WBC at diagnosis</p><p><bold>Conclusions</bold>: The present study suggests that the use of a simplified and low cost <italic>IKZF1</italic> deletion analysis technique is capable of detecting patients at higher risk of relapse and may be useful in the stratification of patients with B lineage ALL in future treatment protocols. Larger multicentric studies are necessary to confirm these Results:</p></sec><sec id="pbc26772-sec-4380"><label>P-049</label><title>Angiogenesis in Children with Acute Lymphoblastic Leukemia Based on Serum VEGF Concentration Assay</title><p><underline underline-style="single">G. Sobol‐Milejska</underline><sup>1</sup>, A. Mizia‐Malarz<sup>1</sup>, K. Musioł<sup>1</sup></p><p><italic><sup>1</sup>Medical University of Silesia ‐ Upper Silesia Centre for Child's Health, Department of Oncology‐Hematology and Chemotherapy, Katowice, Poland</italic></p><p><bold>Background/Objectives</bold>: Angiogenesis is a process essential for growth and development of all human tissues. VEGF has a key role in angiogenesis stimulation.The purpose of the study was to assess angiogenesis in children with acute lymphoblastic leukemia (ALL) based on serum VEGF level determined at diagnosis and at remission (day 33 ), with further subject subdivision into different risk groups</p><p><bold>Design/Methods</bold>: Forty children, aged 3‐12 y, with newly diagnosed ALL, treated according to the ALLIC 2002 protocol were enrolled in the study. They were classified to 3 groups: SRG‐18pts, IRG 12pts HRG 10pts. The control group‐20 healthy children. VEGF serum concentration was determined at diagnosis and on day 33. of treatment.</p><p><bold>Results</bold>: At baseline, serum levels of VEGF were determined in the entire study group and healthy controls. The median of VEGF serum level of 185.2 pg/mL (22.3‐684.4) in study patients was comparable to the one of controls (144.6 pg/mL; 32.7‐237.9). was comparable to the one of controls (144.6 pg/mL; 32.7‐237.9).</p><p>The median values of serum VEGF at diagnosis were comparable between the SRG and the control groups, and significantly higher in IRG and HRG as compared to the control group. At remission the median of serum VEGF level was significantly higher in all study groups, as compared to the controls.</p><p>The median of serum VEGF levels in group SRG was significantly higher at remission. The median values of serum VEGF on day 33 were higher in groups IRG and HRG without statistical signification.</p><p><bold>Conclusions</bold>: The significant higher level of serum VEGF in children with ALL in comparison with healthy control, both at the diagnosis and in the remission, could suggest the intensification of angiogenesis in the bone marrow, at diagnosis. There is a tendency for higher serum VEGF level in the groups with less satisfying prognosis,which suggests the needs of further studies.</p></sec><sec id="pbc26772-sec-4390"><label>P-050</label><title>Thrombosis in Childhood Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">D. Sosothikul</underline><sup>1</sup>, N. Yupensuk<sup>1</sup>, K. Chiengthong<sup>1</sup>, S. Lauhasurayotin<sup>1</sup>, P. Techavichit<sup>1</sup>, P. Seksarn<sup>1</sup></p><p><italic><sup>1</sup>Chulalongkorn University‐ King Chulalongkorn Memorial Hospital, Department of Pediatrics, bangkok, Thailand</italic></p><p><bold>Background/Objectives</bold>: Thromboembolism is a serious complication associated with morbidity in childhood acute lymphoblastic leukemia (ALL). The risk of thrombotic complication in childhood ALL ranges widely from 1‐37% worldwide.To study prevalence and risk factor of thrombosis in childhood ALL.</p><p><bold>Design/Methods</bold>: A retrospective descriptive study in patients with thrombosis in children diagnosed as ALL at King Chulalongkorn Memorial Hospital,Thailand from 2005 to 2016.</p><p><bold>Results</bold>: The prevalence of thrombosis in 220 cases of childhood ALL was 5.5 %. Twelve patients were diagnosed with thromboembolism (4 males and 8 females). Age ranged from 4 to 14 years (median 9.7 years). Most thromboembolism events occurred during the induction phase of chemotherapy (83%). Patients with high risk and very high risk ALL were likely to develop thromboembolism event (67%). Clinical manifestation of thrombosis events was cerebral thrombosis (67%) followed by deep vein thrombosis (33%). The risk factors of thrombotic event were the administration of asparaginase (58%) followed by the indwelling of central line (33%). Older children more than age 10 years were at higher risk for developing cerebral thrombosis. Management of thrombotic events was low‐molecular‐weight heparin at 1 mg/kg/dose twice a day for 1‐3 months then switched to warfarin until the risk factors were resolved. Doppler ultrasound, computed tomography, magnetic resonance imaging were the methods used in thrombosis detection and follow up for resolving. Median time for resolving cerebral thrombosis and deep vein thrombosis was 5.6 and 3.2 months, respectively. Transfusion of fresh frozen plasma before starting asparaginase treatment is currently recommended for preventing recurrent thrombotic events.</p><p><bold>Conclusions</bold>: The prevalence of thrombosis in childhood ALL is quite high especially in older children and does interfere with the treatment plan. Thrombosis among childhood ALL is often observed in patients receiving asparaginase and central line insertion. Preventive strategies in this group of patients should be considered.</p></sec><sec id="pbc26772-sec-4400"><label>P-051</label><title>Circulating Endothelial Cells and Metabolic Status in Childhood Cancer Survivors</title><p>E. Athanasopoulos<sup>1</sup>, G. Martimianaki<sup>1</sup>, E. Kampouraki<sup>1</sup>, M. Stratigaki<sup>1</sup>, E.A. Markaki<sup>1</sup>, N. Katzilakis<sup>1</sup>, <underline underline-style="single">E. Stiakaki</underline><sup>1</sup></p><p><italic><sup>1</sup>University of Crete‐ University Hospital of Heraklion, Pediatric Hematology‐Oncology, Heraklion Crete, Greece</italic></p><p><bold>Background/Objectives</bold>: Circulating Endothelial Progenitor Cells (CEPCs) play a significant role in the maintenance of vascular integrity, balancing the anti‐coagulation mechanisms and regulating the leukocyte trafficking. Additionally, it is well‐established, that patients who underwent chemotherapy have increased incidence of hypertension and obesity. Nevertheless, numerous studies have shown a negative correlation between CEPCs and obesity, underlining poor vascular repair.</p><p><bold>Objective</bold>:The study of CEPCs in childhood survivors of Acute Lymphoblastic Leukemia (ALL) and solid tumors (ST) and the investigation of their levels in correlation with patients Body Mass Index (BMI) and blood pressure (BP).</p><p><bold>Design/Methods</bold>: Four colour flow cytometry was performed to determine the subpopulations <bold>CD34+CD45negdimCD133+</bold>, <bold>CD34+CD45negdimVEGFR2</bold>+ and <bold>CD34+CD45negdimCD133+VEGFR2+</bold> of CEPCs in the peripheral blood from children with ALL(n=104), ST(n=97) and children without malignancies as control group(n=125).The BMI and BP of the patients were calculated and the percentiles were established specific by the age and gender.</p><p><bold>Results</bold>: Patients characteristics.
<table-wrap id="nlm-table-wrap-2" xml:lang="en" orientation="portrait" position="anchor"><table frame="hsides" rules="groups"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"><bold>ALL</bold></th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"><bold>ST</bold></th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"><bold>CONTROL</bold></th><th align="left" rowspan="1" colspan="1"></th></tr><tr style="border-bottom:solid 1px #000000"><th align="left" rowspan="1" colspan="1"><bold>Time post‐treatment</bold></th><th align="left" rowspan="1" colspan="1"><bold>N</bold></th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"><bold>N</bold></th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"></th><th align="left" rowspan="1" colspan="1"></th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1"><bold><1year</bold></td><td align="left" rowspan="1" colspan="1"><bold>20</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>21</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>1‐3years</bold></td><td align="left" rowspan="1" colspan="1"><bold>28</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>33</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>>= 3years</bold></td><td align="left" rowspan="1" colspan="1"><bold>56</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>43</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>BMI</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Normal weight</bold></td><td align="left" rowspan="1" colspan="1"><bold>56</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>53</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Overweight/Obese</bold></td><td align="left" rowspan="1" colspan="1"><bold>48</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>44</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>BP</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Normal BP</bold></td><td align="left" rowspan="1" colspan="1"><bold>60</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>58</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>High‐normal BP/Hypertension</bold></td><td align="left" rowspan="1" colspan="1"><bold>44</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>39</bold></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1"><bold>Μean</bold></td><td align="left" rowspan="1" colspan="1"><bold>SE</bold></td><td align="left" rowspan="1" colspan="1"><bold>Μean</bold></td><td align="left" rowspan="1" colspan="1"><bold>SE</bold></td><td align="left" rowspan="1" colspan="1"><bold>Μean</bold></td><td align="left" rowspan="1" colspan="1"><bold>SE</bold></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>CD34(+)VG(+)</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00316</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00044</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00575</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00124</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.003231142</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00292</bold></td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>CD34(+)CD133(+)VG(+)</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00290</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00044</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00474</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.00096</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.000332029</bold></td><td align="left" rowspan="1" colspan="1"><bold>0.0003</bold></td></tr></tbody></table><permissions><copyright-holder>John Wiley & Sons, Ltd.</copyright-holder><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions></table-wrap></p><p>The levels of CEPCs in ALL did not show any significant difference between the time post treatment. In solid tumors the levels of CEPCs during the 1<sup>st</sup> year post‐treatment are significantly higher than those in the following years. The correlation between BMI and CEPCs in ALL and ST group, showed statistically significant difference between overweight/Obese survivors. The study of BP status in ALL and ST have no significant difference.</p><p><bold>Conclusions</bold>: The levels of CEPCs are increased during the 1st year after treatment of solid tumors, finding that needs further investigation in relation with metabolic factors in childhood cancer survivors.</p></sec><sec id="pbc26772-sec-4410"><label>P-052</label><title>Presence of Minimal Residual Disease Detected by Flow Cytometry is a Predictor of Early Relapse in Patients with T Cell Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">P. Subramanian</underline><sup>1</sup>, P. Tembhare<sup>1</sup>, G. Chaterjee<sup>1</sup>, S. Goghale<sup>1</sup>, Y. Badrinath<sup>1</sup>, N. Patkar<sup>1</sup>, G. Narula<sup>2</sup>, B. Arora<sup>2</sup>, S. Banavali<sup>2</sup></p><p><italic><sup>1</sup>Tata Memorial Centre, Hematopathology Laboratory, Mumbai, India; <sup>2</sup>Tata Memorial Centre, Medical Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: We investigated the value of assessment of post‐induction minimal residual disease (MRD) in bone marrow by flow cytometry (FC) in childhood T cell Acute Lymphoblastic Leukemia (T‐ALL).There are a few studies on the relevance of Minimal residual disease (MRD) evaluation in (T‐ALL). AIEOP‐BFM group showed that late (Day‐78) MRD response determines overall risk‐of‐relapse and event‐free‐survival (EFS) using RQ‐PCR. A larger study by COG (Brent Wood et al. ASH, 2014) showed that post‐induction (Day‐29) FC‐MRD was more relevant in prediction of EFS.</p><p><bold>Design/Methods</bold>: We studied post‐induction (Day‐35) MRD (PI‐MRD) in bone marrow samples from 100 children under the age of 16 years with T‐ALL treated using modified MCP‐841 protocol between 2014 & 2016. In T‐ALL with early‐T cell‐precursor (ETPALL) immunophenotype, patients received Dexamethasone in place of Prednisolone. MRD was performed using 10‐color FC‐MRD assay on Navios flow cytometer and analysis was performed with Kaluza software v‐1.3 (Beckman Coulter).</p><p><bold>Results</bold>: Median age of patients was 11.5 years (range 2–15 y; M:F–4.6). Initial immunophenotype was ETPALL in 12/100 patients. PI‐MRD was positive in 58/100 (58%) with median level of 0.23% (range, 0.002%‐6%). PI‐MRD positivity was significantly high in ETPALL as compared to non‐ETPALL (93% vs 53%; <italic>p</italic>=0.01). Median follow‐up of all patients was 13.2 months (3‐38 months). Patients were categorised MRD negative (MRD‐N) if PI‐MRD was negative and MRD positive (MRD‐P) if PI‐MRD was positive with any level. Thus, 42% were categorized as MRD‐N & 58% as MRD‐P. Twenty patients relapsed & of them six died (2 were ETPALL & 18 non‐ETPALL; 3 MRD‐N & 17 MRD‐P) within 26 months. Median EFS of MRD‐P patients was significantly inferior as compared to MRD‐N (26 months vs. did not reach; & 70.67% vs. 92.86%; <italic>p</italic>=0.0017).</p><p><bold>Conclusions</bold>: We conclude that post‐induction FC‐MRD positivity is a predictor of early relapse in childhood T‐ALL.</p></sec><sec id="pbc26772-sec-4420"><label>P-053</label><title>Monocytic Lineage Switch in B‐Cell‐Precursor Acute Lymphoblastic Leukemia in Children – Temporary Escape or Mechanism of Chemotherapy Resistance?</title><p>M. Twardoch<sup>1</sup>, A. Sonsala<sup>1</sup>, L. Sedek<sup>2</sup>, M. Pierzyna<sup>2</sup>, J. Bulsa<sup>1</sup>, J. Kulis<sup>1</sup>, I. Malinowska<sup>3</sup>, J. Trelinska<sup>4</sup>, E. Niedzielska<sup>5</sup>, K. Derwich<sup>6</sup>, W. Badowska<sup>7</sup>, M. Niedzwiecki<sup>8</sup>, G. Sobol‐Milejska<sup>9</sup>, K. Muszynska‐Roslan<sup>10</sup>, A. Koltan<sup>11</sup>, G. Karolczyk<sup>12</sup>, M. Woszczyk<sup>13</sup>, T. Ociepa<sup>14</sup>, J. Kowalczyk<sup>15</sup>, <underline underline-style="single">T. Szczepański</underline><sup>1</sup></p><p><italic><sup>1</sup>Medical University of Silesia, Department of Pediatric Hematology and Oncology, Zabrze, Poland; <sup>2</sup>Medical University of Silesia, Department of Microbiology and Immunology, Zabrze, Poland; <sup>3</sup>Medical University of Warsaw, Department of Pediatric Hematology and Oncology, Warsaw, Poland; <sup>4</sup>Medical University‐ Lodz, Department of Pediatric Oncology‐ Hematology and Diabetology, Lodz, Poland; <sup>5</sup>Medical University‐ Wroclaw, Department of Bone Marrow Transplantation‐ Pediatric Hematology and Oncology, Wroclaw, Poland; <sup>6</sup>University of Medical Sciences‐ Poznan, Department of Pediatric Hematology‐ Oncology and Transplantology, Poznan, Poland; <sup>7</sup>Regional Specialistic Pediatric Hospital, ‐, Olsztyn, Poland; <sup>8</sup>Medical University‐ Gdansk, Department of Pediatric Hematology‐ Oncology and Endocrinology, Gdansk, Poland; <sup>9</sup>Medical University of Silesia, Department of Pediatrics, Katowice, Poland; <sup>10</sup>Medical University‐ Bialystok, Department of Pediatric Oncology, Bialystok, Poland; <sup>11</sup>Collegium Medicum in Bydgoszcz, Department of Pediatric Hematology and Oncology, Bydgoszcz, Poland; <sup>12</sup>Regional Specialistic Pediatric Hospital, ‐, Kielce, Poland; <sup>13</sup>Chorzow Center of Pediatrics and Oncology, ‐, Chorzow, Poland; <sup>14</sup>Pomeranian Medical University, Department of Pediatrics‐ Hematology and Oncology, Szczecin, Poland; <sup>15</sup>Medical University‐ Lublin, Department of Pediatric Hematology and Oncology, Lublin, Poland</italic></p><p><bold>Background/Objectives</bold>: In a small proportion of childhood B‐cell‐precursor acute lymphoblastic leukemia (BCP‐ALL), the leukemic blasts switch their immunophenotype towards monocytic lineage (swBCP‐ALL). The aim of the study was to determine the frequency and immunophenotypic features of patients with swBCP‐ALL in Poland.</p><p><bold>Design/Methods</bold>: The study group comprised 940 pediatric patients with BCP‐ALL, aged 0‐18 years (median 4.6 years) treated according to the ALL‐IC‐BFM 2009 protocol in 14 Polish hemato‐oncology centers between 2012 and 2017. Bone marrow or peripheral blood samples were stained at diagnosis and during follow up with 7‐ and 8‐color monoclonal antibody panels. Data were analyzed using Infinicyt software (Cytognos SL, Spain) and FACSDiva (BD Bioscience, USA).</p><p><bold>Results</bold>: The monocytic lineage switch during the induction treatment was observed in 29/940 (3.1%) BCP‐ALL patients and was usually associated with high expression of CD34 (27/29 cases), weak or partial expression of CD10 (24/29 cases) and expression of CD2 (11/13 cases) at diagnosis.</p><p>In all patients with detectable aberrant monocytoid cells during follow up, weak expression of CD19 and CD34 was found. The expression of CD10 and CD22 in most patients with swBCP‐ALL was decreased in comparison to diagnosis. Furthermore, at least partial expression of CD2, CD14, CD13 and CD33 was detected on residual blasts in most patients with swBCP‐ALL. In addition, in all swBCP‐ALL patients expression of CD2 observed at diagnosis was maintained during treatment.</p><p>Finally, the MRD levels at day 15 were significantly higher in swBCP‐ALL patients compared with the remaining BCP‐ALL patients with positive MRD level (MRD>0) (median MRD level: 10.45%, and 0.68%, respectively; p<0.01).</p><p><bold>Conclusions</bold>: In conclusion, swBCP‐ALL is a rare subset of BCP‐ALL cases detected mainly during induction treatment. Significantly higher MRD levels at day 15 suggest slower response to induction treatment in swBCP‐ALL patients. Further investigation and follow up is needed to determine, if the monocytic lineage switch has significant clinical value.</p></sec><sec id="pbc26772-sec-4430"><label>P-054</label><title>Minimal Residual Disease and ETV6‐RUNX1 Predicts Improved Outcomes of Hypodiploid Acute Lymphoblastic Leukemia (ALL): A Single Centre Experience of 254 Children</title><p><underline underline-style="single">S. Tandon</underline><sup>1</sup>, G. Narula<sup>1</sup>, M. Prasad<sup>1</sup>, B. Arora<sup>1</sup>, P. Subramanium<sup>2</sup>, P. Tembere<sup>2</sup>, S. Gujral<sup>2</sup>, D. Shetty<sup>3</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Centre, paediatric hemato‐oncology, Mumbai, India; <sup>2</sup>Tata Memorial Centre, Haematopathology, Mumbai, India; <sup>3</sup>Tata Memorial Centre, cytogenetics, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Hypodiploidy constitutes 5 % of ALL with poorer prognosis on currently available therapy. Our study evaluated clinico‐epidemiological profile, outcomes, cytogenetic, MRD correlation of this subset of paediatric ALL.</p><p><bold>Design/Methods</bold>: Data of all children with ALL having hypodiploidy on conventional cytogenetics from Jan2008‐Nov2016 was retrospectively analyzed from electronic medical records and patient charts. Children were treated on different institutional protocols before and after Feb‐2013. Principal differences were use of high‐dose cytarabine and cranial radiation in the earlier era, and routine use of MRD and high‐dose methotrexate in the latter.</p><p><bold>Results</bold>: B ALL was diagnosed in 3208 children during the study period; 254(8%) had hypodiploidy. Median age was 6 years (1‐15), M: F 2.5:1. Median leukocyte counts were 15.6x10<sup>9</sup>/L(0.3‐400) and LDH 723U/L(133‐20783). Fifty‐eight (23%) had bulky disease and 11(4.3%) CNS involvement. NCI‐SR and HR were 116(45.6%) and138(54.3%) respectively. High and low hypodiploidy were seen in 198(78%) and 31(12%) respectively, modal number (MN)45 in 12(4.7%), and near haploid 5(2%). Seventy‐two (28.3%)had normal cytogenetics, ETV6‐RUNX1 65(26%), other cytogenetics 37(14.4%.), t(1;19) 26(10.2%), trisomies 26(10.1%), BCR‐ABL 19(7.5%), MLL 9(3.5%). Of 222 patients evaluable for outcome, 171(77%) achieved remission, 51(23%) did not, 4(7.8%) failed induction. Of 95 children with post‐induction MRD, 19(20%) were positive, 15(79%) of which became negative post ‐consolidation. At a median follow‐up of 32 months (1‐84), projected 7‐year OS and EFS were 65.5% and 50% respectively. CNS status, NCI risk, prednisolone response were not significant. High and low hypodiploidy had better outcomes than near haploidy (p<0.01). ETV6‐RUNX1 correlated with improved OS and EFS (p<0.01). Post‐induction MRD‐negativity translated to significantly improved OS and EFS (p<0.01). Very‐early isolated medullary relapse was the commonest form of treatment failure.</p><p><bold>Conclusions</bold>: Hypodiploidy remains a high‐risk subset of childhood B‐ALL. Post‐induction MRD‐negativity and ETV6‐RUNX1 had better survival within this subset, while near haploidy portends poor outcome.</p></sec><sec id="pbc26772-sec-4440"><label>P-055</label><title>Immunoglobulin Levels in Children on Treatment for Acute Lymphoblastic Leukemia</title><p>C. Bajwa<sup>1</sup>, <underline underline-style="single">A. Trehan</underline><sup>1</sup>, A. Rawat<sup>1</sup>, D. Bansal<sup>1</sup></p><p><italic><sup>1</sup>Postgraduate Institute of Medical Education & Research, Pediatrics, Chandigarh, India</italic></p><p><bold>Background/Objectives</bold>: Chemotherapy results in depression of humoral immunity. This predisposes patients to severe infections which may be recurrent and occasionally, life threatening. This study evaluated immunoglobulin levels in children with Acute Lymphoblastic Leukemia (ALL).</p><p><bold>Design/Methods</bold>: Observational prospective study performed from June 2015 – October 2016. Children with relapsed disease and a known underlying immunodeficient state were excluded. Immunoglobulin levels (IgG, IgM & IgA) were analyzed at the following time points in each patient: (i) At diagnosis, (ii) end of induction and consolidation therapy, (iii) end of the delayed intensification phase of chemotherapy</p><p><bold>Results</bold>: Thirty five children, mean age: 5.17± 3.2 years ; 31: B precursor cell ALL ; 4:T cell ALL were evaluated. The immunoglobulin levels at diagnosis were normal for age with IgG being on the upper side of normal. IgM and IgG levels decreased after induction and consolidation therapy. IgM declined to the lower limit of normal for age with 14(40%) children having low IgM levels. IgG did not fall below normal for age. Levels did not fall further after intensification therapy. At no time did IgA levels alter. Forty percent children had 1 episode of FN, 17% had 2 episodes of FN and 7 (20%) had > 3 episodes of FN, whilst 23 children did not have FN. Children with greater episodes of FN did not have lower levels of immunoglobulins.</p><p><bold>Conclusions</bold>: Chemotherapy results in an altered immune profile. IgG and IgM levels both decrease after initiation of chemotherapy with nearly 40% children having low IgM levels at the end of intensive therapy. A larger patient cohort would help delineate severity of fall between the ALL risk groups. Patients need repeat evaluation of their immunoglobulin profile after therapy to look for recovery of immune function. Replacement therapy may deserve recommendation in patients with recurrent episodes of infections.</p></sec><sec id="pbc26772-sec-4450"><label>P-056</label><title>Childhood Leukemia in an ETV6‐Related Thrombocytopenia Family</title><p><underline underline-style="single">S. Unal</underline><sup>1</sup>, F. Gumruk<sup>1</sup>, M. Cetin<sup>1</sup>, A. Shimamura<sup>2</sup></p><p><italic><sup>1</sup>Hacettepe University Medical School, Division of Pediatric Hematology, ANKARA, Turkey; <sup>2</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Bone Marrow Failure and MDS Program, Boston, Turkey</italic></p><p><bold>Background/Objectives</bold>: ETV6‐related thrombocytopenia is an autosomal dominant thrombocytopenia that has been recently identified in a few families and has been reported to have leukemia predisposition. Normal size, autosomal dominantly inherited thrombocytopenia has been reported in patients with <italic>RUNX1, ANKRD26</italic> and <italic>ETV6</italic>.</p><p><bold>Design/Methods</bold>: A currently 11 year‐old boy was referred to our center with a diagnosis of acute lymphoblastic leukemia (ALL) at 5 years of age.</p><p><bold>Results</bold>: Previous history revealed a follow‐up period with a diagnosis of immune thrombocytopenia (ITP) in the preceeding 2 years. During the past medical history prior to ALL diagnosis, median platelet count was 35x10<sup>9</sup>/L and did not receive any specific treatment for ITP. Family history revealed thrombocytopenia (plt 59 x10<sup>9</sup>/L, MPV 8.1 fl) in father but the etiology was not identified. The hemogram at admission for ALL revealed Hgb 8.6 g/dl, WBC 4.4x10<sup>9</sup>/L, plt 13 x10<sup>9</sup>/L, MCV 92.6 fl, MPV 9.1 fl. The bone marrow aspiration revealed diffuse leukemic infiltration with L1 type blasts and immunephenotype was CALLA positive pre‐B cell ALL. Cytogenetics revealed 46, XY karyotype. CNS cytology was negative and St Jude Total XV protocol for ALL was initiated. After cessation of treatment protocol, he still could not achieve a normal paltelet count (plt 47 x10<sup>9</sup>/L). DEB test for Fanconi anemia was negative. Molecular work‐up revealed ETV6:1358M mutation in both the patient and the father.</p><p><bold>Conclusions</bold>: ETV6‐related thrombocytopenia should be considered in families with dominant inheritance pattern and patients should be followed for leukemia development.</p></sec><sec id="pbc26772-sec-4460"><label>P-057</label><title>Evaluation of PCR‐Based MRD Testing in Children with Acute Lymphoblastic Leukemia Treated According to All IC BFM 2009 Protocol: Slovak Experience</title><p><underline underline-style="single">A. Vaská</underline><sup>1</sup>, M. Makohusová<sup>2</sup>, E. Bubanká<sup>3</sup>, I. Oravkinová<sup>4</sup>, P. Švec<sup>1</sup>, O. Fábri<sup>1</sup>, L. Copáková<sup>5</sup>, J. Trnka<sup>6,7</sup>, J. Zuna<sup>6,7</sup>, E. Froňková<sup>6,7</sup>, A. Kolenová<sup>1</sup></p><p><italic><sup>1</sup>Comenius University Children´s Hospital, Department of Pediatrics, Bratislava, Slovak Republic; <sup>2</sup>Comenius University – Medical School and University Children's Hospital, Department of Pediatric Oncology and Hematology, Bratislava, Slovak Republic; <sup>3</sup>Children's University Hospital, Department of Pediatric Oncology and Hematology, Banská Bystrica, Slovak Republic; <sup>4</sup>University Children´s Hospital Kosice, Department of Pediatric Hematology and Oncology, Košice, Slovak Republic; <sup>5</sup>National Cancer Institute, Department of Clinical Oncology, Bratislava, Slovak Republic; <sup>6</sup>Charles University and University Hospital Motol, Department of Paediatric Haematology and Oncology‐ 2nd Faculty of Medicine, Prague, Czech Republic; <sup>7</sup>Childhood Leukaemia Investigation Prague, CLIP, Prague, Czech Republic</italic></p><p><bold>Background/Objectives</bold>: In the treatment of childhood acute lymphoblastic leukemia (ALL) the detection of minimal residual disease (MRD) is a significant determinant of patient outcome. The aim of the study was to evaluate the impact of routine PCR‐based MRD testing on stratification criteria of the ALLIC BFM 2009 protocol</p><p><bold>Design/Methods</bold>: From 2013 to 2016, 89 patients (age‐range 1‐18 years) were enrolled into ALL IC BFM 2009 protocol. The patients were stratified into a standard (SRG), intermediate (IRG) and high‐risk group (HRG) according to age, WBC, the presence of hypodiploidy, <italic>ETV6‐RUNX1</italic>, <italic>BCR‐ABL1</italic> and<italic>MLL‐AF4</italic> and the prednisone response. Bone marrow response to induction therapy was assessed primarily by morphology and secondly by flow cytometry on days 15 and 33. PCR‐based MRD testing was performed on days 33 and 78 (week 12), before protocol M or first high‐risk block, respectively. To the routine PCR‐based MRD and survival evaluation 68 patients were included; finally, in 61 patients PCR‐based MRD testing was determined.</p><p><bold>Results</bold>: Based on MRD stratification criteria, 13 patients were stratified into the HRG (19.1%), 45 patients to IRG (66.2%) and 10 to SRG (14.7%). Three‐year overall survival and three‐year event‐free survival rates were 92.5% (N=68; 2 deaths) and 84.6% (N=68; 7 events), respectively. In the study group with determined PCR‐based MRD testing on day 33 (N=61), MRD positivity was statistically significantly associated with T precursor type (P=0.002), bone marrow response on day 15 (P=0.048) and with event accuracy (P=0.042). MRD negativity was significantly associated with <italic>TEL/AML1</italic> fusion gene (P=0.011). There was no significant association of PCR‐based MRD testing on day 78 with any analyzed factor</p><p><bold>Conclusions</bold>: Results showed the prognostic value of PCR‐based MRD detection for prediction of events in the study group and also confirmed previous findings treatment impact on the prognosis for children with ALL during induction.</p><p>Acknowledgement: MZ SR 2012/7‐UKBA‐7.</p></sec><sec id="pbc26772-sec-4470"><label>P-058</label><title>Secondary T(16;21)(P11;Q22) In A Pediatric Patient with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">M. Velazquez‐Aviña</underline><sup>1</sup>, J. Ponce‐Cruz<sup>1</sup>, A. Carranza‐Castañón<sup>1</sup>, E. García‐Jiménez<sup>1</sup>, M. Chávez‐Zuñiga<sup>1</sup>, J. Peñaloza‐González<sup>1</sup></p><p><italic><sup>1</sup>Hospital Juárez de México, Pediatric Oncology, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: The t(16;21) (p11; q22) translocation is a rare chromosomal disorder that occurs mainly in Acute Myeloid Leukemia, Myelodysplastic Syndromes and blast crisis of Chronic Myeloid Leukemia. Recently, the karyotype along with this gene has been found in Ewing Sarcoma. It has been observed that in this type of alterations the TLS / FUS‐ERG gene is present. This karyotype represent an unfavorable prognostic sign because of the high resistance to chemotherapy and the high percentage of relapses.</p><p><bold>Design/Methods</bold>: We present the first case of a pediatric patient with Acute Lymphoblastic Leukemia (ALL) at relapse with a secondary chromosomal t(16; 21) (p11; q22).</p><p><bold>Results</bold>: A 15 year‐old female with ALL L2 type (FAB). Bone marrow showed 96% lymphoblasts. Leukemic cells expressed CD34 +, TdT, CD10 +, CD19 +, CD22 +, CD38 +, CD79a + and CD13 +. Cytogenetic study was performed without showing any alterations. Treatment was given with St. Jude XIII, with favorable evolution until week 76. At that moment, the patient presented pancytopenia hemoglobin 7.6 g per dL, 48,000 platelets per mm3, and leucocyte count of 800 per mm3. Bone marrow showed 97% of lymphoblasts. The immunophenotype presented CD10 +, CD13 +, CD22 +, CD24 +, CD34 +, CD38 +, CD123 +, CD58 +, CD66c +, CD79a +, Tdt, lambda, CD81 + expression. Cytogenetics reported t(16; 21) (p11; q22).</p><p>It was decided to start treatment with NOPHO 93 and ATEDOX with complete remission within the first cycle of chemotherapy. She was presented to the Hematopoietic Stem Cell Transplantation (HSCT) program.</p><p><bold>Conclusions</bold>: Only 4 cases have been reported in pediatric patients with t(16; 21) (p11; q22) and this is the first case report with this abnormality as a secondary finding. This represents a therapeutic challenge and we propose to treat this kind of patient as an Acute Myeloblastic Leukemia and salvage therapy with HSCT.</p></sec><sec id="pbc26772-sec-4480"><label>P-059</label><title>Posterior Reversible Encephalopathy Syndrome Treatment Based on Symptoms and Imaging Findings in Pediatric Patients with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">M. Velazquez‐avina</underline><sup>1</sup>, J. Peñaloza‐González<sup>1</sup></p><p><italic><sup>1</sup>Hospital Juárez de México, Pediatric Oncology, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: Posterior reversible encephalopathy syndrome (PRES) is an uncommon side effect of some chemotherapeutic agents, particularly methotrexate. The clinical presentation depends on the area of brain hypoperfusion. To date there is no standardized treatment, but a myriad of drugs and procedures have been proposed.</p><p>The purpose of this study is to report our experience in the treatment of this syndrome in patients with acute lymphoblastic leukemia (ALL).</p><p><bold>Design/Methods</bold>: We performed a retrospective record review and included patients with LLA with neurologic focal symptoms two weeks after methotrexate treatment regardless route of administration. The study period was from October 2004 to December 2014.</p><p>The demographic and clinical characteristics are described as means or proportions according to variable type.</p><p><bold>Results</bold>: We reviewed 176 charts of eligible patients, of which eight (4.5%, 4 female, 4 male) presented PRES. The average age was 11.2 years. Seven patients had high‐risk ALL (87.5%) and 1 (12.5%) standard risk ALL. The onset of symptoms started at an average of 7.3 days after intravenous (n=6; 75%), or intrathecal (n=2; 25%) methotrexate. None of the cases had simultaneous routes of administration.</p><p>Patients with localized ischemia (n=3) were treated citicoline (10‐20 mg/kg/d) for 5‐7 days, with seizures (n=2) were treated with valproate for 6 months (15 mg/kg/d); and with areas of brain edema were treated with dexametasone (0.5 mg/kg/d) for 5 days. All patients with brain ischemia without seizures (n=3) were treated with hyperbaric oxygen therapy. Five patients had multiple simultaneous therapy according to clinical and imaging characteristics. Symptoms recovery was present at 10 days postreatment average. None of the patients had permanent neurological sequelae.</p><p><bold>Conclusions</bold>: According to our findings, complete recovery of PRES can be achieved if therapy is started early based on symptoms and MRI findings. If no contraindication is present, multiple simultaneous therapy can be safely prescribed.</p></sec><sec id="pbc26772-sec-4490"><label>P-060</label><title>Outcome of All Induction Chemotherapy in Children Belonging to the Economically Weaker Sections of a Low‐Middle Income Country</title><p><underline underline-style="single">N. Verma</underline><sup>1</sup>, A. Kumar<sup>2</sup>, V. Pooniya<sup>2</sup></p><p><italic><sup>1</sup>King George Medical University, Pediatrics, Lucknow, India; <sup>2</sup>King George's Medical University, Pediatrics, Lucknow, India</italic></p><p><bold>Background/Objectives</bold>: Most of the children suffering from Acute Lymphoblastic Leukemia (ALL) from the Economically Weaker Sections (EWS) are unable to reach apex cancer institutes or corporate hospitals for their treatment. They are either treated in government medical centers or die in absence of optimal treatment. There is a dearth of information on the outcome of induction chemotherapy in this group of children</p><p><bold>Design/Methods</bold>: Data of all children with ALL belonging to EWS (Annual income less than USD $1490) treated in a Government Hospital in North India from Jan 2016 to July 2016 was retrospectively reviewed. Children were administered a risk stratified induction chemotherapy (3 drug induction for standard risk and 4 drug induction for high risk ALL). Treatment was provided free of cost by support from government and NGOs.</p><p><bold>Results</bold>: Out of the total 69 newly diagnosed ALL registered in Pediatric Oncology clinic at KGMU, from 1st Jan 2016 to 31st July 2016, 57 (83%) belonged to EWS (44 boys, 13 girls). Eleven children (19%) abandoned treatment during induction. Of the 46 children who took treatment as per protocol (43 B‐cell, 3 T‐cell ALL), 18 had standard‐risk disease, while 28 had high‐risk disease. At presentation 54% children were undernourished (33% ‐ moderate; 21% ‐ severe undernutrition), 28% had hypoalbuminemia. Complications during induction chemotherapy were encountered in 59% (27/46) children, leading treatment interruptions (of > 2 days) in 46% (21/46) and death in 30% (14/46) children. Causes of death included infections (10), Tumor Lysis syndrome (3), and bleeding (1). 70% (32/46) children completed there induction chemotherapy and all of them were in morphological remission.</p><p><bold>Conclusions</bold>: Outcome of ALL induction in children from EWS is poor. A significant proportion of these children are undernourished. Despite the provision of free treatment, abandonment rates are high. The risk of complications and death is also higher in these children.</p></sec><sec id="pbc26772-sec-4500"><label>P-061</label><title>Prevalence and Predictors of Invasive Fungal Infections in Children with Persistent Febrile Neutropenia Treated for Acute Leukemia‐ A Prospective Study</title><p><underline underline-style="single">J. Yadav</underline><sup>1</sup>, A. Singh<sup>1</sup>, R. Seth<sup>1</sup>, I. Xess<sup>2</sup>, M. Jana<sup>3</sup>, S. Kabra<sup>1</sup></p><p><italic><sup>1</sup>ALl India Institute of Medical Sciences, Pediatrics, Delhi, India; <sup>2</sup>ALl India Institute of Medical Sciences, Microbiology, Delhi, India; <sup>3</sup>ALl India Institute of Medical Sciences, Radiology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Febrile neutropenia is the most frequent life threatening complication of chemotherapy among children with cancer. Fungal infections are emerging concern due to improved survival secondary to better supportive care and aggressive chemotherapy. The study was planned to ascertain prevalence and predictors of invasive fungal infection following revised EORTC criteria.</p><p><bold>Objectives</bold>: To ascertain the prevalence of invasive fungal infections (IFI) during febrile neutropenic episodes in children with acute leukemia, and determine the predictors for IFI; and to identify the etiological fungal species causing IFI.</p><p><bold>Design/Methods</bold>: In this observational study children between 1‐12 years of age on chemotherapy for acute leukemia with febrile neutropenia were enrolled. Diagnosis of IFI was based on EORTC criteria and was classified as proven, probable and possible IFI. Prevalence was reported in mean ± 95% CI form and etiological species were presented in form of frequency distribution.</p><p><bold>Results</bold>: 319 episodes involving 187 children of febrile neutropenia were screened and 74 were enrolled. Seventeen episodes fulfilled EORTC criteria for IFI giving a prevalence of 22.97% (13.99‐ 34.21). Documented cases were further classified into proven‐3(17.6%), probable 11(64.8%) and possible‐3(17.6%). On multivariate analysis, abnormal CXR and clinical sinusitis were found to be important predictors of IFI. Most common fungus isolated was Aspergillus sp. followed by Candida sp. Aspergillus and candida species were most commonly isolated from sputum and blood respectively. Most common isolate in oral scrapping was Candida followed by Aspergillus. All the episodes in which we isolated Aspergillus were positive for galactomannan antigen test. Out of 74 cases, six (8.1%) were blood culture positive sepsis.</p><p><bold>Conclusions</bold>: Prevalence of invasive fungal infection in the study was 23%. Abnormal chest x ray and clinical sinusitis were found to be important predictors of IFI.</p></sec><sec id="pbc26772-sec-4510"><label>P-062</label><title>Acute Lymphoblastic Leukemia Outcome and Survival in Turkey: Marmara Experience</title><p><underline underline-style="single">B. Yilmaz</underline><sup>1</sup>, N. Eker<sup>1</sup>, O. Dogru<sup>1</sup>, G. Tokuc<sup>1</sup>, E. Senay<sup>1</sup>, B. Berk<sup>1</sup></p><p><italic><sup>1</sup>Marmara University Pendik Training and Research Hospital, Pediatric Hematology and Oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children accounting for approximately 25% of all pediatric cancers. The 5‐year survival is approximately 85% in developed countries. We examined the our ALL patients 5‐year survival rates and causes of mortality.</p><p><bold>Design/Methods</bold>: A total of 120 patients with acute lymphoblastic leukemia (one‐18 years) diagnosed between 2011 to 2016 were included in the study. The patients with secondary malignancy, age <1year and children with relapsed disease were excluded. All patients were stratified and treated according to St‐Jude Total XV Study Protocol.</p><p><bold>Results</bold>: The mean duration of follow‐up was 29 months found. The five‐year overall survival was 77% found. Seventeen patients were lost to follow up. Unfortunately, the most common cause of death was infection‐related complications (82%.[14/17 patients]). We did not see any difference in the risk of mortality among risk groups (Log Rank p=0.14). But standard risk better survival than other two risk groups. The children with Pre‐B cell leukemia had better survival compared to other types of cell leukemia although it was statically significant (Log Rank, p<0.0001) (pre‐B 81% vs T‐cell:62% vs Burkitt leukemia 50%)</p><p><bold>Conclusions</bold>: The infectious complications are still a major cause of a death in developing countries (etc. Turkey) during the treatment of children with ALL. Our patients died mainly of infectious diseases and sepsis leading to present difference in the success of leukemia treatment with developed countries.</p></sec><sec id="pbc26772-sec-4520"><label>P-063</label><title>Prognostic Value of Neuropilin‐1 /CD304 in Children with B‐Lineage Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">M. Zakaria</underline><sup>1</sup>, M. Hesham<sup>1</sup>, D. El nemer<sup>2</sup>, M. Hashem<sup>2</sup>, H. Naguib<sup>2</sup></p><p><italic><sup>1</sup>Faculty of medicine‐ Zagazig University‐Egypt, Pediatrics, Zagazig, Egypt; <sup>2</sup>Faculty of medicine‐ Zagazig University‐Egypt, clinical pathology, Zagazig, Egypt</italic></p><p><bold>Background/Objectives</bold>: Neuropilin‐1 (NRP‐1) is a novel receptor for vascular endothelial growth factor (VEGF) which expressed in endothelial and tumor cells and promotes proliferation and chemotaxis of leukemic cells in response to VEGF. Inhibition of NRP‐1 functions may provide a new therapeutic strategy for treatment of ALL. We aimed To study NRP‐1/CD304 expression profile of normal B lineage and leukemic lymphoblasts, its prognostic value and its role in Minimal Residual Disease detection.</p><p><bold>Design/Methods</bold>: A prospective case‐control study was conducted on forty newly diagnosed patients with acute B‐lymphoblastic leukemia (22males and 18 females) with a mean age of 6.68±4.70 years and forty age and sex matched subjects as a control group. Expression of NRP‐1 (CD304) by flow cytometry was done at diagnosis and at the end of induction therapy.</p><p><bold>Results</bold>: Forty five % of the cases were positive for CD304 expression and 55% were negative. There were no statistically significant differences between cases with positive and–ve expression of CD304 regarding clinical presentation, morphology, immunophenotyping and CNS infiltration. But there were statistical significance differences between them as regards to relapse (77.7% relapsed cases were CD304 positive) and prognosis (55% of cases with positive CD304 expression died). There were positive significant correlation with CD 304% and age, bone marrow blast cells and LDH level and –ve significant correlation with WBCs count and Hb level. There was no significant difference between CD304 positive and negative cases regarding overall Survival rate, while Disease‐free survival at 12 months was 75.4% in CD304 positive cases and 33.3% in negative cases with a high significant difference.</p><p><bold>Conclusions</bold>: Neuropilin‐1(CD304) with a high expression on bone marrow blasts can be considered as a marker for bad prognosis in children with B‐lineage ALL and could be used during follow‐up and disease monitoring.</p><p><bold>Acknowledgment</bold>: The authors thank all the participants of the study for their unstinted cooperation.</p></sec><sec id="pbc26772-sec-4530"><label>P-064</label><title>Preliminary Data of Multicenter Project Concerning Asparaginase Activity – Focus on Silent Inactivation</title><p><underline underline-style="single">B. Zalewska‐Szewczyk</underline><sup>1</sup>, K. Wyka<sup>1</sup>, J. Walenciak<sup>1</sup>, A. Dusza<sup>2</sup>, O. Michon<sup>3</sup>, A. Mizia‐Malarz<sup>4</sup>, K. Ospa<sup>5</sup>, N. Sekula<sup>6</sup>, J. Urbanska‐Rakus<sup>7</sup>, W. Mlynarski<sup>1</sup></p><p><italic><sup>1</sup>Medical University of Lodz, Department of Pediatrics‐ Oncology‐ Hematology and Diabetology, Lodz, Poland; <sup>2</sup>Medical University of Warsaw, Department of Pediatrics‐ Hematology and Oncology‐, Warsaw, Poland; <sup>3</sup>Medical University of Silesia‐ katowice, Department of Pediatrics‐ Hematology and Oncology in Zabrze, Zabrze, Poland; <sup>4</sup>Medical University of Silesia‐ Katowice, Department of Oncology‐ Hematology and Chemotherapy, Katowice, Poland; <sup>5</sup>Mediacal University of Wroclaw, Deparment of Bone Marrow Transplantation‐ Pediatric Oncology and Hematology, Wroclaw, Poland; <sup>6</sup>Medical University of Lublin, Department of Pediatric Hematology‐ Oncology and Transplantation, Lublin, Poland; <sup>7</sup>Center of pediatric and Oncolgy in Chorzow, Department of Pediatric Hematology and Oncology, Chorzow, Poland</italic></p><p><bold>Background/Objectives</bold>: Asparaginase is a crucial agent of acute lymphoblastic leukemia (ALL). However its use is limited due to hypersensivity, moreover the generated anti‐asparaginase antibodies can lead to the inactivation of the drug without symptoms of allergy. This implies the risk of ineffective treatment.</p><p>The aim of the study is to evaluate the incidence of silent inactivation and allergy to asparaginase in children with newly diagnosed ALL.</p><p><bold>Design/Methods</bold>: In June 2016, we started systematic monitoring of asparaginase activity in patients treated in 7 Polish pediatric centers. The current report summarizes 10 months of study duration. At present, 113 children, treated according to ALLIC 2009 protocol were enrolled in the study. In case of overt allergy/insufficient drug activity, asparaginase preparation was changedfro native E.coli asparaginase to pegylated E. coli asparaginase, and subsequently Erwinase. Asparaginase activity for native preparations used 2 or 3 times weekly was determined using ELISA method before each subsequent dose, and for pegylated asparaginase on 8<sup>th</sup> and 15<sup>th</sup> day after administration.</p><p><bold>Results</bold>: In total 776 asparaginase measurements were performed. Among 113 children the preparation was changed in 23 patients to pegylated asparaginase and in 8 patients subsequently to Erwinase. In 9 children treated with native E. coli asparaginase and in 6 children treated with pegylated asparaginase silent inactivation was found. On the basis of previous analyzes, indicating the importance of asparaginase for the outcome of ALL, it can be stated that implementation of systematic monitoring of asparaginase activity improved the effectiveness of treatment in 15 (13%) studied children.</p><p><bold>Conclusions</bold>: Preliminary data analysis indicate that 13% of children exhibit insufficient asparaginase activity during treatment according to the ALL IC 2009 protocol, despite the lack of clinically apparent allergy. Because of the clinical relevance of the study, and the importance to the effectiveness of therapy, it is advisable to continue the study.</p></sec></sec><sec id="pbc26772-sec-4540"><title>Haematology ‐ Myeloid Leukemias, Myelodysplastic and Myeloproliferative Syndromes</title><sec id="pbc26772-sec-4550"><label>P-065</label><title>Spectrum of Genetic Abnormalities in Slovak Children with AML During Period 2000‐2014</title><p><underline underline-style="single">M. Achbergerova</underline><sup>1</sup>, J. Puskacova<sup>1</sup>, M. Makohusova<sup>1</sup>, P. Svec<sup>1</sup>, O. Fabri<sup>1</sup>, L. Copakova<sup>2</sup>, M. Cermak<sup>2</sup>, M. Leitnerova<sup>2</sup>, E. Bubanska<sup>3</sup>, I. Oravkinova<sup>4</sup>, Z. Lysa<sup>1</sup>, E. Kaiserova<sup>1</sup>, A. Kolenova<sup>1</sup></p><p><italic><sup>1</sup>Children's University Hospital, Department of Pediatric Hematology and Oncology, Bratislava, Slovak Republic; <sup>2</sup>National Cancer Institute, Department of Clinical Oncology, Bratislava, Slovak Republic; <sup>3</sup>Children's University Hospital, Department of Pediatric Oncology and Hematology, Banska Bystrica, Slovak Republic; <sup>4</sup>Children's University Hospital, Department of Pediatric Oncology and Hematology, Kosice, Slovak Republic</italic></p><p><bold>Background/Objectives</bold>: Acute myeloid leukemia (AML) is relatively rare in children. In the Slovak Republic, approximately 2‐8 new cases of childhood AML are diagnosed per year. We sought to describe the incidence of cytogenetic aberrations associated with AML and to evaluate the event‐free and overall survival among children and adolescents with AML in our population.</p><p><bold>Design/Methods</bold>: In total, 122 children and adolescents age 0‐18 years were diagnosed with AML between 2000 and 2014. These children were treated according to AML BFM strategy at one of three Slovak centres of pediatric hematology and oncology. Bone marrow samples were analyzed at a central laboratory using conventional cytogenetics, fluorescence in‐situ hybridization (FISH) and molecular genetic methods. A retrospective analysis was based on our laboratory and clinical data from Slovak clinical cancer registry of children and adolescents.</p><p><bold>Results</bold>: Incidence of selected cytogenetic aberrations was as follows: t(15,17) was present in 9.02%; t(8,21) in 4.92%; inv(16) in 4.10%; MLL rearrangement in 7.38%; nine cases of AML (7.38%) were children with Down syndrome. Five‐year event‐free survival (EFS) and overall survival (OS) rates in this cohort were 49,0% (N=122; 57 deaths) and 53.2%(N=122; 62 events), respectively. Sixty‐six patients were stratified into the high risk group with OS and EFS 52.95% (32 deaths) and 46.87% (36 events), respectively; in standard risk group rates 63.2% for OS (N=36; 13 deaths) and 60.58% for EFS (N=36; 14 events) were achieved. Patients with positive t(15,17) abbrevation achieved better and the same rates for OS and EFS (73.7%) in contrast to patients without this genetic change (54.9% and 50.8%).</p><p><bold>Conclusions</bold>: Based on these results, we have planned a new strategy with the aim of improving outcomes for these children by centralizing treatment at a single center, optimizing the timing of stem cell transplant, and implementing additional genetic testing at the AML BFM central laboratory in Germany.</p><p><bold>Acknowledgement</bold>: APVV‐15‐0250.</p></sec><sec id="pbc26772-sec-4560"><label>P-066</label><title>Outcome of Pediatric Acute Myeloid Leukemia in a Developing Country: Is this the Impact of Invasive Fungal Infection?</title><p>A. Ahmed<sup>1</sup>, A. Kamel<sup>1</sup>, E. Kandeel<sup>2</sup>, <underline underline-style="single">E. Ebeid</underline><sup>1</sup></p><p><italic><sup>1</sup>National Cancer Institute, pediatric oncology, Cairo, Egypt; <sup>2</sup>National Cancer Institute, clinical pathology, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Acute myeloid leukemia (AML) remains a challenging disease in developing countries. To identify Overall Survival (OS), Disease Free Survival (DFS) and their correlation with different risk factors, as well as demonstration of the common causes of mortality.</p><p><bold>Design/Methods</bold>: A retrospective descriptive study included 103 newly diagnosed AML patients age less than 18 years receiving treatment at national cancer institute, Cairo University, Egypt in the period from January 2008 till December 2010.Risk factors including age, gender, initial WBC, cytogenetics, CNS status and antifungal prophylaxis were collected.</p><p><bold>Results</bold>: The 2 years DFS was 27.1%, with a median survival of 10 months, and 2 years OS was 30.4% with a median survival of 16 months and 95% confidence interval (5.4‐14.8), (11.24‐20.76) respectively. Early deaths were seen in 15 patients (14.6%) mainly due to infections. Late deaths were seen in 48 patients mainly due to progressive disease and infections. Infection related mortality (IRM) represented 42.9% from all mortality causes, (26.2%) of the patients. About 74 patients showed picture of possible fungal pneumonia (39 patients during induction chemotherapy, 17 post first consolidation and 18 post second consolidation). Regarding antifungal prophylaxis, primary prophylaxis fluconazole was given in 21 patients (20.4%). Regarding secondary prophylaxis, 45 patients received itraconazole, 24 patients received voriconazole. Analysis of the data revealed statistically significant correlation between DFS and response to induction chemotherapy (p value<0.001), presence of chloroma (p value 0.040) and voriconazole prophylaxis (P value<0.001). Correlation with OS was statistically significant with response to induction chemotherapy (P value0.002), association with favorable cytogenetic (t (8, 21) and inv 16) (p value 0.039), with chloroma (p value 0.023) and voriconazole prophylaxis (p value 0.001).</p><p><bold>Conclusions</bold>: Infection related mortality is an important cause of poor survival outcome in our study population. These results warrant the use of anti‐mold primary prophylaxis for all pediatric patients with AML.</p></sec><sec id="pbc26772-sec-4570"><label>P-067</label><title>Polish Experience of the Treatment of Acute Promyelocytic Leukemia in Children from 2005 to 2016</title><p><underline underline-style="single">M. Czogala</underline><sup>1</sup>, K. Pawinska‐Wasikowska<sup>1</sup>, T. Ksiazek<sup>2</sup>, A. Rodziewicz<sup>3</sup>, B. Sikorska‐Fic<sup>4</sup>, J. Skalska‐Sadowska<sup>5</sup>, R. Tomaszewska<sup>6</sup>, K. Muszynska‐Roslan<sup>7</sup>, D. Grabowski<sup>8</sup>, I. Karpinska‐Derda<sup>9</sup>, K. Mycko<sup>10</sup>, K. Zielezinska<sup>11</sup>, J. Pohorecka<sup>12</sup>, B. Przybyszewski<sup>13</sup>, W. Balwierz<sup>1</sup></p><p><italic><sup>1</sup>Institute of Pediatrics Jagiellonian University Medical College, Department of Pediatric Oncology and Hematology, Kraków, Poland; <sup>2</sup>Institute of Pediatrics Jagiellonian University Medical College, Department of Medical Genetics, Kraków, Poland; <sup>3</sup>Medical University of Wroclaw‐ Poland, Department of Bone Marrow Transplantation‐ Pediatric Oncology and Hematology, Wroclaw, Poland; <sup>4</sup>Medical University of Warsaw, Department of Pediatrics‐ Hematology and Oncology, Warsaw, Poland; <sup>5</sup>Medical University of Poznan, Department of Pediatric Oncology‐ Hematology and Transplantology, Poznan, Poland; <sup>6</sup>Medical University of Silesia, Department of Pediatrics Hematology and Oncology, Zabrze, Poland; <sup>7</sup>Medical University of Bialystok, Department of Pediatric Oncology, Bialystok, Poland; <sup>8</sup>Medical University of Lublin, Department of Pediatric Hematology and Oncology, Lublin, Poland; <sup>9</sup>Chorzow Pediatrics and Oncology Center, Department of Hematology and Oncology, Chorzow, Poland; <sup>10</sup>Medical University of Lodz, Department of Pediatrics‐ Oncology‐ Hematology and Diabetology, Lodz, Poland; <sup>11</sup>Pomeranian Medical University, Department of Pediatrics‐ Hematology and Oncology, Szczecin, Poland; <sup>12</sup>Province Children's Hospital, Department of Hematology and Oncology, Kielce, Poland; <sup>13</sup>Province Children's Hospital, Department of Pediatrics and Hematology and Oncology, Department of Pediatrics and Hematology and Oncology, Poland</italic></p><p><bold>Background/Objectives</bold>: Acute promyelocytic leukemia (APL) characterized by translocation t(15;17) comprises about 5‐10% of childhood acute myeloid leukemia. The aim of the study was analysis of the treatment outcome of APL in children in Poland from 2005 to 2016.</p><p><bold>Design/Methods</bold>: All 36 patients with genetically confirmed APL treated in Poland in analyzed period were eligible for the study, 33 of them were treated with AML‐BFM‐2004 Interim (2005‐2015 – period I) and 3 with AML‐BFM 2012 (2015‐2016 – period II). Median observation time was 42 months and 8 months respectively in periods I and II. All patients in the period I received standard chemotherapy with all‐trans retinoic acid (ATRA), in the period II two patients were treated with induction chemotherapy, ATRA and arsenic trioxide (ATO), one patients with ATRA‐ATO without chemotherapy. We analyzed survival rates and the treatment failures.</p><p><bold>Results</bold>: Probability of 5‐years overall survival (OS), event free survival (EFS) and relapse free survival (RFS) were 0.822±0.067; 0.828± 0.064 and 0.960±0.036 respectively for all analyzed patients. Four (11%) early deaths (5‐10 days from diagnosis) caused by severe coagulation disorders were observed. White blood cell count at diagnosis was significantly higher in children who died early compared to the other patients (median [range]: 91.6×10<sup>3</sup>/μl [40‐196×10<sup>3</sup>/μl] vs 5.6 ×10<sup>3</sup>/μl [0.45‐140 ×10<sup>3</sup>/μl], p=0.012). One patient (2.4%) died of severe infection in course of disease progression 1.9 month after diagnosis. Relapse occurred in one patient (2.4%), 13.5 months after first remission, the patient died because of disease progression. All events occurred in the patients from the period I, there were no deaths after the year 2012.</p><p><bold>Conclusions</bold>: Treatment outcome in analyzed group is similar to the results reported by other study groups. The main cause of deaths were coagulation disorders at the beginning of disease. Early, accurate diagnosis followed by the specific treatment enables to reduce number of early deaths.</p></sec><sec id="pbc26772-sec-4580"><label>P-068</label><title>Clinical Characteristics and Outcome of Children with Acute Myeloid Leukemia Below One Year of AGE: A Single Centre Experience from a Developing Country</title><p><underline underline-style="single">S. Eissa</underline><sup>1</sup>, S. Semary<sup>1</sup>, M. Hammad<sup>1</sup>, K. Shaaban<sup>2</sup>, S.I. Salem<sup>3</sup>, D. Yassin<sup>4</sup>, M. Jamal<sup>5</sup>, D. Albeltagi<sup>6</sup>, A. Hadad<sup>1</sup></p><p><italic><sup>1</sup>Children's Cancer Hospital‐Egypt, Pediatric hematIology/oncology, Cairo, Egypt; <sup>2</sup>Children's Cancer Hospital‐Egypt, Flow Cytometry Lab, Cairo, Egypt; <sup>3</sup>Children's Cancer Hospital‐Egypt, Cytogenetics Lab, Cairo, Egypt; <sup>4</sup>Children's Cancer Hospital‐Egypt, Molecular Genetics Lab, Cairo, Egypt; <sup>5</sup>Children's Cancer Hospital‐Egypt, Clinical Pharmacy, Cairo, Egypt; <sup>6</sup>Children's Cancer Hospital‐Egypt, Clinical Research Department, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Myeloid leukemia occurring in children below one year of age has distinctive clinical and biological features than that occurring in older children. Hyperleukocytosis, extra‐medullary disease and CNS involvement as well as Mixed Lineage Leukemia gene rearrangements <italic>(MLL‐r)</italic> at diagnosis are common.</p><p><bold>Design/Methods</bold>: Retrospective analysis of the clinical and biological features of infants with AML treated at our cancer center during the period from July 2007 till December 2015.</p><p><bold>Results</bold>: A total of 60 patients were diagnosed. Patients with Down syndrome were excluded. Thirty two males (53%) and 28 females (46.7%), male to female ratio (1:1.2). Mean age at diagnosis was 5.4, range (1 – 11.9) months, initial Total Leukocytic Count (TLC) ranged between(1‐370) ×10<sup>9</sup>/L, mean 71 ×10<sup>9</sup>/L. Extra‐medullary disease was present in 18 (30%) of patients. Nine patients (15%) had CNS disease at presentation. Monocytic differentiation was present in 28 (46.7%) and amegakaryoblastic leukemia M7 in 18(30%) of patients. <italic>MLL</italic> gene rearrangements were present in 17 (28.3%) patients, with t (9, 11) being the most frequent; found in 7(11.7%) patients. Other cytogenetic abnormalities as t(1, 22) and inv (16) were diagnosed less frequently in 6(10%) and 3 (5%) of patients respectively. All patients with t(1,22) had M7 and all those with inv (16) had M4Eo morphology. Multiple trisomies were identified in 7 (11.7 %) patients. Most patients experienced significant chemotherapy toxicity and 36 (60%) required ICU admission. Of the whole cohort, 25 (41.7%) patients achieved complete remission after induction, of them 21 patients (84%) are still alive in first complete remission (CR).</p><p><bold>Conclusions</bold>: Dealing with infants with myeloid leukemia is a real challenge especially in countries with limited resources. Improving supportive care, refinement of the risk stratification to identify those who require more intensive chemotherapy including transplantation is required to improve outcome. Best survival was for those who entered into CR after induction (84%).</p></sec><sec id="pbc26772-sec-4590"><label>P-069</label><title>Mutation of Genes Affecting the RAS Pathway Associated with PTPN11 in Pediatric Acute Myeloid Leukemia</title><p><underline underline-style="single">F. Gomes Andrade</underline><sup>1</sup>, F. Vicente dos Santos Bueno<sup>1</sup>, I. Sardou Cezar<sup>1</sup>, G. Dallapicola Brisson<sup>1</sup>, E. Pereira Noronha<sup>1</sup>, E. Terra‐Granado<sup>1</sup>, M.S. Pombo‐de‐Oliveira<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Câncer, Research Center, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: Deregulation of the <italic>RAS</italic> signaling cascade is often caused by somatic mutations in genes encoding proteins which influence the activity of this pathway and include <italic>NRAS</italic>, <italic>KRAS</italic>, <italic>FLT3</italic>, <italic>PTPN11</italic>, and c‐<italic>KIT</italic>. Our aim was to describe a comprehensive mutational screen of key exons of these genes in a cohort of 439 unselected pediatric acute myeloid leukemia (p‐AML) cases at diagnosis and to evaluate their prognostic value in the probability of overall survival (pOS).</p><p><bold>Design/Methods</bold>: Hotspot regions of <italic>NRAS</italic>, <italic>KRAS</italic>, <italic>FLT3</italic>, <italic>PTPN11</italic>, and c‐<italic>KIT</italic> were directly sequenced for the screen of mutations. Survival analysis was performed in a subset of patients treated following BFM‐AML2004 guidelines, out of clinical trials.</p><p><bold>Results</bold>: <italic>RAS</italic> pathway mutations were found in 35.1% of the study cohort, mainly represented by <italic>FLT3</italic> (16.2%), followed by <italic>NRAS</italic> (6.4%), c‐<italic>KIT</italic> (4.3%), <italic>KRAS</italic> (3.4%), and <italic>PTPN11</italic> (2.5%). Mutations were rare among <italic>KMT2A</italic> rearranged cases (12.7%) and rarely observed concomitant in more than one gene (8.8%). Two boys (7 and 13 year old) presented mutation in <italic>PTPN11</italic> and <italic>NRAS</italic> or <italic>KRAS</italic>, respectively. Both died less than 1 month after diagnosis. The cumulative 5‐year pOS for p‐AML was 36.0±3.8% (excluding acute promyelocytic leukemia). Patients with skin color considered White presented better outcome than Non‐Whites (pOS 43.4±5.9% and 29.5±4.9%, respectively), as well as patients aged >12 years old (pOS 37.2±5.1%) and those with <italic>CBFb</italic>‐<italic>MYH11</italic> (pOS 73.7±11.3%). <italic>PTPN11</italic> mutations in exon 3 were found in overall analysis to be associated with adverse prognosis, and identified by multivariate analysis as independent prognostic factor (hazard ratio of 3.6; 95% confidence interval of 1.7‐7.7).</p><p><bold>Conclusions</bold>: Although there is a need of further action to improve the overall survival rates of p‐AML patients, these aberrations are likely to guide the stratification and may direct the development of novel therapeutic targeted therapies.</p></sec><sec id="pbc26772-sec-4600"><label>P-070</label><title>Outcome of Acute Myeloblastic Leukemia in Indian Children in a Newly Established Pediatric Cancer Center</title><p><underline underline-style="single">K. Viswanathan</underline><sup>1</sup>, S. Jayabose<sup>1</sup>, A. Annamalai<sup>1</sup>, N. Iyer<sup>1</sup>, V. Bharathi<sup>1</sup>, K. Rathnam<sup>1</sup></p><p><italic><sup>1</sup>Meenakshi Mission Hospital & Research Centre, Pediatric Hematology‐Oncology, Madurai, India</italic></p><p><bold>Background/Objectives</bold>: There is paucity of data on the outcome of childhood AML in India. The objective of this study is to analyze the outcome of childhood AML in our pediatric cancer center established in 2010; and compare the outcomes with two different treatments.</p><p><bold>Design/Methods</bold>: We reviewed the data on 78 children consecutively diagnosed from 2010 to 2016, including 5 MDS‐AML and 5 APL, one DS‐AML and one acute megakaryoblastic leukemia; and 12 AML with chloroma. Male: female, 34:44. Median age: 9 years; (range, 0.5 to 21years). First 40 patients seen in 2010 to 2013 (Group I) were treated on a modified MRC‐10 regimen. The next 38 patients (Group II) received a less intensive regimen (induction with cytarabine plus daunorubicin; and reduced doses of mitoxantrone in consolidation); but nine received allogeneic stem cell transplantation (SCT), 7 in first remission and two in second remission–6 from matched siblings; 3 haplo‐identical parents.</p><p><bold>Results</bold>: One patient moved to another center; none abandoned treatment. Sixty‐three of 77 (81.8%) achieved complete remission (CR). Overall, 40 patients (51.9%) are alive, including all 9 who received SCT; and 8 of 12 patients with chloroma. Median follow‐up is 24 months (range, 3 ‐ 80). Estimated 3‐yr overall survival (OS): 42.3%. All 12 refractory patients, and 15 of 17 relapsed patients, and 4 of 5 MDS‐AML patients died of disease. Deaths during induction and in remission were higher, 7.5% and 21.8% respectively in Group I; vs 2.7% and 9.7% in Group II, but not statistically significant. Estimated 3‐year OS was higher for group II (51% vs 38%), but not statistically significant (p= 0.15).</p><p><bold>Conclusions</bold>: MRC‐10 based regimen results in excessive treatment‐related mortality in Indian children with AML. But use of less intensive induction and consolidation, with allogeneic stem cell transplant for intermediate and high‐risk patients is likely to improve their survival.</p></sec><sec id="pbc26772-sec-4610"><label>P-071</label><title>Clinical Features of Myeloid Sarcoma in Indian Children with Acute Myeloblastic Leukemia</title><p><underline underline-style="single">S. Jayabose</underline><sup>1</sup>, N. Iyer<sup>1</sup>, K. Viswanathan<sup>1</sup>, A. Annamalai<sup>1</sup></p><p><italic><sup>1</sup>Meenakshi Mission Hospital & Research Centre, Pediatric Hematology‐Oncology, Madurai, India</italic></p><p><bold>Background/Objectives</bold>: Myeloid sarcoma (MS) is defined as extramedullary lesions in acute myeloblastic leukemia (AML) The reported incidence and prognostic significance MS has been variable; and there are no data on MS in Indian children. The objective of our study is to review the clinical features of children with MS in a single institution seen over a period of 7 years.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed the data on all cases of AML, including 3 isolated MS seen from 2010 to 2016: clinical and molecular features, details of treatment and their outcome.</p><p><bold>Results</bold>: Among 83 consecutively diagnosed cases of AML, 12 patients had MS: three had isolated MS without AML; excluding those three, 9 of 80 (11%) had AML with MS (AML‐MS); Median age: 8 years (range, 1‐20). Male: female, 9:3. Three had disseminated MS, involving two or more sites–including asymptomatic pelvic and intracranial lesions. None had leukemic cells in spinal fluid. Seven of 9 patients with AML‐MS had t(8;21). Cytogenetics was not done in the three cases of isolated MS. Ten patients received treatment as per a modified MRC‐10 protocol; one had less intensive treatment—induction with cytarabine pus daunorubicin, and consolidation with high‐dose cytarabine; one infant was treated according to COG 2971. Eleven patients had 3 to 4 doses intrathecal cytarabine. Five had local radiation: 4 in first remission; one in second remission. Two had allogeneic stem cell transplant (SCT); one in second remission. Eight patients are alive, including all 3 with isolated MS and the two who had SCT. Median follow‐up of surviving patients: 48 months (range, 9‐70).</p><p><bold>Conclusions</bold>: MS occurs in approximately 11% of Indian children with AML. It is frequently associated with t(8;21); and may be associated with occult and asymptomatic disseminated lesions. Prognostic significance of AML‐MS is unclear; but isolated MS may have a better prognosis than AML‐MS.</p></sec><sec id="pbc26772-sec-4620"><label>P-072</label><title>Analysis of Prognostic Factors in Children with Acute Myeloid Leukemia (M4/M5)</title><p><underline underline-style="single">C. kai</underline><sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children'S Hospital Affiliated to Shanghai Jiaotong University, Hematology and Oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: To investigate the clinical efficacy and prognostic factors of M<sub>4</sub>/M<sub>5</sub> subtypes in children with acute myeloid leukemia (AML).</p><p><bold>Design/Methods</bold>: A retrospective analysis of the clinical data of M<sub>4</sub>/M<sub>5</sub> subtypes in our hospital from January 2009 to December 2014 was carried out. The long‐term efficacy, prognosis and relapse factors were analyzed.</p><p><bold>Results</bold>: (1) The clinical data of 46 cases were collected, among which 38 cases were treated with more than 2 courses, including male 22 cases, female 16 cases, M<sub>4</sub> 19 cases and M<sub>5</sub> 19 cases. The median age was 5 years.5‐year overall survival rate (OS) and 5‐year event‐free survival rate (EFS) were 57.7±9.3% and 47.2 ±8.9%, 5‐y EFS of M<sub>4</sub> and M<sub>5</sub> were 52.4 ±12.7% and 45.4 ±11.9%.(2) Compared with the international risk stratification: 5‐y EFS of favorable‐risk, intermediate‐risk and poor‐risk were 77.2 ±12.4%, 49.5±14.9% and 25 ±19.8% (P=0.043). (3) Single factor analysis showed extramedullary infiltration, d8 assessment and treatment were prognostic factors (P=0.028, 0.020 and 0.029);Multivariate analysis showed extramedullary infiltration (HR=5.323, 95%CI, 1.620‐17.490, P=0.006) and less than 6 courses (HR= 6.186, 95%CI 1.726‐22.176, P=0.005) were the independent risk factors of affecting survival.</p><p><bold>Conclusions</bold>: (1) Strengthening treatment and adequate courses are the keys to improve the overall curative effect in children with M<sub>4</sub>/M<sub>5</sub> subtypes.(2) Extramedullary infiltration was the risk factor for survival and recurrence in M<sub>4</sub>/M<sub>5</sub> subtypes. (3) We advise the children who have the initial symptoms and molecular biology with poor prognostic factors to choose hematopoietic stem cell transplantation as early as possible.</p></sec><sec id="pbc26772-sec-4630"><label>P-073</label><title>Control of Childhood Acute Myeloid Leukaemia with A Dose Reduced Induction Treatment in Malawi</title><p><underline underline-style="single">A. Mpasa</underline><sup>1</sup>, S. Wachepa<sup>1</sup>, P. wasswa<sup>1</sup>, M. Butia<sup>1</sup>, I. Kumwenda<sup>1</sup>, M. Chasela<sup>1</sup>, P. Ward<sup>2</sup></p><p><italic><sup>1</sup>Baylor College Of Medicine Children's Foundation, Paediatric haematology and oncology, Lilongwe, Malawi; <sup>2</sup>UNC project‐Malawi, oncology, Lilongwe, Malawi</italic></p><p><bold>Background/Objectives</bold>: Childhood Acute Myeloid Leukaemia (AML) is challenging to treat, in low income countries (LICs) like Malawi. Limited supportive care resources preclude the use of effective treatment protocols, as used in high income countries. In Malawi, AML is treated supportively, without chemotherapy. However, inadequate blood product support and community palliative services results in poor symptom control, particularly of bleeding. In order to alleviate symptoms through disease control, we used a modified chemotherapy protocol for childhood AML. We hereby share our experience of using this protocol at Kamuzu Central Hospital.</p><p><bold>Design/Methods</bold>: Between February and December 2016, children with AML, without FAB‐M3 subtype, were treated with a modified induction protocol. This comprised of Doxorubicin 20mg/m<sup>2</sup> for 4 days and Cytarabine 100mg/m<sup>2</sup> twice a day for 10 days. Ciprofloxacin, Itraconazole and Co‐trimoxazole were used as infection prophylaxis. The diagnosis of AML was established by assessment of bone marrow morphology. Data was collected on the demographics, baseline clinical and hematological features, toxicity, remission status and survival at the end of induction.</p><p><bold>Results</bold>: Nine (64%) children, were treated on this induction protocol. Median age was 9 years (range 6‐12) and 4 (44%) were male. Baseline median hematological parameters were White cell count: 66 × 10<sup>6</sup>/L (range 10.7‐269); Platelets 32 × 10<sup>9</sup>/L (range 6‐92); Neutrophils 8.8 × 10<sup>6</sup>/L (range 0.54‐160) and haemoglobin 5.7g/dl (range 2.0‐9.4). Seven patients (77.7%) suffered from febrile neutropenia. Two patients (22.2%) suffered from mucositis. Median time to count recovery was 23.5 days (range 20‐44). Median duration of admission was 25 days (range 20‐48). Of evaluable patients, post induction overall survival and complete remission rate were 8/9(88.8%) and 8/8 (100%) respectively. Median Lansky score at admission and discharge were 80 (range 10‐100) and 100 (range 50‐100), respectively.</p><p><bold>Conclusions</bold>: This modified chemotherapy regimen holds promise as a deliverable, safe and effective regimen for control of AML in LICs.</p></sec><sec id="pbc26772-sec-4640"><label>P-074</label><title>Characteristics and Outcome of Children with Acute Myeloid Leukemia and Down Syndrome Ineligible for Clinical Studies</title><p><underline underline-style="single">K. Nakashima</underline><sup>1,2</sup>, D. Hasegawa<sup>2,3</sup>, T. Miyamura<sup>2,4</sup>, A. Hama<sup>2,5</sup>, S. Iwamoto<sup>2,6</sup>, K. Terui<sup>2,7</sup>, D. Tomizawa<sup>2,8</sup>, S. Adachi<sup>2,9</sup>, T. Taga<sup>2,10</sup></p><p><italic><sup>1</sup>Kyushu University School of Medicine, Department of Pediatrics, Fukuoka, Japan; <sup>2</sup>Japan Children's Cancer Group, AML committee, Tokyo, Japan; <sup>3</sup>St. Luke's International Hospital, Department of Pediatrics, Tokyo, Japan; <sup>4</sup>Osaka University School of Medicine, Department of Pediatrics, Osaka, Japan; <sup>5</sup>Nagoya University Graduate School of Medicine, Department of Pediatrics, Nagoya, Japan; <sup>6</sup>Mie University School of Medicine, Department of Pediatrics, Mie, Japan; <sup>7</sup>Hirosaki University Graduate School of Medicine, Department of Pediatrics, Hirosaki, Japan; <sup>8</sup>National Center for Child Health and Development, Division of Leukemia and Lymphoma‐ Children's Cancer Center, Tokyo, Japan; <sup>9</sup>Kyoto University, Department of Human Health Sciences, Kyoto, Japan; <sup>10</sup>Shiga University of Medical Science, Department of Pediatrics, Shiga, Japan</italic></p><p><bold>Background/Objectives</bold>: High survival rates of 80‐90% are reported on recent clinical trials for children with acute myeloid leukemia (AML) and Down syndrome (DS: AML‐DS) with reduced‐dose chemotherapies. However, there are certain number of children with AML‐DS complicated with congenital heart disease (CHD), gastrointestinal anomaly, severe infection, and/or other complications, thus are ineligible for clinical trials.</p><p><bold>Design/Methods</bold>: Because data on outcomes of such children are scarce, we retrospectively analyzed clinical characteristics and outcomes of children with AML‐DS who were excluded from the Japanese clinical studies conducted between January 2000 and December 2015: AML99‐DS, CCLSG9805‐DS, JPLSG AML‐D05 and AML‐D11.</p><p><bold>Results</bold>: Thirteen children (6 boys and 7 girls) were identified and were ineligible for the following reasons; CHD (N=8), pulmonary fibrosis (N=1), hypoxic encephalopathy (N=1), rapid progression from transient abnormal myelopoiesis (N=1), complicated with hemophagocytosis (N=1), and age excess of 21 years at diagnosis (N=1). Median age at diagnosis was 14 months (range, 5 months to 21.4 years). <italic>GATA1</italic> mutation was detected in three out of four screened cases. Among all, twelve cases were treated with curative intent. Four cases received low‐dose cytarabine‐based chemotherapy (10‐30 mg/m2/day): three with severe CHD failed to achieve remission and died of disease; one with pulmonary fibrosis successfully achieved remission but eventually died of infectious complications. Eight cases underwent dose‐modified standard chemotherapy for AML‐DS: six are alive in remission, whereas two had relapsed (one died of disease and another are alive with disease). The patient with hypoxic encephalopathy received best supportive care and died of disease. Finally, six remains in continuous remission, one is alive with disease, and six died (five of leukemia and one of infection).</p><p><bold>Conclusions</bold>: Optimal dose intensity of curative chemotherapy for children with AML‐DS harboring severe comorbidities should be explored.</p></sec><sec id="pbc26772-sec-4650"><label>P-075</label><title>Epigenetic Therapy for Treatment Pediatric Acute Myeloid Leukemia</title><p><underline underline-style="single">V. Nemirovchenko</underline><sup>1</sup>, A. Popa<sup>1</sup>, G. Mentkevich<sup>1</sup></p><p><italic><sup>1</sup>Federal State Budgetary Institution «N.N.Blokhin Russian Cancer Research Center» under the Russian Academy of Medical Sciences, Children Hematology, Moskow, Russia</italic></p><p><bold>Background/Objectives</bold>: The majority of children with acute myeloid leukemia (AML) respond to initial chemotherapy and achieve a complete remission, yet only a minority experience long‐term survival because a large proportion of patients eventually relapse with therapy‐resistant disease. The combination of epigenetic drugs (DNA hypomethylating agent, histone deacetylase inhibitor, all‐trans retinoic acid) with chemotherapy may improve the results of treatment children with AML.</p><p><bold>Design/Methods</bold>: We report outcomes for 138 children who underwent chemotherapy for de novo AML between 2002 and 2016. Median age was 5.5±1.1 years. Forty (29.0%) children were included into AML‐2002 protocol, 70 (48.9%) – AML‐2007 protocol, 31 (22.5%) – AML‐2007 protocol. There were Standard, Intermediate and High risk groups. The vast majority was High risk ‐ 47.8%. he patients got (Induction therapy, Intensification, Consolidation, Maintenance therapy) after AML‐2002 protocol. Valproic acid (VPA) and all‐trans‐retinoic acid (ATRA) were added to the chemo after AML‐2007 protocol. The patients included into AML‐2012 protocol received chemotherapy with epigenetic drugs (VPA, ATRA, Decitabine).</p><p><bold>Results</bold>: The number of the good responses on the 15th day of the therapy was the same: AML‐2002 – 77.5%; AML–2007 – 80.6%; AML‐2012 – 74.2% (p=0.9). We achieved complete remission in 32 (80.0%) of the patients after Induction AML‐2002 protocol, 62 (92.5%) – after AML‐2007and 30 (100%) – after AML‐2012 (p=0.015). Probability of 5‐year disease free survival was 46.5±8.3% (median follow up 79.6±12.9 month) for protocol AML‐2002, 53.5±6.6% (median follow up 72.8±7.1 month) – AML‐2007 and 67.2±11.1% (median follow up 41,1±4,6 month) – AML‐2012 (р=0,035). Overall survival was 47.9±8.2% (median follow up 85.7±12.7 month) for protocol AML‐2002, 53.5±6.6% (median follow up 71.9±6,8 month) – AML‐2007 and 69.3±9.2% (median follow up 40.5±3.9 month) – AML‐2012 (р=0.1).</p><p><bold>Conclusions</bold>: The use of these drugs can be therapeutic used as part of a combination with other therapeutic modalities.</p></sec><sec id="pbc26772-sec-4660"><label>P-076</label><title>Impacts of HUWE1 Knockdown in Human Hematopoietic Stem Cells with A KRAS (G12V) Mutation</title><p><underline underline-style="single">M. Ruckert</underline><sup>1</sup>, A. Brouwers‐Vos<sup>2</sup>, L.G. Gonzaga<sup>3</sup>, J.J. Schuringa<sup>2</sup>, V.S. Silveira<sup>1</sup></p><p><italic><sup>1</sup>University of São Paulo, Department of Genetics, Ribeirão Preto, Brazil; <sup>2</sup>University Medical Center Groningen, Experimental Hematology, Groningen, The Netherlands; <sup>3</sup>University of São Paulo, Department of Pediatrics, Ribeirão Preto, Brazil</italic></p><p><bold>Background/Objectives</bold>: Acute lymphoid leukemia (ALL) is the most common childhood malignancy. Philadelphia chromosome (Ph) is present in 5% of childhood cases. Ph positive leukemias express the tyrosine kinase BCR‐ABL, that is responsible for constitutive activation of RAS pathway and mediates leukemic cells proliferation. Even with high cure rates, a lot of patients develop resistance to treatment and relapse. Previously published data suggests association between hyperactivation of RAS pathway and favorable treatment outcome, pointing to a new research approach. HUWE1 participates in negative feedback mechanism controlling Shoc2 activity in activation of ERK1/2. Thus, it can be assumed that loss of HUWE1 would lead to increased activation of ERK1/2 and, therefore, hyperactivation of RAS pathway.</p><p><bold>Objectives</bold>: To evaluate the impacts of <italic>HUWE1</italic> knockdown in human hematopoietic stem cells with <italic>KRAS</italic> mutation.</p><p><bold>Design/Methods</bold>: CD34+ cord blood cells were transduced with miR‐E lentiviral particles for gene knockdown. Flow cytometry, differentiation markers and CFC assays were performed.</p><p><bold>Results</bold>: Co‐cultures transduced with both <italic>KRAS</italic> and sh<italic>HUWE1</italic> showed reduction in growth when compared to the ones transduced with shSCR. When compared to non‐transduced cells, all 3 groups presented higher cumulative growth. The cobblestone area formation follows the same pattern shown by cumulative growth. In sorted co‐cultures, after 3 weeks in culture, non‐transduced cells differentiated mainly in granulocytic cells while <italic>HUWE1</italic> knockdown shifted differentiation towards the myelomonocytic cells. In CFC assays, neither colony formation units (CFU‐GM) nor burst‐formation units (BFU‐E) were strongly affected by knockdown of <italic>HUWE1</italic>. <italic>KRAS</italic> mutant cells were severely impacted in BFU‐E formation. Cells showing knockdown of <italic>HUWE1</italic> as well as the <italic>KRAS</italic> mutation were severely impacted in both types of colony formation units.</p><p><bold>Conclusions</bold>: These results suggest that <italic>HUWE1</italic> has an impact in human hematopoietic stem cell differentiation, besides acting together with <italic>KRAS</italic> mutation in events such as proliferation and colony formation capacity.</p><p>Financial Support: FAPESP (Process 2015/12146‐5)</p></sec><sec id="pbc26772-sec-4670"><label>P-077</label><title>Tyrosine Kinase Inhibitor Responses in Pediatric CML Patients: Hacettepe Experience</title><p><underline underline-style="single">İ. Yaman Bajin</underline><sup>1</sup>, S. Aytaç<sup>1</sup>, B. Kuşkonmaz<sup>1</sup>, Ş. Ünal<sup>1</sup>, V. Okur<sup>1</sup>, D. Çetinkaya<sup>1</sup>, M. Çetin<sup>1</sup>, F. Gümrük<sup>1</sup></p><p><italic><sup>1</sup>Hacettepe University, Department of Pediatrics‐ Division of Pediatric Hematology, ANKARA, Turkey</italic></p><p><bold>Background/Objectives</bold>: Chronic myeloid leukemia (CML) is a rare malignancy of childhood which is composed of 3% of all pediatric leukemias. Tyrosine kinase inhibitors (TKIs) revolutionazed CML treatment and made it possible to avoid allogeneic stem cell transplant (SCT) for most of the patients. Here, we aimed to investigate the TKI responses of patients diagnosed CML in our department.</p><p><bold>Design/Methods</bold>: Patients diagnosed with CML, did not underwent SCT and is still on follow‐up since 2012 in Hacettepe University Department of Pediatric Hematology were included. Four patients who underwent SCT between this period were excluded. The clinical features and TKI responses of these patients were evaluated.</p><p><bold>Results</bold>: There were nine patients. Age at diagnoses were median 13 years (10‐16 years). Two girls and 7 boys. Treatment was started with imatinib for all of the cases. Two patients responded imatinib and major molecular response (MMR) was achieved in 4 and 9 months respectively. Two patients were diagnosed within the three months and MR have not been checked yet. The other 4 patients did not responded imatinib therapy in 18 months, since they do not have an eligible donor we replaced imatinib with dasatinib therapy. One patient achieved MMR with imatinib in 3 months but he developed leukopenia so imatinib replaced with dasatinib for this case. Patients achieved MMR with dasatinib except one. In this case dasatinib replaced with nilotinib and MMR achieved within 3 months of nilotinib treatment. One patient needed to interrupt dasatinib therapy because of gastrointestinal bleeding, after 1 week of interruption dasatinib started again no bleeding observed and he is still on molecular remission.</p><p><bold>Conclusions</bold>: TKIs are effective in the CML treatment and MMR could be achieved with the change between these drugs when an adverse events occur or an eligible donor could not be found and SCT is not an option.</p></sec><sec id="pbc26772-sec-4680"><label>P-078</label><title>Clinical Study of Children with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide: A Multicenter Study</title><p>H. Jiang<sup>1</sup>, J. Zhu<sup>1</sup>, <underline underline-style="single">J. Yang</underline><sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children's Hospital, Hematology/Oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: Acute promyelocytic leukemia (APL) is rare in children. Due to the lack of long‐term follow‐up, results of ATO and the concern about long‐term ATO related toxicity, the main protocol for children with newly diagnosed APL is still a combination of ATRA and chemotherapy. Few studies have demonstrated the efficacy of ATO in the treatment of children with APL. In this study, we retrospectively analyzed 25 children with newly diagnosed APL treated with ATO in mulicenter.</p><p><bold>Design/Methods</bold>: To evaluate the efficacy of Children with acute promyelocytic leukemia (APL) treated with arsenic trioxide (ATO), we retrospectively reviewed 25 newly diagnosed APL patients treated mainly with all‐trans‐retinoic acid (ATRA) and ATO from 2 hospitals. According to different risk stratification by NCCN, 25 patients were separated into 2 groups, low risk group and high risk group.</p><p><bold>Results</bold>: Overall, 24 of 25 patients achieved hematological complete remission (HCR). In one case, the patient failed to enter HCR, because of early death. The median duration required to achieve HCR was 34 days (range, 26‐63 days). The median date to achieve molecular complete remission was 56 days (range, 30‐207 days). The 5‐year EFS and OS of 25 patients were (88.0±6.5)% and (96.0±3.9)%, respectively. The 5‐year EFS of low risk group and high risk group patients were (92.9±6.9)% and (81.8±11.6)% (P=0.44). ATO related side effects were mild, including abnormal liver tests and electrocardiogram, but were invertible after supportive therapy. At the end of each chemotherapy course, the urine arsenic concentration remained low and no chronic arsenic toxicity or second malignancies were found during the follow‐up period.</p><p><bold>Conclusions</bold>: The ATRA plus ATO regimen is a promising and better treatment for childhood APL with positive PML‐RARa fusion gene. It was necessary to make risk stratification in APL patients.</p></sec></sec><sec id="pbc26772-sec-4690"><title>Haematology ‐ Lymphomas</title><sec id="pbc26772-sec-4700"><label>P-079</label><title>Superior Outcome and Lower Cumulative Chemotherapy Doses in Adolescents and Young Adults (AYA) with Non‐Advanced Diffuse Large B‐Cell Lymphoma (DLBCL) Treated with Pediatric Chemotherapy Regimen</title><p><underline underline-style="single">Z. Afify</underline><sup>1</sup></p><p><italic><sup>1</sup>Primary Children Hospital, Oncology, Salt Lake City, Usa</italic></p><p><bold>Background/Objectives</bold>: Systematic data on the optimal treatment for AYA with DLBCL are lacking. Many are treated by R‐CHOP with favorable outcome. However pediatric based chemotherapy regimens have yielded equal or superior results. We present a series of AYA with DLBCL referred by medical oncologists to our children hospital in consideration for treatment on pediatric protocol.</p><p><bold>Design/Methods</bold>: Retrospective review of patients diagnosed with DLBCL between ages 16 and 24 years from 1/2002 to 3/2017. PMBCL was excluded. Clinical characteristics, staging, treatment details and outcome data were collected. These were compared with published data in young adults above 18 years of age treated by R‐CHOP.</p><p><bold>Results</bold>: Six AYA with DLBCL were identified. Five were male. Age at diagnosis ranged from 16‐20 years. Four were above 18 years old. Sites of presentation were bone n=4, rectum=1, abdomen n=1. None had bone marrow or CNS involvement. Stage was I‐III Murphy/St Jude. This corresponds to Ann Arbor staging I‐IV. All six patients are alive and lymphoma free at last follow up (2‐6 years, median 5 years). None received radiation therapy. All patients were treated per FAB/LMB regimen: Group A therapy (COPAD) n=1, Group B4 therapy (COP, COPADM1&2, CYM1&2) n=5. Cumulative chemotherapy doses in 5 patients who received group B therapy were Cyclophosphamide 3.3 g/m2, Doxorubicin 120 mg/m2, Prednisone 900 mg/m2, Vincristine 6 mg, Methotrexate 12 g/m2, and Cytarabine 1000 mg/m2. There were 7 intrathecal chemotherapy administrations (methotrexate, Cytarabine, hydrocortisone). Compared to this regimen, 6 courses of R‐CHOP consist of 1.2‐2.5 fold cumulative doses of cyclophosphamide (4.5 grams/m2), Hydroxydaunorubicin (300 mg/m2), Vincristine (12 mg).</p><p><bold>Conclusions</bold>: In AYA with non‐advanced DLBCL, pediatric chemotherapy regimen provides an alternative to R‐CHOP, eliminates the use of radiation therapy and provides lower cumulative Anthracyline and alkylating doses. Pediatric regimen may reduce risk of long term cardiac and second cancer effects.</p></sec><sec id="pbc26772-sec-4710"><label>P-080</label><title>Childhood Hodgkin Lymphoma: Single Center Experience</title><p><underline underline-style="single">E. Ataseven</underline><sup>1</sup>, Z. Siviş<sup>1</sup>, B. Malbora<sup>1</sup>, F.B. Belen<sup>1</sup>, B. Güneş<sup>1</sup>, S. kamer<sup>2</sup>, Y. Anacak<sup>2</sup>, B. Atabay<sup>1</sup>, M. Türker<sup>1</sup>, H. Öniz<sup>1</sup></p><p><italic><sup>1</sup>Izmir Tepecik Research and Training Hospital, Pediatric Hematology and Oncology, Izmir, Turkey; <sup>2</sup>Ege University Faculty of Medicine, Department of Radiation Oncology, İzmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: Childhood Hodgkin lymphoma(HL) is a type of cancer of the lymphoid system.According to the Turkish Pediatric Oncology Group(TPOG) statistics lymphomas are the most common solid tumors of childhood(26,8%) and 9.9% of them are Hodgkin lymphomas.With current chemotherapy and radiotherapy regimens,most of the children with HL survive.</p><p>In this study,our aim is to evaluate the clinical characteristics and treatment outcome of HL cases treated in our institution.</p><p><bold>Design/Methods</bold>: We evaluated the recordings of the patients with HL treated between 1987‐2016 retrospectively.Demographic and clinical features,treatment results,overall survival(OS) and event free survival(EFS) rates were evaluated.</p><p><bold>Results</bold>: 104 patients were eligible out of 133 patients(F/M= 27 /77).The mean age was 9.5±3.7 years.Most common complaint was lump in the neck(n=82).B symptoms were present in 42.3%(n:44).Most common B symptom was found to be fever.Histopathologic diagnosis revealed 65.3% mixed cellularity,19.2% nodular sclerosis.Stage distribution was as follows:Stage‐1 in 14.4%,Stage‐2 in 46.1%,Stage‐3 in 19.2%, Stage‐4 in 20.1%.In stage 4 patients,most common metastatic site was lung(n:12).Fifty‐eight patients were treated according to the GPOH 90/95 protocol,remaining patients were treated with other regimens(ABVD(n:10),MOPP/ABVD(n:25),MOPP(n:8),COPP(n:3)).Radiotherapy was performed to the primary tumor site in 91 cases.Relapse occurred in 16 patients,most of them were treated with MOPLACE(n:7) chemotherapy.Remission was achieved in 3 patients,10 patients died because of disease progression,3 patients refused treatment.Median follow‐up‐time was 10 years(1 month‐30 years).5‐years EFS and OS were 76%,86% respectively.Between GPOH 90/95 and ABVD,MOPP/ABVD treatment groups no significant difference was found in survival(p=0,882) and relapse rates(p=0,047).</p><p><bold>Conclusions</bold>: When our results were compared with the literature,it was seen that the most common type is mixed cellularity in accordance with the previous reports.In1970's 5‐years OS was 81%,in 2002 5‐years OS increased to 90%.Our survival rates were lower than original protocols.It was thought that it might be due to the fact that most patients in the study belonged to the era before 90's lowering the overall OS and EFS.</p></sec><sec id="pbc26772-sec-4720"><label>P-081</label><title>Presentation of Burkutt's Lymphoma in a Tertiary Hospital in Ghana</title><p><underline underline-style="single">M. Barnabas</underline><sup>1</sup>, V. Paintsi<sup>2</sup></p><p><italic><sup>1</sup>komfo Anokye Teaching Hospital, Cild Health Directorate, Kumasi, Ghana; <sup>2</sup>komfo Anokye Teaching Hospital, Child Health Directorate, Kumasi, Ghana</italic></p><p><bold>Background / Objectives</bold> Burkett's lymphoma (BL) is the most frequent subtype of Non‐Hodgkin's lymphoma seen in childhood in sub‐Sahara Africa. BL is highly aggressive with a doubling time of approximately 24 hours. It responds favorably if diagnosed accurately and treated early. Prompt recognition and initiation of therapy are essential for improved survival. This study seeks to review the clinical presentation and imaging findings of patents’ with Burkett's lymphoma in the pediatric population</p><p><bold>Design/Methods</bold>: This was a hospital‐based retrospective study which reviewed all the clinical and histopathological records of patients with Burkett's Lymphoma at the paediatric cancer unit ‐ Komfo Anokye Teaching Hospital from January 2016 to December, 2016.</p><p><bold>Results</bold>: There were 35 children diagnosed, with male to female ratio of 3:2. The median age was 8years (Range; 2years‐15years).The maximum duration of symptoms was 4 weeks. The commonest symptom was swelling with the majority sites involved being abdomen 42.9%, jaw 25.7%, combined jaw and abdomen (14.2%) and other body sites (17%). Other presenting symptoms include fever (25.7%), weight loss 6(17.14%), proptosis 3(8.57%), night sweats 2(5.7%), anaemia 1(2.85%) and difficulty in breathing 1(2.85%). Stage III was the commonest stage seen at presentation in 13(37.14%) of the patients and those with stage IV were 5(14.3%), been the rarest. Stage I was 10(28.3%), whilst stage II was seen in 7(28%). Intent of treatment was 71.4% of patients for palliation and 28.6% of the patient's curative intent.</p><p><bold>Conclusions</bold>: Although Burkett's lymphoma is relatively cheap and easy to treat as compared to the other cancers, most of the patients presented with advanced disease impacting on the survival. Increased education on early warning signs for parents and healthcare personnel needs to be undertaken to reduce advanced disease at presentation.</p></sec><sec id="pbc26772-sec-4730"><label>P-082</label><title>Clinical Characteristics and Outcome of Pediatric‐Type Follicular Lymphoma: Report from a Pediatric Cancer Center in a Developing Country</title><p><underline underline-style="single">S. Eissa</underline><sup>1</sup>, S. Semary<sup>1</sup>, A. Salama<sup>2</sup>, A. Elhaddad<sup>1</sup></p><p><italic><sup>1</sup>Children's Cancer Hospital‐Egypt, Pediatric HematIology/Oncology, Cairo, Egypt; <sup>2</sup>National Cancer Institute ‐ Egypt, Pathology Department, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Follicular lymphoma (FL) is rare to occur in children. Its pediatric variant (pFL) had been recently included in the updated WHO classification of lymphoid malignancies (2016). Patients usually present with a low stage disease, that is t(14,18) and BCL2 negative.</p><p><bold>Design/Methods</bold>: Retrospective analysis of the cases diagnosed with FL presented to our cancer center during the period between July 2007 to December 2016.</p><p><bold>Results</bold>: Over a period of 9 years, 3 patients were diagnosed with FL at our cancer center. All patients were males, presented with stage II disease, morphologically grade 3a. The first case: 7 years old male who presented with cervical lymphadenopathy and B symptoms. Tumor was CD20, BCL6 positive, CD3, BCL2 negative, MIB‐1 (80%). He received R‐CHOP (Rituximab immunotherapy plus cyclophosphamide, doxorubicin, vincristine and prednisone) and is under follow up from July 2011 till now. The second case: An 8 years old male who had atypical lymphoid hyperplasia diagnosed 1 year prior to the diagnosis of FL in April 2014. Tumor was positive to CD20 and BCL6 and negative BCL2 with low expression of Ki‐67. He received R‐CHOP chemotherapy and involved field radiotherapy (IFRT) in addition and placed under follow up since April 2015. The third case: An 12 years old male presented with bilateral cervical and parotid lymph node enlargement. Biopsy showed positive reaction to CD20 in the neoplastic cells. BCL2 diffusely highlighted the neoplastic cells. BCL6 and CD10 were positive. Ki67 labeling index was high (60%). He received R‐CHOP chemotherapy and is currently under follow up since June 2014.</p><p><bold>Conclusions</bold>: Patients with pFL presented to our center had localized disease, responded well to chemotherapy and had durable complete remission. Trial of less intensive chemotherapy, omission of radiotherapy and inclusion of new agents as Bendamustine with Rituximab based therapy should be attempted to minimize the late effects.</p></sec><sec id="pbc26772-sec-4740"><label>P-083</label><title>Hodgkin Lyphoma in Children: A Single Center Experience in Turkey</title><p><underline underline-style="single">N. Eker</underline><sup>1</sup>, G. Tokuc<sup>1</sup>, B. Yılmaz<sup>1</sup>, E. Senay<sup>1</sup>, B. Berk<sup>1</sup>, O. Dogru<sup>1</sup></p><p><italic><sup>1</sup>Marmara University, Pediatric Hematology and Oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Hodgkin Lymphoma (HL) is one of the most frequent cancers in adolescent and young adults and is curable in more than 90% of cases. The aim of this study was to assess the demographic, clinic data, prognostic factors and treatment/follow‐up results of children who were diagnosed with Hodgkin lymphoma and followed in our center of Pediatric Oncology, Marmara University Medical Faculty, Istanbul, Turkey, for 20 years.</p><p><bold>Design/Methods</bold>: Children with HL who were diagnosed and treated at our center between 1996 and 2016 were retrospectively analyzed.</p><p><bold>Results</bold>: A total of 87 children with a mean age of 9,5±3,9 years were treated for HL. Fifty‐eight patients (67%) were males and 29 (33%) were females. Among them, 52% presented with advanced‐stage (stages III and IV) disease, 39 % had B symptoms, and 50,6% had mixed cellularity type of HL. Multiagent chemotherapy was the mainstay of treatment. All patients were treated with risked adapted ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) or COPP‐ABV (Cyclophoshamide, Vincristine, Procarbazine, Prednisone, Adriamycin, Bleomycin, Vinblastine) chemotherapy and also received involved field radiotherapy. During th follow up ten patients had relapsed. The 5‐year overall survival rate was 87%, respectively. Stage, treatment risk groups, presence of B symptoms and histopathologic subtype had no significant effect on overall survival in univariate analysis while relapsed disease was the only significant factor on overall survival.</p><p><bold>Conclusions</bold>: Hodgkin lymphoma can be cured with chemotherapy combined with low dose IFRT however relapsed disease is still the significant factor on overall survival.</p></sec><sec id="pbc26772-sec-4750"><label>P-084</label><title>Venous Thromboembolism in Childhood Cancer: Hodgkin Lymphoma is a High‐Risk Diagnosis</title><p><underline underline-style="single">N. El‐Haj</underline><sup>1</sup>, B. Lau<sup>1</sup>, J. Friderici<sup>2</sup>, J. Luty<sup>3</sup>, M. Richardson<sup>3</sup>, S. Grewal<sup>3</sup></p><p><italic><sup>1</sup>Baystate Medical Center, Internal Medicine and Pediatrics, Springfield, USA; <sup>2</sup>Baystate Medical Center, Biostatics and Epidemiology, Springfield, USA; <sup>3</sup>Baystate Medical Center‐ D'Amour Center for Cancer Care, Pediatric Hematology‐Oncology, Springfield, USA</italic></p><p><bold>Background/Objectives</bold>: Venous thromboembolism (VTE) is understudied in pediatric cancer patients. This study evaluates risk of VTE in children with cancer and identifies high‐risk diagnostic groups.</p><p><bold>Design/Methods</bold>: This single center retrospective cohort study included patients under 21 years old diagnosed with cancer between 1/01/2007‐6/30/2016 and followed from date of diagnosis to date of VTE, age 21, or end of study, whichever occurred first. The institution's Tumor Registry captured a primary diagnosis of cancer and a secondary diagnosis of VTE was extracted using ICD codes. Patients were excluded if they were under the care of adult providers or sub‐specialists, had insufficient documentation, or were inaccurately identified. For patients diagnosed with HL, demographic, treatment and disease‐related variables were obtained by manual chart review.</p><p><bold>Results</bold>: The study included 181 patients split into 3 groups: HL (n=18), ALL +T‐Non‐Hodgkin lymphoma (T‐NHL) (n=51), and other cancers (n=112). VTE was diagnosed in 10 patients (6%). VTE occurred among 27.8% of HL patients; 5.9% of ALL/T‐NHL patients; and 1.8% of other cancer patients; corresponding hazard ratios: HL vs. ALL/T‐NHL 5.1 (95% CI 1.21, 21.3); HL vs. other cancers 17.2 (95% CI 3.3, 88.7). Patients with HL only developed VTE in major upper body veins. Median time from HL diagnosis to VTE was 52 days (29 to 245 days), and all VTE incidents occurred prior to radiation. Within our cohort of patients with HL and VTE, 60% received chemotherapy per GPOH‐HD95 regimen. Both patients with refractory HL who proceeded with autologous bone marrow transplant had prior VTE during first line therapy for HL. All patients with HL and VTE had a negative family history, and thrombophilia workup performed in 3/5 patients was unremarkable.</p><p><bold>Conclusions</bold>: In our cohort, HL represented a high‐risk group for VTE. If a larger cohort confirms these results, these children may be candidates for prophylactic anticoagulation during initial treatment.</p></sec><sec id="pbc26772-sec-4760"><label>P-085</label><title>Clinical Characteristics and Outcome of Children and Adolescents with Anaplastic Large‐Cell Lymphoma in China: A Retrospective Study from the Chinese Children's Cancer Group</title><p><underline underline-style="single">Y.J. Gao</underline><sup>1</sup>, M. Xie<sup>2</sup>, H. Jiang<sup>3</sup>, X. Guo<sup>4</sup>, J. Yan<sup>5</sup>, A.G. Liu<sup>6</sup>, J. Lu<sup>7</sup>, X.L. Ju<sup>8</sup>, X.J. Yuan<sup>9</sup>, R.M. Jin<sup>10</sup>, J.Y. Tang<sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center, Department of Hematology and Oncology, Shanghai, China; <sup>2</sup>Xiangya Hospital‐ Central South University, Department of Pediatric Hematology & Oncology, Changsha, China; <sup>3</sup>Children's Hospital of Shanghai, Department of Hematology & Oncology, Shanghai, China; <sup>4</sup>West China Second University Hospital of Sichuan University, Department of Pediatric Hematology & Oncology, Chengdu, China; <sup>5</sup>Tianjin Medical University Cancer Institute & Hospital, Department of Pediatric Oncology, Tianjin, China; <sup>6</sup>Tongji Hospital‐ Tongji Medical College‐ Huazhong University of Science & Technology, Department of Pediatric Hematology & Oncology, Wuhan, China; <sup>7</sup>Children's Hospital of Soochow University, Department of Hematology & Oncology, Soochow, China; <sup>8</sup>Qilu Hospital of Shandong University, Department of Pediatric Hematology & Oncology, Jinan, China; <sup>9</sup>Xinhua Hospital, Department of Pediatric Hematology & Oncology, Shanghai, China; <sup>10</sup>Wuhan Union Hospital, Department of Pediatric Hematology & Oncology, Wuhan, China</italic></p><p><bold>Background/Objectives</bold>: To provide a description review and improve our understanding of the clinical characteristics and outcome of pediatric anaplastic large cell lymphoma (ALCL) in China. And the results can serve as baseline data to guide our future therapeutic protocol development.</p><p><bold>Design/Methods</bold>: We retrospectively evaluated clinical characteristics and outcomes of 80 children (≤16 years) with newly histopathologically‐confirmed ALCL (52 boys, 28 girls) treated by ten large single institutions in China between January 2009 and June 2014.</p><p><bold>Results</bold>: Two patients (3%) had Stage I disease, 9 (11%) had Stage II, 64 (80 %) had Stage III, and 5 (6%) had Stage IV. Phenotyping demonstrated a predominance of T‐cell phenotype in 72.5% of cases (58/80). Sixty‐five patients (81%) were treated with the CCCG‐BNHL‐2010 regimen (a Chinese national‐wide protocol for pediatric ALCL) and 15 cases (19%) treated with other regimens. At a median follow‐up of 25.2 months (range, 7.1‐74.8 months), the 3‐year of event‐free survival (EFS) was 65%±6% in all patients. The 3‐year EFS was 57%±7% and 78%±11% for patients with or without B symptoms, respectively<italic>(P=0.01)</italic>. Twenty‐four patients experienced disease progression or relapse. The median time from initial diagnosis to tumor failure was 7.0 months (ranged, 1.5 ‐42.6 months). At the last evaluation, there were 5 patients still alive after disease progression and relapse.</p><p><bold>Conclusions</bold>: The presenting features and outcome of children and adolescents with ALCL in this study were similar to those reported by other countries. Establishment of therapeutic strategies to improve survival for patients with disease progression or relapse should be the priority in our future clinical study.</p></sec><sec id="pbc26772-sec-4770"><label>P-086</label><title>B Cell Non‐Hodgkins Lymphoma (BNHL) and Residual Disease on Scan at Disease Assessment in Children Under 12</title><p><underline underline-style="single">K. Green</underline><sup>1</sup>, D. Cheng<sup>2</sup></p><p><italic><sup>1</sup>Great Ormond Street Hospital for Children, Oncology, London, United Kingdom; <sup>2</sup>Great Ormond Street Hospital for Children, Haematology, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Children with BNHL have good outcomes with intensive upfront chemotherapy. Disease relapse or progression is associated with very poor outcome. Early disease assessment and escalation of chemotherapy is necessary when there is no clear radiological early‐treatment response. The value of post‐treatment imaging surveillance and biopsy of residual imaging abnormalities in detecting and preventing disease relapse/progression is unclear.</p><p>We evaluated whether our patients with BNHL with residual radiological abnormalities received follow‐up imaging and biopsies, and how these investigations affected clinical outcomes.</p><p><bold>Design/Methods</bold>: Retrospective data of all children diagnosed with BNHL between 2012‐2017 at a UK tertiary paediatric oncology centre was collected. Patient age at diagnosis, gender, histology, MYC status, and bone marrow or CNS involvement were recorded. Chemotherapy regimes were recorded, including escalation from Group B to C. Follow‐up imaging and clinic letters were analysed, with residual disease categorised according to formal radiology reports.</p><p><bold>Results</bold>: 27 children aged 1 to 11 years were diagnosed with BNHL; 23 males (85%) and 4 females (15%). 7 children had bone marrow positivity (26%), and 4 children CNS positivity (15%). 17 children (63%) were MYC positive. 20 children (74%) received group B treatment, and 7 (26%) group C treatment. 5 children (18%) demonstrated poor response to COP chemotherapy and were escalated to group C.</p><p>At end of treatment, 5 children (19%) had “no residual disease”, and 15 children (55%) “almost certainly had no residual disease”. 6 children (22%) had abnormal findings; 4 underwent biopsy to exclude active disease. None of the children undergoing follow up imaging demonstrated disease relapse. One child died during treatment without achieving remission.</p><p><bold>Conclusions</bold>: None of our patients with residual imaging abnormalities at treatment completion had disease relapse or progression, questioning the clinical need for long term imaging, particularly if involving radiation. Biopsy provided reassurance without altering patient management.</p></sec><sec id="pbc26772-sec-4780"><label>P-087</label><title>Risk Factors for Relapse in Children with Hodgkin Lymphoma Treated with Chemotherapy Alone Protocols</title><p><underline underline-style="single">V. Gupta</underline><sup>1</sup>, R. Sonowal<sup>1</sup>, T.B. Singh<sup>2</sup>, S.K. Gupta<sup>3</sup></p><p><italic><sup>1</sup>Institute of Medical Sciences‐ Banaras Hindu University, Pediatrics, Varanasi, India; <sup>2</sup>Institute of Medical Sciences‐ Banaras Hindu University, Statistics, Varanasi, India; <sup>3</sup>Institute of Medical Sciences‐ Banaras Hindu University, Surgery, Varanasi, India</italic></p><p><bold>Background/Objectives</bold>: Hodgkin lymphoma displays characteristic epidemiological, clinical and pathological features in different geographical areas. Objective was to analyze demographic profile, disease characteristics, event free survival (EFS), overall survival (OS) and risk factors for relapse in patients with Hodgkin lymphoma (HL) treated with chemotherapy only protocols.</p><p><bold>Design/Methods</bold>: Retrospective observational study was carried out in a university teaching hospital. Children below the age of 15 years diagnosed with Hodgkin lymphoma between Jan 2005 to Dec 2014 were included in the study.</p><p><bold>Results</bold>: 90 patients with mean age of 8.13 ± 2.65 years (median age 8 years; range 4.5‐15 years) were diagnosed and treated for HL during study period. Male to female ratio was 7.2:1. 12.2% and 87.8% patients had early and advanced stage disease respectively. B symptoms were present in 87.8% patients. Mean duration of symptoms was 9.66 ± 6.30 months (median 8 months; range 2‐36 months). Mixed cellularity was commonest histologic type. Overall survival (OS) and event free survival (EFS) was 88.8% and 84.5% respectively. OS in early stage and advanced stage disease was 90.0% and 89.0% respectively. In patients with or without bulky disease it was 53.3% and 92.2%. The EFS in early stage and advanced stage disease was 90.0% and 83.8% respectively. It was 59.3% for patients with bulky disease and 86.5% for those without bulky disease. Older age (≥10 years), bulky disease, low hemoglobin (≤7.0 g/dl), high leucocyte count (≥12000/mm<sup>3</sup>) at the time of diagnosis and protocol used (COPP) were risk factors for relapse.</p><p><bold>Conclusions</bold>: Our patient population had younger age, advanced disease, more B symptoms and bulky disease. Still, we achieved good OS and EFS with chemotherapy alone protocols. Patients with bulky disease had poor overall and event free survival. If radiotherapy is included in the protocol for bulky disease, the survival rates can be improved further.</p></sec><sec id="pbc26772-sec-4790"><label>P-088</label><title>Treatment of Paediatric Hodgkins Lymphoma‐ An Experience from a Paediatric Tertiary Centre</title><p><underline underline-style="single">Y. Gupta</underline><sup>1</sup>, D. Hobin<sup>1</sup></p><p><italic><sup>1</sup>Birmingham Children's Hospital, Pediatric Oncology, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: We present a retrospective analysis of 39 pediatric patients with HL who received treatment at our center over a period of 4 years from 2013 to 2016 and aim to study the response to chemotherapy in pediatric patients with HL.</p><p><bold>Design/Methods</bold>: Patients diagnosed with HL were divided into 3 treatment groups depending on the stage of disease (1). The patients in group 1 received 2 cycles of vincristine, etoposide, prednisolone, doxorubicin (OEPA), group 2 received 2 cycles of OEPA and 2 cycles of either cyclophosphamide, vincristine, prednisolone, dacarbazine (COPDAC) and group 3 received 2 cycles of OEPA and 4 cycles of COPDAC. Patients with inadequate response received radiotherapy. Early PET response to treatment was analyzed.</p><p><bold>Results</bold>: Of the 39 patients, 21 were in group 1, 4 in group 2 and 14 in group 3.</p><p>Of the 21 (53.8%) patients in group1, Complete metabolic response (CMR) was seen in 16 (76.1%) and partial response in 2 (9%) patients PET was not done in 3(%). 3 (14.2%) patients had a relapse. There were no deaths. Event free survival (EFS) and Overall survival (OS) for group 1 patients was 85.7% and 100%</p><p>Of the 4(10.2%) patients in group 2, CMR was seen in 4 (100%) patients. 1(25%) patients had a relapse. EFS and OS for group 2 patients was 75% and 100%.</p><p>Of 14(35.9%) patients in group 3, CMR was seen in 13(92.8%) patients and partial response in 1 (7.1%) patients. 1 (7.1%) patients had a relapse. EFS and OS for group 3 patients was 92.8% and 100% respectively.</p><p><bold>Conclusions</bold>: EFS for all patients treated for HL is 84.5% and overall survival is 100%. This study emphasizes the excellent outcome for pediatric HL to treatment. However, a study with a larger cohort of patients who are followed up for a longer time is required.</p></sec><sec id="pbc26772-sec-4800"><label>P-089</label><title>Retrospective Analysis of Outcomes to Different Chemotherapy Regimens in Pediatric Hodgkins Lymphoma</title><p><underline underline-style="single">Y. gupta</underline><sup>1</sup>, D. Hobin<sup>1</sup></p><p><italic><sup>1</sup>Birmingham Children's Hospital, paediatric oncology, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Retrospective analysis of 81 pediatric patients with Hodgkins Lymphoma who received treatment over a period of 10 years from 2006 to 2016 and study the response to different chemotherapy regimens and hence identify the regimens with best outcomes.</p><p><bold>Design/Methods</bold>: Patients with HL were divided into 3 treatment groups depending on the stage. The patients in group 1 received 2 cycles of vincristine, etoposide, prednisolone, doxorubicin (OEPA) or 3 cycles of cyclophosphamide, vincristine, prednisolone (CVP), group 2 received 2 cycles each of OEPA and either cyclophosphamide, vincristine, prednisolone, dacarbazine (COPDAC) or cyclophosphamide, vincristine, procarbazine, prednisolone (COPP) or cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) and group 3 received 2 cycles of OEPA and 4 cycles of COPDAC or COPP.</p><p><bold>Results</bold>: Of the 25 patients in group1, 21 patients treated with 2 cycles of OEPA 3 relapsed (EFS and OS, 85.7% and 100%) and 4 with 3 cycles of CVP, 2 relapsed (EFS and OS, 50% and 100%).</p><p>Of the 11 patients in group 2, 4 treated with 2 cycles each of OEPA and COPDAC, 1 relapsed (EFS and OS, 75% and 100%), 4 treated with 2 cycles of OEPA and 2 cycles of COPP (100 % EFS and OS), 3 treated with 2 cycles each of OEPA and CHOP, 1 relapsed and 1 died (EFS and OS 6.6%).</p><p>Of 45 patients in group 3, 14 treated with 2 cycles of OEPA and 4 cycles of COPDAC, 1 relapsed (EFS and OS, 92.8% and 100%), 31 treated with 2 cycles of OEPA and 4 cycles of COPP, 6 relapsed, 4 died (EFS and OS, 80.6% and 87%).</p><p><bold>Conclusions</bold>: For group 1 patients treatment with OEPA x2 chemotherapy, group 2 patients OEPA X 2, COPP X2, and for group 3 patients OEPA X 2, COPDAC X 4 have shown to have a better outcome.</p></sec><sec id="pbc26772-sec-4810"><label>P-090</label><title>Evaluation of Musculoskeletal Complaints and Skeletal Involvements in Children with Newly Diagnosed Lymphoma and Solid Tumors</title><p><underline underline-style="single">D. Ince</underline><sup>1</sup>, M. Erdem<sup>1</sup>, F. Yenigurbuz<sup>1</sup>, D. Kizmazoglu<sup>1</sup>, E. Ataseven<sup>1</sup>, H. Guleryuz<sup>2</sup>, K. Mutafoglu<sup>1</sup>, and N. Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University Institute of Oncology, Dept. of Pediatric Oncology, Izmir, Turkey; <sup>2</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiodiagnostics, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: To evaluate patients who had musculoskeletal complaints at admission and/or skeletal involvement at diagnosis in our center.</p><p><bold>Design/Methods</bold>: Medical records of whole patients with diagnosis of lymphoma and solid tumors were analyzed retrospectively. Patients who admitted with musculoskeletal complaints and who had skeletal involvement at diagnosis were selected for analysis. Patient characteristics, complaints, skeletal involvement sites, misdiagnoses, differantial diagnosis diffuculities were analyzed.</p><p><bold>Results</bold>: There was 1061 patients with diagnosis of lymphoma and solid tumor in our clinic between 1988‐2016. One hundred ninetyfour of them admitted with musculoskeletal system complaints and/or skeletal involvement at diagnosis. The median age at diagnosis for these 194 patients was 9yrs(4mos‐17.8yrs), M/F:1.3. The median duration of complaints was 2mos (1day‐2yrs). Before definitive diagnosis was done, patients had been admitted mean 2 times (1‐6) to doctors. Oncologic diagnosis were as follows Ewing sarcoma 21.6%, LHH 15.5%, neuroblastoma 14.5%, osteosarcoma 13.9%, lymphoma 11.4%, rhabdomyosarcoma 8.2%. Misdiagnosises were as follows artiritis 8%(n:16), artralgia 3%(n:5), myalgia 6%(n:11), muscle spasm 3%(n:5), lymphadenitis 5%(n:10), growth pain 2%(n:4), JRA 3%(n:6), osteomyelitis 2%(n:4), bone edema 1%(n:2), ARF 2%(n:4), trauma 7%(n:14), avascular necrosis 0.5%(n:1), FMF 1%(n:2), scoliosis 0.5%(n:1). Dominant complaints: skeletal63%, constituonal26%, others: pain64%, swelling42%, walking impairement31%, fever20%, weight loss26%, night sweating9%, anorexia19%, weakness28%. Skeletal system pain: articular16%, nonarticular25%, artricular+nonarticular21%. Other symptoms: Headache3%, neckache4%, backache11%, extremity pain38%, leg weakness12%, sensory impairment5%, sphincter disfunction5%, spinal cord compression8%. Physical examination: artritis10%, artralgia32%, nonartricular bone sensitiveness19%, rash %4, petechia0.5%, ecchymosis1%, hepatomegaly8%, splenomegaly4%, lymphadenopaty20%. Blasts in peripheral blood smear1.5%, bone marrow aspiration13%, blood count cytopenia20%, ESR36%, LDH >500U/L 25%, CRP >5mg/dl 27%, ANA(+)0.5%. Abnormal findings on: graphy44%, BT46%, MRI39%, bone sintigraphy50%.</p><p><bold>Conclusions</bold>: Musculoskeletal complaints and rheumatic diagnoses with atypical clinical features should be reevaluated because of possible underlying malignancy. Suspicion of malignancy must be ruled out by simple investigations. Medical history, through physical examination, laboratory, radiological evaluations are important for diagnosis.</p></sec><sec id="pbc26772-sec-4820"><label>P-091</label><title>Hodgkin's Lymphoma in Paediatric Population: Analysis of Short Term Outcomes with ABVD and Non ABVD Based Treatment Protocols</title><p><underline underline-style="single">N. Jadhav</underline><sup>1</sup>, B. Dubashi<sup>1</sup>, S. Kayal<sup>1</sup>, P. Madasamy<sup>1</sup>, J. Pattnaik<sup>1</sup>, J. Singh<sup>1</sup>, M. Paramanandhan<sup>1</sup>, E. Jafa<sup>1</sup></p><p><italic><sup>1</sup>Jawaharlal Institute of Post graduate Medical Education and Research, Medical Oncology, PONDICHERRY, India</italic></p><p><bold>Background/Objectives</bold>: Hodgkin's Lymphoma is one of the success stories in modern oncology. Cure rates as high as 90% are possible with the current modalities of treatment. ABVD has established itself as standard of care in adults. Contrary, there is no standard of care for paediatric Hodgkin's. Also there is no randomized trial comparing ABVD verses non ABVD regimens.</p><p><bold>Design/Methods</bold>: Consecutive patients diagnosed with Hodgkin's lymphoma, treated at Regional Cancer Center JIPMER were analyzed retrospectively. Data was retrieved from the records section and patients were analyzed for clinical profile and outcomes with ABVD and non ABVD based treatment protocols.</p><p><bold>Results</bold>: A total of 47 patients were registered from October 2009 till January 2017. Median age of presentation was 12 years with male to female ratio of 3.27. Most common presenting complain was neck mass, seen in 63.82% of patients. Median symptom duration was 12 months prior to first contact with an Oncologist. B symptoms were seen in 44.68% of patients and bulky disease in 42.55%. Extra‐nodal involvement was seen in 12.76% of patients. 53.19% patients presented in early stage with 60% being early stage unfavorable. Most common histology was classical Hodgkin's mixed cellularity (55.31%) with 86.95% and 58.69% positivity for CD30 and PAX5. 57.44% patients were treated with ABVD and 23.4% with non‐ABVD protocols. 42.55% patients received RT, 45% each for bulky disease and as a part of combined modality treatment. Toxicity was seen in 42.55% of patients with febrile neutropenia in 21.27% and bleomycin lung in 11.76%. Overall till date 76.56% of patients on regular follow up are in CR</p><p><bold>Conclusions</bold>: Outcomes for pediatric Hodgkin's are promising despite late presentation to an Oncologist in our setup. Response rates with ABVD and non ABVD regimens are comparable but associated with different toxicities.</p></sec><sec id="pbc26772-sec-4830"><label>P-092</label><title>Burkitt Lymhoma in a Boy with Cryptogeneic Cirrhosis: What is the Best Way to Treat?</title><p><underline underline-style="single">Z. Karakas</underline><sup>1</sup>, D. Tugcu<sup>1</sup>, A. Karagenc<sup>1</sup>, S. Cantez<sup>2</sup>, P. Odalı<sup>1</sup>, G. Atay<sup>3</sup>, S. Hancerli<sup>4</sup>, S. Karaman<sup>1</sup></p><p><italic><sup>1</sup>Istanbul University ‐ Istanbul Medical Faculty, Pediatric Hematology/Oncology, Istanbul, Turkey; <sup>2</sup>Istanbul University ‐ Istanbul Medical Faculty, Pediatric Gastroenterology, Istanbul, Turkey; <sup>3</sup>Istanbul University ‐ Istanbul Medical Faculty, Pediatric Intensive Care, Istanbul, Turkey; <sup>4</sup>Istanbul University ‐ Istanbul Medical Faculty, Pediatric Infection, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: To describe an uncommon occurence of Burkitt lymphoma in a boy with cryptogeneic cirrhosis and discuss the treatment of lymphoma in the presence of liver failure.</p><p><bold>Design/Methods</bold>: A fifteen‐year‐old‐boy was first referred for a cervical mass.Medical history revealed that he has been under regular follow‐up with the diagnosis of idiopathic cirrhosis for about 9 years.The pathologic diagnosis was Burkitt lymphoma(BL).He was evaluated as stage II and BFM NHL 2012 study protocol was began.</p><p><bold>Results</bold>: Hepatic failure developed after full dose prophase and two days 50% reduced AA block, and chemotherapy could not be continued. On 14 <sup>th</sup> day,he was transferred to Pediatric Intensive Care Unıt due to hepatic and respiratory failure,massive ascites with diagnoses of sinusoidal obstruction syndrome,and sepsis.<italic>Klebsiella Pneumoniae</italic> was detected in hemoculture. After an effective treatment, he was re‐transferred to our clinic on 28 <sup>th</sup> day of therapy.Considering life threatening complications even after reduced dose chemotherapy,he was discussed at local tumor council and decided to continue with single six rituximab therapy.Complete remission was achieved just after the first course of rituximab. After the first cure,liver functions impaired and next rituximab could be given one month later.He is still in remission for BL with stable signs of chronic liver failure.He is a candidate for liver transplantation. He had alive donor for liver transplantation. The liver transplant council decided to follow up until the end of chemotherapy because the patient was stable.</p><p><bold>Conclusions</bold>: Burkitt lymphoma is very chemo‐sensitive tumor with successful results with chemotherapy. But as in our case,in the presence of comcomitant liver failure, treatment of this well‐known tumor could be very difficult. Targeted therapies might be an effective alternative instead of conventional treatment protocols in such extraordinary presentations.</p></sec><sec id="pbc26772-sec-4840"><label>P-093</label><title>Evaluation of Metabolic Tumor Volum and Total Lesion Glicolysis in Pediatric Hodgkn Lymphomas at Diagnosis and After 4 Chemotherapy Courses</title><p>D. Massano<sup>1</sup>, E. Carraro<sup>1</sup>, M.P. Boaro<sup>1</sup>, M.S. Buzzaccarini<sup>2</sup>, <underline underline-style="single">G. Scarzello</underline><sup>2</sup>, A. Zanella<sup>3</sup>, G. Basso<sup>1</sup>, M. Pillon<sup>1</sup>, P. Zucchetta<sup>3</sup></p><p><italic><sup>1</sup>University Hospital of Padua, Pediatric Onco‐Hematology Unit, Padua, Italy; <sup>2</sup>IOV Istituto Oncologico Veneto, Nuclear Medicine and Radiation Therapy Unit, Padua, Italy; <sup>3</sup>University Hospital of Padua, Nuclear Medicine Department, Padua, Italy</italic></p><p><bold>Background/Objectives</bold>: Recent studies demonstrated how qualitative and semi‐quantitative measures, obtained with ad interim evaluation with positron emission tomography (PET), could predict the clinical response in patients with Hodgkin Lymphoma (HL). The aim of our study was to evaluate some semi‐quantitative PET measures to predict the response in pediatric patients with HL.</p><p><bold>Design/Methods</bold>: We measured the Standard Uptake Value (SUV)‐max, SUV‐peak, Metabolic Tumor Volume (MTV) and Total Lesion Glicolysis (TLG) in the PET imagings obtained at staging and after 4 chemotherapy courses COPP/ABV or ABVD. Patients were treated according to the AIOEP‐LH‐2004 protocol. Patients were defined good responders (GR) if they were in complete remission (CR) at the end of follow‐up, otherwise they were defined as no‐responders (NR). Statistical analysis was performed with the <italic>Mann</italic>‐<italic>Whitney</italic> test.</p><p><bold>Results</bold>: Ninety‐four PET datasets of 47 children were analyzed. Mean follow‐up was 44 months. At the end of the follow‐up 41 patients were in CR and only 6 were NR. All relapsed patients, or refractory to the first line therapy, suffered of Nodular <italic>Sclerosis HL stage III or IV</italic>.</p><p><italic>The PET imagings done at diagnosis showed a higher burden of disease in NR patients compared to GR patients: MTV (223 vs. 127, p =0.03) and TLG (891 vs. 614, p=0.04). Also SUV‐max and SUV‐peak were higher but without statistical significance. After 4 chemotherapy courses only TLG remain higher in PR group (9.3 vs. 5.1, p=0.04) while MTV was slightly higher in GR group (1.7 vs. 1.6, p=0.04)</italic>.</p><p><bold>Conclusions</bold>: The MTV and TLG are two semi‐quantitative parameters that could predict the clinical response in patients with HL. A larger cohort study is needed to confirm these preliminaries data.</p></sec><sec id="pbc26772-sec-4850"><label>P-094</label><title>Factors Associated with Time to Diagnosis of Childhood and Adolescent Non‐Hodgkin Lymphoma in Peru</title><p><underline underline-style="single">M. Oscanoa</underline><sup>1</sup></p><p><italic><sup>1</sup>hospital Nacional Edgardo Rebagliati, Oncology, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Time to diagnosis (TD) or “lag time” is the time between a patient's first symptom recognition to a diagnosis of cancer. Delayed TD allows tumor progression and poor outcome in Non‐Hodgkin Lymphoma (NHL) in some studies, although it remains controversial.</p><p><bold>Objectives</bold></p><p>The aim of this study was to define clinical and socio‐demographic factors associated to TD, which includes “Parents delay” (PD) and “Medical delay” (MD) in children and adolescents diagnosed with NHL in Lima, Peru.</p><p><bold>Design/Methods</bold>: A total of 46 patients younger than 18 years of age diagnosed with NHL between January 2012 and October 2016 were retrospectively evaluated. Clinical and demographic variables such as type of diagnosis, clinical stage, sex, age and parental characteristics were analyzed to evaluate their effects on TD, PD and MD.</p><p><bold>Results</bold>: Forty‐six patients were included in the study. The median age was 10 years (range 3‐17) and 68.5% were male. Histological subtypes were mature B‐cell NHL in 40%, lymphoblastic NHL in 31.4%, T/NK lymphoma in 14.3%, anaplastic large cell lymphoma in 5.7% and hydroa‐vacciniforme‐like lymphoma in 5.7%. Stage III and IV tumors were seen in 77.2% of cases. The TD ranged between 2 weeks and 17.5 months (median, 8 weeks), with a median of PD and MD of 2 and 6 weeks, respectively. Among histological subtype, we could not found significant differences in TD. Age, parental age or level of education, metastatic disease, clinical stage and sex did not affect significantly TD.</p><p><bold>Conclusions</bold>: In our country, median TD was comparable to described in developing countries, where index of suspicion of childhood cancer remains low. It is necessary to establish strategies for optimizing early diagnosis based on associated factors.</p></sec><sec id="pbc26772-sec-4860"><label>P-095</label><title>Epigenetic Silencing of the Tumor Suppressor Genes SPI1, PRDX2, KLF4, DLEC1, and DAPK1 in Childhood and Adolescent Lymphomas*</title><p>F.G. Pinarli<sup>1</sup>, F. Alpaslan Pinarli<sup>2</sup>, I. Ozdemir<sup>3</sup>, A. Okur<sup>1</sup>, P. Uyar Gocun<sup>4</sup>, N. Baran Aksakal<sup>5</sup>, <underline underline-style="single">C. Karadeniz</underline><sup>1</sup></p><p><italic><sup>1</sup>Gazi University Medical Faculty, Pediatric Oncology, Ankara, Turkey; <sup>2</sup>Diskapi Yildirim Beyazit Research Hospital, Medical Genetics, Ankara, Turkey; <sup>3</sup>Gazi University Medical Faculty, Pediatrics, Ankara, Turkey; <sup>4</sup>Gazi University Medical Faculty, Pathology, Ankara, Turkey; <sup>5</sup>Gazi University Medical Faculty, Public Health, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: The aim of the study was to investigate the expression and methylation status of seven distinctive genes with tumor suppressing properties in childhood and adolescent lymphomas.</p><p><bold>Design/Methods</bold>: A total of 96 patients with Hodgkin Lymphoma (HL, n=41), Non‐Hodgkin Lymphoma (NHL, n=15), and reactive lymph node proliferation (n=40, as controls) who were followed‐up between the years 2000‐2015 at the Department of Pediatric Oncology are included in the research. The expression status of <italic>CDKN2A, SPI1, PRDX2, DLEC1, FOXO1, KLF4</italic> and <italic>DAPK1</italic> genes were measured with QPCR method after the RNA isolation from paraffin blocks of tumor tissue and cDNA conversion. DNA isolation was performed from samples with low gene expression followed by methylation PCR study specific to promotor regions of these genes in order to investigate the methylation patterns.</p><p><bold>Results</bold>: We found that <italic>SPI1, PRDX2, KLF4, DLEC1</italic> and<italic>DAPK1</italic> genes are significantly less expressed in the patients than the control group (p=0.0001). However, expression of <italic>CDKNA2</italic> and <italic>FOXO1</italic> genes in the patient and control groups were not statistically different. The methylation ratios of all genes excluding the <italic>CDKN2A</italic> and <italic>FOXO1</italic> were significantly higher in the HL and NHL groups than the controls (p=0.0001).</p><p><bold>Conclusions</bold>: We showed that <italic>SPI1, PRDX2, DLEC1, KLF4 and DAPK1</italic> genes are epigenetically silenced via hypermethylation in the tumor tissue samples of children with HL and NHL. Due to our finding that <italic>CDKN2A</italic> gene was not expressed in both of the patient and control groups, we concluded that it is not specific to malignancy. <italic>As FOXO1</italic> gene was similarly expressed in both of the patient and control groups, its relation with malignancy could neither be found. Future studies may show if these genes will be candidates for biomarkers or therapeutic targets in childhood and adolescent lymphomas.</p><p>*This study has been supported by a research grant of Turkish Pediatric Oncology Group (TPOG)</p></sec><sec id="pbc26772-sec-4870"><label>P-096</label><title>Expert Consensus for Waldeyer's Ring Involvement in Pediatric Hodgkin Lymphoma</title><p><underline underline-style="single">J. Seelisch</underline><sup>1</sup>, J. Flerlage<sup>2</sup>, K. Kelly<sup>3</sup>, L. Kurch<sup>4</sup>, C. Mauz‐Koerholz<sup>5</sup>, K. McCarten<sup>6</sup>, M. Metzger<sup>2</sup>, S. Voss<sup>7</sup>, A. Punnett<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Hematology/Oncology, Toronto, Canada; <sup>2</sup>St. Jude Children's Research Hospital, Oncology, Memphis, USA; <sup>3</sup>Roswell Park Cancer Institute, Hematology/Oncology, Buffalo, USA; <sup>4</sup>University Hospital of Leipzig, Nuclear Medicine, Leipzig, Germany; <sup>5</sup>Martin‐Luther‐University Medical Center, Hematology/Oncology, Halle, Germany; <sup>6</sup>Hasbro Children's Hospital, Pediatric Radiology, Providence, USA; <sup>7</sup>Boston Children's Hospital, Radiology, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Waldeyer's Ring (WR) involvement in pediatric Hodgkin lymphoma (HL) is a rare phenomenon of unclear definition. International pediatric HL specialists formed the WR working group of CAYAHL (Childhood, Adolescent, Young Adult HL). Existing literature was reviewed, cases were collected and consensus recommendations for WR involvement were established.</p><p><bold>Design/Methods</bold>: A systematic review was conducted for literature involving WR and HL.</p><p><bold>Results</bold>: 1499 titles/abstracts were reviewed, 75 papers at full text, and 24 included (8 pediatric). Nineteen further pediatric cases were collected from the group.</p><p><bold>Conclusions</bold>: Historically involvement of WR was determined by examination, ideally by ENT with biopsy confirmation. There are currently no standard clinical criteria to define involvement, rendering clinical evaluation highly subjective.</p><p>Diagnostic, contrast‐enhanced CT and FDG‐PET are the standard of care for newly diagnosed HL. Review of both modalities is required to determine disease presence in WR given that normal/reactive lymphoid tissue may be avid on PET alone. Abnormality or asymmetry of both anatomy and metabolic activity should be assessed. Where PET avidity of WR structures approaches that of the primary mass, involvement should be considered. MRI is excellent for assessing head and neck tissues and should be considered for further delineation of PET‐CT findings.</p><p>Indeterminate PET findings on initial staging that cannot be confirmed with CT/MRI should be reviewed with early response assessment. If metabolic activity normalizes at early response assessment, involvement is likely and should be considered in ongoing treatment.</p><p>Tonsils can demonstrate physiologically increased metabolic activity making response assessment with FDG‐PET challenging. Thus, standard Deauville criteria cannot be applied. We suggest that the disappearance of asymmetric uptake and a symmetric uptake in palatine tonsils that does not markedly exceed (20%) the uptake of the adenoid region be considered adequate response.</p><p>In clinical trials, final involvement should be determined by central review and a prospective database of WR involvement maintained.</p></sec><sec id="pbc26772-sec-4880"><label>P-097</label><title>Clinical Characteristics and Treatment Outcome of Pediatric Non‐Hodgkin Lymphoma in East Asia</title><p><underline underline-style="single">J.J. Seo</underline><sup>1</sup></p><p><italic><sup>1</sup>Asan Medical Center, Pediatrics, Seoul, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Pediatric non‐Hodgkin lymphoma (pNHL) comprises a heterogeneous group of lymphoid neoplasms, and is known to have different aspects from adult disease and geographical differences in incidence. We performed this study to delineate the characteristics and outcomes of pNHL in East Asia.</p><p><bold>Design / Methods</bold>: Medical records of 749 patients with pNHL treated in 4 participating institutions of Beijing, Shanghai, Nagoya, Seoul, and in TPOG centers of Taiwan from January 2008 to December 2013 were reviewed retrospectively. Demographic and clinical features, survival outcomes and putative prognostic factors were analyzed.</p><p><bold>Results</bold>: Median age at diagnosis was 8 years. The most common pathologic subtype was Burkitt lymphoma (BL) (36%) followed by lymphoblastic lymphoma (LL) (30%), anaplastic large cell lymphoma (ALCL) (14%) and diffuse large B cell lymphoma (DLBCL) (13%). Most patients (81%) had advanced disease at diagnosis. Bone marrow (BM) and CNS involvement were more frequently observed in BL and LL. The 5‐year overall survival and event‐free survival (EFS) rates were 89% and 84%, respectively at a median 50.5 months of follow up. 5‐year EFS rates were excellent in BL, LL and DLBCL (88, 88, 89%, respectively), and lower in ALCL and PTCL (71, 56%, respectively) (<italic>P</italic><0.001). CNS involvement, high LDH (>250 IU/mL) and advanced disease at diagnosis were associated with significantly poorer outcomes (<italic>P</italic><0.05). Ninety one patients (12%) experienced relapse at median 8 months after diagnosis. Patients with ALCL and PTCL relapsed more frequently than other subtypes (<italic>P</italic><0.001). Patients relapsed within 12 months from diagnosis, and relapsed BL and LL showed significantly poorer outcomes.</p><p><bold>Conclusions</bold>: The clinical characteristics and treatment outcomes of pNHL in East Asian countries were similar to those observed in Western countries, but some peculiar clinical aspects were observed as well. This international study is expected to provide a platform for future collaborative study on NHL in East Asia.</p></sec><sec id="pbc26772-sec-4890"><label>P-098</label><title>ZUCH‐S3, An Antibody Targeting B Lymphocytes, Is a Potential Therapeutic Agent for B‐Lineage Malignancies</title><p><underline underline-style="single">H. Shen</underline><sup>1</sup>, S. Li<sup>1</sup>, Q. Shu<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Hematology‐Oncology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: Monoclonal antibody (mAb)‐based targeted therapy is one of the most promising strategies to cure cancers. ZUCH‐S3mAb was a novel antibody generated using hybridoma technique with human B lymphoma Raji cells immunogens in our laboratory, which presented potential to be a therapeutic agent for hematologic malignancies.</p><p><bold>Design/Methods</bold>: We investigated the reactivity profile of ZUCH‐S3mAb and identified the targeting antigen by flow cytometry. The internalization of ZUCH‐S3mAb was studied by the method applying papain digestion and flow cytometry. The capacity of ZUCH‐S3mAb specifically binding to S3Ag and activating complement was determined by complement dependent cytotoxicity (CDC).</p><p><bold>Results</bold>: The results showed that the antibody ZUCH‐S3mAb (murine IgG1κ) was a new clone of anti‐CD79a. It reacted with extracellular portion of CD79a protein. ZUCH‐S3 antigen was strictly expressed on B‐lineage lymphoma cells such as Burkitt's lymphoma, DLBCL and CLL cells from patients. ZUCH‐S3mAb was quickly internalized into the target cells once binding to the antigen. When the antibody was incubated with targeting cell Raji at 37°C, the degrees of internalization at different time points were 5.9% (0.25h), 9.5% (0.5h), 34.8% (1h), 64.8% (2h) and 74.6% (3h), 75.1% (4h), respectively. ZUCH‐S3mAb VL and VH gene was inserted into plasmid pcDNA3.1, and the recombinant plasmids encoding ZUCH‐S3mAb were transfected into CHO cells. The Western blotting analysis showed the culture supernatants bound to the extracts from Raji cells. The activities of CDC on Raji cells were in a dose dependent manner and the inhibition rates of Raji cells were 15.3%, 40.9%, 68.6% and 75.2% at the concentrations of 0.05μg/ml, 0.1μg/ml, 1μg/ml, 5μg/ml, respectively.</p><p><bold>Conclusions</bold>: ZUCH‐S3mAb is a novel antibody targeting extracellular portion of CD79a, which has the potential to be a therapeutic agent for B‐lineage malignancies.</p></sec><sec id="pbc26772-sec-4900"><label>P-099</label><title>Lymphocyte Depleting Induction Agents and Posttransplant Lymphoproliferative Disorder (PTLD) in Children with Intestinal Transplants (ITX)</title><p><underline underline-style="single">K. Stanley</underline><sup>1</sup>, K. Soltys<sup>2</sup>, G. Bond<sup>2</sup>, G. Mazariegos<sup>2</sup>, S. Ranganathan<sup>3</sup>, R. Sindhi<sup>2</sup></p><p><italic><sup>1</sup>Children's Hospital of Pittsburgh of UPMC, Department of Pediatric Hematology Oncology, Pittsburgh, USA; <sup>2</sup>Children's Hospital of Pittsburgh of UPMC, Department of Transplant Surgery, Pittsburgh, USA; <sup>3</sup>Children's Hospital of Pittsburgh of UPMC, Department of Pathology, Pittsburgh, USA</italic></p><p><bold>Background/Objectives</bold>: Lymphocyte depleting induction immunosuppression decreases rejection severity and reduces maintenance immunosuppression requirements after ITx alone or with liver (L‐ITx) in children. Whether PTLD rates vary with induction agent is unknown.</p><p><bold>Design/Methods</bold>: Retrospective chart review of subjects who received ITx from January 2000 through present at the Children's Hospital of Pittsburgh of UPMC.</p><p><bold>Results</bold>: Of 193 ITx, 25 underwent alemtuzumab induction and 147 underwent rabbit anti‐thymocyte globulin (rATG) induction. Alemtuzumab‐induced subjects were older, compared with rATG‐induced subjects with median age of 5 years (range <1‐24) vs 3 years (range <1‐22) (p=0.5, NS), experienced lower incidence of early (60‐day) acute cellular rejection (13/25 or 52% vs 96/147 or 65.3%, p=0.262, NS, Fisher's exact) and higher incidence of PTLD (7/25 or 28% vs 20/147 or 13.6%, p=0.078, NS, Fisher's exact).</p><p>The alemtuzumab and rATG groups were similar with regards to liver containing grafts (4/25 or 16% vs 22/145 or 15%), PTLD onset during the first post‐transplant year (5/7 or 71.4% vs 16/20 or 80%), association with EBV (6/7 or 85.7% vs 18/20 or 90%), incidence of monomorphic PTLD (4/7 or 57.1% vs 11/20 or 55%), and location in the intestine allograft (4/7 or 57.1% vs 11/20 or 55%).</p><p>All subjects were treated with immunosuppression reduction. Within the alemtuzumab group, treatment also included rituximab in 4 and chemotherapy (with combination of cyclophosphamide and steroids) in 2 children, and enterectomy in 4 (3 from rejection/graft failure, 1 from PTLD). PTLD resolved in all of these subjects. One child died of infection. Within the rATG group, treatment included rituximab in 11 and chemotherapy in 6 children, and enterectomy in 7 (5 from rejection/graft failure, 2 from PTLD). Six children died: 3 due to PTLD, 2 of infection and 1 of renal failure.</p><p><bold>Conclusions</bold>: rATG induction is associated with a trend toward lower PTLD incidence compared with alemtuzumab.</p></sec><sec id="pbc26772-sec-4910"><label>P-100</label><title>Minimal Disseminated Disease Evaluation in T‐Cell Acute Lymphoblastic Lymphoma</title><p><underline underline-style="single">G.K. Viswanathan</underline><sup>1</sup>, P. Tembhare<sup>1</sup>, S. Gujral<sup>1</sup>, N. Patkar<sup>1</sup>, Y. Badrinath<sup>1</sup>, S. Ghogale<sup>1</sup>, N. Deshpande<sup>1</sup>, M. Rajotiya<sup>1</sup>, S.D. Banavali<sup>2</sup>, G. Narula<sup>2</sup>, G. Chatterjee<sup>1</sup>, D. Dhaliwal<sup>1</sup>, P.G. Subramanian<sup>1</sup></p><p><italic><sup>1</sup>Advanced Centre for Treatment‐ Research and Education in Cancer ACTREC‐ Tata Memorial Centre TMC, Hematopathology Laboratory, Mumbai, India; <sup>2</sup>Tata Memorial Hospital TMH‐Tata Memorial Centre TMC, Pediatric Hemato‐Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: T‐lymphoblastic lymphoma (T‐LBL) with minimal disseminated disease (MDD) is defined as T‐LBL with <25% morphologically identifiable blasts in peripheral blood (PB) and/or bone marrow (BM) along with presence of BM involvement detected by flowcytometric immunophenotyping (FCM‐IPT). Published literature of this rare subgroup is sparse. This study aims at identifying MDD in T‐LBL using 10‐colour FCM‐IPT and study their clinical features.</p><p><bold>Design/Methods</bold>: A retrospective analysis of 40 children of T‐LBL (diagnosed on mediastinal and/or lymph node biopsy) with predominantly lymphomatous presentation and <25% blasts in PB/BM was done. Clinical and laboratory and FCM‐IPT data were studied. FCM‐IPT was performed on a 10‐color flowcytometer.</p><p><bold>Results</bold>: Mean age was 10.2 years (range:2‐18 years). M:F ratio was 2.1:1. Mean hemoglobin, WBC count and platelet count were 12.7g/dl, 11.7x10^9/L and 411x10^9/L (142‐875) respectively. CSF examination was negative in all cases indicating rarity of CNS involvement in this subgroup. MDD was seen in 14 cases (35%) and ranged from 0.007% to 18.5% (mean:1.4%; median:1.2%). Mean (range) morphologically identifiable bone marrow blast/hematogones count in the group without MDD was 2.7% (1‐4%) and in the group with MDD was 3.7% (0‐15%). Seven(50%) cases of T‐LBL with MDD showed <5% blasts in BM indicating sensitivity and necessity of FCM‐IPT. PET‐CT was insensitive to identify MDD.</p><p><bold>Conclusions</bold>: MDD is present in one‐third(35%) of T‐LBL with <25% blasts in PB/BM. This underlines the importance of performing FCM‐IPT in cases with <25% blasts and even in cases of <5% blasts on morphology. Identification of minimal disseminated disease in T‐LBL is important as (1) limited published data are available, (2) these studies show inferior event free survival in T‐LBL with MDD as compared to patients without MDD and (3) there is a need for post‐induction BM examination for residual disease detection in MDD positive cases and intensification of therapy if positive.</p></sec><sec id="pbc26772-sec-4920"><label>P-101</label><title>Improved Outcome of Newly Diagnosed Childhood Mature B‐Cell Lymphoma/Leukemia with High Tumor Burden Treated with Rituximab Combining BFM95‐Based Protocol: A Report from Shanghai, China</title><p><underline underline-style="single">Y. Fu</underline><sup>1</sup>, H. Wang<sup>1</sup>, X. zhai<sup>1</sup>, X. Qian<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital of Fudan University, Hematology and oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: Rituximab has become a standard medicine in the treatment of adult patients with DLBCL. Currently, there was a limited number of clinical trials in children showing that rituximab can be combined with BFM and other protocols safely with good efficacy. The absence of similar study in China for childhood patients with newly diagnosed B‐NHL/B‐ALL encouraged us to study the efficacy of rituximab in the Chinese population.</p><p><bold>Design/Methods</bold>: In this study, we explored the efficiency of rituximab in childhood B‐NHL. We found that 46 newly diagnosed mature B‐NHL which were stage III and stage IV/B‐AL children were treated with BFM95‐based protocol combined with rituximab. Compared with historical data of BFM90‐based protocol.</p><p><bold>Results</bold>: Our study recuited 35 males and 11 females with an average age of 6.9 years who were treated with R+BMF95 chemotherapy. Among the historical control of 23 patients treated with BFM90 chemotherapy, 5 were female. Compared with patients treated with BFM90 protocol, the 5‐year EFS of patients under R+BMF95 was higher (83.7±5.7% vs 69.6%±9.6% in R+BMF95 and BFM‐90 respectively) (P=0.11). Among subgroups of our patients, the 5‐year EFS of patients with stage III was 87.3±6.1% vs 77.8±9.8% (P=0.30), stage IV/B‐AL was 72.7%±13.4% vs 40.0±21.9% (P=0.09) between patients treated with R++BMF95 and BFM‐90 respectively, these difference were not statistically significant neither. Among patients whose LDH level were <500 U/L at diagnosis, R+BFM95 protocol reached 100% survival during our follow‐up, nevertheless the 5‐year EFS of patients in this group was not statistically different from that of patients treated with BFM90 (92.3±7.4%, P=0.2994). Among patients had LDH >500 U/L at diagnosis, the 5‐year EFS in R+BFM95 group was 77.2±7.7% and significantly higher than that of BFM90 group (40.0±15.5%, P=0.005).</p><p><bold>Conclusions</bold>: We found that rituximab has improved the event‐free survival (EFS) of childhood B‐NHL/B‐AL with LDH > 500 U/L in China.</p></sec><sec id="pbc26772-sec-4930"><label>P-102</label><title>Hemophagocytic Lymphohistiocytosis (HLH) Associated ALK‐Positive Anaplastic Large Cell Lymphoma (ALCL) with Leukemic Involvement and Central Nervous System (CNS) Disease: A Single Institution Case Series</title><p><underline underline-style="single">L. Amos</underline><sup>1</sup>, N. Wood<sup>1</sup>, M. Hetherington<sup>1</sup>, A. Hays<sup>1</sup></p><p><italic><sup>1</sup>Children's Mercy Hospital, Hematology/Oncology/BMT, Kansas‐City, USA</italic></p><p><bold>Background/Objectives</bold>: ALCL is a form of non‐Hodgkin's lymphoma which represents 10‐15% of childhood lymphomas. Leukemic and CNS involvement in ALCL is extremely rare. In addition, ALCL has rarely been reported in association with HLH. HLH is a life‐threatening disorder of immune dysregulation involving macrophage and T‐cell activation with cytokine release causing multi‐organ dysfunction. The objective of this case series is to report the disease course of two patients with fulminant HLH secondary to ALCL with leukemic and CNS involvement.</p><p><bold>Design/Methods</bold>: Here we present two patients that were admitted to our pediatric intensive care unit (PICU) with multi‐organ system failure requiring intubation and continuous renal replacement therapy (CRRT) due to metabolic acidosis. Both met diagnostic and laboratory criteria for HLH. Both had bone marrow and peripheral blood evaluations with FISH analysis showing an ALK gene rearrangement, consistent with ALCL in leukemia phase. Patient 1 was a 2 year old male. He had a brain MRI done that showed numerous enhancing lesions consistent with metastasis. Patient 2 was a 16 year old female. Her CSF analysis showed evidence of disease with ALK positive cells. In addition, she was found to have non enhancing lesions in the deep white matter of her brain on MRI.</p><p><bold>Results</bold>: Both patients were treated with HLH directed therapy, followed by ALCL directed therapy. Both received additional treatment to the CNS with intrathecal chemotherapy. Patient 2 also received craniospinal irradiation (CSI). Both patients are off therapy and have no evidence of disease.</p><p><bold>Conclusions</bold>: This case series highlights two patients with the rare presentation of HLH associated ALCL with leukemic and CNS involvement. The diagnosis of HLH should be considered in ALCL patients presenting in the leukemic phase. This also suggests that the leukemic phase may lead to elevated cytokines that cause HLH.</p></sec><sec id="pbc26772-sec-4940"><label>P-103</label><title>High Survival Rates in Hodgkin's Lymphoma in a Developing Country: No Mortality in Protocol Patients without A CO‐ MORBID Problem</title><p><underline underline-style="single">N. Yazici</underline><sup>1</sup>, F. Sarialioglu<sup>1</sup>, H.C. Onal<sup>2</sup>, A. Erbay<sup>1</sup>, B. Hasbay<sup>3</sup>, S. Demir<sup>4</sup>, A. Temiz<sup>5</sup>, G.N. Nursal<sup>6</sup></p><p><italic><sup>1</sup>Baskent University, Department Of Pediatric Oncology‐Hematology, Adana, Turkey; <sup>2</sup>Baskent University, Department Of Radiation Oncology, Adana, Turkey; <sup>3</sup>Baskent University, Department Of Pathology, Adana, Turkey; <sup>4</sup>Baskent University, Department Of Radiology, Adana, Turkey; <sup>5</sup>Baskent University, Department Of Pediatric Surgery, Adana, Turkey; <sup>6</sup>Baskent University, Department Of Nuclear Medicine, Adana, Turkey</italic></p><p><bold>Background/Objectives</bold>: Different centers use different protocols according to their physical conditions in Turkey for Hodgkin's lymphoma. Usually choice of protocol depends on success and superiority of survival in original regimen. However local factors are different and it is impossible to take same results. In this study, treatment results of German Pediatric Oncology‐Hematology Hodgkin's Disease 95 (GPOH‐HD95) regimen are presented.</p><p><bold>Design/Methods</bold>: In our department, PET/BT is routinely used in staging of every patient before and at the end of chemotherapy. GPOH‐HD regimen is used in its original version and radiotherapy had been used in involved fields (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1200/JCO.2012.45.3266">https://doi.org/10.1200/JCO.2012.45.3266</ext-link>). Patients were hospitalized for minimum 7 days at diagnosis for adaptation to treatment. The rest of treatment was continued in outpatient basis.</p><p><bold>Results</bold>: Between January 2006 –December 2015 there were 42 patients with Hodgkin's lymphoma. Thirty three of them were untreated. Mean age was 11,4 years (2,8‐16,6 years); there were 23 males. Seventeen of them were mixed cellular type, There were 15 cases of risk group (RG)1; 10 of them were RG2, and 8 of them were RG3. Median follow up was 55.6 months. A patient with RG1 and stage 2A Hodgkin disease at diagnosis had a relapse at 50<sup>th</sup> month of follow up. He is still under follow up in second remission for a year. A patient with ataxia telengiectasia which had been exitus with pulmonary complications was excluded. There was no mortality in our series of protocol patients. Event‐free and overall survival for 5 years were % 95,5 and %100 respectively.</p><p><bold>Conclusions</bold>: The results of the GPOH‐HD95 protocol in our center were as successful as the original protocol despite local factors. We think that treatment related toxicity should be reduced with some modifications in our patients such as omitting radiotherapy in complete metabolic response with PET/CT after chemotherapy without procarbazine in male patients.</p></sec><sec id="pbc26772-sec-4950"><label>P-104</label><title>Role of Surgery in Management of Paediatric Abdominal Lymphoma</title><p><underline underline-style="single">O. Zakaria</underline><sup>1</sup></p><p><italic><sup>1</sup>King Faisal University, College Of Medicine, Al Ahsa, Saudi Arabia</italic></p><p><bold>Background/Objectives: BACKGROUND</bold>: The abdomen is one of the most frequent sites for lymphoma in children. The role of surgery has been limited to intra‐abdominal resectable tumours or as a diagnostic procedure in case of disseminated disease. Laparotomy without total excision of the tumour does not improve survival; moreover, it may cause complications and delays initiation of chemotherapy.</p><p><bold>AIM OF THE WORK</bold>: This study was undertaken to assess the role of surgery in the management of children and adolescents presenting with intra‐abdominal lymphoma in order to create certain criteria to select the proper surgical modality for managing those patients.</p><p><bold>Design/Methods: PATIENTS AND METHODS</bold>: This case‐series, retrospective study was done on 83 patients of abdominal lymphoma over a period of seven years from 2000 to 2015. Patients' files were reviewed regarding the full clinical examinations, laboratory and radiological investigations as well as surgical and diagnostic procedures. Collected data were tabulated and statistically analyzed using SPSS program package.</p><p><bold>Results</bold>: Twenty seven patients (32.5%) presented with huge pelvi‐abdominal mass and 27 (32.5%) had generalized lymphadenopathy beside their abdominal affection. The remaining 29 (35%) patients presented with symptoms of an acute abdomen. A total of 38 laparotomies were done. 27 patients underwent emergency laparotomy for acute abdomen and 10 patients had elective abdominal exploration. Lymph node biopsies were taken in 18 patients and laparoscopy procedures were performed in 8 patients as a diagnostic tool. Out of the total 83, the remaining 20 patients underwent true cut needle biopsy for diagnosis of their disease.</p><p><bold>Conclusions</bold>: Surgery still has a role in treatment of lymphoma whether non Hodgkin or Hodgkin's. However, in disseminated metastatic disease, aggressive debulking of the tumour should be avoided as chemotherapy is to be instituted primarily. Surgical resection does not cause significant change in morbidity or mortality.</p></sec><sec id="pbc26772-sec-4960"><label>P-105</label><title>Abnormalities of the Thyroid in Survivors of Childhood Hodgkin's Disease</title><p><underline underline-style="single">D. Zvyagintseva</underline><sup>1</sup>, S. Kuleva<sup>2</sup>, S. Ivanova<sup>3</sup>, T. Semiglazova<sup>3</sup>, E. Tsyrlina<sup>3</sup>, S. Novikov<sup>3</sup></p><p><italic><sup>1</sup>NN Petrov Research Research of Oncology Institute, Department of chemotherapy and combined treatment of malignant tumors in children, Saint ‐ Petersburg, Russia; <sup>2</sup>N.N. Petrov Research Institute of Oncology, Department of chemotherapy and combined treatment of malignant tumors in children, Saint ‐ Petersburg, Russia; <sup>3</sup>N.N. Petrov Research Institute of Oncology, Department of chemotherapy and combined treatment of malignant tumors in children, St. Petersburg, Russia</italic></p><p><bold>Background/Objectives</bold>: Overall 5‐year survival rate for childhood Hodgkin's lymphoma (HL) is now around 90‐95%, therefore late sequelae of treatment, especially endocrine diseases, have become more important.</p><p><bold>Aims</bold>: to investigate the late side effects of childhood Hodgkin's lymphoma therapy on the thyroid gland among childhood cancer survivors.</p><p><bold>Design/Methods</bold>: This report analyzed the function of the thyroid gland in 78 patients successfully treated in childhood with HD, according to two different protocols of therapy. The patients were divided into three groups depending on the treatment: group 1 ‐ risk‐adapted therapy according DAL‐HD protocol (n=42), group 2 ‐ risk‐adapted therapy according SPbHL protocol (n=86), and BEACOPP + radiotherapy (RT) (n=15). The treatment methods correlated with the appearance of thyroid dysfunction.</p><p><bold>Results</bold>: After median follow‐up of 7.5 years, thyroid dysfunction was detected in 20 of 78 patients (25.6%). The thyroid abnormalities were: hypothyroidism (n= 16, 20,5 %), thyroid nodules (n=4, 5,1%), and thyroid malignancy (n=1, 1,28%). [С1] Сervical irradiation and 39 Gy doses of radiation were found to constitute risk factors for thyroid abnormalities.</p><p><bold>Conclusions</bold>: This study confirms the high incidence of thyroid abnormalities in patients treated for Hodgkin's lymphoma with combination therapy of chemotherapy with head/neck/thorax radiotherapy and strengthens the importance of a long‐term follow‐up.</p></sec><sec id="pbc26772-sec-4970"><label>P-106</label><title>Treatment Outcomes of Adolescents with Hodgkin's Lymphoma</title><p><underline underline-style="single">D. Zvyagintseva</underline><sup>1</sup>, S. Kulyova<sup>2</sup>, S. Ivanova<sup>2</sup></p><p><italic><sup>1</sup>NN Petrov Research Research of Oncology Institute 2 Saint‐Petersburg State Pediatric Medical University, Department of chemotherapy and combined treatment of malignant tumors in children, Saint ‐ Petersburg, Russia; <sup>2</sup>NN Petrov Research Research of Oncology Institute, Department of chemotherapy and combined treatment of malignant tumors in children, St. Petersburg, Russia</italic></p><p><bold>Background/Objectives</bold>: Survival rates after a diagnosis of Hodgkin's lymphoma (HL) have improved substantially over the past 40 years. But adolescents who are between 10 and 17 years old seem to experience poorer survivals.</p><p><bold>Objective</bold>: To provide a descriptive review and improve our understanding of the treatment outcome of Hodgkin's lymphoma.</p><p><bold>Design/Methods</bold>: A retrospective review of 106 patients aged 10‐17 years old with HL treated at our institution from 1996‐2014 was performed. Survival analysis was performed using the Kaplan‐Meier method.</p><p><bold>Results</bold>: Median age was 13.8 years, 44% were boys, and 56% were girls. Forty‐three patients (41%) had I‐II stage, 63 patients (59%) had advanced disease (III‐IV stage). About half of patients (46 or 43%) had a B‐stage disease. The majority patients (84 or 79%) had nodular sclerosis, 4 patients (4%) ‐ the lymphocyte predominance and 12 (12%) ‐ mixed cellularity, in 6 cases (6%) morphological type was not diagnosed. Patients were treated with risk‐adapted therapy (chemotherapy and radiation) according to DAL‐НD (40 or 39%) or SPbHL (56 or 54%) protocols. Seven (7%) patients were treated with BEACOPP. The radiation dose ranged from 20 to 35 Gy. The 5‐years overall survival was 89,5±3,4%, disease‐free survival was 86±3,8%, event‐free survival was 78,5±4,4%, the 10‐years survival was 85,7±4%, 81±5% и 76,9±4,6%, respectively.</p><p><bold>Conclusions</bold>: The presenting features of adolescents with HL and efficiency in this study were better than at young adult (overall survival was 83%) but it is worse than at children (overall survival was 95%). Adolescent's Hodgkin's lymphoma is very curable diseases but require a personalized management in oncohematological units.</p></sec><sec id="pbc26772-sec-4980"><label>P-107</label><title>Prognostic Factors of Young Adults Hodgkin's Lymphoma</title><p>D. Zvyagintseva<sup>1</sup>, <underline underline-style="single">S. Kuleva</underline><sup>2</sup>, S. Ivanova<sup>3</sup>, A. Karitskiy<sup>3</sup></p><p><italic><sup>1</sup>NN Petrov Research Research of Oncology Institute 2 Saint‐Petersburg State Pediatric Medical University, Department of chemotherapy and combined treatment of malignant tumors in children, Saint ‐ Petersburg, Russia; <sup>2</sup>NN Petrov Research Research of Oncology Institute 2 Saint‐Petersburg State Pediatric Medical University, Department of chemotherapy and combined treatment of malignant tumors in children, ST. PETERSBURG, Russia; <sup>3</sup>NN Petrov Research Research of Oncology Institute, Department of chemotherapy and combined treatment of malignant tumors in children, St. Petersburg, Russia</italic></p><p><bold>Background/Objectives</bold>: Hodgkin's lymphoma is approximately 12% of all malignant tumors in patients aged 19‐29. The risk‐adapted treatment program in this group is not used.</p><p><italic>The aim of the study</italic> was to identify prognostic unfavorable factors in young adults with HL.</p><p><bold>Design/Methods</bold>: The study included data of 87 patients aged 19 to 29 years (the average age was 24 ± 4 years). Thirty‐four (39.1%) was men, 53 was women (60.9%), sex ratio 1: 1.6. Forty‐seven patients (54%) had I‐II stage, 40 patients (46%) had advanced disease (III‐IV stage). More than half of patients (47 or 54%) had a B‐stage disease. The majority patients (76 or 87.4%) had nodular sclerosis, 2 patients (2.3%) ‐ the lymphocyte predominance and 5 (5.7%) ‐ mixed cellularity, in 4 cases (4.6%) morphological type was not diagnosed. All patients received from 2 to 11 cycles of primary chemotherapy (median of 4 cycles) with ABVD (48 patients, or 55.2%), BEACOPP (36 or 41,4%), MOPP (2 or 2.3%), and COPP (one patient) following radiation in 57 patients (65.5%). The radiation dose ranged from 20 to 51 Gy.</p><p><bold>Results</bold>: Correlation matrix included 35 factors. Significant impact on overall and event‐free survival was had stage IV disease (p = 0.035813), extranodal lesion (p = 0.002746), the involvement of the pericardium (p = 0.039394), the value of ESR 35 mm / h (p = 0.012357), white blood cell count more 11,5x10<sup>9</sup> / l (p = 0.026490), the level of lymphocytes less than 9% (p = 0.001053), fibrinogen value of more than 7.5 g / l (p = 0.048856), the effectiveness of therapy (p = 0.000789) and the volume of tumor more than 210 cm<sup>3</sup> / m<sup>2</sup> (p = 0.017734).</p><p><bold>Conclusions</bold>: Using the identified unfavorable prognostic factors, it is possible to stratified patients on risk groups and to determine the treatment program.</p></sec><sec id="pbc26772-sec-4990"><label>P-108</label><title>Thyroid Abnormalities in Survival of Childhood Hodgkin's Lymphoma</title><p><underline underline-style="single">D. Zvyagintseva</underline><sup>1</sup>, S. Keuleva<sup>1</sup>, E. Tsyrlina<sup>1</sup>, S. Novikov‐<sup>1</sup>, T. Semiglazova<sup>1</sup></p><p><italic><sup>1</sup>N.N. Petrov Research Institute of Oncology, Department of chemotherapy and combined treatment of malignant tumors in children, Saint ‐ Petersburg, Russia</italic></p><p><bold>Background/Objectives</bold>: Long‐term side effects of treatment modalities for childhood Hodgkin's lymphoma (HL) are focused in modern researches. Thyroid dysfunction has been reported especially following head and neck irradiation.</p><p><bold>Aims</bold>: to determine the critical cut‐off point of radiation dose on neck and thyroid gland in children and adolescents with Hodgkin's lymphoma for predictive dosimetric variables with the Youden method.</p><p><bold>Design/Methods</bold>: One hundred and forty‐three patients with proved HL (aged 2‐ 17 years) were included in the study. The patients were divided into three groups depending on the treatment: group 1 ‐ risk‐adapted therapy according DAL‐HD protocol (n=42), group 2 ‐ risk‐adapted therapy according SPbHL protocol (n=86), and BEACOPP + radiotherapy (RT) (n=15). Eligibility criteria for inclusion in the current analysis were: diagnosis of the cancer at age ≤18 years, treatment with chemotherapy and RT (neck/thorax) and a time interval of ≥6 months after completion of the therapy. Thyroid function tests, thyroid gland ultrasound examinations were evaluated in this groups.</p><p><bold>Results</bold>: The mean follow‐up period was 7,5 years (range: 0‐22). One hundred twenty‐six patients (88.1%) of 143 received a total dose of 15‐46 Gy head/neck/thorax RT. A cut‐off point at 39 Gy of radiation dose on neck and thyroid gland in children and adolescents with Hodgkin's lymphoma for predictive dosimetric variables was found. The ROC curve area was 0.717 ± 0.108 (CI 0.590‐0.822), p = 0.0445. The maximum Youden index was 0.3929.</p><p><bold>Conclusions</bold>: Total dose of 39 Gy on neck and thyroid gland was the critical cut‐off values for the development of thyroid dysfunction.</p></sec><sec id="pbc26772-sec-5000"><label>P-109</label><title>Linear Regression Model “Bulky Disease” of Hodgkin Lymphoma in Adolescents</title><p>D. Zvyagintseva<sup>1</sup>, <underline underline-style="single">S. Ivanova</underline><sup>1</sup>, S. Kulyova<sup>1</sup>, A. Karitsky<sup>1</sup></p><p><italic><sup>1</sup>NN Petrov Research Institute of Oncology‐ Saint‐Petersburg State Pediatric Medical University‐ St. Petersburg‐ Russia, Department of children`s chemoterapy and combined modality therapy, Saint ‐ Petersburg, Russia</italic></p><p><bold>Background/Objectives</bold>: The predictive value of Hodgkin's lymphoma tumor burden has been discussed for about 20 years. However, the evidence based on modern research, has become possible to use only in recent years. The purpose of the study was assessment of influence of relative tumor burden on long‐term outcomes.</p><p><bold>Design/Methods</bold>: The study included data on 106 patients aged from 10 to 18 years old (middle age of 14 years) with biopsy‐proved Hodgkin lymphoma. Boys were 44%, girls were 56%. Thirty‐eight patients (35.8%) had II stage and thirty‐nine (36.8%) had III stage of the disease. B symptoms occurred in 46 patients (43.4%). In 66 patients (62.3%) were identified the b‐stage disease. All patients were treated according to pediatric protocols: 40 (38.8%) patients ‐ according to DAL‐HD, and 56 (54.3%) ‐ according to SPBLH program. Seven teenagers (6.8%) were treated according to BEACORP scheme. Chemotherapy regimen was followed by extend‐ or involved‐field or subtotal radiation with doses from 20 to 51 Gy in 68 patients (66%).</p><p><bold>Results</bold>: Overall survival at 5 years was 91% (range 89‐93%), disease‐free survival was 88% (85‐91%). The optimum cut‐off level according ROC method for relative tumor burden has been established at 122.7 cm<sup>3</sup>/m<sup>2</sup>. The ROC curve area was 0.717, p = 0.00010. The maximum Youden index was 0.4113. Overall survival in the cohort of patients with this volume and above was 69.6%, with a tumor volume of less than 122.7 cm<sup>3</sup>/m<sup>2</sup>, overall survival was 97.2% (p = 0.00002).</p><p><bold>Conclusions</bold>: The relative tumor burden is the parameter which is significantly changing survival rates in adolescents with Hodgkin lymphoma. The determinate can be intercorrelated and included from the final multifactor analysis.</p></sec></sec><sec id="pbc26772-sec-5010"><title>Haematology ‐ Stem Cell Transplantation (Haematological Diseases/Technique and Supportive Care)</title><sec id="pbc26772-sec-5020"><label>P-110</label><title>Acute Kidney Injury After Total Body Irradiation: Associated Factors and Natural History</title><p><underline underline-style="single">M. Abugideiri</underline><sup>1</sup>, M. Ferris<sup>1</sup>, J. Switcheko<sup>2</sup>, N. Madden<sup>1</sup>, C. Butker<sup>1</sup>, E. Butker<sup>1</sup>, R. Cassidy<sup>1</sup>, D. Tanenbaum<sup>1</sup>, B. Eaton<sup>1</sup>, N. Esiashvili<sup>1</sup></p><p><italic><sup>1</sup>Winship Cancer Institute of Emory University, Department of Radiation Oncology, Atlanta, USA; <sup>2</sup>Winship Cancer Institute of Emory University, Department of Biostatistics & Bioinformatics, Atlanta, USA</italic></p><p><bold>Background/Objectives</bold>: To evaluate factors associated with acute kidney injury (AKI) in pediatric patients after total body irradiation (TBI) based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation (HSCT).</p><p><bold>Design/Methods</bold>: The records were reviewed for 129 consecutive pediatric patients (range, 1‐21 years) who underwent TBI‐based myeloablative conditioning for hematologic malignancies at a single institution between January 2003 and May 2014. TBI total dose ranged from 10.5‐14Gy and TBI dose‐rate ranged from 5.57‐20.85cGy/min. AKI was defined as a doubling of the baseline creatinine in the first 100 days after TBI. Univariate and multivariable analyses were performed to determine associations between variables.</p><p><bold>Results</bold>: AKI developed in 96 patients (74.4%). TBI total dose (P=0.095), dose rate (P=0.680), and dose per fraction (P=0.373) were not significant predictors for AKI. For chemotherapy, 99.2% of patients received a regimen containing Cytoxan. AKI was not increased with the additions of Ara‐C (P=0.156), VP‐16 (P=0.428), or Fludarabine (P=0.840). Neither infection (P=0.142), nor acute GVHD (P=0.874) were associated with increased AKI. AKI was not increased in patients with a low pre‐TBI glomerular filtration rate (GFR) (P=0.561). The majority of patients with AKI had normalization of their creatinine after HSCT (67.9%), however, persistent renal dysfunction after TBI was associated with a higher incidence of transplant related mortality (TRM) (P<0.001) and worse overall survival (OS) (P<0.001), both of which remained significant on multivariable analysis (P<0.001).</p><p><bold>Conclusions</bold>: A high incidence of AKI was noted in this series. Despite this, no significant factors were identified as agents that increase the incidence of AKI in this series and other variables must be identified as potential causes of AKI. AKI did not appear to result in long‐term renal damage in the majority of patients; however, persistent renal dysfunction was associated with worse OS and TRM. Additional attention must be paid to factors that facilitate normalization of kidney function after AKI.</p></sec><sec id="pbc26772-sec-5030"><label>P-111</label><title>Basiliximab is well Tolerated and Effective in the Treatment of Steroid‐Refractory Acute Gut Graft‐Versus‐Host Disease After Pediatric Allogeneic Stem Cell Transplantation</title><p><underline underline-style="single">F. Ansari</underline><sup>1</sup></p><p><italic><sup>1</sup>FMRI‐ Gurgaon, pediatric hematoncology and stem cell transplant, Bhiwandi, India</italic></p><p><bold>Background/Objectives</bold>: Background‐Anti‐CD(25) monoclonal antibodies (Mabs) have been evaluated for the treatment of steroid‐refractory acute graftnegativersus‐host disease (GVHD) in patients undergoing hematopoietic stem cell transplantation (HSCT) mainly in adults after matched donors for years, but there is paucity of data in pediatric patients.</p><p>Aims and Objective‐ To evaluate the efficacy of the chimeric Mab, basiliximab in pediatric patients with steroid‐refractory acute gut GVHD after matched and haploidentical HSCT.</p><p><bold>Design/Methods</bold>: Material and Methods‐Basiliximab was evaluated in 11 patients with steroid‐refractory acute gut GVHD after matched and haploidentical SCT. Patients were transplanted from a matched sibling (n = 3) or haploidentical (n =8) donor because of acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 2), fanconi anemia (n = 2), thalassemia (n = 2) and immunodeficiency (n = 1). Basiliximab was given at a dose of 2 x 10 mg (<40kg) and 2 x 20 mg(>40kg) on 2 consecutive days after steroid‐refractory acute gut GVHD had developed. Basiliximab was repeated on day 8 in cases of persistent GVHD. A median of four basiliximab infusions (range 2‐12) were given to these patients.</p><p><bold>Results</bold>: Results‐None had infusion‐associated or cytokine‐related side‐effects after basiliximab. Eight of 11 patients (72.7 %) responded to basiliximab, 5/11 (45.4%) had a complete response (CR) of acute gut GVHD and 3/11 (27.2%) had a partial response (PR). Three of 11 patients (27%) did not respond.</p><p><bold>Conclusions</bold>: Conclusion‐These data suggested that basiliximab was effective to treat steroid‐refractory acute gut GVHD after pediatric matched/haploidentical SCT</p></sec><sec id="pbc26772-sec-5040"><label>P-112</label><title>Bone Marrow Transplantation in Pediatric Population; 15 Year Experience from Single Centre</title><p><underline underline-style="single">S.H. Ansari</underline><sup>1</sup></p><p><italic><sup>1</sup>National Institute of Blood Diseases and Bone Marrow Transplantation, Haematology‐ Bone Marrow Transplantation, karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Hematopoietic stem cell transplantation (HSCT) as a rescue procedure in patients with malignant & non malignant disorders treated with cytotoxic regimens in patients with aberrant, or defective hematopoietic cells, including marrow failure and autoimmune disorders. In both situations, however, HSCT also has therapeutic effects to eradicate the patients disease. The objective of the study was to assess the outcome of bone marrow transplantation in pediatric population with malignant and non malignant hematological disorders.</p><p><bold>Design/Methods</bold>: A total of 205 pediatric patients underwent transplantation between January 2000 and December 2014 at National Institute of Blood Diseases and Bone Marrow Transplantation for various hematological disorders, both malignant and non‐malignant. Both Haematopoietic Stem cells as well as peripheral blood transplantation methods were employed. For allogenic transplantaion, HLA‐matched siblings were the donors. Two years post‐transplant survival was calculated using Kaplan‐Meier survival function.</p><p><bold>Results</bold>: The mean follow‐up period was 301 ± 265 days. Acute episodes of graft versus host disease(GvHD) were observed in 11% and chronic GvHD in 7% of the patients. Overall survival among patients undergoing stem cell transplantation during past five years was 70%. Six months Disease free survival was 42% in aplastic anemia (AA), 69.1% in Beta thalassemia major(BTM), 40% in hematological malignancies and 45.4% in Fanconis anemia.</p><p><bold>Conclusions</bold>: In this study the overall survival among patients undergoing stem cell transplantation during past five years was 70% with the less incidence of acute and chronic GvHD reported from other parts of the world.</p></sec><sec id="pbc26772-sec-5050"><label>P-113</label><title>Outcome of Children with Cancer and/or Allogeneic Hematopoietic Stem Cell Transplantation in the Intensive Care Unit: Experience at a Large European Pediatric Cancer Center</title><p><underline underline-style="single">C. Barking</underline><sup>1</sup>, K. Masjosthusmann<sup>2</sup>, G. Rellensmann<sup>2</sup>, K. Ehlert<sup>1</sup>, S. Zöllner<sup>1</sup>, S. Jocham<sup>1</sup>, B. Bohnenkamp<sup>3</sup>, A. Kremer<sup>3</sup>, E. Rieger‐Fackeldey<sup>2</sup>, A.H. Groll<sup>1</sup></p><p><italic><sup>1</sup>University Children's Hospital, Pediatric Hematology and Oncology, Muenster, Germany; <sup>2</sup>University Children's Hospital, General Pediatrics, Muenster, Germany; <sup>3</sup>University Hospital Muenster, Medical Controlling, Muenster, Germany</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer treatment and hematopoietic stem cell transplantation (HSCT) carry considerable risks of morbidity. We analyzed intensive care unit (ICU) admissions in children and adolescents treated for cancer or undergoing HSCT who developed life‐threatening complications.</p><p><bold>Design/Methods</bold>: Patients ≤ 21 years with hematological or oncological disorders or status post allogeneic HSCT receiving care at the Department of Pediatric Hematology and Oncology admitted to the ICU between 2003 and 2013 for life‐threatening conditions were identified through a search of the University Hospital´s Medical Controlling database. Demographics, disease related parameters, medical course during the ICU stay, short‐ and long‐term outcome were analyzed. Causes of death and parameters with potential impact on outcome were analyzed by uni‐ and multivariate analysis.</p><p><bold>Results</bold>: During the study period, 140 patients had 188 admissions to the ICU for a life‐threatening medical condition. The majority of patients (60.6%) had a hematological malignancy, and 38.3% were post allogeneic HSCT; the median age was 10.4 years (range, 0.0– 20.5). Main reasons for ICU admission were respiratory insufficiency (85; 45.2%), cardiovascular insufficiency (52; 27.7%) and sepsis (51; 27.1%). Mortality in the ICU was 19.1% (36) and related to organ failure and acute complications (28; 77.8%) or irreversible progress of the underlying malignancy (8; 22.2%). Mortality rates at 30, 100 and 365 days post discharge from the ICU were 24.5%, 30.9%, and 39.9%, respectively. Parameters significantly associated with death in the ICU included status post allogeneic HSCT, prior ICU admission(s), the number of days in the ICU, the presence of infections, occurrence and number of organ failures and the number of supported organ systems.</p><p><bold>Conclusions</bold>: The outcome of pediatric cancer/HSCT patients admitted for acute, life‐threatening conditions was not as dismal as reported for some centers in the literature. Most patients benefitted from ICU care and survival was predominantly compromised by the evolution of complications.</p></sec><sec id="pbc26772-sec-5060"><label>P-114</label><title>Various Ebstein Barr Virus Manifestation in Children after Allogeneic Stem Cell Transplantation from Unrelated Donors</title><p><underline underline-style="single">W. Czogala</underline><sup>1</sup>, J. Gozdzik<sup>1,2</sup>, M. Wozniak<sup>1</sup>, A. Krasowska‐Kwiecien<sup>1,2</sup>, A. Dluzniewska<sup>1</sup>, S. Skoczen<sup>1,2</sup>, O. Wiecha<sup>1</sup>, A. Sarnecka‐Paruch<sup>1</sup></p><p><italic><sup>1</sup>University Children's Hospital of Krakow, Transplantation Department, Krakow, Poland; <sup>2</sup>Jagiellonian University Medical College, Department of Immunology‐ Chair of Clinical Immunology and Transplantation, Krakow, Poland</italic></p><p><bold>Background/Objectives</bold>: Epstein – Barr Virus (EBV) infections remain to be a considerable reason of severe complications in patients after allogeneic stem cell transplantation from unrelated donors (MUD ‐ HST). Clinical status of these complications vary from negligible viraemia to life – threatening PTLD.</p><p><bold>Design/Methods</bold>: There have been 85 MUD‐HST performed on our Transplantation Ward from 2007 to 2015 in children aged from 1 to 20 years. Clinical infection status was examined every 7 days by real‐time PCR in blood serum. Other body fluids or/and tissues were examined in case the clinical disease status was unclear.</p><p><bold>Results</bold>: Escalating EBV replication was confirmed in 28 (33%) patients. EBV infection after MUD – HST developed as: primary infection (3 patients), EBV reactivation (17), probable EBV disease (5), confirmed EBV disease (1) and posttransplant lympheproliferative disease (PTLD) (2). Reduction of immunosuppressive drugs was implemented as a first choice procedure in case of non – symptom EBV infection after MUD – HST. When subsequent replications or clinical development occured, rituximab (1 to 8 doses) was implemented. In 27 cases such treatment was successful. In 2 cases (one with confirmed disease and one with PTLD) there was a low DNA virus detection in blood, yet it coexisted with a massive EBV replication in tonsil tissue. In one case of PTLD with lymphatic tissue of the throat involvement we observed treatment resistance and chemotherapy was added to treatment. In this case there was a non ‐ significant and variable viraemia detection, while tonsils remained infected. The boy died regardless to treatment.</p><p><bold>Conclusions</bold>: Systematic virus replication development monitoring is an effective PTLD prophylaxis. Low viraemia detection does not exlude tissue involvement and in presence of suspected symptoms diagnostics should be enlarged.</p></sec><sec id="pbc26772-sec-5070"><label>P-115</label><title>Unmanipulated Stem Cell Transplantation with POS Transplantation Cyclophosphamide. An Excellent Alternative in Latinoamerican Population</title><p><underline underline-style="single">M. Perez Garcia</underline><sup>1</sup>, A. OLAYA VARGAS<sup>1</sup>, G. LOPEZ HERNANDEZ<sup>1</sup>, N. Ramirez Uribe<sup>1</sup>, L. Vollbrechthaussen<sup>1</sup>, Y. Melchor Vidal<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Pediatria ‐ Insurgentes 3700‐C, bone marrow transplantation, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: As the chance of finding a HLA genotypically identical sibling donor is 25%. Unrelated donnor is not available at our country yet. Cord blood stem cell source is limited by dose.</p><p>The use of high dose pos transplant cyclophosphamide (PT‐CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide.</p><p>Manipulated haploidentical stem cell transplantation (ex vivo) have demonstrated good results. Several studies achieved 2 year overall survival from 40‐70% and 4 year OS 36‐46%, and GVHD incidence from 47%.80%</p><p>Objective: To determinate feasibility and overall survival with pos transplantation cyclophosphamide.</p><p><bold>Design/Methods</bold>: Prospective, longitudinal study was performed</p><p>All patients with ALL in CR2 lacked 1) Matched Sibling Donor 2) Umbilical cord blood units with nucleated cells ≥ 4×10 <sup>7</sup> /kg recipient body weight and ≥ 4/6 HLA matched antigen with molecular typing. The order preference of donor selection was a) mother b) father c) brother or sister. Patients with any severe condition were not elegible. This study was aproved by Investigation Comitee and written informed consent was obtained from parental guardians of all patients and donors</p><p><bold>Results</bold>: Forty patients were elegible: Age 0.6‐17.9 years. 68% male and 22% female. CD34 dose were 2‐12 ×10e6/kg. Median of day for neutrophil graft was 15.7 (10‐35 days). Primary failure was 10%.</p><p>Three years Overall survival was 65%, Acute Graft versus host disease was 35% and chronic graft versus host disease 20%</p><p>Incidence of viral infection was 15%: adenovirus, cytomegalovirus and BK virus were common and Immune reconstitución shows a delay of CD4+ and CD8+ delay, until 1 year postransplantation</p><p><bold>Conclusions</bold>: PTCy is an option at our country to face lack of unrelated donor and umbilical cord blood with good dose. It´s a factible procedure.</p><p>More studies should be achieved in order to demonstrate the better source</p></sec><sec id="pbc26772-sec-5080"><label>P-116</label><title>Haploidentical Transplantation with T Cell Depletion for Systemic Relapses of Aggressive Pediatric Solid Tumors</title><p><underline underline-style="single">E. Ramos Elbal</underline><sup>1</sup>, M. Plaza Fornieres<sup>2</sup>, J.P. Muñoz Pérez<sup>1</sup>, M. Del Pozo Carlavilla<sup>1</sup>, M.V. Martinez Sánchez<sup>3</sup>, A.M. Galera Miñarro<sup>1</sup>, M.E. Llinares Riestra<sup>1</sup>, M.D.M. Bermúdez Cortés<sup>1</sup>, J. Monserrat Coll<sup>1</sup>, A. Sánchez Salinas<sup>1</sup>, M. Blanquer Blanquer<sup>1</sup>, J.A. Campillo Marquina<sup>3</sup>, A. Minguela Puras<sup>3</sup>, J.M. Moraleda Jiménez<sup>1</sup>, J.L. Fuster Soler<sup>1</sup></p><p><italic><sup>1</sup>Hospital Clínico Universitario Virgen de la Arrixaca, Stem cell transplantation and cell therapy unit, El Palmar Murcia, Spain; <sup>2</sup>Hospital Clínico Universitario Virgen de la Arrixaca, Murcia Biohealth Research Institute, El Palmar Murcia, Spain; <sup>3</sup>Hospital Clínico Universitario Virgen de la Arrixaca, Immunology service, El Palmar Murcia, Spain</italic></p><p><bold>Background/Objectives</bold>: The prognosis after systemic relapse (SR) of aggressive pediatric solid tumors is poor. After haploidentical stem cell transplantation (Haplo‐SCT), with ex vivo T depletion, alloreactive NK cells may exert an antitumor effect. We analyzed the procedure and results of Haplo‐SCT in six patients (6 to 15 years old) with SR of Ewing sarcoma (ES, 3), neuroblastoma (2) and osteosarcoma (1).</p><p><bold>Design/Methods</bold>: Three patients (2 ES, 1 osteosarcoma) were in second complete remission (2CR) after resection of lung metastases and second line chemotherapy and 3 had active disease. Donor selection (parents) was based on KIR and KIR‐ligand genotyping (donor and recipient) and KIR expression (donor) by flow cytometry. Ex vivo manipulation of the graft consisted of double CD3+/CD19+ (2) or CD3αβ+/CD19+ (4) depletion. The conditioning consisted of fludarabine, busulfan and thiotepa (5) or radioactive mIBG followed by fludarabine, melphalan, thiotepa and ATG (1). Prophylaxis of graftnegativersus‐host disease (GVHD) was done with mycophenolate (1) or cyclosporine and methotrexate (5).</p><p><bold>Results</bold>: On average, 10.3 × 10<sup>6</sup>/kg CD34+, 6.75 × 10<sup>6</sup>/kg CD3+ and 23.62 × 10<sup>6</sup>/kg CD56+ were infused. Graft failure occurred in two patients (CD3+/CD19+ depletion), and both were rescued with matched HLA sibling allograft. No patient died from complications of Haplo‐SCT, one developed acute grade III/IV, steroid‐resistant GVHD responding to photopheresis. Four patients suffered tumor progression and died 3 to 12 months after Haplo‐SCT. Two patients with ES in 2CR at transplantation are alive and disease free 51 and 60 months after Haplo‐SCT, respectively.</p><p><bold>Conclusions</bold>: Haplo‐SCT was a safe option for these heavily pre‐treated patients with no treatment‐related mortality in our series. Graft rejection was associated with CD3+ depletion but not with CD3αβ+ depletion. Only patients transplanted in 2CR have a real chance for long‐term disease‐free survival.</p></sec><sec id="pbc26772-sec-5090"><label>P-117</label><title>High Dose Chemotherapy (HDCT) and Autologous Stem Cell Transplant (ASCT) in Childhood Cancer‐ Experience from the Royal Marsden Hospital</title><p><underline underline-style="single">N. Roy Moulik</underline><sup>1</sup>, J. Indranee<sup>1</sup>, T. Petterson<sup>1</sup>, S. Vaidya<sup>1</sup></p><p><italic><sup>1</sup>Royal Marsden Hospital, Paediatric Oncology, Greater London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: High dose chemotherapy and autologous stem cell transplant (ASCT)form an integral part of treatment protocols for some of the childhood cancers and is being increasingly used for relapsed and refractory solid tumours as well as brain tumours and lymphomas in children.The clinical course and complications of autologous transplant for childhood cancers between 2010 and 2017 is described.</p><p><bold>Design/Methods</bold>: In this retrospective study all children undergoing high dose chemotherapy and autologous stem cell transplant between January 2010 and March 2017 were included. Relevant data were retrieved from patient records and analysed using conventional statistics.</p><p><bold>Results</bold>: Eighty‐two children (M:F 8:9) with a mean age of 5.2±4.4 years underwent ASCT for various cancers, most commonly neuroblastoma (47%).Neutrophil and platelet engraftment after ASCT were seen after 13.6±2.9 and 27.3±15.6 days respectively. Platelet recovery was longer in patients with neuroblastoma receiving BuMel conditioning compared to other diagnosis (p<0.001).Common complications included mucositis (100%) and febrile neutropenia (90%). Culture positive sepsis was seen in 17(20.7%) cases whereas 42 (51%) patients needed parenteral nutrition for mucositis. Hepatic and renal dysfunction were observed in 33 (43.4%) and 4 (4.7%) of cases respectively. Hepatic sinusoidal obstruction syndrome (SOS) was seen in 14(17%)patients; of which 13 had Busulfan based conditioning. Median duration of parenteral nutrition and antibioticswere 8(0‐35) and 9(0‐28) days respectively.Twelve(14%) patients needed escalation of care to HDU/PICU for sepsis (8) or SOS (4). Mean duration of hospitalisation was 30.5±8.7 days and was significantly different among various conditioning regimens (p<0.001).There was no transplant related mortality within Day+100 following ASCT.</p><p><bold>Conclusions</bold>: Complications of ASCT in childhood cancer occurring during the period of cytopenia between conditioning and engraftment are frequently related to the underlying diagnosis and conditioning regimen. Despite commonly occurring complications the immediate outcome for ASCT is excellent with optimum supportive care.</p></sec><sec id="pbc26772-sec-5100"><label>P-118</label><title>Psycho‐Affective Implications in Pediatric Hematopoietic Stem‐Cell Transplantation. A Qualitative‐Quantitative Study</title><p><underline underline-style="single">F. Sinatora</underline><sup>1</sup>, A. Traverso<sup>1</sup>, N. Di Florio<sup>1</sup>, A. Porreca<sup>1</sup>, S. Zanato<sup>1</sup>, A. Marzollo<sup>1</sup>, M. Tremolada<sup>2</sup>, M. Pillon<sup>1</sup>, E. Calore<sup>1</sup>, M. Tumino<sup>1</sup>, C. Mainardi<sup>1</sup>, C. Cattelan<sup>1</sup>, G. Basso<sup>1</sup>, C. Messina<sup>1</sup></p><p><italic><sup>1</sup>University of Padua, Department of Women's and Children's Health, Padova, Italy; <sup>2</sup>University of Padua, Department of Developmental Psychology and Socialisation, Padova, Italy</italic></p><p><bold>Background/Objectives</bold>: Only few studies have focused on the analysis of quantitative and qualitative data in patients undergoing HSCT during childhood (Bingen et al., 2012). The aim of the study was to investigate the perception of illness experience in patients, survivors and their families, and to correlate quantitative and qualitative data.</p><p><bold>Design/Methods</bold>: Three different populations answered an open‐ended single question about disease experience by writing a brief composition. Group_A, tested before transplantation and after a year, included patients, parents and siblings. Group_B was composed of pediatric HSCT survivors, parents and siblings, and Group_B_over included adult survivors, at least 5 years after pediatric transplantation. The Child Behavior Checklist 6‐18 (Achenbach and Rescorla, 2001) and the 36‐Item Short Form Health Survey (Ware et al, 2000) were also administered. The T‐LAB (Ver. 8.1.4, Lancia, 2012) was used for qualitative analyses.</p><p><bold>Results</bold>: Semantic differences in Group A indicate that the disruption of familiar unity and the way the disease is faced have a major impact on the mental health of family members. Despite 5 years from HSCT, in the second group, the theme of familiar disruption, as well as the inability to refer directly to the disease and to the fear of death are associated with clinical scores in the scales considered. The third group shows significant differences with respect to gender and the type of transplant.</p><p><bold>Conclusions</bold>: Results seems to suggest that clinicians should take into account the impact that the disease and HSCT could have on mental health, during all the phases of care. Moreover, the care approach should focus attention on how the disease affects the whole family and relationships between its members.</p></sec><sec id="pbc26772-sec-5110"><label>P-119</label><title>Pediatric Haploidentical Transplant: An Indian Experience</title><p><underline underline-style="single">N. Singh</underline><sup>1</sup></p><p><italic><sup>1</sup>FMRI‐ Gurgaon, Pediatric Hematoncology and Stem cell transplant, Gurgaon, India</italic></p><p><bold>Background/Objectives</bold>: Background‐Out of an estimated 20,000 patients requiring an Allogeneic HSCT in India, only 500 odd patients receive one. Keeping in cognizance the resource constraints, the major reason for the discordance lies in the lack of alternate donors. Whilst unrelated donor marrow and cord suffice for the ethnic majorities in Europe and the USA, such registries provide for less than 10% of HSCT recipients due to both cost and an available match.</p><p>Aims and Objective‐To initiate a Pediatric Haploidentical Family Donor HSCT program in our Institute.</p><p><bold>Design / Methods</bold>: Material and Methods‐We chose a Post‐transplant Cyclophosphamide (PTCY) based approach in all except one in which TCR alpha beta CD 19 depletion was used with PBSC as the graft source. We have carried out 22 transplants in 20 patients over the last 3 years (AML‐7; ALL‐6; CML‐BC‐1; Fanconi Anemia‐3; Thalassemia‐2, Wiskott Aldrich Syndrome‐1). All received PBSC with PTCY on days 3 and 4 followed by cyclosporine/tacrolimus and MMF except one. The conditioning regimen comprised of Fludarabine/Busulphan/Melphalan(AML),Fludarabine/Thiotepa/Melphalan(ALL),Fludarabine/Cyclo/TBI(FA), Fludarabine /Busulphan/ATG(Thalassemia).</p><p><bold>Results</bold>: Results‐16/20 patients surviving beyond 21 days had successful engraftment with full donor Chimerism, 2 patients undergoing a second Haploidentical HCT engrafted as well. Acute GVHD grade 2‐4 developed in 7/20 patients. Day 100 NRM was 6/20 (30%) and the overall survival at 1 year was 70%. The major cause of NRM was infection with Gram Negative Bacilli accounting for 70% of the deaths. Chronic GVHD occurred in 14% of the evaluable patients. With stringent monitoring for CMV and preemptive therapy, none succumbed to CMV disease</p><p><bold>Conclusions</bold>: Conclusion‐Haploidentical HCT based on PTCY and PBSC graft is feasible and probably the most viable form of alternate donor HCT in resource constrained settings.</p></sec><sec id="pbc26772-sec-5120"><label>P-120</label><title>Allogenic Hematopoeitic Stem Cell Transplant for High Risk Acute Pediatric Leukemia: Single Center Experience from India</title><p><underline underline-style="single">V. khandelwal</underline><sup>1</sup>, D. choudhary<sup>1</sup>, S. sharma<sup>1</sup>, D. doval<sup>1</sup>, P. banthia<sup>1</sup>, A. bakliwal<sup>1</sup>, R. setia<sup>2</sup>, A. handoo<sup>3</sup></p><p><italic><sup>1</sup>BLK superspeciality hospital, haematooncology and BMT, Delhi, India; <sup>2</sup>BLK superspeciality hospital, Transfusion medicine, Delhi, India; <sup>3</sup>BLK superspeciality hospital, Haematology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: To analyze retrospectively the outcome of allogenic hematopoeitic stem cell transplant(HSCT) for High Risk Acute Pediatric Leukemia.</p><p><bold>Design/Methods</bold>: 42 transplants were done for 41 patients over period of 4 years; Median age ‐16 years (range 3‐21). The diagnosis was: acute lymphoblastic leukemia in 26(63%) patients, acute myeloid leukemia14(34%), and acute Promyelocytic Leukemia in one. 33% were in first remission (CR1), 40% in second (CR2), and 27 %in third or with refractory disease (CR3). Transplant type: MSD‐30; Haploidentical HSCT‐ 10 and MUD‐ 2. Conditioning regimen: Cy/TBI‐ 13; BU/Cy‐ 13; Flu/Mel‐ 4; Flu/Cy/TBI‐ 6; Bu/flu/Cy ‐3; In vitro T cell depletion and Flu/Mel/ATG/Thiotepa ‐ 2 patients; Flu/AraC/Ida/Mel‐1. GVHD prophylaxis was Cyclosporine and Methotrexate in 31; PTCy with Tacrolimus/MMF in 9, and Tacrolimus/MMF in 2 patients.</p><p><bold>Results</bold>: Out of 42 transplants, 5 received bone marrow, 37 received G‐ CSF mobilized peripheral blood stem cells. A median 7 million of CD34+ cells/kg was infused. A total of 39 transplants (93%) engrafted. Median time for Neutrophil and platelet engraftment was 11 days and 17 days respectively. Seven patient developed hemorrhagic cystitis.Acute GVHD (GR II – IV) was seen in 12(29%) and chronic GVHD in 3 patients. CMV reactivation was seen in 5 patients. Chimerism at day + 100 was available in 25(60%) cases; all of them had full donor hematopoiesis. Primary rejection was seen in 2 and secondary rejection in 1 patient. Fourteen patients(34%) died, the causes were; relapse (n: 7), Infection (n: 4), GVHD (n: 3).Median follow up period was 260 days with overall survival (OS) for the whole group 66%. Discriminated OS according to remission status was 71% in CR1, 70% in CR2 and 54% in CR3.</p><p><bold>Conclusions</bold>: Allogenic HSCT in pediatric high risk leukemia shows encouraging results.PTCy based haploidentical HSCT is also one option in developing countries and is cost effective.</p></sec><sec id="pbc26772-sec-5130"><label>P-121</label><title>Outcomes of Refractory and Relapsed Hodgkin's Lymphoma with Autologous Stem Cell Transplantation: A Single Institution Experience</title><p><underline underline-style="single">R. Wali</underline><sup>1</sup>, H. Saeed<sup>1</sup>, N. Patrus<sup>1</sup>, S. Javed<sup>1</sup>, S.J. Khan<sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Memorial Cancer Hospital, Paediatric Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Hodgkin Lymphoma (HL) is the most common cancer in children, adolescents and young adults with a peak incidence between the ages of 20 and 34. The overall survival (OS) rate of newly diagnosed HL is approximately 80–90%. However, a subset of these patients with HL has refractory disease to first line therapies or experience disease relapse. For these patients, conventional salvage therapies and autologous stem cell transplant is often considered the standard of care.</p><p>Our analysis reports outcomes in these patients.</p><p><bold>Design/Methods</bold>: A retrospective analysis was done on patients with Hodgkin's Lymphoma who had refractory or relapsed disease at Shaukat Khanum Hospital from September 2009 till December 2013 after IRB approval. Patients who had high dose chemotherapy followed by stem cell rescue were selected for this analysis.</p><p><bold>Results</bold>: A total of 567 patients were registered at the Hospital. Sixty (10.6%) of the patient had either Primary Progressive/Refractory disease or Relapse after finishing with first line chemotherapy. High dose chemotherapy followed by stem cell was given on 25 patients (42%). Thirteen patients had PD (40%), 5 had early relapse (22%) and 7 had late relapse (38%). A number of salvage regimens were used which included EPIC, DHAC and Gemcitibine/Vinorelbine. Re‐evaluation was done before taking patients to high dose and showed CR in 17 (68%), PR in 6 (24%) and PD in 2 (8%) patients. Twenty one patients (84%) are in remission after transplant with 2 (8%) dead due to septicemia and 2(2%) patients progressed after treatment. Overall survival is 95% at 4 years with event free survival of 80% at 4 years.</p><p><bold>Conclusions</bold>: Our retrospective analysis shows good outcomes in patients who had progressive refractory and relapse disease. Survival is superior in chemo sensitive disease.</p></sec></sec><sec id="pbc26772-sec-5140"><title>Solid Non Brain Tumours ‐ Neuroblastoma</title><sec id="pbc26772-sec-5150"><label>P-122</label><title>Prognostic Significance of MGMT Expression in Peripheral Neuroblastic Tumors</title><p><underline underline-style="single">D. Abdallah</underline><sup>1</sup>, S. Fadel<sup>2</sup>, N. Mashalli<sup>3</sup></p><p><italic><sup>1</sup>Alexandria faculty of medicine‐ Egypt, pathology department, Alexandria, Egypt; <sup>2</sup>Alexandria faculty of medicine, oncology, Alexandria, Egypt; <sup>3</sup>Alexandria faculty of medicine, Pathology, Alexandria, Egypt</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is the most common extracranial solid malignancy in childhood. Disease with favourable biologic features is curable with surgery alone, high risk disease is essentially incurable and new treatment strategies are needed for these patients. Temozolamide has shown clinical activity against neuroblastoma. MGMT overexpression was a resistant factor to this drug.</p><p><bold>Design/Methods</bold>: MGMT expression was assessed immunohistochemically on formalin fixed paraffin embedded blocks from 32 neuroblastoma cases. It was then correlated with clinicopathologic parameters as: age, site, histopathology and stage as well as prognostic factors as: fate, treatment protocol, overall survival (OS) and disease free survival (DFS)</p><p><bold>Results</bold>: 32 neuroblastic tumors were studied, ages ranged from 2ms to 10 years, 17 were females and 15 were males, 27 cases were abdominal and 5 cases were thoracic. No significant correlation was found between MGMT expression and patient`s age, tumor site, histologic type, grade of differentiation and stage.</p><p>No significant correlation was noted between MGMT expression and follow‐up data: including fate, DFS and OS as well as treatment protocol</p><p><bold>Conclusions</bold>: MGMT expression is not a prognostic factor in neuroblastoma. This result must be validated on a larger number of cases.</p></sec><sec id="pbc26772-sec-5160"><label>P-123</label><title>The Relation of Microenvironment Associated Gene Expression with Risk Classification in Neuroblastoma</title><p><underline underline-style="single">S. Aktas</underline><sup>1</sup>, P. Ercetin<sup>1</sup>, E. Serinan<sup>1</sup>, M. Aydın<sup>1</sup>, Z. Altun<sup>1</sup>, N. Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University, Institute of Oncology, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: Tumor microenvironment is a significant and current topic for invasion, spreading, metastasis and survival of cancer cells. Neuroblastoma is usually poor in terms of stroma and inflammatory elements. It shows a wide spectrum of clinical behaviors from very aggressive forms to spontaneous regression so tumor microenvironment should be considered and evaluated. The aim of the study was to compare microenvironment associated gene expressions of low, intermediate and high risk neuroblastoma with normal control cells and mature ganglioma.</p><p><bold>Design/Methods</bold>: CFLAR, TNFSF10, BCL2L1, PIK3R1, PPP3CA, EGFR, FGF1, FGF14, FGF23, TGFBR1, polo‐like kinase 1, CD47 expression levels were analyzed with real‐time PCR from RNA and cDNA samples of fresh tumor tissues. Fold change analysis were evaluated in compare with control group.</p><p><bold>Results</bold>: 28 cases were included with 39 months mean age (1‐168 months) and 19 were female, 9 were male. There were 9 high, 5 intermediate and 11 low risk cases. Three cases were mature ganglioneuroma. When gene expression profile of high risk cases were compared with control TNFSF10, BCL2L1, FGF1, FGF23 and CD47 expressions were increased while CFLAR, PPP3CA, EGFR and FGF14 were decreased. BCL2L1, FGF1 and CD47 expressions were increased in intermediate risk cases. BCL2L1 expression which was increased in all cases, was found to be more in ganglioneuroma cases. High expression of EGFR stood out in low risk cases. PPP3Ca expression was decreased in all cases. CD47 gene which has a role in immune escape, did not show difference in ganglioneuroma while significantly increased in low risk cases. TGFBR1, PLR, FGF14 did not show expression difference in neuroblastoma.</p><p><bold>Conclusions</bold>: When ganglioneuroma, low, intermadiate and high risk neuroblastoma were considered as a spectrum TNSF10 and FGF showed a gradient increase which suggested as candidate risk defining malignancy marker. The increased expression of CD47 was also suggested a remarkable immune escape role for neuroblastoma.</p></sec><sec id="pbc26772-sec-5170"><label>P-124</label><title>The Effects of Rosiglitazone on Minimal Residual Disease Model of Neuroblastoma</title><p><underline underline-style="single">Z. Altun</underline><sup>1</sup>, M. Ayla<sup>1</sup>, S. Aktas<sup>1</sup>, A. Pamukoglu<sup>1</sup>, P. Ercetin<sup>1</sup>, N. Olgun<sup>2</sup></p><p><italic><sup>1</sup>Dokuz Eylul University, Basic Oncology, Izmir, Turkey; <sup>2</sup>Dokuz Eylul University, Pediatric Oncology, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: The major problem in advanced neuroblastoma is presence of minimal residual disease (MRD).We investigated the effect of peroxisome proliferator‐activating receptor (PPR) agonist, antidiabetic rosiglitazone (RGZ), which regulating cell proliferation and differentiation, on neuronal stem cell differentiation by using MRD model.</p><p><bold>Design/Methods</bold>: PPRgamma expressed and not expressed, SH‐SY5Y and KELLY neuroblastoma cells were used for MRD model with using increasing LD90 doses of recurrent cisplatin (CDDP) for 1.5 year. CDDP(10‐400 uM), RGZ(0,1‐100uM) and CP‐RGZ combinations were applied and viability of cells was determined with using WST‐1, apoptosis with Annexin‐V/PI and differentiation with using immunohistochemically S‐100 and flow cytometric Oct‐3, Nestin and Sox‐2.</p><p><bold>Results</bold>: In MRD model of SH‐SY5Y cells, viabilities and apoptosis were 37.3% and 74.5% with CDDP, 35.3 % and 82.9 % with RGZ100, 33.2% and % 83.4 with CDDP‐RGZ. S‐100 expression was similar in both MRD model and normal cells. In CDDP treated KELLY cells, differentiation was slightly increased. In CDDP‐RGZ combination, differentiation was not different from CDDP. RGZ treatment to MRD model of SH‐SY5Y cells caused less differentiation. Differentiation of survivaed cells was similar both CDDP treated and control cells. The CP‐RGZ application revealed that the remaining cells were less differentiated than CP alone. In particular, expression of Oct‐3 and Sox‐2 in SH‐SY5Y cells caused reduction in CP‐RGZ administration in MRD model.</p><p><bold>Conclusions</bold>: CDDP and RGZ and combinations in neuroblastoma MRD‐developing KELLY cells cell death at similar levels, whereas in PPRγ expressed SH‐SY5Y cells, RGZ killed more cells than CDDP and in combination. CP‐RGZ was effective in decreasing Nestin and Sox‐2 expressions of neuronal stem cell differentiation markers in SH‐SY5Y MRD model. Examination of the effects of PPRgamma‐agonist antidiabetic agents, such as rosiglitazone, in the <italic>in vivo</italic> models of metastatic neuroblastoma may provide a new perspective on neuroblastoma therapy.</p><p><bold>Acknowledgments</bold>. This study was supported by TPOG.</p></sec><sec id="pbc26772-sec-5180"><label>P-125</label><title>Effectiveness and Toxicity of Headstart I and II Protocols: Experience from a Low‐Middle Income Country</title><p>A. Elshahoubi<sup>1</sup>, <underline underline-style="single">N. Amayiri</underline><sup>2</sup>, E. Khattab<sup>3</sup>, H. Halalsheh<sup>1</sup>, E. Bouffet<sup>4</sup></p><p><italic><sup>1</sup>King Hussein Cancer Center, Pediatric Hematology and oncology, Amman, Jordan; <sup>2</sup>KHCC‐Jordan, Pediatric Oncology Department, Amman, Jordan; <sup>3</sup>King Hussein Cancer Center, Stem Cell transplantation‐ Pediatric Department‐ KHCC‐ JordanE, Amman, Jordan; <sup>4</sup>The Hospital for Sick Children‐ Canada, Neuro‐oncology Division, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: HeadStart protocols (HS), a high‐dose chemotherapy strategy for infants with malignant CNS tumors, reported variable success and toxicity profiles. Their benefit‐risk ratio is rarely reported from low‐middle income countries (LMIC). We aimed to evaluate our HS experience at KHCC/ Jordan.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed charts of children diagnosed with CNS tumors and treated with HS (2006‐2015). Data collected included patients’ demographics, chemotherapy complications and cost.</p><p><bold>Results</bold>: Eighteen patients, median age 27 months at diagnosis (10‐62months), were identified (twelve HS‐I, six HS‐II). Twelve (66%) had non‐metastatic disease and four (22%) had GTR. Pathology was ATRT (9), PNET (6) and Medulloblastoma (4). Three patients didn't complete induction cycles (2 ATRT progressed, I PNET failed stem‐cell collection). Fifteen patients (83%) completed induction chemotherapy; eleven (61%) went into CR/PR, two stabilized, two progressed. Seven patients didn't receive SCT (tumor progression(2), financial causes(2), failed stem cell collection(1), family decline(1) and (1)unknown. Six patients (40%) received radiotherapy; two (residual ATRT) following SCT, two (ATRT) with financial limitations, two (1 ATRT, 1 Medulloblastoma) upon tumor progression. Seventy‐one chemotherapy cycles were administered (median interval 23 days). Complications during induction and consolidation phases were febrile neutropenia (75% &100%), documented infections (11% &13%), PICU admissions (3% &0), and mucosits (11% & 88%), respectively. Three patients (20%) developed hearing deficit and one tubulopathy. At last follow up, 5 patients are alive: three patients with Medulloblastoma (9, 18, 71months); one received CSI 18/54Gy and chemotherapy at relapse. Two patients (29%) with ATRT are alive (8, 27months); both received focal radiation on residual tumor. No chemotherapy‐related deaths occurred. The median hospitalization was 78 days (71‐94days).The median cost of treatment was 91,000$.</p><p><bold>Conclusions</bold>: Toxicity of HS was manageable for LMIC, but the financial cost was high for a limited survival. Better selection criteria (e.g. high risk medulloblastoma, HS‐I, and financial support) may outbalance survival over cost.</p></sec><sec id="pbc26772-sec-5190"><label>P-126</label><title>Minimally Invasive Surgery in Children with Intraabdominal Neuroblastoma</title><p><underline underline-style="single">E. Andreev</underline><sup>1</sup>, T. Shamanskaya<sup>2</sup></p><p><italic><sup>1</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, pediatric surgery and oncology, Moscow, Russia; <sup>2</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, pediatric oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: One of the promising areas in pediatric oncology is MIS in children with thoracoabdominal neuroblastoma.We investigated and comparing the result of laparoscopy and laparotomy treatment.</p><p><bold>Design/Methods</bold>: Radical surgical treatment was performed in 224 patients(01.2012 ‐ 10.2016).Laparoscopy was performed in 39(17.4%).Patients were treated according to NB2004 protocol.Image‐defined risk factors(IDRF) and size of the tumor were used to select patients.To compare the effects of laparotomy with those of laparoscopy in patients with neuroblastomas without IDRFs, the following items were retrospectively compared: largest tumor dimension, volume of blood loss, time required to initiate postoperative feeding, locoregional recurrence rate, survival, etc.</p><p><bold>Results</bold>: 31 patients without IDRFs(20 at low‐medium risk and 11 at high risk) underwent laparotomy, and 39 patients without IDRFs(31 low‐medium risk and 8 at high risk) underwent laparoscopy.Median age was 14 months(1 – 69) after laparotomy and 11 months(3 – 62) after laparoscopy (p=0.68).Median duration of surgery was 120(70‐200) and 135(50 ‐ 300) min(p=0.15).Median postoperative time required for resuming meal consumption was significantly longer in the laparotomy group(2 days; 1–4) than that in the laparoscopy group(0 days;0–10;p=0,000005).Median blood loss was significantly higher in the laparotomy group(20 ml;0–200) than in the laparoscopy group(0 ml;0‐100;p = 0,01).Median time of draenage removal was higher in the laparotomy group(4 ml;0‐8) than in the laparoscopy group(2 days;0‐13;p= 0,001).Median time of analgesia was higher in the laparotomy group(4 days;2‐6) than in the laparoscopy group(2 days;1‐5;p=0,000002).Median time of antibacterial therapy was higher in the laparotomy group(6 days;3‐11) than in the laparoscopy group(5 days;1‐10;p=0,000002).Median follow‐up time was 36 months.We have not differences in intraoperative and postoperative complications, local reccurence and mortality in postoperative period.</p><p><bold>Conclusions</bold>: MIS in children with intraabdominal neuroblastoma is an effective technique which enables to carry out radical surgery in the absence of contraindications and IDRF and provides minimally invasiveness and good cosmetic effect without worsening oncological prognosis.</p></sec><sec id="pbc26772-sec-5200"><label>P-127</label><title>MYCN Mediates Metabolic Reprogramming in Childhood Neuroblastoma</title><p><underline underline-style="single">M. Arsenian Henriksson</underline><sup>1</sup>, G. Oliynyk<sup>1</sup>, M.V. Ruiz Perez<sup>1</sup>, J. Dzieran<sup>1</sup>, H. Zirath<sup>1</sup>, H. Johassson<sup>2</sup>, J. Lehtio<sup>2</sup></p><p><italic><sup>1</sup>Karolinska institutet, Microbiology‐ Tumor and Cell Biology, Stockholm, Sweden; <sup>2</sup>Karolinska institutet, Oncology/Pathology, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma (NB), which arises from the developing sympathetic nervous system, is one of the most aggressive solid tumors of early childhood. Amplification of the <italic>MYCN</italic> oncogene is found in around 30% of NB patients and is associated with rapid tumor progression and poor prognosis. Our recent findings show that targeting of MYCN with small molecules including JQ1 and 10058‐F4 results in metabolic changes including mitochondrial dysfunction leading to accumulation of lipid droplets in NB cells (Zirath <italic>et al</italic>, PNAS 100, 10258‐10263, 2013).</p><p><bold>Design/Methods</bold>: To investigate downstream effects of MYCN targeting we have performed quantitative proteomics of <italic>MYCN</italic>‐amplified NB cells where MYCN has been downregulated using short hairpin RNA against MYCN. We identified over 7,000 proteins of which around 2250 have been used for identification of novel pathways involved in neuroblastoma pathogenesis. We have also performed metabolic flux analysis.</p><p><bold>Results</bold>: We found that primary metabolic processes including protein, lipid and nucleic acid metabolic processes were the most significantly affected activities upon MYCN downregulation. For analysis of the impact of MYCN expression on glycolysis and mitochondrial capacity we performed metabolic flux measurements using a Seahorse XF analyser. Our data show that <italic>MYCN‐</italic>amplified NB cells have a high metabolic potential and that they primarily use oxidative phosphorylation for their energy consumption. We also found that MYCN not only positively regulates the respiratory capacity but also significantly enhances glycolysis. Importantly, we demonstrate that MYCN positively regulates the ability of NB cells to oxidize exogenous fatty acids.</p><p><bold>Conclusions</bold>: Taken together, our findings show that MYCN expression enhances the bioenergetic capabilities and that NB cells can shift their metabolic processes depending on the available nutrition. Our data highlights the importance of metabolic pathways for tumor aggressiveness, which may be the basis for future cancer therapies for patients with NB.</p></sec><sec id="pbc26772-sec-5210"><label>P-128</label><title>The Chemotherapy Response of Very Early Stage in Neuroblastoma Patients with N‐MYC Amplification</title><p><underline underline-style="single">C. huang</underline><sup>1</sup>, X. ma<sup>1</sup>, Z. yue<sup>1</sup>, M. jin<sup>1</sup>, D. zhang<sup>1</sup>, W. zhao<sup>1</sup>, Q. zhao<sup>1</sup>, X. wang<sup>1</sup>, C. duan<sup>1</sup>, T. xing<sup>1</sup>, S. li<sup>1</sup>, Y. chen<sup>1</sup>, X. chai<sup>1</sup></p><p><italic><sup>1</sup>Beijing Children's Hospital, Hematology Oncology Center‐ Capital Medical University, Bei Jing, China</italic></p><p><bold>Background/Objectives</bold>: To summarize the clinical features of neuroblastoma with N‐myc amplification. Analyse the bio‐features and evaluate the effect of chemotherapy in early stage</p><p><bold>Design/Methods</bold>: The research analyzed the medical records of 38 patients with N‐myc amplification of NB from Feb 2012 to Dec 2016 in Beijing children's hospital. The regimen were according to the protocol of our hospital, which based on the N7 protocol. The data were reviewed for the medical history. Analysised the viration of biomarker and the primary site, to object the short‐term effect of chemotherapy.</p><p><bold>Results</bold>: 38 cases admitted in the research, The primary site of tumor is retroperitoneal, adrenal area. 27 cases are positive in bone marrow cytomorpholigic examination. The proportion of tumor range 10‐50% is 3 cases, above 50% is 14 cases. Of all the cases, 37 reported that they had the lactate dehydrogenase (LDH) level higher than the normal. Only 1 case under 500U/L. 29 cases above 1000U/L. The diameter of tumor lager than 10cm are 32 cases. 33 cases measure the volume. 12 cases are <100cm3, 11 cases range 100cm3 ‐500cm3,10 cases larger than 500cm3. All the 38 cases have finished 2 courses chemotherapy. 35 cases reduce to under 1000U/L. Among the 38 cases, 36 cases’ bone marrow examination reverse to negative. According to the imageological examination, the overall response rate after 2 courses chemotherapy is 84.8%. 1 case achieve VGPR, 21 cases achieve PR, 7 cases achieve MR, 2 cases are NR, while 2 cases show PD.</p><p><bold>Conclusions</bold>: NB with N‐myc gene amplification are sensitive to chemotherapy. Chemotherapy can minish the burden of tumor in early stage. But because of the huge burden and the huge size of tumor, it is not the ripe opportunity to receive the surgery or the autologous stem cell transplantation. The patient should go on receiving chemotherapy for remission of disease.</p></sec><sec id="pbc26772-sec-5220"><label>P-129</label><title>Characteristics of Mediastinal Neuroblastoma Detected by Chance in Children Older Than 18 Months in Japan</title><p><underline underline-style="single">Y. Cho</underline><sup>1,2</sup>, A. Iguchi<sup>1</sup>, J. Ohshima<sup>1</sup>, M. Sugiyama<sup>1</sup>, Y. Terashita<sup>1</sup>, T. Ariga<sup>1</sup></p><p><italic><sup>1</sup>Hokkaido University Hospital, Pediatrics, Sapporo, Japan; <sup>2</sup>Hokkaido Cancer Center, Pediatrics, Sapporo, Japan</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is an aggressive malignant and heterogeneous tumor in children. Cases under 18 months old, or cases with primary tumor arising from mediastinum tend to have a better prognosis. We sometimes detect by chance cases with mediastinal neuroblastoma when doing an imaging examination for mild respiratory illness in older children. Clarifying their characteristics is important for appropriate treatment.</p><p><bold>Design/Methods</bold>: We analyzed patients with neuroblastoma diagnosed at Hokkaido University Hospital and Hokkaido Cancer Center from 1989 to 2016 retrospectively. Cases under 18 months old, and cases detected by mass screening or with apparent tumor‐related symptoms were excluded. Analytical factors included primary site, detection, stage, pathology, molecular biology, treatment and outcome.</p><p><bold>Results</bold>: Out of 221 patients with neuroblastoma, 11 cases were with mediastinal neuroblastoma detected by chance over 18 months old. Nine cases were detected by X‐rays for examining pneumonia/ bronchitis, 1 by abdomen CT scan, 1 by health checkup. Serum NSE levels were from 12.4 to 26.4 (cut off; 12 ng/mL), VMA in urine from 4.3 to 37.1 (cut off; 13mcrg/mgCr), and HVA from 0.7 to 56 (cut off; 27mcrg/mgCr). Eight cases were totally resected with video‐assisted thoracoscopic surgery/ open thoracic surgery. Two were limited to partial resection even in open thoracic surgery. One had only biopsy for diagnosis. Eight cases were in INSS stage 1, one case in stage 2, and 2 cases in stage 3. Six cases were ganglioneuroblastoma and 5 were ganglioneuroma. MYCN gene was not amplified in any case. Chemotherapy was performed for 2 cases before 2000. Cases after 2000 had no chemotherapy even with partial resection. All were alive for more than 3 years after diagnosis.</p><p><bold>Conclusions</bold>: Almost every case with mediastinal neuroblastoma detected by chance over 18 months old showed characteristics of low risk group. Good prognosis can be expected without drastic treatment.</p></sec><sec id="pbc26772-sec-5230"><label>P-130</label><title>Minimal Residual Disease in Bone Marrow of Patients with High Risk Neuroblastoma in 31 Patients from a Single Institution in Argentina</title><p><underline underline-style="single">M. CIMOLAI</underline><sup>1</sup>, A. MEDINA<sup>1</sup>, R. MITCHELL<sup>2</sup>, P. RUBIO<sup>1</sup>, J. ROSSI<sup>2</sup>, P. ZUBIZARRETA<sup>1</sup>, W. CACCIAVILLANO<sup>1</sup>, C. ALONSO<sup>1</sup></p><p><italic><sup>1</sup>Hospital de Pediatría Prof. dr. Juan P. Garrahan, Hematology and Oncology, Buenos Aires, Argentina; <sup>2</sup>hospital de Pediatría Prof. dr. Juan P. Garrahan, Immunology and Rheumatology Department, Buenos Aires, Argentina</italic></p><p><bold>Background/Objectives</bold>: The outcome of neuroblastoma (NB) is dependent on several well stablished prognostic factors. Bone marrow (BM) evaluation by conventional cytology, at diagnosis and during treatment, has limited sensitivity and it is not suitable for minimal residual disease (MRD) detection. PHOX2B measurment by quantitative‐RT‐PCR has been described as a sensitive and specific marker for MRD analysis. Our aim was to perform molecular MRD evaluation at different time points in order to evaluate the prognostic value of PHOX2B in our population of high‐risk patients.</p><p><bold>Design/Methods</bold>: Quantitative RT‐PCR for PHOX2B was performed in 271 BM samples from 31 patients with high‐risk‐NB treated at the Garrahan Pediatric Hospital with first or second line treatment protocols. A median of 8 samples per patient were evaluated [range: 2‐19]. Median follow‐up time was 13 [range: 3‐44] months. The prognostic impact of MRD at diagnosis (n=22), after cycle 3 (n=22), after cycle 5 (n=20), or at any follow‐up time (n=28) was evaluated using Fisher's and Log‐rank‐tests.</p><p><bold>Results</bold>: PHOX2B was detected in 21/22 evaluable samples at diagnosis, and in 9/22 after cycle 3, and no correlation was found between outcome and MRD status at both time points. However, molecular BM remission (PHOX2B not detectable) was associated with a better outcome for MRD negativity after cycle 5 (10/20; Fisher‐p=0.0364; 2‐y‐pEFS: 64±17% versus 33±19%; Log‐Rank‐p=0.0928) or MRD negativity at any follow‐up time (9/28; Fisher‐p<0.0001; 2‐y‐pEFS: 80±18% versus 24±11%; Log‐Rank‐p=0.0038).</p><p><bold>Conclusions</bold>: Despite the limited number of patients included in the study, negative MRD in BM samples after cycle 5, or at every follow‐up time during treatment, seems to identify a group of patients with high‐risk‐NB with a significant better outcome. No association was found between PHOX2B at diagnosis or after cycle 3 of treatment. These preliminary results suggest that PHOX2B‐could be a useful MRD marker in our population of patients with high‐risk NB.</p></sec><sec id="pbc26772-sec-5240"><label>P-131</label><title>MLN8237 Induces Cellular Senescence by Down‐Regulation of N‐MYC in Neuroblastoma</title><p><underline underline-style="single">A. Liu</underline><sup>1</sup>, L. Ding<sup>2</sup>, Y. Yang<sup>3</sup>, Y. Liu<sup>4</sup>, J. Sun<sup>5</sup>, Q. Hu<sup>5</sup></p><p><italic><sup>1</sup>Tongji Hospital‐ Tongji Medical College‐ Huazhong University of Science & Technology, Pediatrics, Wuhan, China; <sup>2</sup>Tongji Hospital ‐ Tongji Medical College ‐ Hua Zhong University of Science and T, Pediatrics, Wuhan, China; <sup>3</sup>Tongji Hospital‐Tongji Medical College‐ Huazhong University of Science & Technology, Experimental Medicine Center, Wuhan, China; <sup>4</sup>UT Southwestern Medical Center, Radiation Oncology, Dallas, USA; <sup>5</sup>Tongji Hospital‐Tongji Medical College‐ Huazhong University of Science & Technology, Pediatrics, Wuhan, China</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is one of the most common malignancy pediatric solid tumors and the prognosis of high‐risk neuroblastoma is still poor. MYCN amplification is a risk factor and the stability of N‐MYC is closely linked to Aurora A. In this study, we investigated the effect and molecular mechanism of senescence induced by MLN8237 (Alisertib), a small molecule that selective inhibit Aurora A, in high risk neuroblastoma.</p><p><bold>Design/Methods</bold>: Senescence was detected by SA‐β‐gal staining. The related proteins expressions were analyzed by Western blot. In vivo experiments were carried out in tumor xenograft model mice.</p><p><bold>Results</bold>: MLN8237 could induce neuroblastoma cells senescence by N‐MYC down‐regulation via inhibiting the phosphorylation of Aurora A. It could also inhibit tumor growth and prolong the survival time of xenograft tumor mice. However, some senescent cells tended to recover from cell cycle arrest during the MLN8237 treatment in vitro. We found MLN8237 activated the interleukin‐6 and signal transducer and activator of transcription factor‐3 (IL‐6/STAT3) pathway, which could promote the tumor progression and recurrence. When IL‐6/STAT3 of senescence neuroblastoma cells were inhibited by LLL12, a small molecule STAT3 inhibitor, senescence reversion could be suppressed.</p><p><bold>Conclusions</bold>: MLN8237 Induces Cellular Senescence by down‐regulation of N‐MYC in Neuroblastoma and then activates the IL‐6/STAT3 pathway of senescent cells. These results provide a new relapse mechanism of neuroblastoma and exploring novel therapeutic targets on cellular senescence and IL‐6/STAT3 signaling.</p></sec><sec id="pbc26772-sec-5250"><label>P-132</label><title>The Value of Detection of Circulating Tumor Cell in Neuroblastoma Patients on the Prognosis and Treatment Evaluation</title><p><underline underline-style="single">K. Dong</underline><sup>1</sup>, X. liu<sup>1</sup>, R. Dong<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital of Fudan University, surgery, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: Circulating tumor cells (CTCs) has been shown to be associated with prognosis and therapeutic efficacy in many tumors. We detection the peripheral blood circulating tumor cells in neuroblastoma and discuse its value on the prognosis and treatment evaluation.</p><p><bold>Design/Methods</bold>: There were 28 newly diagnosed cases of neuroblastoma. The circulating tumor cells were collected by the negative enrichment method combined with i‐FISH. The relationship between the number of circulating tumor cells and the clinical factors were analyzed. In addition, the peripheral blood CTC of other types solid tumors was examined to assess the difference with neuroblastoma.</p><p><bold>Results</bold>: In children with distant metastases, the number of CTCs is higher than those in other types of tumors. The number of CTCs in the high, middle and low risk groups of children were statistically different (Mean rank diff = 8.583). The number of CTC in children with N‐myc positive was lower than that in N‐myc‐negative children (p = 0.6133). 24‐hour urine VMA has no relationship with CTC numbers, but serum NSE has positive correlation with CTC numbers, Spearman test, r = 0.463 95% CI (0.09713, 0.7186), p = 0.0131. There was significant difference between the distant metastasis group and non‐metastasis group (p <0.0001). For those whose CTC number >10, the number is significantly went down in 80% of the patients after the chemotherapy. After 16 months of follow‐up, The ROC curve shows AUC‐ROC is 0.81, 95% CI (0.57, 1.04) and the cutoff was 6. The survival time for those CTCs number>5 at the time of dignose was shorter.</p><p><bold>Conclusions</bold>: The number of peripheral blood CTC in children with neuroblastoma is higher than in other solid tumors.</p><p>CTC number is associated with COG classification, distant metastasis, and serum NSE levels.</p><p>The survival time of those children with peripheral blood CTC number> 5 is shorter than those number<5.</p></sec><sec id="pbc26772-sec-5260"><label>P-133</label><title>Combination of Micro‐RNA 128A Downregulation and TERT Overexpression Predicts Unfavorable Outcome in Neuroblastoma Patients</title><p><underline underline-style="single">A. Druy</underline><sup>1</sup>, G. Tsaur<sup>2</sup>, E. Shorikov<sup>3</sup>, A. Zaychikov<sup>4</sup>, Y. Olshanskaya<sup>1</sup>, L. Saveliev<sup>5</sup>, L. Fechina<sup>4</sup></p><p><italic><sup>1</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Laboratory of Cytogenetics and Molecular Genetics, Moscow, Russia; <sup>2</sup>Research Institute of Medical Cell Technologies, Laboratory of Cellular Therapeutics of Oncohematological Disorders, Yekaterinburg, Russia; <sup>3</sup>PET‐technology Center of Nuclear Medicine, PET diagnostics, Yekaterinburg, Russia; <sup>4</sup>Regional Children's Hospital N1, Department of Pediatric Oncology, Yekaterinburg, Russia; <sup>5</sup>Ural State Medical University, Chair of Laboratory Medicine, Yekaterinburg, Russia</italic></p><p><bold>Background/Objectives</bold>: Clinical heterogeneity is a hallmark of neuroblastoma (NB). TERT hyperexpression was identified as adverse prognostic marker, while significance of microRNA expression profile in NB is undiscovered.</p><p>Aim. Investigation of prognostic significance of miR128A and TERT expression in primary NB.</p><p><bold>Design / Methods</bold>: RNA samples from 103 fresh‐frozen NB tissues were subjected to qRTPCR for miR128A and TERT expression evaluation. Copy number variations were determined by MLPA and FISH. Correspondence of miR128A and TERT expression levels to event‐free survival (EFS) was proved by ROC‐analysis and established threshold levels (TL) were utilized for group separation in subsequent survival analysis. Median of follow‐up time achieved 5.8 years.</p><p><bold>Results</bold>: Abundant TERT expression and lack of miR128A expression resulted in superior frequency of adverse events (p=0.027, TL=4,7E‐3 and p=0.004, TL=4.6E‐2 respectively). EFS in group of patients with TERT expression above 4,7E‐3 (group TERT) was 0.66SE0.07, in patients with miR128A expression below 4.6E‐2 (group miR128A) was 0.64SE0.15, patients harboring both TERT overexpression and lack of miR128A expression (group miR128/TERT) had dismal outcome: EFS 0.29SE0.11, comparing to patients without these abnormalities (group neither): EFS 0.92SE0.06, p<0.001. Analogously cumulative incidence of progression in the group TERT was 0.32SE0.07, miR128A – 0.36SE0.15, miR128A/TERT – 0.71SE0,11, neither – 0.08SE0.06, p<0.001.</p><p>MYCN amplified (MNA) cases were accumulated in the groups TERT and miR128/TERT (p=0.061), while gain of chromosome 17, 9p and 14q deletions prevailed in the group neither (p=0.014, 0.043 and 0.017 accordingly). MNA and 14q deletion had prognostic significance in the correspondent groups (p<0.001, p=0.022). The classifier was proposed for distinguishing patients with unequal outcome: MNA EFS=0.25SE0.11, MYCN single copy patients divided into groups miR128A/TERT (0.40SE0.15), miR128A (0.60SE0.15) and TERT (0.74SE0.08). Group neither was separated basing on presence (0.71SE0.17) or absence (EFS=1.00) of 14q deletion, p<0.001.</p><p><bold>Conclusions</bold>: Levels of miR128A and TERT expression together with cytogenetic data allow discriminating patients into groups with significantly different outcome.</p></sec><sec id="pbc26772-sec-5270"><label>P-134</label><title>Magnetic Resonance Guided High Intensity Focused Ultrasound Treatment Effects in a Mouse Model of Neuroblastoma</title><p><underline underline-style="single">A. Fahy</underline><sup>1</sup>, S. Papp<sup>2</sup>, K. Piorkowska<sup>3</sup>, A. Waspe<sup>3</sup>, S. Pichardo<sup>4</sup>, C. Abraham<sup>4</sup>, L. Curiel<sup>4</sup>, L. Zhang<sup>5</sup>, S. Baruchel<sup>5</sup>, G. Somers<sup>6</sup>, J.T. Gerstle<sup>1</sup></p><p><italic><sup>1</sup>Hospital for Sick Children, General and Thoracic Surgery, Toronto, Canada; <sup>2</sup>University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Canada; <sup>3</sup>Hospital for Sick Children, Center for Image Guided Innovation and Therapeutic Interventions, Toronto, Canada; <sup>4</sup>Thunder Bay Regional Research Institute, Image‐Guided Interventions, Thunder Bay, Canada; <sup>5</sup>Hospital for Sick Children, Department of Hematology/Oncology, Toronto, Canada; <sup>6</sup>Hospital for Sick Children, Department of Pathology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Magnetic Resonance guided High intensity focused ultrasound (MRgHIFU) is a non‐invasive technology that uses an extracorporeal focused ultrasound transducer to converge high intensity focused ultrasound (HIFU) energy onto a specific tissue target via MR guidance. This focused ultrasound energy can induce localized thermal necrosis of benign or malignant tissue while simultaneous MR thermometry can monitor the temperatures of surrounding structures to avoid unintended thermal injuries. We aimed to evaluate the effects of MRgHIFU in a mouse model of neuroblastoma (NBL).</p><p><bold>Design/Methods</bold>: NOD/SCID mice (n=18) were inoculated with a CHLA‐15 NBL cell line in the left hind limb and tumor growth monitored until size reached 5mm in largest dimension. Tumors (n=10) were treated with MRgHIFU at 42.5 acoustic Watts for 20 seconds. Control tumors (n=8) were imaged but not treated. Immediately post‐treatment, mice were euthanized and the tumors immersion fixed in 10% neutral buffered formalin, paraffin embedded, and stained with H&E and elastin trichrome for gross and histological evaluation.</p><p><bold>Results</bold>: Tumors reached 5.1 +/‐ 1.7 mm in size (treated = 5.8 +/‐ 1.9 mm, untreated 4.2 +/‐ 0.6 mm). HIFU treatment increased the temperature in the tumors to a range between 55°C and 80°C. Histological changes in the treated tumors included confluent necrosis, diffuse single cell necrosis, and large areas of intratumoral hemorrhage. Untreated tumors had sporadic single cell necrosis and small areas of intratumoral hemorrhage but no areas of confluent necrosis.</p><p><bold>Conclusions</bold>: MRgHIFU can be used to cause localized thermal necrosis of tumors in a mouse model of NBL. Further work is underway to investigate the effect of MRgHIFU on tumor growth and mouse survival. MRgHIFU may offer a potential additional local therapy to patients with recurrent or refractory high risk NBL.</p></sec><sec id="pbc26772-sec-5280"><label>P-135</label><title>Does Salvage Chemotherapy Regimen Intensity Embark on Clearance of Bone Marrow Neuroblastoma?</title><p><underline underline-style="single">A. elhemaly</underline><sup>1</sup>, M. fawzy<sup>1</sup>, A. Hamoda<sup>1</sup>, E. moussa<sup>2</sup>, H. reda<sup>3</sup>, S. elmenawi<sup>4</sup></p><p><italic><sup>1</sup>national cancer institute and children cancer hospital of egypt, pediatric oncology, Cairo, Egypt; <sup>2</sup>children cancer hospital of egypt and elmonofia university, pediatric oncology, Cairo, Egypt; <sup>3</sup>national cancer institute and children cancer hospital of egypt, clinical pathology, Cairo, Egypt; <sup>4</sup>children cancer hospital of egypt, clinical research, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: neuroblastoma is the most common extracranial solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at “high risk” of treatment failure. This study aim was to evaluate the impact of salvage chemotherapy ICE (Ifosfamide, Carboplatin, and Etoposide) versus TC (Topotecan/Cyclophosphamide) when administered to neuroblastoma high risk patients having residual bone marrow disease after primary tumor control on first line treatment regimen.</p><p><bold>Design/Methods</bold>: the present retrospective study included 2 matched groups of eligible stage 4 neuroblastoma patients with persistent bone marrow disease. Each group consisted of 36 patients. Group (1) patients received ICE whereas less intensive TC was administered to Group (2). Data analysis included epidemiological variables, pathology subtype, NMYC gene status, primary tumor response and their correlation with bone marrow disease clearance on each regimen.</p><p><bold>Results</bold>: higher tendency of complete bone marrow clearance was reported in patients received ICE compared to TC; 33.3% versus 22.2%, respectively. However, the difference was not statistically significant (p= 0.293).</p><p><bold>Conclusions</bold>: TC regimen appears to be non‐inferior to ICE as salvage treatment in attempt to clear bone marrow neuroblastoma residual, with the privilege of being less toxic and can be given on outpatient basis. Yet, further randomized trials of larger study sample size and with survival impact analysis are warranted.</p></sec><sec id="pbc26772-sec-5290"><label>P-136</label><title>Quality Indicators in Neuroblastoma (NBL) Treatment</title><p>P. Hoogerbrugge<sup>1</sup>, <underline underline-style="single">S. Dijkstra</underline><sup>2</sup>, M. Van Noesel<sup>1</sup>, L. Tytgat<sup>1</sup>, M. Wijnen<sup>1</sup>, K. Kraal<sup>1</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Ped Oncology, Utrecht, The Netherlands; <sup>2</sup>Princess Máxima Center for Pediatric Oncology, Honours Program UMCU, Utrecht, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: To improve neuroblastoma (NBL) treatment within a center, and compare NBL treatment between centers, quality indicators may be helpful as surrogate markers of effective treatment. In our study, we report data of 4 quality indicators (diagnostic work‐up, thyroid protection at MIBG‐scanning, treatment‐delay and use of tumor board meetings) that may correlate with treatment effectivity and toxicity.</p><p><bold>Design/Methods</bold>: A cross‐sectional, retrospective analysis was performed of Dutch patients treated for NBL in the national centralized facilities of the Princess Máxima Center. Medical records were reviewed to extract information on demographics, treatment and quality of care indicators. The variables recorded included 1: time‐interval from presentation to complete diagnosis,2: use of thyroid prophylaxis before MIBG imaging, 3: chemotherapy intervals and 4: use of tumor‐board meetings. Analysis of surgical procedures is topic of another study, and not included in this analysis.</p><p><bold>Results</bold>: Data of 47 patients treated between 2014 and 2017 were available for analysis. Patients were classified INSS stage I in 2% of cases, stage II in 11%, stage III in 19%, stage IV in 65% and stage IVS in 2%. Sixty‐six percent of patients with NBL were stratified for DCOG‐NBL high‐risk treatment. The median time between presentation and complete diagnostic work‐up (urinary catecholamines, pathology, MIBG‐scan) was 8 days (range 2‐42 days). Prescription of thyroid‐prophylactic treatment prior to MIBG‐scans was recorded in 190 of 200 MIBG‐scans (95%). In only 2 patients, the interval between diagnosis and the end of the 6<sup>th</sup> chemotherapy‐course was more than 120% of the originally planned, protocol‐based interval. Finally, we found that 75% (123 of 164) of the protocol‐based evaluations were discussed in tumor‐board meetings.</p><p><bold>Conclusions</bold>: Identification and analysis of quality‐indicators in neuroblastoma treatment is feasible, and may provide tools to improve treatment over time and compare treatment quality between various centers.</p></sec><sec id="pbc26772-sec-5300"><label>P-137</label><title>Individualized Risk Assessment in Neuroblastoma: Does The Tumoral Metabolic Activity in I‐123‐MIBG‐SPECT Predict the Outcome?</title><p>J. Rogasch<sup>1</sup>, <underline underline-style="single">P. Hundsdoerfer</underline><sup>2</sup>, C. Furth<sup>1</sup>, F. Wedel<sup>1</sup>, F. Hofheinz<sup>3</sup>, P.C. Krüger<sup>4</sup>, H. Lode<sup>5</sup>, W. Brenner<sup>1</sup>, A. Eggert<sup>2</sup>, H. Amthauer<sup>1</sup>, I. Schatka<sup>1</sup></p><p><italic><sup>1</sup>Charité University Medicine, Department of Nuclear Medicine, Berlin, Germany; <sup>2</sup>Charité University Medicine, Pediatric Oncology, Berlin, Germany; <sup>3</sup>PET Center‐ Helmholtz Zentrum Dresden‐Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany; <sup>4</sup>University Medicine Greifswald, Institute for Diagnostic Radiology and Neuroradiology, Greifswald, Germany; <sup>5</sup>University Medicine Greifswald, Department of Pediatric Oncology and Hematology, Greifswald, Germany</italic></p><p><bold>Background/Objectives</bold>: Risk‐adapted treatment in children with neuroblastoma (NB) occurs according to clinical and genetic factors. This study evaluated the significance of metabolic tumor volume (MTV) and its asphericity (ASP) in pretherapeutic I‐123‐MIBG‐SPECT (IMS) for individualized image‐based prediction of outcome.</p><p><bold>Design/Methods</bold>: Retrospective analysis in 23 children (f:11; m:12; median age, 1.8 [0.3‐6.8] years) with primary diagnosis of NB consecutively examined by pretherapeutic IMS. Primary tumor's MTV and ASP were defined using semi‐automatic thresholds. Cox regression, ROC analysis (cut‐off determination) and Kaplan‐Meier (KM) analyses with log‐rank test for event‐free survival (EFS) were performed for ASP, MTV, laboratory parameters (such as urinary homovanillic acid‐to‐creatinine ratio [HVA/C]), clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined by <italic>Harrell's C</italic> and LR χ<sup>2</sup>.</p><p><bold>Results</bold>: Median follow‐up was 36 [7‐107] months (disease progression/relapse, n=8; death, n=4). ASP (<italic>p</italic>=0.029; hazard ratio [HR], 1.032 for one‐unit increase), MTV (<italic>p</italic>=0.038; HR, 1.012) and MYCN (<italic>p</italic>=0.047; HR, 4.67) were the only significant predictors of EFS in univariate Cox; only ASP also in multivariate analysis (<italic>p</italic>=0.026; HR, 1.042). Mean EFS for high (>32.0%) vs. low ASP was 21 vs. 88 months (<italic>p</italic>=0.013), and for high (>46.7 ml) vs. low MTV 22 vs. 87 months (<italic>p</italic>=0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS.</p><p><bold>Conclusions</bold>: In this explorative study, pretherapeutic image‐derived and laboratory markers of tumoral metabolic activity in neuroblastoma (ASP, MTV, urinary HVA‐to‐creatinine ratio) allowed to identify children with high and low risk for progression/relapse treated according to current therapy protocols.</p></sec><sec id="pbc26772-sec-5310"><label>P-138</label><title>Interim Results of a Clinical Trial of IDRF for Intermediate‐Risk Neuroblastoma from the Japan Neuroblastoma Study Group (JNBSG)</title><p><underline underline-style="single">T. Iehara</underline><sup>1</sup>, I. Yokota<sup>2</sup>, A. Yoneda<sup>3</sup>, T. Kamijo<sup>4</sup>, A. Nakazawa<sup>5</sup>, A. Kikuta<sup>6</sup>, T. Takimoto<sup>7</sup>, S. Teramukai<sup>2</sup>, H. Hajime<sup>1</sup>, A. Nakagawara<sup>8</sup>, T. Tajiri<sup>9</sup></p><p><italic><sup>1</sup>Kyoto Prefectural University of Medicine, Pediatrics, Kyoto, Japan; <sup>2</sup>Kyoto Prefectural University of Medicine, Biostatistics, Kyoto, Japan; <sup>3</sup>Osaka City General Hospital, Pediatric surgery, Oasaka, Japan; <sup>4</sup>Saitama Cancer Center, Research Institute for Clinical Oncology, Saitama, Japan; <sup>5</sup>National Center for Child Health and Development, Pathology, Tokyo, Japan; <sup>6</sup>Fukushima Medical University, Pediatric Oncology, Fukushima, Japan; <sup>7</sup>National Center for Child Health and Development, Center for Clinical Research and Development, Tokyo, Japan; <sup>8</sup>Saga Medical Center Koseikan, Saga Medical Center Koseikan, Saga, Japan; <sup>9</sup>Kyoto Prefectural University of Medicine, Pediatrics surgery, Kyoto, Japan</italic></p><p><bold>Background/Objectives</bold>: We aim to reduce the incidence of treatment complications and improve the outcomes for neuroblastoma in intermediate‐risk patients by using low‐dose preoperative chemotherapy without myeloablative chemotherapy, and to make the treatment decision at the time of the operation based on the image‐defined risk factors (IDRFs).</p><p><bold>Design/Methods</bold>: Prospective single‐arm studies (JN‐I‐10) were conducted. Patients with INSS stage 3 without <italic>MYCN</italic> amplification, including children of >12 months of age with favorable histology and 12‐18 months of age with unfavorable histology, were treated with low‐dose induction regimen B (vincristine/cyclophosphamide/pirarubicin) or C (vincristine/cyclophosphamide/carboplatin). If no IDRFs were present, the patient underwent surgery. The resectability of the tumors was judged based on the IDRF every 3 courses. When the response rate was insufficient, the treatment was changed to up to 9 courses of regimen D (vincristine/cyclophosphamide/pirarubicin/cisplatin).Patients with stage 4 without <italic>MYCN</italic> amplification, including children <12 months and 12‐18 months of age with favorable histology and a DNA index of >1, were treated with 5 to 6 courses of regimen D. When possible, surgical resection was performed based on the IDRF after 3 courses. Target sample size was 73.</p><p><bold>Results</bold>: At the planned interim analysis, 38 eligible patients were enrolled in this trial (stage 3, n=9; stage 4, n=29). The median age was 8 months (range, 0–45 months). The 3‐year progression‐free survival rates of the whole study population, the stage 3 patients and the stage 4 patients were 84.4% (99.99%CI: 35.5‐97.3), 88.9% (99.99%CI: 0.2‐99.8), and 82.5% (99.99%CI: 22.6‐97.5), respectively. Ten percent of the whole study population showed ileus, while 20% showed pleural effusion and ascites as early complications after surgery; however there were no long‐term complications of surgery. The trial was decided to continue.</p><p><bold>Conclusions</bold>: Our treatment strategy did not increase the incidence of long‐term complications. This trial was decided to continue.</p></sec><sec id="pbc26772-sec-5320"><label>P-139</label><title>GSTP1 Gene Expression and A313G Polymorphism Can Affect Neuroblastoma Outcome</title><p><underline underline-style="single">M. Inomistova</underline><sup>1</sup>, N. Khranovska<sup>1</sup>, O. Skachkova<sup>1</sup>, G. Klymniuk<sup>2</sup>, S. Pavlyk<sup>2</sup></p><p><italic><sup>1</sup>National Cancer Institute, Laboratory of Experimental Oncology, Kiev, Ukraine; <sup>2</sup>National Cancer Institute, Department of Pediatric Oncology, Kiev, Ukraine</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma ‐ malignant paediatric tumour of sympathetic nervous system and is often accompanied with <italic>MYCN</italic> amplification (MNA). Study of glutathione‐S‐transferase P1 (GSTP1) which affects the chemotherapy efficiency can help to understand the mechanism of neuroblastoma progression.</p><p><bold>Design/Methods</bold>: Case group comprised of 144 children with neuroblastoma and control group of 158 healthy donors. A313G <italic>GSTP1</italic> polymorphism was detected with allele‐specific PCR in DNA from peripheral blood of patients and healthy donors. <italic>GSTP1</italic> expression level (EL) was analysed with qRT‐PCR in tumour samples using TaqMan primers and probes.</p><p><bold>Results</bold>: Polymorphism distribution in patients with neuroblastoma (A313A – 51.4%, A313G – 38.9%, G313G – 9.7%) complied with Hardy‐Weinberg equilibrium (P=0.46). G313G genotype was observed in patients with advanced stages (8.8% ‐ III and 12.2% ‐ IV stages) and earlier occurrence age of neuroblastoma (median ‐ 18 months, A313A – 28 months, A313G – 34 months). Most patients with MNA had A313A genotype (63.1%) while most G313G patients had non‐MNA neuroblastoma (77%).</p><p>The highest <italic>GSTP1</italic> EL was observed in tumours with unfavourable clinical features (early occurrence age; advanced stages; recurrent and metastatic foci). Lower EL was observed in MNA tumour samples and in patients with A313A genotype.</p><p>Analysing 3‐year overall survival (OS) we established that patients with G313G genotype had significantly lower OS (11.4% vs 45.8% ‐ A313A, P=0.03; vs 37% ‐ A313G, P=0.04). With ROC‐analysis we assessed the optimal criterions for patients distribution according to <italic>GSTP1</italic> EL (p=0.04, AUC: 0.64) and analysed OS according to <italic>GSTP1</italic> polymorphism and EL. OS was significantly higher in patients with A313G and low <italic>GSTP1</italic> EL comparing to other groups (P<0.05).</p><p><bold>Conclusions</bold>: <italic>GSTP1</italic> G313G genotype was associated with unfavourable prognosis in neuroblastoma, while patients with A313G and low <italic>GSTP1</italic> EL had higher OS. Analysis of <italic>GSTP1</italic> polymorphism and expression along with other biomarkers is an important step to improve neuroblastoma risk stratification.</p></sec><sec id="pbc26772-sec-5330"><label>P-140</label><title>Immunohistological Characterization of Intra‐Tumor Hypoxia Biomarkers in Neuroblastomas</title><p><underline underline-style="single">S. Jannier</underline><sup>1</sup>, M. Luc<sup>2</sup>, L. Benoit<sup>2</sup>, L. Marie<sup>3</sup>, D. Aurélie<sup>3</sup>, E.W. Natacha<sup>1</sup></p><p><italic><sup>1</sup>Hopitaux Universitaires de Strasbourg, Oncology, Strasbourg, France; <sup>2</sup>Hopitaux Universitaires de Strasbourg, Pathology, Strasbourg, France; <sup>3</sup>University of Strasbourg, EA3430, Strasbourg, France</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is the second most frequent pediatric solid tumor. In high risk neuroblastoma, Nmyc amplified and/or metastatic patients’ overall survival is only 40% and there is no hope of cure in case of relapse. Intra‐tumor hypoxia appears to be correlated with an aggressive phenotype and resistance to chemotherapy as recently described in neuroblastoma, but no specific study described precisely the Pi3K/AKT/mTor/HIF‐1a pathway involvement. The pathway activation seems to be linked to poor prognostic tumors. Recently, <italic>ATRX</italic> mutations has also been described in association with high‐risk neuroblastoma and possibly linked to their hypoxia.</p><p><bold>Design/Methods</bold>: A retrospective study was designed to characterize to target by immunohistochemistry (IHC) Pi3K, AKT, mTor and ATRX in neuroblastomas in 26 patients of Strasbourg's center, who have signed with their parents an informed consent.</p><p><bold>Results</bold>: Six biomarkers were analyzed by IHC: HIF1‐a, HIF2‐a, pAKT, pERK, pS6RP and ATRX. All patients were negative for HIF1‐a. HIF2‐a was overexpressed in 16 patients out of the 26, which among those 10 patients were high risk patients. Among the 4 pAKT positive patients, 3 out of 4 were also HIF2‐a positive and 2 out of 4 had a pERK, pS6RP and HIF2‐a co‐expression. Positivity for pERK (9 patients) and pS6RP (9 patients) were mainly localized in vessels and only 5 patients had concomitant pERK and pS6RP positive stainings. Loss of ATRX was observed in 8 patients without any correlation with the other markers.</p><p><bold>Conclusions</bold>: This preliminary study shows the implication of hypoxia signaling pathway, and mainly HIF2‐a in neuroblastomas.</p></sec><sec id="pbc26772-sec-5340"><label>P-141</label><title>Treatment Of Intermediate‐Risk Neuroblastoma: Experience of Russian Federal Center</title><p><underline underline-style="single">D. Kachanov</underline><sup>1</sup>, T. Shamanskaya<sup>1</sup>, E. Andreev<sup>2</sup>, D. Shevtsov<sup>1</sup>, N. Merkulov<sup>2</sup>, A. Kazakova<sup>3</sup>, S. Talypov<sup>2</sup>, G. Tereschenko<sup>4</sup>, V. Roschin<sup>5</sup>, D. Konovalov<sup>5</sup>, A. Nechesnyuk<sup>6</sup>, Y. Olshanskaya<sup>3</sup>, E. Feoktistova<sup>4</sup>, Y. Likar<sup>7</sup>, S. Varfolomeeva<sup>1</sup></p><p><italic><sup>1</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Clinical Oncology, Moscow, Russia; <sup>2</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Surgery, Moscow, Russia; <sup>3</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Cytogenetics, Moscow, Russia; <sup>4</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Radiology, Moscow, Russia; <sup>5</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Pathology, Moscow, Russia; <sup>6</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Radiation Oncology, Moscow, Russia; <sup>7</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Nuclear Medicine, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The aim of the study was to analyze the clinical characteristics and results of therapy of patients with intermediate‐risk neuroblastoma treated in Russian federal center.</p><p><bold>Design/Methods</bold>: 270 patients with neuroblastoma were treated for the period 01.2012‐06.2015 (42 months). The diagnosis has been established on the basis of the international criteria. FISH was done to assess the status of 1p and 11q. Patients were stratified and treated according to the German NB2004 protocol. 19 (7.1%) patients were stratified to the intermediate‐risk group. Therapy consists of 6 cycles of multiagent chemotherapy, surgery, radiation therapy to the MIBG‐avid residual primary tumor after induction chemotherapy, 4 cycles of maintenance therapy and 9 cycles of 13‐cis‐retinoic acid.</p><p><bold>Results</bold>: Male:female ratio was ‐ 0.58:1. The median age was 10.4 months (range 1.6‐91.5). The most common site of primary tumor was retroperitoneum ‐ 12 (63.2%). Stage distribution: stage 4 ‐ 12 (63.2%) cases, stage 3 ‐ 6 (31.5%), stage 2 ‐ 1 (5.3%). 3 (15.8%) had segmental chromosomal aberrations. 17 (89.4%) patients received per protocol therapy, 2 were treated with protocol modification because of treatment‐related complications. Surgery was done in 18 patients, macroscopic residual tumor was observed in 16 (88.8%). Radiation therapy was done in 3 (15.7%). After induction therapy 12 (63.2 %) patients achieved complete and very good partial response. There was no difference in response rate between stage 4 and stage 2/3 (<italic>р</italic> = 0.65). Median follow‐up was 37.0 months (range – 20.4–57.3). Progression/relapse was observed in 4 (21.0 %) cases. 4‐year OS was 100%. 4‐year EFS of the whole cohort was 78.9 ± 9.3 %. EFS in patients treated without protocol violations was 93.7 ± 6.0 %.</p><p><bold>Conclusions</bold>: Intensification of therapy in patients with intermediate‐risk neuroblastoma, compared with patients in the observation group, allows achieving satisfactory results given that therapy was provided without violations.</p></sec><sec id="pbc26772-sec-5350"><label>P-142</label><title>CNS Relapses of High‐Risk Neuroblastoma: Analysis of Risk Factors and Clinical Outcomes</title><p><underline underline-style="single">T. Shamanskaya</underline><sup>1</sup>, D. Kachanov<sup>1</sup>, S. Ozerov<sup>2</sup>, G. Tereschenko<sup>3</sup>, Y. Likar<sup>4</sup>, V. Roschin<sup>5</sup>, Y. Olshanskaya<sup>6</sup>, A. Kazakova<sup>6</sup>, A. Nechesnyuk<sup>7</sup>, S. Varfolomeeva<sup>1</sup></p><p><italic><sup>1</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Clinical Oncology, Moscow, Russia; <sup>2</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Surgery, Moscow, Russia; <sup>3</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Radiology, Moscow, Russia; <sup>4</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Nuclear Medicine, Moscow, Russia; <sup>5</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Pathology, Moscow, Russia; <sup>6</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Cytogenetics, Moscow, Russia; <sup>7</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Radiation Oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: CNS relapses in patients with high‐risk neuroblastoma are an extremely unfavorable clinical event. The aim of the study was to analyze the frequency of occurrence and the factors predisposing to the development of the CNS involvement in patients with high‐risk neuroblastoma at the time of the first relapse.</p><p><bold>Design/Methods</bold>: Patients with high‐risk neuroblastoma who received treatment for the period 01.2012 ‐ 12.2015 were included in the analyses. Patients were stratified to risk groups and treated according to German NB2004 protocol. High‐dose preparative regimens included melphalan/etoposide/carboplatin (MEC) (till June 2013) and treosulfan/melphalan (TreoMel) (since July 2013).</p><p><bold>Results</bold>: 111 patients were analyzed. 58/111 (52.3%) had progression/relapse, CNS involvement was observed in 10/58 (17.2%). Isolated CNS involvement was noted in 7/10 (70%). Median age at the time of the neuroblastoma diagnosis in patients with CNS involvement was 27.3 months (range 1,8‐43,5). Male: female ratio was 1.5:1. The primary tumor located in the abdomen in 9/10 cases, unknown primary in 1/10. All 10 patients had stage 4 disease. <italic>MYCN</italic> amplification was detected in 8/10 (80%). Median time from diagnosis till progression/relapse was 15.2 months (range 5.9‐20.0). Comparison between two groups of relapsed patients (CNS involvement/ lack of CNS involvement) by sex, age, site of the primary tumor, <italic>MYCN</italic> gene status, skull metastases, bone marrow involvement at the onset of the disease, the number of metastatic compartments, response to induction therapy before auto‐HSCT, type of preparative regimen (CEM vs Treo/Mel) showed no statistically significant difference. 2‐year overall survival after the development of CNS‐relapse in the study group was 13.1 ± 12.1%.</p><p><bold>Conclusions</bold>: CNS involvement at the time of relapse is a frequent event in high‐risk neuroblastoma. The introduction of CNS MRI into the standard work‐up at the time of relapse/progression will allow timely detection of metastases to optimize the therapeutic strategy.</p></sec><sec id="pbc26772-sec-5360"><label>P-143</label><title>Complete Clinical Response in High‐Risk Neuroblastoma After ALK‐Inhibitor Mono‐Therapy Specifically Targeting the Novel Activating I1171T ALK Mutation</title><p><underline underline-style="single">P. Kogner</underline><sup>1</sup>, D. Treis<sup>1</sup>, J. Siaw<sup>2</sup>, S. Fransson<sup>3</sup>, J. Guan<sup>2</sup>, P. Svenberg<sup>1</sup>, M. Hansson<sup>4</sup>, S. Wessman<sup>5</sup>, L. Gordon<sup>6</sup>, J. Stenman<sup>7</sup>, P.J. Svensson<sup>7</sup>, J.I. Johnsen<sup>1</sup>, T. Martinsson<sup>3</sup>, R.H. Palmer<sup>2</sup>, B. Hallberg<sup>2</sup></p><p><italic><sup>1</sup>Karolinska Institutet, Childhood Cancer Research Unit, Stockholm, Sweden; <sup>2</sup>Gothenburg University, Medical Biochemistry and Cell Biology, Göteborg, Sweden; <sup>3</sup>Gothenburg University, Clinical Genetics, Göteborg, Sweden; <sup>4</sup>Gothenburg University, Pathology, Göteborg, Sweden; <sup>5</sup>Karolinska Institutet, Oncology Pathology, Stockholm, Sweden; <sup>6</sup>Karolinska Institutet, Pediatric Radiology, Stockholm, Sweden; <sup>7</sup>Karolinska Institutet, Pediatric Surgery, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Personalized medicine and implementation of successful targeted therapies requires understanding of complex molecular mechanisms. Activating ALK‐aberrations are important genetic factors in neuroblastoma development and aggressiveness, and have been suggested for novel targeted therapies. Embryonal childhood tumors with underlying Fanconi anemia are not available for conventional chemotherapy and have a very poor outcome.</p><p><bold>Design/Methods</bold>: A 15 month‐old patient with 11q‐deleted HR‐neuroblastoma with bonemarrow, multiple bone and intracranial metastases, was started on SIOPEN COJEC‐induction with severe long‐lasting multi‐organ toxicity already after second chemotherapy‐course found to be due to underlying Fanconi anemia confirmed with chromosome‐breakage analysis and germline FANCA‐mutations (c.2728C>T/c.4161‐2A>C). Subsequently tumor sequencing revealed a novel somatic neuroblastoma ALK(c.3215T>C; I1171T) mutation. In search for therapeutic opportunities the biological nature of this ALK‐mutation was characterized preclinically.</p><p><bold>Results</bold>: We show here that this novel ALK tyrosine kinase domain mutation of I1171 to threonine generates a potent gain‐of‐function mutant, as observed in cell culture model systems. ALK<sup>I1171T</sup>‐expressing PC12 cells showed ligand‐independent ALK activation, neurite outgrowth and downstream signaling activation. Further, ALK<sup>I1171T</sup> mediated foci formation in NIH3T3 transformation analysis. Finally, second‐generation ALK‐inhibitor ceritinib/LDK378 showed 14‐fold better ability to abrogate ALK<sup>I1171T</sup> compared with crizotinib.</p><p>When life‐threatening platinum‐induced toxicity with multiorgan complications had been handled/subsided targeted treatment with ceritinib/LDK378 (450mg/m<sup>2</sup>‐540mg/m<sup>2</sup>) was started as compassionate use. Elevated urinary catecholamine‐markers were normalized after the first 4‐week‐treatment cycle. Hemoglobin normalized and platelets improved to stable levels (>100). Metastatic disease gradually resolved and MRI showed 1/3‐reduction of the primary tumor that was then radically removed after 6 months’ treatment. Complete radiological work‐up (MRI/CT‐scan/mIBG), urinary catecholamines and bonemarrow investigations confirmed complete response after 21 months of ALK‐inhibitor treatment without significant side‐effects (only mild GI‐symptoms were noted).</p><p><bold>Conclusions</bold>: Here we show that the ALK(I1171T)‐mutation is activating and promotes neuroblastoma aggressiveness. Monotherapy with ALK‐inhibitor ceritinib induced complete response in a child with metastatic high‐risk neuroblastoma unable to receive conventional treatment.</p></sec><sec id="pbc26772-sec-5370"><label>P-144</label><title>Exome Sequencing to Identify Novel Neuroblastoma Predisposition Genes</title><p>C. Derpoorter<sup>1</sup>, K. Vandepoele<sup>2</sup>, A. Diez‐Fraile<sup>1</sup>, K. Vandemeulebroecke<sup>1</sup>, N. Van Roy<sup>3</sup>, B. De Wilde<sup>1</sup>, T. Lammens<sup>1</sup>, <underline underline-style="single">G. Laureys</underline><sup>1</sup></p><p><italic><sup>1</sup>Ghent University Hospital, Department of Pediatric Hematology‐Oncology and Stem Cell Transplantation, Ghent, Belgium; <sup>2</sup>Ghent University Hospital, Department of Laboratory Medicine, Ghent, Belgium; <sup>3</sup>Ghent university Hospital, Center for Medical Genetics Ghent CMGG, Ghent, Belgium</italic></p><p><bold>Background/Objectives</bold>: Genetic susceptibility to cancer has been the subject of considerable interest in unraveling the etiology and natural history of cancer and plays an essential role in understanding the molecular biology of cancer. Familial clustering of childhood cancers is among the strongest suggestive situation of a genetic susceptibility.</p><p><bold>Design/Methods</bold>: Exome sequencing was used to identify novel cancer predisposition genes in a family with a boy affected by neuroblastoma and his second cousin by a ganglioneuroma. Interestingly, we previously identified a <italic>de novo</italic> constitutional translocation t(1;17)(p36.2;q11.2) in the boy, which was absent in the affected second cousin (Laureys et al., 1995; Laureys et al, 1990).</p><p><bold>Results</bold>: Predisposing variants were put forward as candidates through selection of non‐synonymous, rare/novel variants, shared by the affected second cousins and mothers (being first cousins) and not found in the spousal controls. Amongst others, we identified a deleterious mutation in <italic>CLEC12B</italic> (c.790A>G; p.E264K) located at the C‐terminal end of the lectin C‐type domain in a highly conserved region and potentially interferes with ligand interaction or homodimerization. Interestingly, Hoffmanns and colleagues, have shown that CLEC12B (12p13.2) binds PTPN11 and PTPN6. Interfering with this interaction protects against natural killer cell‐mediated cytotoxicity, indicating that mutations within <italic>CLEC12B</italic> may affect immune surveillance. Both PTNP11 and PTNP6 are well‐known cancer predisposition genes (Hoffmann et al., 2007; Seishima et al., 2007; Jongmans et al., 2011). <italic>In silico</italic> analysis revealed that somatic mutation frequencies for <italic>CLEC12B</italic> vary from 2.2% in medulloblastoma to 0.4% in head and neck carcinoma.</p><p><bold>Conclusions</bold>: This and ongoing work highlights the value of using index families with multiple children affected by cancer, as a valuable source to identify novel cancer predisposition genes.</p><p>*TL and GL are shared senior authors</p></sec><sec id="pbc26772-sec-5380"><label>P-145</label><title>External Beam Radiotherapy is not Associated with the Incidence, Severity or Duration of Sinusoidal Obstruction Syndrome</title><p><underline underline-style="single">J. Lucas Jr.</underline><sup>1</sup>, S. Braunstein<sup>2</sup>, V. Tolbert<sup>3</sup>, A. Sunkara<sup>4</sup>, G. Kang<sup>4</sup>, R. Goldsby<sup>3</sup>, M. Krasin<sup>1</sup>, S. Federico<sup>5</sup>, C. Dvorak<sup>3</sup>, V. Santana<sup>5</sup>, W. Furman<sup>5</sup>, K. Matthay<sup>2</sup>, L. Cunningham<sup>6</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Radiation Oncology, Memphis, USA; <sup>2</sup>University of California San Francisco, Radiation Oncology, San Francisco, USA; <sup>3</sup>University of California San Francisco, Pediatrics, San Francisco, USA; <sup>4</sup>St Jude Children's Research Hospital, Biostatistics, Memphis, USA; <sup>5</sup>St Jude Children's Research Hospital, Oncology, Memphis, USA; <sup>6</sup>St Jude Children's Research Hospital, Bone Marrow Transplantation and Cellular Therapy, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Sinusoidal Obstruction Syndrome (SOS) is a morbid complication of High Risk Neuroblastoma (HRNB) therapy. We evaluated associations between external beam radiotherapy (EBRT), I131‐MIBG, chemotherapy, and clinical factors on SOS incidence, duration and severity in HRNB patients.</p><p><bold>Design/Methods</bold>: 98 newly diagnosed HRNB patients treated from 1997 to 2016 at multiple institutions with induction and consolidation chemotherapy, autologous stem cell transplant, radiotherapy and maintenance therapy[FS1] were retrospectively reviewed. We examined patient, laboratory, and treatment characteristics up to 100 days post‐transplant. SOS prophylaxis, treatment, and complications (intubation, multi‐organ failure, etc.) were documented. Generalized linear regression was used to assess the associations of covariates with the incidence, duration and severity of SOS.</p><p><bold>Results</bold>: Sixteen patients were diagnosed with SOS (median time from transplant to SOS, 22 days [range, 9‐130]). The median duration of SOS was 13 days (range, 3‐63). All but 2 cases of SOS preceded EBRT. The median time to EBRT from transplant in patients with and without SOS was 8.6 and 5.3 weeks respectively (p<0.001). Earlier time to EBRT, prescription dose (Gy), and liver dose (Dmean, D25, D50, D75) did not impact the incidence, duration, recurrence or severity of SOS. Induction (ANBL0532 vs. other, p=0.005), and consolidation [(MEC vs. BuMel, <italic>β</italic>=‐1.6263, p=0.005), (MEC vs. MEC‐PT, <italic>β</italic>=‐3.0, <italic>P</italic><.001)] chemotherapy impacted the duration of SOS. SOS‐associated death occurred in one patient who received I131‐MIBG during consolidation. SOS incidence and complications were not different across I131‐MIBG (N=8) and non‐I131‐MIBG (N=90) treated patients (p=0.6). However, 2/2 I131‐MIBG treated patients who developed SOS required ICU support, compared to 4/14 (29%) non‐MIBG treated patients (p=0.12).</p><p><bold>Conclusions</bold>: In this modern‐treatment cohort, EBRT dose, volume and timing after transplant did not impact the incidence, severity, recurrence or duration of SOS. Induction and transplant conditioning impacted the duration and severity of SOS.</p></sec><sec id="pbc26772-sec-5390"><label>P-146</label><title>Studies of the Mechanism in Epithelial‐Mesenchymal Transition Induced by TGF‐Β1 in Neuroblastoma Cells</title><p>J. Shao<sup>1</sup>, <underline underline-style="single">Z. Lu</underline><sup>2</sup></p><p><italic><sup>1</sup>Shanghai Children's Hospital, Hematology/Oncology, Shanghai, China; <sup>2</sup>Shanghai Children's Hospital, Surgery, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is the second most common extracranial malignant solid tumor that occurs in childhood. Metastasis is one of the major causes of death in neuroblastoma patients. The epithelial‐mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. This study investigated the mechanism in EMT induced by transforming growth factor (TGF)‐β1 in SK‐N‐SH human neuroblastoma cells.</p><p><bold>Design/Methods</bold>: The present study focused on the regulatory effects of TGF‐β1 on the EMT in human neuroblastoma SK‐N‐SH cells and the correlation with transcription factor Gli using quantitative RT‐PCR, western blot analysis, immunocytochemistry, cell transfection, etc.</p><p><bold>Results</bold>: We identified that the mRNA and protein expression levels of E‐cadherin were significantly decreased while α‐SMA were significantly increased after SK‐N‐SH cells were treated with different concentration of TGF‐β1. A scratch test and transwell migration assay revealed that cell migration was increased significantly with increasingly higher concentrations of TGF‐β1. Which means TGF‐β1 can induce the EMT in SK‐N‐SH cells to increase SK‐N‐SH cell migration. Interference the expression of Smad2/3 did not affect the expression of the key molecules in the EMT. Further investigation found the expression of transcription factor Gli increased significantly in EMT induced by TGF‐β1 in SK‐N‐SH cells. Interfering with the expression of Gli1/Gli2 can inhibit the EMT induced by TGF‐β1 in SK‐N‐SH cells. GANT61, which target to inhibitors transcription factor Gli1 and Gli2, can reduce the proliferation of cells, promote cell apoptosis.</p><p><bold>Conclusions</bold>: The authors conclude that TGF‐β1 can induce the EMT in SK‐N‐SH cells to increase SK‐N‐SH cell migration. EMT induced by TGF‐β1 in SK‐N‐SH cells may does not depend on the Smad signaling pathway. Transcription factor Gli participates in the EMT induced by TGF‐β1 through Smad independent signaling pathways.</p></sec><sec id="pbc26772-sec-5400"><label>P-147</label><title>Synergistic Effect of Curcumin and Nanoceria in the Treatment of Childhood Neuroblastoma</title><p><underline underline-style="single">J. Mazar</underline><sup>1</sup>, A. Rosado<sup>1</sup>, T. Westmoreland<sup>1</sup>, C. Neal<sup>2</sup>, I. Kalashnikova<sup>2</sup>, S. Das<sup>3</sup>, S. Seal<sup>2</sup></p><p><italic><sup>1</sup>Nemours Children's Hospital, Biomedical Research, Orlando, USA; <sup>2</sup>University of Central Florida, Materials Science and Engineering‐ Advanced Materials Processing Center, Orlando, USA; <sup>3</sup>University of Central Florida, Nanoscience Technology Center, Orlando, USA</italic></p><p><bold>Background/Objectives</bold>: <italic>MYCN</italic>‐amplification is associated with poor prognosis in human neuroblastoma, reflective of a low overall survival rate in children with this gene amplification. As a result, we are investigating novel molecular formulations of nanoceria and dextran‐nanoceria with curcumin, each demonstrated to have anti‐cancer properties, synthesized and applied as a treatment for neuroblastoma. Anti‐cancer activities of these formulations were explored in neuroblastoma cells that were both <italic>MYCN‐</italic>amplified and <italic>MYCN‐</italic>non‐amplified.</p><p><bold>Design/Methods</bold>: To test these formulations, we utilized the <italic>MYCN</italic>‐amplified neuroblastoma cell lines IMR‐32 and SMS‐KAN, as well as the non‐amplified cell lines SK‐N‐AS and LA‐N‐6. The effects induced in neuroblastoma cells by these nano‐formulations with curcumin were examined by MTS, Caspase 3/7, ROS, and TUNEL assays, as well as by qRT‐PCR and Western blot analysis for changes in gene expression. HUVEC cells served as control cells to evidence the cyto‐protective effects of ceria nanoparticles.</p><p><bold>Results</bold>: Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells while producing no or minor toxicity towards healthy cells. Death of neuroblastoma cells was confirmed to be due to apoptosis induced via BCL‐2/BAX ratio disruption and reactive oxygen species accumulation. Additionally, expression of HIF‐1α was analyzed and shown to be up‐regulated in samples treated with ceria due to ceria's oxygen buffering capacity.</p><p><bold>Conclusions</bold>: Treatment of human neuroblastoma cells, both <italic>MYCN‐</italic>amplified and <italic>MYCN‐</italic>non‐amplified, with ceria nanoparticles successfully induced cell death. The additional coating of the nanoceria with dextran appeared to further enhance this phenotype. An analysis of the cause of cell death suggested that apoptosis was induced due to the stabilization of HIF‐1α, indicating induction of hypoxic conditions and significant accumulation of reactive oxygen species. Overall, ceria treatments showed a more pronounced effect in <italic>MYCN‐</italic>amplified cells, which are traditionally more resistant to drug therapies.</p></sec><sec id="pbc26772-sec-5410"><label>P-148</label><title>Stage IV Neuroblastoma Treatment, Eleven Years Experience Hospital De Ninos Ricardo Gutierrez Buenos Aires Argentina</title><p><underline underline-style="single">A.</underline><underline underline-style="single">Oller</underline><sup>1</sup>, M.F. Gutierrez<sup>1</sup>, M. Urbieta<sup>1</sup>, G. Puppa<sup>1</sup>, S. Colli<sup>2</sup>, M. Garcia Lombardi<sup>1</sup>, S.M. Acosta<sup>1</sup>, R. Ramirez<sup>1</sup></p><p><italic><sup>1</sup>Hospital de Niños Ricardo Gutierrez, Oncology Unit, Capital Federal, Argentina; <sup>2</sup>Hospital de Niños Ricardo Gutierrez, Pathology, Capital Federal, Argentina</italic></p><p><bold>Background/Objectives</bold>: To describe clinic, biologic and histological features and overall survival(OS) of patients(p) with stage IV (SIV) NBL treated at Hospital de Niños Ricardo Gutiérrez (HNRG) Oncology Unit, Buenos Aires Argentina.</p><p><bold>Design/Methods</bold>: A retrospective and descriptive analysis of medical records from p with SIV NBL admitted between April 1<sup>st</sup> 2004 to December 31<sup>st</sup> 2015. Variables evaluated were sex, age, primary site, tumor size, histology, N‐myc status, urinary catecholamines status, treatment, and overall survival. After diagnosis p received chemotherapy induction with cyclophosphamide, vincristine, doxorubicin, cisplatin, VP‐16. Local resection was performed follow by high doses chemotherapy with autologous stem cell transplantation; primary tumor‐bed radiotherapy and retinoic acid as maintenance. Kaplan‐Meier method analysis was used to determine overall survival(OS)</p><p><bold>Results</bold>: Sixty‐six p were diagnosed with NBL, 29(44%) were stage IV NBL. Average age at presentation was 14.4 month, ratio men:women 3:1. Primary site was adrenal gland (86%), tumor size >0.10m in 75.8%. Most common histology was poorly differentiated NBL (24%), N‐myc status by fish was performed in twenty tumor samples, amplified in 50%. Thirteen (44,8%) p completed treatment, 6/12p (46.1%) are alive. Sixteen p did not complete treatment and die due tumoral progression during induction (55.1%) or to infectious complications (31.2%), which most take place before 2008. Relapsed get 51%, from which bone marrow represented 20%.</p><p><bold>Conclusions</bold>: Results obtained indicate that 50% of studied patients with stage IV NBT presented N‐myc amplification. Global OS is 17.3% For patients who reach complete treatment OS is 46.1%, comparable with results of international cooperative groups. In addition, an improvement in survival is observed associated with an amelioration in healthcare in the last years.</p></sec><sec id="pbc26772-sec-5420"><label>P-149</label><title>Exploring the Genomic Profiles of Neuroblastomas by Comparative Analysis of Exome Sequencing Versus aCGH Data</title><p><underline underline-style="single">W. Przybyla</underline><sup>1</sup>, G. Trøen<sup>2</sup>, K. Beiske<sup>2,3</sup>, L.O. Baumbusch<sup>1</sup></p><p><italic><sup>1</sup>Oslo University Hospital Rikshospitalet, Department of Pediatric Research‐ Division of Pediatric and Adolescent Medicine, Oslo, Norway; <sup>2</sup>Oslo University Hospital Radiumhospitalet, Department of Pathology, Oslo, Norway; <sup>3</sup>University of Oslo, Medical Faculty‐ Institute of Clinical Medicine, Oslo, Norway</italic></p><p><bold>Background/Objectives</bold>: Next generation sequencing will contribute to personalized pediatric oncology in the near future, in particular for biologically and clinically heterogeneous diseases requiring multi‐modal therapeutic approaches like neuroblastoma (NB) ‐ one of the major challenges in pediatric oncology. In NB specific copy number variations and rearrangements of single genes have been reported including amplification of MYCN (20%) and mutations of the ALK gene. We hypothesize that comparative genomic analysis of mutations and copy number variations will provide novel information about genes and signalling pathways relevant for the heterogeneity and relapse in high‐risk NB.</p><p><bold>Design/Methods</bold>: Samples of tumor and normal DNA from high‐risk NB patients (n=20) are available from an existing diagnostic biobank. Clinical and pathological information like age and histopathology are known from routine diagnostics. Additionally, FISH analyses have determined MYCN amplification status and possible chromosomal losses of 1p and 11q, and gain of 17q. Samples of the primary tumors were analyzed by whole exome sequencing using the Illumina HiSeq2500 platform with a mean coverage of 300. Additionally, the same DNA samples were investigated by array comparative genomic hybridization (aCGH) applying the Affymetrix SNP platform (CytoScan HD array).</p><p><bold>Results</bold>: Preliminary results reveal a high concordance between aCGH profiles and copy number information provided by sequencing. Detailed studies were performed to investigate specific genomic biomarkers. Further, we studied cancer mutation hotspots or predicted driver mutations and mutational signatures in these samples.</p><p><bold>Conclusions</bold>: Our project represents the first exome sequencing approach on NB in Norway. We have compared array and sequencing data to the expression of relevant genes and will enlarge our cohort with samples during different time points of treatment. We expect that these data will reveal novel insights into the genomics of NB and finally pave the way towards genetic‐clinical cancer platforms for actionable gene targets.</p></sec><sec id="pbc26772-sec-5430"><label>P-150</label><title>Cytotoxic Activity of Difluoromethylornithine Compared with Fenretinide in Neuroblastoma Cell Lines</title><p><underline underline-style="single">M. Makena</underline><sup>1</sup>, H. Cho<sup>1</sup>, T. Nguyen<sup>1</sup>, B. Koneru<sup>1</sup>, D. Verlekar<sup>1</sup>, A. Hindle<sup>1</sup>, B. Rodriguez<sup>1</sup>, M. Kang<sup>1</sup>, C.P. Reynolds<sup>1</sup></p><p><italic><sup>1</sup>Texas Tech University Health Sciences Center, Cancer Center, Lubbock, USA</italic></p><p><bold>Background/Objectives</bold>: Maintenance therapy with 13‐cis‐retinoic acid and immunotherapy (given after completion of intensive cytotoxic therapy) improves outcome for high‐risk neuroblastoma patients. The synthetic retinoid fenretinide (4‐HPR) achieved multiple complete responses in relapse/refractory neuroblastoma in early‐phase clinical trials, has low systemic toxicity, and has been considered for maintenance therapy clinical trials. Difluoromethylornithine (DFMO, an irreversible inhibitor of ornithine decarboxylase with minimal single agent clinical response data) is being used for maintenance therapy of neuroblastoma. We evaluated the cytotoxic activity of DFMO and fenretinide in neuroblastoma cell lines.</p><p><bold>Design/Methods</bold>: We tested sixteen neuroblastoma cell lines in bone marrow level hypoxia (5% O<sub>2</sub>) using the DIMSCAN cytotoxicity assay. Polyamines were measured by HPLC‐mass spectrometry and apoptosis by TUNEL flow cytometry.</p><p><bold>Results</bold>: At clinically achievable levels (100 μM), DFMO significantly decreased (P < 0.05) polyamine putrescine (measured by HPLC‐mass spectrometry) and achieved modest cytotoxicity (< 1 log (90% cytotoxicity). Prolonged exposures (7 days) or culture in 2% and 20% O<sub>2</sub> did not enhance DFMO cytotoxicity. At clinically achievable levels (30 μM) fenretinide induced multi‐log cell kills (> 3 logs (99.9% cytotoxicity) in all neuroblastoma cell lines tested. Even at lower concentrations (10 μM) fenretinide induced > 1 log cytotoxicity in fourteen cell lines tested. DFMO did not show a significant increase (P > 0.05) in apoptosis (TUNEL assay). Apoptosis by fenretinide was significantly higher (P < 0.001) compared to DFMO or controls.</p><p><bold>Conclusions</bold>: DFMO as a single agent has minimal cytotoxic activity for neuroblastoma.</p></sec><sec id="pbc26772-sec-5440"><label>P-151</label><title>Evolving Biopsy Techniques for Neuroblastoma in Children</title><p><underline underline-style="single">E. Rosenfeld</underline><sup>1</sup>, G. Campagna<sup>1</sup>, Y. Yu<sup>1</sup>, S. Vasudevan<sup>1</sup>, J. Nuchtern<sup>1</sup>, E. Kim<sup>1</sup>, S. Commander<sup>1</sup>, B. Naik‐Mathuria<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Surgery, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: In order to obtain adequate tissue for diagnosis and tissue banking of neuroblastoma, surgical wedge biopsy is commonly performed. In the past decade, our experience with percutaneous needle core biopsy has evolved. The purpose of this study was to compare the adequacy and safety of biopsy techniques.</p><p><bold>Design/Methods</bold>: Following IRB‐approval, we retrospectively reviewed patients who underwent biopsy for intermediate or high‐risk neuroblastoma at our institution between 2011‐2016 (recent cohort). Procedure details and outcomes were collected. Statistical analysis was performed using Wilcoxon rank tests with a p‐value<0.05 considered significant. Data from the recent cohort was compared to previously published data from 2002‐2010 (historic cohort).</p><p><bold>Results</bold>: Since 2011, percutaneous ultrasound‐guided needle core biopsy has been more commonly utilized (47% [16/34] recent cohort vs 34% [11/32] historic). The majority (94%) of percutaneous biopsies were performed by a surgeon with intravenous access port placement under the same anesthetic. The number of needle core samples obtained increased from median 7 (historic cohort) to 25 (recent cohort). Of the surgical cases, 61% were laparoscopic (previously all were open), and one patient had laparoscopic‐assisted percutaneous needle core biopsy. Biopsy adequacy in the recent cohort was similar in percutaneous and surgical specimens (94% percutaneous vs 89% surgical; p=1), with improved adequacy of percutaneous specimens compared to historic cohort (71% percutaneous vs 100% surgical). Transfusion requirements (13% percutaneous vs 28% surgical, p=) and other complications (0% percutaneous vs 17% surgical, p=) were higher following surgical biopsy. Operative time, hospital length of stay, and time to chemotherapy initiation were similar. Larger tumors were more likely to have a percutaneous biopsy (82±37 cm percutaneous vs 47±29 cm surgical; p=0.04).</p><p><bold>Conclusions</bold>: When multiple cores are obtained, surgeon‐performed percutaneous needle core biopsy is adequate for complete tissue diagnosis of neuroblastoma and can be safely performed. This can be considered as an alternative to surgical wedge biopsy.</p></sec><sec id="pbc26772-sec-5450"><label>P-152</label><title>Is Reck Gene Polymorphism is Linked with Predisposition and Prognosis of Wilms' Tumor? A Case Control Study</title><p><underline underline-style="single">M.R.</underline><underline underline-style="single">Safarinejad</underline><sup>1</sup></p><p><italic><sup>1</sup>Clinical center for urological disease diagnosis and private clinic specialized in urological and andrological genetics‐ Tehran‐ Iran, Urology, Terhran, Iran</italic></p><p><bold>Background/Objectives</bold>: The reversion‐inducing‐cysteine‐rich protein with Kazal motifs (RECK) gene is a new transformation suppressor gene that was linked to some malignancies. We examined the association between RECK gene polymorphisms and the clinicopathologic characteristics of Wilms’ tumor.</p><p><bold>Design/Methods</bold>: Two <italic>single nucleotide</italic> polymorphism (SNP) (rs10972727 and rs11788747) were analyzed using PCR‐RFLP protocol. The study subjects included 87 patients with Wilms’ tumor and 174 healthy subjects as controls (1:2 ratio). We gathered patients with Wilms’ tumor within last 2 decade.</p><p><bold>Results</bold>: For rs10972727 polymorphism, the genotype frequency distributions were in Hardy‐Weinberg equilibrium in patients (χ<sup>2</sup> = 3.2, <italic>P</italic> = 0.062, <italic>P</italic> = 0.72) and controls (χ<sup>2</sup> = 2.2, <italic>P</italic> = 1.77, <italic>P</italic> = 0.84). A significant alteration in both genotype distribution and allele frequency between Wilms’ tumor patients and healthy controls were detected for rs10972727 SNP. There was a statistically significant association between the presence of C allele and the Wilms’ tumor (OR = 5.02, 95% CI: 2.87 –8.31; <italic>P</italic> = 0.001). According to the logistic regression analysis, Wilms’ tumor patients with RECK TC and CC genotype have a 3.82‐fold, and 3.73‐fold increased risk for Wilms’ tumor (OR = 3.82, 95% CI: 2.42–7.71; <italic>P</italic> = 0.006, and OR = 3.73, 95% CI: 2.83 –7.63; <italic>P</italic> = 0.002, respectively.</p><p><bold>rs11788747 polymorphism</bold>: Both the patients and control subjects were in Hardy‐Weinberg equilibrium for the rs11788747 SNP polymorphism (χ<sup>2</sup> = 2.2, <italic>P</italic> = 0.056, <italic>P</italic> = 0.73; χ<sup>2</sup> = 2.2 = 0.054, <italic>P</italic> = 0.61). In single locus analysis, genotype distribution and allele frequency did not demonstrate a statistically significant difference between the cases and controls. We did not find a significant association between the rs11788747 polymorphism genotypes and the Wilms’ tumor.</p><p><bold>Conclusions</bold>: We found statistically significant differences in genotype distribution and allelic frequencies in RECK gene between Wilms’ tumor patients and controls for the rs10972727 SNP.</p></sec><sec id="pbc26772-sec-5460"><label>P-153</label><title>Primary Yolk SAC Tumor of the Prostate in Children</title><p><underline underline-style="single">M.R. Safarinejad</underline><sup>1</sup></p><p><italic><sup>1</sup>Clinical center for urological disease diagnosis and private clinic specialized in urological and andrological genetics‐ Tehran‐ Iran, Urology, Terhran, Iran</italic></p><p><bold>Background/Objectives</bold>: Primary yolk sac (endodermal sinus) tumors (ESTs) are rare malignancies that most commonly driven from the testes or ovaries. To our best knowledge, only six cases of prostatic ESTs have been reported until now in the literature.</p><p><bold>Design/Methods</bold>: In the last 2 decade, we have had six cases of prostatic ESTs. In this manuscript we report our experiences with this rare neoplasms and a brief literature review has also be done. All of the cases have underwent six courses of cisplatin‐based combination chemotherapy followed by same session retroperitoneal lymph node dissection, cystoprostatectomy and ileal conduit urinary diversion.</p><p><bold>Results</bold>: None of the cases had a history of previous testis cancer and all of them were primary.</p><p>At the presentation 4 (66.6%) of patients had metastatic disease, most commonly to the liver. When patient had on localized tumor in the lung or liver, they were also removed surgically. The median free of tumor survival was 36±4.6 months. Two patients died rapidly within 6‐month of diagnosis. Both of them had metastatic diseases during presentations.</p><p><bold>Conclusions</bold>: Despite significant advances in imaging and treatment modalities during the last two decade, yolk sac tumor of the prostate remained a significant challenge for physicians dealing with these children.</p></sec><sec id="pbc26772-sec-5470"><label>P-154</label><title>Hemorrhagic Brain Metastases in Neuroblastoma</title><p><underline underline-style="single">S. Sorrentino</underline><sup>1</sup>, C. Manzitti<sup>1</sup>, M. Conte<sup>1</sup>, G. Morana<sup>2</sup>, A. Piccardo<sup>3</sup>, A. Garaventa<sup>1</sup></p><p><italic><sup>1</sup>G.Gaslini Institute, Oncology, Genoa, Italy; <sup>2</sup>G.Gaslini Institute, Neuroradiology, Genoa, Italy; <sup>3</sup>Galliera Hospital, Nuclear Medicine, Genova, Italy</italic></p><p><bold>Background/Objectives</bold>: In 70% of the cases, neuroblastoma (NB) presents with metastases mostly at skeletal and bone marrow level. Involvement of the central nervous system (CNS) is rare and usually associated with metastases of theca, skull base and orbit. The occurrence of CNS parenchymal localizations is an exceptional event with dismal prognostic outcome.</p><p><bold>Design/Methods</bold>: We have recently observed two cases of stage 4 <italic>MYCN</italic>‐amplified NBs who have developed parenchymal CNS metastases during the clinical course.</p><p><bold>Results</bold>: Both were treated according to HR‐NBL‐01 protocol. Symptoms at relapse were severe headache and vomiting for both patients. Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) performed at time of relapse suggested the hemorrhagic nature of the lesions, that were localized in the temporal and cerebellar lobes, respectively. CNS relapses were documented at stop therapy in the former patient, three months later in the latter. The hemorrhagic characteristics of the lesions made difficult to immediate recognize their tumoral nature, as several causes (<italic>i.e.</italic>, vascular malformation, post‐traumatic lesion, iatrogenic damage) may have the identical imaging features. 18F‐DOPA‐PET/CT was performed in both patients showing intense peripheral uptake of the tracer at the level of the hemorrhagic lesions. In the former patient surgery was avoided in favor of chemotherapeutic approach consisting of multiple subsequent regimens that did not prohibit slow disease progression with death ensuing nine months later. In the latter the relapse was confirmed histologically following incomplete neurosurgical removal of the mass. She is alive on Temozolomide treatment two months after surgery.</p><p><bold>Conclusions</bold>: The detection of CNS parenchymal metastases in NB patients, both at diagnosis and during the clinical course, is rare. MRI is the method of choice for studying brain lesions. In case of hemorrhagic lesions, 18F‐DOPA‐PET/CT appears a more sensitive tool as it may help to clarify earlier their tumoral nature.</p></sec><sec id="pbc26772-sec-5480"><label>P-155</label><title>Synchronous Neoplasias in Patients Diagnosed with Peripheral Neuroblastic Tumors</title><p><underline underline-style="single">S. Sorrentino</underline><sup>1</sup>, C. Manzitti<sup>1</sup>, M. Conte<sup>1</sup>, G. Erminio<sup>2</sup>, M.L. Garrè<sup>3</sup>, C. Milanaccio<sup>3</sup>, P. D'Angelo<sup>4</sup>, A. Di Cataldo<sup>5</sup>, C. Consarino<sup>6</sup>, E. Viscardi<sup>7</sup>, M. Nantron<sup>1</sup>, L. Amoroso<sup>1</sup>, A. Garaventa<sup>1</sup></p><p><italic><sup>1</sup>G.Gaslini Institute, Oncology, Genoa, Italy; <sup>2</sup>G.Gaslini Institute, Biostatistic and Epidemiology, Genoa, Italy; <sup>3</sup>G.Gaslini Institute, NeuroOncology, Genoa, Italy; <sup>4</sup>G. Di Cristina Hospital, Onco‐hematology Unit, Palermo, Italy; <sup>5</sup>Policlinico ‐ Vittorio Emanuele, Pediatric Onco‐hematology Unit, Catania, Italy; <sup>6</sup>Pugliese‐Ciaccio Hospital, Pediatric Oncology and Hematology Unit, Catanzaro, Italy; <sup>7</sup>Padova University, Pediatric Onco‐hematology Unit, Padova, Italy</italic></p><p><bold>Background/Objectives</bold>: Patients diagnosed with a Peripheral Neuroblastic Tumor (PNT) may occasionally develop a secondary tumor. Instead, the detection of a synchronous malignancy in these patients is much rarer and mainly occurs in subjects harboring a cancer predisposition condition, such as Beckwith‐Wiedemann (SBW) or Li‐Fraumeni syndromes.</p><p><bold>Design/Methods</bold>: In the period 1976‐2016, a total of 3942 NPTs cases have been enrolled in the Italian Neuroblastoma Registry. Of them, 35 developed a secondary tumor and other 6 had a synchronous tumor.</p><p><bold>Results</bold>: Histology of PNT in the latter 6 cases was neuroblastoma in 3, intermixed ganglioneuroblastoma in 2 and ganglioneuroma in one. Synchronous tumors include acute lymphoblastic leukemia (ALL) in 3, acute myeloid leukemia (AML), pilocytic astrocytoma and pancreatoblastoma (PB) in one case each. SBW was present in the patient diagnosed with PB. All patients had localized PNT disease. Five underwent tumor resection as only therapy, while in the sixth one tumor regressed spontaneously. The 4 children diagnostic with leukemia were treated according to specific protocols, while radical tumor surgery was performed in patients with PB and astrocytoma. All these 6 patients are presently in complete remission with a median follow‐up of 38 months (range, 2‐114).</p><p><bold>Conclusions</bold>: The observation of these 6 cases illustrates a clinical condition of rare occurrence but worth of being better understood. More information may derived through retrospective and/or studies on larger patient populations, as SIOPEN might offer.</p></sec><sec id="pbc26772-sec-5490"><label>P-156</label><title>Immunotherapy in the Treatment of Pediatric Patients with High Risk Neuroblastoma “An Education Program for Patients and Their Parents”</title><p><underline underline-style="single">A. van Rooijen</underline><sup>1</sup>, M. Kortlandt<sup>1</sup>, M.M.P. van Noesel<sup>1</sup>, M.P. van Grotel<sup>1</sup>, K.C.J.P. Kraal<sup>1</sup></p><p><italic><sup>1</sup>Princess Máxima center, Pediatric Oncology, Utrecht, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Since August 2016, the PMC has started with the anti‐GD2 therapy for patients with high risk neuroblastoma (NB).</p><p>Immunotherapy; combining anti‐GD2 antibody (CH14.18/Dinutuximab), GM‐CSF, IL‐2 and ISOT [1] has significant side effects such as pain, hypotension, fever, hypersensitivity reactions and capillary leak syndrome.</p><p>Pediatric oncology nurses make a significant contribution in the treatment, including education of families and patients receiving this therapy.</p><p><bold>Design/Methods</bold>: This study investigates which aspects are important for education about immunotherapy and whether this education is appropriate for children between the age of 1 and 8 years old. Based on analysis of studies regarding education of young children, existing educational materials of the DCOG are evaluated and several points of improvement are proposed.</p><p><bold>Results</bold>: Additionally, a brochure has been developed which includes aspects of treatment, logistics and side effects and the issuance of an extensive and informative film for young children undergoing the immunotherapy is scheduled for October 2017.</p><p><bold>Conclusions</bold>: Clear communication with patients about the expected toxicities, as well as proactive and comprehensive supportive care, are integral components to ensure successful completion of antibody infusions[2]. Well‐informed parents and children experience less stress, which enhances the collaboration between parents, their children and the medical team. For this reason, proper education of patients and their families in this intense anti‐GD2 therapy is crucial.</p><p>[1] Alice, L., Yu, M., Andrew, L., Gilman, M., & al, e. (2010, September 30). Anti‐GD2 antibody with GM‐CSF, Interleukin‐2, and Isotretinoin for Neuroblastoma. <italic>The New England Journal of Medicine</italic>, 1324‐1334.</p><p>[2] Bartholomew, J et al (2016), Dinutuximab: a novel immunotherapy in the treatment of pediatric patients with high risk neuroblastoma. <italic>Journal of Pediatric Oncology Nursing, 1‐8</italic></p></sec><sec id="pbc26772-sec-5500"><label>P-157</label><title>Elevated Urinary 3‐Methoxytyramine at Diagnosis is Correlated with High Risk Disease and is Associated with Poor Clinical Outcome in Neuroblastoma Patients</title><p><underline underline-style="single">I. Verly</underline><sup>1,2,3</sup>, A. van Kuilenburg<sup>2</sup>, N. Abeling<sup>2</sup>, S. Goorden<sup>2</sup>, M. Fiocco<sup>4,5</sup>, F. Vaz<sup>2</sup>, M. van Noesel<sup>3,6</sup>, M. Zwaan<sup>7</sup>, G.J. Kaspers<sup>3,8</sup>, H. Merks<sup>1,3</sup>, H. Caron<sup>1</sup>, G. Tytgat<sup>1,3</sup></p><p><italic><sup>1</sup>Academical Medical Center, Pediatric hemato‐oncology, Amsterdam, The Netherlands; <sup>2</sup>Academical Medical Center, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; <sup>3</sup>Princess Máxima Center for Pediatric Oncology/Hematology, Pediatric Oncology/Hematology, Utrecht, The Netherlands; <sup>4</sup>Leiden University Medical Center, Medical Statistics and Bioinformatics, Leiden, The Netherlands; <sup>5</sup>Leiden University, Mathematical institute, Leiden, The Netherlands; <sup>6</sup>University Medical Center Utrecht, Pediatrics, Utrecht, The Netherlands; <sup>7</sup>Sophia Children's Hospital/Erasmus Medical Center, Pediatric Oncology/Hematology, Rotterdam, The Netherlands; <sup>8</sup>VU University Medical Center, Pediatric Oncology/Hematology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Prognosis of patients with neuroblastoma is diverse, indicating the need for more accurate prognostic parameters. Most neuroblastomas excrete catecholamine metabolites, however, their correlation with prognosis has hardly been investigated. Therefore, we performed an in‐depth analysis of a panel of elevated urinary catecholamine metabolites and their correlation with prognosis.</p><p><bold>Design/Methods</bold>: Retrospective study of a panel of 8 urinary catecholamine metabolites in test (n = 96) and validation (n = 205) cohorts of patients with neuroblastoma (all stages) at diagnosis.</p><p><bold>Results</bold>: Multivariate Cox regression model analyses revealed that 3‐methoxytyramine (3MT) was an independent risk factor for Event‐free survival (EFS) and Overall survival (OS). EFS and OS of stage 4 patients with non‐elevated 3MT were significantly better compared to stage 4 patients with elevated 3MT [5‐years EFS: 47.4%±7% versus 17.7%±4%; 5‐years OS: 67.0%±7% versus 26.8%±5%, both p < 0.001]. Also in other clinical subgroups, elevated 3MT was associated with poor survival outcome. In multivariate‐analyses for high risk patients (stage 4 and older than 1 year or any patients with <italic>MYCN</italic> amplification), only age and 3MT were independent risk factors for EFS and OS, and thus independent of the given therapy. Among high risk patients, those with elevated 3MT and age ≥ 18 months had an extremely poor prognosis compared to patients with non‐elevated 3MT and age < 18 [5‐years EFS of 15.2%±4% and 62.2%±18%, respectively, p = 0.005; 5‐years OS of 23.4%±5% and 87.5%±12%, respectively, p = 0.002].</p><p><bold>Conclusions</bold>: elevated 3MT‐levels at diagnosis are associated with high risk disease and poor prognosis. For high risk patients, age and elevated 3MT at diagnosis are the most significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high risk patients with favorable and extremely poor prognosis.</p><p><bold>Acknowledgements</bold>: this study was supported by the Villa Joep Foundation.</p></sec><sec id="pbc26772-sec-5510"><label>P-158</label><title>Epithelial to Mesenchymal Transition in Patients with Neuroblastoma – The Mechanism Underlying Catecholamine Negative Neuroblastoma?</title><p><underline underline-style="single">I. Verly</underline><sup>1,2,3</sup>, A. van Kuilenburg<sup>3</sup>, D. Goedkoop<sup>3</sup>, R. Meinsma<sup>3</sup>, R. Leen<sup>3</sup>, T. van Groningen<sup>4</sup>, M. Broekmans<sup>4</sup>, J. Koster<sup>4</sup>, R. Versteeg<sup>2,4</sup>, J. van Nes<sup>4</sup>, G. Tytgat<sup>1,2</sup></p><p><italic><sup>1</sup>Academical Medical Center, Pediatric hemato‐oncology, Amsterdam, The Netherlands; <sup>2</sup>Princess Máxima Center for Pediatric Oncology/Hematology, Pediatric Oncology/Hematology, Utrecht, The Netherlands; <sup>3</sup>Academic Medical Center, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands; <sup>4</sup>Academic Medical Center, Oncogenomics, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Catecholamine measurements in urine of patients with neuroblastoma is standard practice. When a panel of 8 markers is used, 5% of the patients have no elevated catecholamines at diagnosis (catecholamine negative), and 20% of the patients is negative at time of relapse. Recently, two cell types in neuroblastoma were identified, adrenergic (ADRN)‐type cells expressing markers of adrenergic‐lineage differentiation, and mesenchymal (MES)‐type cells lacking these markers (van Groningen et al., submitted). This phenotypical duality might regulate catecholamine excretion and explain the switch of catecholamine positive to catecholamine negative patients. In this study, we investigated <italic>in vitro</italic> catecholamine excretion in relation to MES‐ and ADRN cell types.</p><p><bold>Design/Methods</bold>: We studied catecholamine excretion in neuroblastoma cell lines (6 MES and 23 ADRN), including two pairs of ADRN‐MES cell lines (SY5Y‐SHEP2 and 691B‐691T). Additionally, SKNBE cells, in which mesenchymal transition can be induced were also used. Subsequently, the presence of the catecholamine biosynthetic enzymes: tyrosine hydroxylase (TH), dopa‐decarboxylase (DDC) and dopamine‐β‐hydroxylase (DBH) in these cell lines was determined by qRT‐PCR and Western‐blot.</p><p><bold>Results</bold>: Among the 23 ADRN cell lines, 10 cell lines (44%) excreted catecholamines. MES cell lines did not excrete catecholamines. In the ADRN‐MES pairs, the ADRN cell lines excreted catecholamines, while their MES cell lines partner did not. Catecholamine excretion was also detected in SKNBE cells with ADRN phenotype, however, it stopped once transition to mesenchymal phenotype was induced. Enzyme profiling revealed that all the excreting cell lines expressed the TH protein, which was absent in all the non‐excreting cell lines.</p><p><bold>Conclusions</bold>: Catecholamine excretion was absent in MES‐type neuroblastoma cells and seems to be an exclusive feature of the ADRN‐cells with TH expression.</p><p><bold>Acknowledgements</bold>: this study was supported by a grant from the Villa Joep Foundation.</p></sec><sec id="pbc26772-sec-5520"><label>P-159</label><title>Efficacy of Ultrasonography in Diagnosis in Neonatal Adrenal Neuroblastoma</title><p><underline underline-style="single">J. Yu</underline><sup>1</sup>, J. Ye<sup>1</sup>, X. Li<sup>1</sup>, X. Yang<sup>1</sup>, J. He<sup>1</sup>, J. Wang<sup>2</sup></p><p><italic><sup>1</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Ultrasound, Hangzhou, China; <sup>2</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Surgical Oncology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: To investigate the efficacy of ultrasonography in diagnosis and follow‐up in neonatal adrenal neuroblastoma (NB).</p><p><bold>Design/Methods</bold>: Twenty‐eight neonatal adrenal neuroblastoma confirmed by pathology in our center from November 2004 to February 2017 were included in this study, including 16 boys and 12 girls. All cases were unilateral. Ultrasonographic image data were analyzed retrospectively.</p><p><bold>Results</bold>: All cases were detected by ultrasound firstly, aged from 34w gestational age to 28 days postpartum, 13(46.43%) cases detected during prenatal routine examination. Major ultrasonographic characteristics: border clear, size of mass from 2.7cm * 1.7cm * 1.7cm to 12.0cm * 11.0cm * 7.5cm, 24 cases were parenchymal masses (19 cases with calcification, 5 cases without calcification), 2 cases were cystic masses, 2 cases were cystic solid masses. NB was considered as the first diagnosis in 27 cases (96.4%). Only 1 case of cystic adrenal neuroblastoma was misdiagnosed as mesenteric cyst.</p><p><bold>Conclusions</bold>: Ultrasound can be used as a preferred imaging method for fetal and neonatal adrenal neuroblastoma, which contributes to early diagnosis and management.</p></sec><sec id="pbc26772-sec-5530"><label>P-160</label><title>Paraneoplastic Syndromes – A Retrospective Clinical Analysis of 8 Cases in Children</title><p><underline underline-style="single">S. Wang</underline><sup>1</sup>, Z. Lu<sup>1</sup>, C. Li<sup>1</sup>, C. Yang<sup>1</sup>, L. Lv<sup>1</sup>, Z. Zhao<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital of Chongqing Medical University, Department of Pediatric Surgical Oncology, Chongqing, China</italic></p><p><bold>Background/Objectives</bold>: Paraneoplastic Syndromes (PSs) are the kinds of rare syndromes, the clinical characteristics have rarely been discussed in children. We analyzed data on the clinical manifestations, diagnoses, treatments, and prognosis in children with PSs to investigate how diagnosis and treatment could be improved.</p><p><bold>Design/Methods</bold>: Eight patients with PSs were enrolled from July 2011 to February 2017. A range of examinations were used to evaluate the patients. Pathological examinations were performed on all of the patients. In addition to either complete tumor resection or puncture biopsy, chemotherapy, corticosteroid therapy and other supportive treatments were also applied in the different patients.</p><p><bold>Results</bold>: Three patients suffered from paraneoplastic neurologic syndromes (PNSs), 3 presented with Ectopic Cushing's syndrome, 1 patient with respiratory failure and 1 had vasoactive intestinal polypeptide (VIP)‐induced intractable diarrhea. Two patients were confirmed as ganglioneuroblastoma (GNB), 4 had neuroblastoma (NB) and 2 had ganglioneuroma(GN). In 6 patients the tumors were completely resected, 2 had puncture biopsy of the tumors. Six patients received chemotherapy, 4 received futher supportive treatments, and 4 received futher corticosteroid therapy. Except for 2 patients who discontinued therapy, the 3 patients who suffered from PNSs achieved complete remission, and the remaining 4 patients who completed follow‐up were classified as having “very good partial remission”.</p><p><bold>Conclusions</bold>: When children present with PNSs such as Opsoclonus‐Myoclonus Syndrome (OMS) and Cerebellar Ataxia, Ectopic Cushing's syndrome, dyspnea and unexplained intractable diarrhea, hypokalemia and dysplasia, clinicians should consider the possibility of neuroblastoma.</p></sec><sec id="pbc26772-sec-5540"><label>P-161</label><title>A Double‐Conditioning Regimen with Thiotepa and Melphalan is Effective for MYCN‐Amplified High‐Risk Neuroblastoma</title><p><underline underline-style="single">F. Yamazaki</underline><sup>1,2</sup>, C. Kiyotani<sup>3</sup>, K. Yamasaki<sup>4</sup>, C. Nitani<sup>4</sup>, K. Okada<sup>4</sup>, H. Fujisaki<sup>4</sup>, Y. Shioda<sup>3</sup>, J. Hara<sup>4</sup>, K. Matsumoto<sup>3</sup></p><p><italic><sup>1</sup>Keio University School of Medicine, Department of Pediatrics, Tokyo, Japan; <sup>2</sup>National Cancer Center Research Institute, Department of Clinical Genomics, Tokyo, Japan; <sup>3</sup>National Center for Child Health and Development, Children's Cancer Center, Tokyo, Japan; <sup>4</sup>Osaka City General Hospital, Department of Pediatric Hematology and Oncology, Osaka, Japan</italic></p><p><bold>Background/Objectives</bold>: Appropriate combinations of induction chemotherapy and high‐dose chemotherapy (HDC) regimens for patients with high‐risk neuroblastoma remain unestablished. Previously, we reported the feasibility and efficacy of a double‐conditioning regimen using two cycles of thiotepa (total 800 mg/m<sup>2</sup>) and melphalan (total 280 mg/m<sup>2</sup>) with a single grafting for neuroblastoma. In the present study, we analyzed the outcomes of the double‐conditioning regimen in patients with high‐risk neuroblastoma in two Japanese institutions.</p><p><bold>Design/Methods</bold>: The medical records of consecutive 34 patients with high‐risk neuroblastoma who received the double‐conditioning regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012 were reviewed.</p><p><bold>Results</bold>: The median patient age at diagnosis was 35 months. <italic>MYCN</italic>‐amplified tumors were observed in 19 patients. Thirty‐two patients had stage 4 tumors. All patients underwent surgical resection of the primary lesion and radiotherapy against the residual lesion. The regimen of induction chemotherapy and timing of surgery varied depending on the institution. The median follow‐up period was 8.6 years (range, 4.8–14.1). Nine patients subsequently received planned tandem HDC with cord blood transplantation. Fifteen patients, including 2 of the 9 patients treated with tandem HDC, have survived without recurrence. The event‐free survival (EFS) rate and the overall survival (OS) rate at 5 years from diagnosis was 47.1% ± 8.6% and 52.9% ± 8.6%, respectively. Three patients died from regimen‐related toxicity. None of the patients developed secondary malignancies. Notably, both the EFS and OS rates at 5 years in patients with <italic>MYCN</italic>‐amplified tumors were 68.4% ± 10.7%, which were significantly superior to those with <italic>MYCN</italic>‐nonamplified tumors (P < 0.01 and P = 0.014). In a multivariate analysis, increased probability of EFS was demonstrated in patients with <italic>MYCN</italic>‐amplification and good remission status during HDC.</p><p><bold>Conclusions</bold>: The double‐conditioning regimen comprising thiotepa and melphalan is an effective regimen for patients with high‐risk neuroblastoma with <italic>MYCN</italic> amplification.</p></sec><sec id="pbc26772-sec-5550"><label>P-162</label><title>Yap Promotes Tumorigenesis and Cisplatin Resistance in Neuroblastoma</title><p><underline underline-style="single">C. yang</underline><sup>1</sup>, W. shan<sup>2</sup></p><p><italic><sup>1</sup>Children's Hospital of Chongqing Medical University, Department of Pediatric surgical oncology, Chongqing, China; <sup>2</sup>hildren's Hospital of Chongqing Medical University, Department of Pediatric surgical oncology, chongqing, China</italic></p><p><bold>Background/Objectives</bold>: The transcriptional co‐activator Yes‐associated protein (YAP) is essential for Hippo pathway‐driven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced tumor staging.</p><p><bold>Design/Methods</bold>: We examined the expression of YAP in clinical tumor specimens and adjacent tissues, and analyzed the relationship between them and tumor staging. The cell viability assay, colony formation assay and Invasion assay were perfomed after siRNA interfering. The expression of YAP and possibly related downstream proteins was detected by westerblot. Human SH‐SY5Y and SH‐SY5Y‐R xenografts were established, low concentration of cisplatin, high concentration of cisplatin, low concentration of cisplatin + peptid 17 was treated for each group. Tumor volume was calculated. After mice were sacrificed, the tumor were peeled off and weighted, YAP expression and apoptosis was performed.</p><p><bold>Results</bold>: Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion <italic>in vitro</italic>. Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors. Additionally, less proliferative and more apoptotic cells were found in the Peptide 17 treatment group. Furthermore, YAP inhibition significantly inhibited cisplatin‐resistant neuroblastoma proliferation, tumorigenesis, and invasion <italic>in vitro</italic>. The combination of Peptide 17 with low‐dose cisplatin efficiently impaired cisplatin‐resistant NB subcutaneous tumor growth, being as effective as high‐dose cisplatin. Notably, the combination therapy caused lesser liver toxicity in mice compared to the high‐dose cisplatin treatment group.</p><p><bold>Conclusions</bold>: Collectively, this work identifies YAP as a novel regulator of neuroblastoma proliferation, tumorigenesis, and invasion and indicates that YAP is a potential therapeutic target for cisplatin‐resistant neuroblastoma.</p></sec><sec id="pbc26772-sec-5560"><label>P-163</label><title>An Evaluation of The Risk Factors in the Surgical Treatment of Intermediate‐Risk Neuroblastoma</title><p><underline underline-style="single">A. Yoneda</underline><sup>1</sup>, K. Santo<sup>1</sup>, S. Nishimoto<sup>1</sup>, Y. Tsukazaki<sup>1</sup>, M. Kamiyama<sup>1</sup>, T. Nakaoka<sup>1</sup>, T. Nakamura<sup>2</sup>, J. Hara<sup>3</sup></p><p><italic><sup>1</sup>Osaka City General Hospital, Pediatric Surgery, Osaka, Japan; <sup>2</sup>Osaka General Medical Center, Pediatric Surgery, Osaka, Japan; <sup>3</sup>Osaka City General Hospital, Pediatric Hematology and Oncology, Osaka, Japan</italic></p><p><bold>Background/Objectives</bold>: With improvement in the treatment results for intermediate‐risk neuroblastoma, minimizing treatment complications should be the top priority. We retrospectively evaluated the risk factors in the surgical treatment of intermediate‐risk neuroblastoma in order to minimize surgical complications.</p><p><bold>Design/Methods</bold>: Of 148 neuroblastoma patients treated at our institute between 1995 and 2016, 15 classified as intermediate‐risk according to the COG risk classification were selected. We divided these patients into two groups according to the presence (group A, n=6) or absence (group B, n=9) of surgical complications.</p><p><bold>Results</bold>: The median age at diagnosis was 7 months (range: 5 days‐3 years). There were 13 INSS stage 3 patients, 2 stage 4 and 1 stage 4S. Eight had retroperitoneal, five adrenal, two mediastinal and one cervical neuroblastomas. Four tumors showed intraspinal extension. The surgical complications were two nephrectomies, one renal atrophy, one bowel obstruction, one ejaculation disorder, one Horner syndrome and one resection of the internal jugular vein. All tumors were resected at least 95% in group A, including 5 complete resections, whereas there were 2 complete resections, three 90% and 50%‐90% resections each and 1 patient without surgery in group B. Five of the six patients in group A and five of the nine patients in group B had tumors with image‐defined risk factors (IDRFs). Only one tumor in group B changed from ‘IDRFs present’ to ‘not present’ after preoperative chemotherapy. All patients were alive without disease after a median follow‐up 143 months (range: 13‐242 months).</p><p><bold>Conclusions</bold>: More than 95% resection and the presence of preoperative IDRFs seems to be surgical risk factors in intermediate‐risk neuroblastoma. As all patients are alive without disease, conservative surgery to avoid complications may be acceptable, even if residual tumor remains after surgery.</p></sec><sec id="pbc26772-sec-5570"><label>P-164</label><title>The Role of UBE4B in Neuroblastoma Differentiation</title><p><underline underline-style="single">P. Zage</underline><sup>1</sup>, J. Lesperance<sup>1</sup>, D. Subramonian<sup>1</sup>, S. Woodfield<sup>2</sup>, R. Guo<sup>3</sup>, A. Bean<sup>4</sup>, D. Lopez‐Terrada<sup>5</sup>, M. Ittmann<sup>5</sup>, S. Hakim<sup>1</sup></p><p><italic><sup>1</sup>University of California ‐ San Diego ‐ Moores Cancer Center, Pediatrics, San Diego, USA; <sup>2</sup>Baylor College of Medicine, Pediatric Surgery, Houston, USA; <sup>3</sup>University of Alabama‐Birmingham, Pathology, Birmingham, USA; <sup>4</sup>University of Texas Health Science Center ‐ Houston, Neurobiology & Anatomy, Houston, USA; <sup>5</sup>Baylor College of Medicine, Pathology, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: UBE4B is an E3/E4 ubiquitin ligase involved in growth factor receptor (GFR) trafficking whose gene is found in the chromosome 1p36 region commonly deleted in high‐risk neuroblastoma tumors. We have previously observed associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and neuroblastoma tumor histology. However, the functional roles of UBE4B in neuroblastoma tumor differentiation are not known.</p><p><bold>Design/Methods</bold>: We screened cell lines and neuroblastoma tumor samples for UBE4B protein expression using Western blot and quantitative immunohistochemistry and analyzed the association of <italic>UBE4B</italic> gene expression with expression of known markers of neuroblastoma tumor differentiation using publicly available databases. We measured UBE4B expression by Western blot in cell lines before and after induction of differentiation with retinoic acid treatment and determined the effects of UBE4B overexpression and depletion on retinoic acid‐induced differentiation using continuous live‐cell imaging of neurite morphology, immunohistochemistry, and Western blot for markers of differentiation. Effects on signaling through the Ras/MAPK pathway were measured using Western blots.</p><p><bold>Results</bold>: UBE4B expression was associated with differentiation in patient tumor samples, and UBE4B gene and protein expression were associated with expression levels of known markers of neuroblastoma differentiation. Retinoic acid treatment resulted in increased UBE4B expression in retinoic acid‐sensitive, but not ‐resistant, neuroblastoma cells, and UBE4B depletion was associated with increased phosphorylation of ERK, increased proliferation, and inhibition of retinoic acid‐induced neuroblastoma differentiation.</p><p><bold>Conclusion</bold>: We have demonstrated associations between UBE4B expression and tumor cell differentiation in gene expression databases and in neuroblastoma tumor samples, and our data suggests that UBE4B expression is required for retinoic acid‐induced differentiation, potentially through effects on ERK activation. These associations between UBE4B and neuroblastoma differentiation combined with the established role of UBE4B in GFR trafficking suggest that UBE4B‐mediated receptor trafficking may contribute to the responses of neuroblastoma tumors to therapy and to the outcomes of patients with neuroblastoma.</p></sec><sec id="pbc26772-sec-5580"><label>P-165</label><title>Treatment of High‐Risk Neuroblastoma Over One Year of Age with Intensive and a Novel Delayed Intensification Chemotherapy</title><p>Y.T. Zhang<sup>1</sup>, <underline underline-style="single">J. Chang</underline><sup>1</sup>, X.D. Zhong<sup>1</sup></p><p><italic><sup>1</sup>First Hospital of Jilin University, Department of pediatric oncology, Changchun, China</italic></p><p><bold>Background/Objectives</bold>: Current “standard” therapy for patients with high‐risk neuroblastoma consists of intensive induction chemotherapy and surgery, myeloablative consolidation chemotherapy, autologous stem cell transplantation, local irradiation and immunotherapy. However, autologous stem‐cell transplantation is expensive. Until recently, anti‐GD2 antibody was not easily accessible in China. What should we do to improve the survival rate of patients with high‐risk neuroblastoma in developing countries? On the basis of these considerations, we designed this study to test the feasibility of adding a novel delayed intensification chemotherapy to a dose‐intensive induction regimen.</p><p><bold>Design/Methods</bold>: Patients enrolled in this study received chemotherapy in accordance with the design of the NB97 trial. At the end of the therapy, patients received three cycles of delayed intensification chemotherapy. The delayed intensification chemotherapy consists of two A1 and one A2 cycle. The A1 cycle consists of 1.5 mg/m<sup>2</sup> of vincristine on day 1, 1.2 g/m<sup>2</sup> of cyclophosphamide on day 2, 100 mg/m<sup>2</sup> of cisplatin on day 3, and 160 mg/m<sup>2</sup> of etoposide on day 4. The A2 cycle is similar to the A1 cycle, however the only difference is that on day 4, 30 mg/m<sup>2</sup> of doxorubicin is substituted for etoposide.</p><p><bold>Results</bold>: Between 2008 to 2011, a total of 51 patients were enrolled, 15 patients were excluded from the study. Of the remaining thirty‐six patients, twenty‐eight patients had completed consolidation chemotherapy. They were finally enrolled. Fifteen patients were long term event‐free survivors. Five patients were alive with tumor whilst eight patients died. The 3‐year EFS and OS were 53.6% (95%CI, 26.74% to 66.12%) and 71.4% (95%CI, 53.59% to 89.27%) respectively.</p><p><bold>Conclusions</bold>: A high rate of survival among patients with high‐risk neuroblastoma was achieved with delayed intensification chemotherapy without the occurrence of a second malignancy. This study warrants further investigation into the long‐term outcomes and EFS in patients with high‐risk neuroblastoma.</p></sec><sec id="pbc26772-sec-5590"><label>P-166</label><title>PLK4 Promotes Neuroblastoma Invasion and Metastasis Through PI3K/AKT Signaling Pathway</title><p><underline underline-style="single">Q. Zhao</underline><sup>1</sup></p><p><italic><sup>1</sup>Tianjin Medical University Cancer Institute and Hospital, Department of Pediatric Cancer, Tianjin, China</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma (NB) is the most common malignant tumor in infancy and the most common extracranial solid tumor in childhood. With the improvement of diagnosis and treatment, the survival rate of patients with low‐risk and intermediate‐risk NB can reach up to 90%. But for high‐risk NBs, the long‐term survival rate is still less than 40%. The pathogenesis of NB is still not explicit, therefore it is of great significance to explore the mechanism of NB tumorigenesis and discovery new therapeutic targets for NB. PLK4, one of the Polo‐like kinase family members, is an important regulator of centriole replication. The abnormal expression of PLK4 was found in several cancers and a recent study has unraveled a novel function of PLK4 as a mediator of invasion and metastasis in Hela cell lines. However, the function of PLK4 in NB development and progression remains to be elucidated.</p><p><bold>Design/Methods</bold>: We evaluated the expression level of PLK4 in NB tissues and detected the function of PLK4 in NB through a series of experiments in vitro and in vivo.</p><p><bold>Results</bold>: The expression level of PLK4 in NB tissues was remarkably up‐regulated and high expression of PLK4 was negatively correlated with the survival rate of NBs, which suggesting that PLK4 was a potential tumor promoting factor of NB. Functional studies indicated down‐regulation of PLK4 suppressed cell proliferation and invasion in SK‐N‐SH and SK‐N‐BE(2) cells. And down‐regulated PLK4 in NB cell lines inhibited epithelial‐mesenchymal transition (EMT) through the PI3K/Akt signaling pathway. Animal experiments demonstrated that PLK4 down‐regulation in SK‐N‐BE(2) cells dramatically suppressed tumorigenesis and metastasis.</p><p><bold>Conclusions</bold>: PLK4 promotes cell proliferation, invasion and metastasis in NB cells and it induces epithelial‐mesenchymal transition by activation of PI3K/Akt signaling pathway. PLK4 may be a promising therapeutic target for NB.</p></sec></sec><sec id="pbc26772-sec-5600"><title>Solid Non Brain Tumours ‐ Renal Tumours</title><sec id="pbc26772-sec-5610"><label>P-167</label><title>Outcome of Wilms Tumor Treated According to the SIOP‐ PODC Approach: Early Experience in a Tertiary Referral Hospital in the Philippines</title><p><underline underline-style="single">J.P. Caneba</underline><sup>1</sup>, A. Moreno<sup>2</sup>, E. Yturralde<sup>3</sup>, C.V. Villafuerte III<sup>4</sup>, J.M. Avila<sup>3</sup>, W. Baltazar<sup>2</sup>, A. Catangui<sup>2</sup>, N. Cupino<sup>4</sup>, P. Fajardo<sup>1</sup>, A.P. Alcasabas<sup>1</sup></p><p><italic><sup>1</sup>University of the Philippines ‐ Philippine General Hospital, Pediatrics, Manila, Philippines; <sup>2</sup>University of the Philippines ‐ Philippine General Hospital, Surgery, Manila, Philippines; <sup>3</sup>University of the Philippines ‐ Philippine General Hospital, Pathology, Manila, Philippines; <sup>4</sup>University of the Philippines ‐ Philippine General Hospital, Radiology, Manila, Philippines</italic></p><p><bold>Background/Objectives</bold>: At Philippine General Hospital, the country's national referral center, Wilms tumor (WT) survival was low at 26% largely due to treatment delays and abandonment from inoperable tumors and infections. In March 2014, the pediatric surgery, pediatric oncology, pathology, and radiology group adopted the SIOP‐PODC WT treatment approach and guidelines.</p><p><bold>Design/Methods</bold>: Review of medical records of newly‐diagnosed patients from March 2014 to August 2016 with study endpoint at December 2016.</p><p><bold>Results</bold>: There were 22 patients with mean age of 2.5 years (0.33‐11). M:F ratio of 1:2.3. Eighteen patients (82%) had localized disease and 4 (18%) were metastatic. All were given neoadjuvant chemo for mean of 6 weeks, (4‐11) and 9 weeks (8‐11), respectively. Only 20 patients had nephrectomy due to abandonment (1) and progressive disease (1). 19 patients (95%) had lymph node sampling and 2 (9%) had tumor spillage. Surgical staging were: Stage I: 6; Stage II: 2; Stage III: 6; Stage IV: 4. Pathology risk grading were: Low: 1; Intermediate: 8; and High: 5. Three were reported as Favorable histology, and 3 were misdiagnoses: neuroblastoma (1), Angiomyolipoma (1) and Multicystic renal dysplasia (1). Thirteen WT patients received SIOP risk‐stratified adjuvant treatment, 4 were off protocol due to poor response (N=3) and progressive disease (N=1), and 1 abandoned treatment. Six patients underwent radiation. At study endpoint, for WT patients: 9 (47%) completed treatment; 3 (16%) on treatment; 5 (26%) abandoned therapy; 1 (5%) relapsed (local); and 1 died due to gastroenteritis 12 months off treatment. The 2 year EFS is 57%, and 2 year OS and abandonment sensitive OS are 89% and 63%, respectively.</p><p><bold>Conclusions</bold>: The adoption of the SIOP‐PODC WT multi‐disciplinary protocol and guidelines has markedly improved survival in our setting and addressed diagnostic and treatment delays. However, efforts are still needed to curb abandonment, and improve protocol adherence and misdiagnosis.</p></sec><sec id="pbc26772-sec-5620"><label>P-168</label><title>Outcome of Wilms’ Tumor in Children: A 10 Year Experience From King Faisal Specialist Hospital and Research Center‐Riyadh</title><p>A. Ali<sup>1</sup>, M. Ayas<sup>1</sup>, T. AlHussain<sup>2</sup>, A. Alkofide<sup>1</sup>, Z. Habib<sup>3</sup>, V. Mohammed<sup>1</sup>, D. Bushnak<sup>4</sup>, I. Abosoudah<sup>5</sup>, A. Nadeem<sup>1</sup>, A. Abbas<sup>1</sup>, S. Khan<sup>1</sup>, M. AlQaisi<sup>4</sup>, A. Ahmad<sup>4</sup>, S. Mohammad<sup>2</sup>, <underline underline-style="single">I. Alfawaz</underline><sup>1</sup></p><p><italic><sup>1</sup>King Faisal Specialist Hospital & Research Centre, Pediatric Hematology/Oncology, Riyadh, Saudi Arabia; <sup>2</sup>King Faisal Specialist Hospital & Research Centre, Pathology & Laboratory Medicine, Riyadh, Saudi Arabia; <sup>3</sup>King Faisal Specialist Hospital & Research Centre, Pediatric Surgery, Riyadh, Saudi Arabia; <sup>4</sup>King Faisal Specialist Hospital & Research Centre, Nursing, Riyadh, Saudi Arabia; <sup>5</sup>King Faisal Specialist Hospital & Research Centre‐Jeddah, Oncology, Jeddah, Saudi Arabia</italic></p><p><bold>Background/Objectives</bold>: Wilms’ tumor (WT) is the most common renal malignancy in children. Outcome data for WT in our region is limited. A retrospective study to evaluate clinical outcomes of pediatric patients (pts) with WT at King Faisal Specialist Hospital and Research Centre, Riyadh (KFSH&RC‐Riyadh) was conducted.</p><p><bold>Design/Methods</bold>: Data of WT pts (ages 0 to 14 years) diagnosed and treated at KFSH&RC‐Riyadh from 2001‐2011 was reviewed. Only histopathology confirmed cases were included.</p><p><bold>Results</bold>: Out of 137 cases identified, 7 cases were excluded due to insufficient data. Median age at diagnosis was 3.4 years (0.3‐13). with 73(56%) females and 57(44%) males. Unilateral disease was observed in 119(91.5%)pts and bilateral in 11(9.5%). Presenting features included: abdominal distension,85%; abdominal pain,41.5%; hematuria,13%; and vascular thrombosis,4%. 66% of pts were stage III,57(44%) and IV,29(22%). Relapse was seen in 34(26%); of which 23(68%) were Stage III and IV. Five‐year OS for all pts was 90.5% [(Stage I(94%); II(89.5%); III(93%); IV(82%); and V(100%)] and EFS 70%[(Stage I(88%); II(68%), III(76%);IV(48%); V(57%)], P value of <0.05 for EFS in pts based on staging. Our results corroborate previously presented data from the Saudi Arabian Pediatric Hematology/Oncology Society(SAPHOS) where a national 5‐year OS and EFS of 86% and 74% respectively (n=67) was reported. Favorable histology was seen in 119(91.5%) while 7(5%) had anaplasia. P value for both OS and EFS was <0.05 for pts comparing favorable histology with anaplasia. For pts <5years, OS and EFS were 93% and 71.6%, and 82% and 65.6%, for >5years of age, respectively.</p><p><bold>Conclusions</bold>: Despite variability in healthcare services and referral patterns, and given that over half of the pts being referred to our center have advanced disease, not amenable to upfront resection, our outcomes for WT are comparable tothe national data as well as to international reports. Further review including specifications of relapsed patients and molecular studies are warranted and underway.</p></sec><sec id="pbc26772-sec-5630"><label>P-169</label><title>Bilateral Wilms Tumors: Treatment Results from a Single Center with Turkish Pediatric Oncology Group Wilms Tumor Study</title><p><underline underline-style="single">B. Aydin</underline><sup>1</sup>, C. Akyuz<sup>1</sup>, B. Yalcin<sup>1</sup>, S. Ekinci<sup>2</sup>, A. Varan<sup>1</sup>, N. Kurucu<sup>1</sup>, M. Buyukpamukcu<sup>1</sup>, T. Kutluk<sup>1</sup></p><p><italic><sup>1</sup>Hacettepe University Cancer Institute, Pediatric Oncology, ANKARA, Turkey; <sup>2</sup>Hacettepe University Faculty of Medicine, Pediatric Surgery, ANKARA, Turkey</italic></p><p><bold>Background/Objectives</bold>: The outcome of patients with BWT has improved due to both preoperative chemotherapy and operative techniques in preservation of renal parenchyma. In this study the results of TPOG Wilms tumor regimen for BWT and outcome of patients from a single center were retrospectively reviewed.</p><p><bold>Design/Methods</bold>: From 1990 to 2016, 33 patients with synchronous BWT were treated with preoperative chemotherapy with vincristine and actinomycine. Chemotherapy was continued until safe nephron sparing surgery (NSS) could be performed as long as radiological tumor response continued or chemotherapy was intensified with adding doxorubicin (D) alternating with VA every 6 weeks.</p><p><bold>Results</bold>: The median follow‐up of non‐failure patients was 68 months (7‐297 months). The median duration of preoperative chemotherapy was 85 days ranged between 14 days and 216 days. Preoperative chemotherapy was modified in 7 patients (21%) with VAD regimen. 6 patients received VAD regimen due to metastases, thrombi in vena cava and possible spontaneous tumor rupture at diagnosis. 24 patients had radical nephrectomy for greater tumor and NSS for the contralateral kidney. Eight patients (24%) had bilateral NSS. EFS and OS rates for VA and VAD was not statistically different. Postoperative tumor stages for stage I, II and III were 55%, 15% and 17%. The 5‐year OS rates were 100%, 90% and 70% for stages I, II and III (p=0.06). Unfavorable histology and nephroblastomatosis were reported in 18% and 27% of patients. 5‐year OS and EFS rates were 50% and 25% in patients with anaplasia, while same rates were 96% and 96% in patients with FH tumors (p=0.03 and p<0.001). 10‐year OS and EFS rates for all patients were 84% and 80%. Only one patient died after bilateral nephrectomy.</p><p><bold>Conclusions</bold>: Our results are comparable with literature. VA is effective for BWT as initial preoperative treatment. VAD combination might help better local control for selected advanced staged tumors.</p></sec><sec id="pbc26772-sec-5640"><label>P-170</label><title>Review of Phase I and II Trials for Wilms Tumour – Can We Optimise the Search for Novel Agents?</title><p><underline underline-style="single">J. Brok</underline><sup>1</sup>, K. Pritchard‐Jones<sup>1</sup>, J.I. Geller<sup>2</sup>, F. Spreafico<sup>3</sup></p><p><italic><sup>1</sup>University College Great Ormond Street Institute of Child Health, Cancer section, London, United Kingdom; <sup>2</sup>Cincinnati Children's Hospital Medical Center‐ University of Cincinnati‐ Cincinnati‐ Ohio, Division of Pediatric Oncology, Cincinatti, USA; <sup>3</sup>Fondazione IRCCS Istituto Nazionale dei Tumori‐ Milan‐ Italy, Department of Hematology and Pediatric Onco‐Hematology, Milano, Italy</italic></p><p><bold>Background/Objectives</bold>: Survival rates for patients with Wilms’ tumour (WT) approximate 90% with refined use of currently available interventions. However, a subgroup of patients with initial high‐risk histopathology or relapsing disease have a poor prognosis and it is a challenge to identify and prioritise the development of new innovative approaches for these subgroups.</p><p><bold>Design/Methods</bold>: We conducted a systematic literature search for published phase I and II clinical trials that registered patients with WTs, and characterised the early‐phase trial activity, quantified response rates and highlighted avenues for further development.</p><p><bold>Results</bold>: We identified 63 trials (48 phase I, three phase I/II, and 12 phase II trials) enrolling 214 patients with WTs, alongside other malignancies. The number of annually recruited WTs did not change significantly and was less than 20% of the potential candidates. The vast majority of the trials were conducted in North America and 56 different interventions were investigated, including conventional chemotherapy and biologically‐targeted therapies. Overall, 33 WTs revealed some degree of tumour control. Of these, five patients demonstrated complete remission (2%), 15 patients partial response (7%) and 13 patients stable disease (6%). None of the included novel biologically‐targeted therapies emerged as promising interventions and only conventional chemotherapy was able to induce a complete and partial response.</p><p><bold>Conclusions</bold>: We conclude that early phase trial recruitment of WTs is below expected and the clinical outcome of the included patients is dismal. Improvement of the availability and recruitment to early‐phase trials for WTs, especially in Europe, is needed.</p></sec><sec id="pbc26772-sec-5650"><label>P-171</label><title>Single Center Study: Retrospective Study of 12 Cases of Malignant Rhabdoid Tumour of the Kidney (MRTK) in Children</title><p><underline underline-style="single">H.Y. Cheng</underline><sup>1</sup></p><p><italic><sup>1</sup>Beijing Children's hospital, surgical oncology, Beijing, China</italic></p><p><bold>Background/Objectives</bold>: To investigate the clinical characteristics and prognostic factors of malignant rhabdoid tumour of the kidney (MRTK) in children.</p><p><bold>Design/Methods</bold>: Twelve patients with MRTK were diagnosed and treated in Our hospital from January 2007 to December 2015. Variables examined were tumor stage, sex, age at diagnosis, surgical radicality, radiotherapy and chemotherapeutic regimens.</p><p><bold>Results</bold>: The median age of all cases was 15.5 months (4 to 42 months) at the time of diagnosis, 75% of patients were male. The most common presenting complaint was intra‐abdominal mass or pain(75%),gross hematuria (33.3%), tumor rupture(25%).8(75%)had positive lymph nodes or distant parenchymal metastases. The median follow‐up was 22.2 months (rang 14‐55 months),9 died and 3 survived.The 1‐and 3‐year survival rates were 50% and 25%.the whole patients underwent surgery and chemotheropy,3 patients treated combining with radiation therapy, no significant improvement in efficacy. There were no differences in survival between males and females, or younger and older children. 3 cases survived include one of stageⅠ,2 cases of stage Ⅲ.One of stage III patient only underwent one cycle chemotherapy after surgery, she survived disease‐free for 43 months.</p><p><bold>Conclusions</bold>: In infants and children has a dismal prognosis, Surgical radicality seems to be of prognostic value in MRTK. Molecular diagnostics and research is warranted to refine diagnostics and classifying prognostic relevant MRTK subtypes.</p></sec><sec id="pbc26772-sec-5660"><label>P-172</label><title>Malignant Paediatric Abdominal Tumors; Experience at the Children Hospital, Lahore</title><p><underline underline-style="single">M. Faizan</underline><sup>1</sup>, M. Saleem<sup>2</sup>, S. Anwar<sup>1</sup>, N. Talat<sup>2</sup>, P. Najam‐ud‐din<sup>3</sup></p><p><italic><sup>1</sup>The Children's Hospital and Institute of Child Health, Paediatric Haematology/Oncology, Lahore, Pakistan; <sup>2</sup>The Children's Hospital and Institute of Child Health, Paediatric Surgery, Lahore, Pakistan; <sup>3</sup>The Children's Hospital and Institute of Child Health, Paediatric Radiology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: To determine the demographics, Presentation, need of any Surgical intervention and Etiology in Paediatric patients with histologically proven Malignant abdominal masses in children.</p><p><bold>Design/Methods</bold>: A retrospective observational Study carried out in the Hematology and Oncology Department at The Children's Hospital and Institute of Child Health, Lahore,Pakistan. All children with Histologically proven malignant abdominal masses from January 1st 2016 till December 31st 2016 were included. Data regarding age, gender, any surgical intervention required and final diagnosis were analyzed. Neonates, Patients with relapse and in whom diagnosis was not confirmed histologically were excluded form the study. Consecutive sampling technique was used and data analyzed using SPSS 21.</p><p><bold>Results</bold>: Total 191 children diagnosed with malignant abdominal tumor were eligible for study. Majority were male 120(63%), 1‐4years of age 101(53%), and 5‐9yrs of age 58(30%). Commonest presentation was abdominal distension and palpable abdominal mass 186 (97%), In majority mothers 175(91%) only noted abdominal distension while mass was clinically palpable as noted by the oncologist. Abdominal pain was present in 43(22.5%) and fever 23(12%). Diagnosis was made on trucut biopsy in 177(93%) while primary surgical intervention required in 13(7%). Etiology of malignant abdominal masses was Wilms tumor 66(34.6%), neuroblastoma 52(27.2%), Non Hodgkin Lymphoma 34(17.8%), Germ cell tumor 16(3.1%), Rhabdomyosarcoma 6(3%), Hepatoblastoma 7(3.7%), hepatocellular carcinoma 3(1.5%),renal synovial cell carcinoma and adrenocortical tumor in 2(1%)patients each while papillary renal cell carcinoma, undifferentiated synovial sarcoma liver was diagnosed in one patient each.</p><p><bold>Conclusions</bold>: Wilms tumor followed by Non Hodgkin Lymphoma is the most common solid Abdominal Malignancy in paediatric age group. Presentation is mostly in advanced stage with a palpable abdominal mass. Need of surgery was avoided by trucut biopsy at presentation for diagnosis. There is a need to train pediatricians and family physicians along with mothers early recognition of abdominal distension and mass for early diagnosis and better prognosis.</p></sec><sec id="pbc26772-sec-5670"><label>P-173</label><title>Treatment of Extra‐Cranial Malignant Rhabdoid Tumor: Results from the Children's Oncology Group AREN0321 Study</title><p><underline underline-style="single">J. Geller</underline><sup>1</sup>, Y.Y. Chi<sup>2</sup>, J. Kalapurakal<sup>3</sup>, N. Daw<sup>4</sup>, F. Hoffer<sup>5</sup>, E. Perlman<sup>6</sup>, P. Ehrlich<sup>7</sup>, E. Mullen<sup>8</sup>, A. Warwick<sup>9</sup>, A. Paulino<sup>10</sup>, Z. Tochner<sup>11</sup>, K. Gow<sup>12</sup>, P. Grundy<sup>13</sup>, E. Gratias<sup>14</sup>, D. Ward<sup>15</sup>, J. Anderson<sup>16</sup>, C. Fernandez<sup>17</sup>, J. Dome<sup>18</sup></p><p><italic><sup>1</sup>Cincinnati Children's Hospital Medical Center, Pediatrics, Cincinnati, USA; <sup>2</sup>Children's Oncology Group, Biostatistics, Gainsville, USA; <sup>3</sup>Ann and Robert H Lurie Children's Hospital of Chicago, Radiation Oncology, Chicago, USA; <sup>4</sup>MD Anderson Cancer Center, Pediatrics, Houston, USA; <sup>5</sup>Quality Asasurance Review Ctr, Radiology, Lincoln, USA; <sup>6</sup>Ann and Robert H Lurie Children's Hospital of Chicago, Pathology, Chicago, USA; <sup>7</sup>C S Mott Children's Hospital, Surgery, Ann Arbor, USA; <sup>8</sup>Dana‐Farber/Harvard Cancer Center, Pediatric, Boston, USA; <sup>9</sup>Walter Reed National Military Medical Center, Pediatric, Bethesda, USA; <sup>10</sup>MD Anderson Cancer Center, Radiation Oncology, Houston, USA; <sup>11</sup>Childrens Hospital of Philadelphia, Radiation Oncology, Philadelphia, USA; <sup>12</sup>Seattle Children's Hospital, Surgery, Seattle, USA; <sup>13</sup>University of Alberta Hospital, Pediatrics, Edmonton, Canada; <sup>14</sup>eviCore Healthcare, Oncology, Bluffton, USA; <sup>15</sup>St Jude Children's Research Hospital, Pharmacy, Memphis, USA; <sup>16</sup>Merck, Oncology, North Wales, USA; <sup>17</sup>IWK Health Centre, Pediatric and Bioethics, Halifax, Canada; <sup>18</sup>Children's National Medical Center, Pediatrics, Washington DC, USA</italic></p><p><bold>Background/Objectives</bold>: In National Wilms Tumor Studies 1‐5, 4‐year overall survival (OS) for patients with advanced malignant rhabdoid tumor (MRT) was 23%. AREN0321 evaluated a more intensive regimen containing vincristine, doxorubicin, cyclophosphamide alternating with cyclophosphamide, carboplatin, etoposide (Regimen UH‐1), with radiotherapy, with the goal to improve event‐free survival (EFS) and OS.</p><p><bold>Design/Methods</bold>: Patients with stages I‐IV extra‐cranial MRT were eligible. The study was designed to detect an OS of 42%, using the historical OS of 25% as a fixed standard for comparison. Patients with stage IV measurable disease had the option to receive vincristine in combination with irinotecan (VI) in an upfront window.</p><p><bold>Results</bold>: 39 patients with MRT were enrolled (30 with renal,9 with extra‐renal primary tumors). Median age was 11.7 months (range, 1.1‐109.6 months). Stage distribution was I (2), II (5), III (23), and IV (9). No tumor response was seen in the 3 patients who received VI window therapy. Among those with relapse/progression, median time to progression was 5.6 months. The 4‐year EFS and OS estimates for the entire cohort were both 35.9% (95% CI: 18.1%‐53.7%). EFS estimates according to stage were 100% each for stage I and II, 26.1% (95% CI: 0.7%‐51.5%) for stage III and 11.1% (95% CI: 0%‐31.6%) for stage IV. EFS estimates were 43.3% (95% CI: 22%‐64.6%) for renal tumors and 11.1% for extra‐renal tumors. Impact of age, radiotherapy, germline INI1 status and toxicity will be evaluated.</p><p><bold>Conclusions</bold>: Regimen UH1 did not improve survival for the collective group of patients with MRT, though it may have improved outcomes for patients with low‐stage disease.. There was no salvage for patients with relapse or progression. For advanced‐stage MRT, novel therapeutic strategies such as integration of targeted biologics in combination with chemotherapy are needed.</p></sec><sec id="pbc26772-sec-5680"><label>P-174</label><title>Clear Cell SARCOMA of the Kidney (CCSK) in Pediatric Patients: A 28 Years Study from One Institution in Brazil</title><p>F.N. Gutierrez<sup>1</sup>, <underline underline-style="single">F. Rebelo</underline><sup>1</sup>, R. Carvalho<sup>1</sup>, S. Nogueira<sup>1</sup>, S. Coelho<sup>1</sup>, F. Lima<sup>2</sup>, S. Ferman<sup>2</sup>, M. Grabois<sup>2</sup></p><p><italic><sup>1</sup>Instituto Nacional de Câncer, Pediatric Surgery, Rio de Janeiro, Brazil; <sup>2</sup>Instituto Nacional de Câncer, Pediatric Oncology, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: To retrospectively analyze pediatric patients with clear cell sarcoma of the kidney admitted to our institution from February 1987 to December 2015.</p><p><bold>Design/Methods</bold>: Case report forms of pediatric patients (age range: 10 months‐6 years) were retrospectively analyzed. Collected data included demographics, clinical presentation, surgical and oncology management and Follow up. Patients data were updated on March 2017.</p><p><bold>Results</bold>: Among 51 patients diagnosed with non Wilms renal tumors, 24 patients (11 boys, 13 girls) had histopathological diagnosis of CCSK. The median age at diagnosis was 29 months (range: 9 months to 6 years). Presenting symptoms included abdominal mass first noticed by the family in 70,8% of cases, 3 patients had hematuria, 1 patient had abdominal pain. The median time from initial symptoms to suspected diagnosis was 60 days (range: 1 day to 270 days). The mean tumor volume was evaluated pre‐chemotherapy in 8/24 patients and was 644 cm3 (range: 213 to 918 cm3). No patient presented metastasis at diagnosis. Twenty four patients had radical nefrectomy either upfront (14 cases) or after neoadjuvant chemotherapy (10 cases). In 21/24 patients there was free surgical margins and in 3 cases without report. Lymphadenectomy was performed in 15 cases, of which 6 were positive. Surgical stage was: I (n=7), II (n=7) and III (n=10).Overall survival in 7 years was 73.7%. Survival by stage was: 83.3% for stage I, 62.5% for stage II was and 71% stage III. Eight patients had disease relapse: bone (n=4), brain (n=1), lung (n=1), local (n=1), bone and lung (n=1) and 5 of 8 patients died of disease.</p><p><bold>Conclusions</bold>: With multidisciplinary care, treatment result was good. There was no significant difference in survival in relation to initial stage.</p></sec><sec id="pbc26772-sec-5690"><label>P-175</label><title>Surgical Management and Outcomes of Renal Tumors Among Children with IVC/Intracardiac Extension</title><p><underline underline-style="single">H. Halepota</underline><sup>1</sup>, M. Arshad<sup>1</sup>, S. khan<sup>1</sup></p><p><italic><sup>1</sup>Aga Khan university, Paediatric Surgery, Karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Determine outcomes of renal tumor with inferior vena cava(IVC)and intracardiac(IC)extension in our institute. These subset of patients, presents a technical challenge to surgeon especially with constrained resources.</p><p><bold>Design/Methods</bold>: Retrospective cross sectional study.All patients from 1‐16 years of age from January 1998 till June 2016 included</p><p><bold>Results</bold>: During the study period 60 patients with renal tumors were managed. 18 (30%)patients presented with IVC and /or IC extension majority involving right kidney (13/18), most common age at presentation ranged between 1‐5 years. Out of 18 children 55%were male and 45% were female. The level of Tumor extension into IVC was below the diaphragm in 10 (55.5%), above the diaphragm in 8 (44.44%) out of which 5 extending into IC (27.8%).Wilms tumor (83%) was the most common tumor type followed by renal cell carcinoma. Most patients 9(60%) with Wilm's tumor had IVC extension below diaphragm. 7 out of these 9 patients had no recurrence after 5 years of follow up. One had lung metastasis due to tumor spillage and one patient with stage 5 disease expired. Most (5/9) of the patients had received preoperative chemotherapy, 3 underwent direct thrombectomy. 5 patients had intra‐atrial extension; all received preoperative chemotherapy 2 showed no recurrence after 5 years. 2 patients had Renal cell carcinoma and 1 had Rhabdoid tumor.</p><p><bold>Conclusions</bold>: In our study 30% incidence of IVC and or IC Tumor extension is much higher than the reported series.This high incidence can be explained that many of these patients were referred from other institutions.2 patients in our study had surgical complications: In our study no patient required cardiopulmonary bypass as preoperative chemotherapy reduced the thrombus to IVC., most patients received pre‐operative chemotherapy as well as preoperative radiotherapy in case of metastatic disease. 61% of these patients are disease free on five years of follow up.</p></sec><sec id="pbc26772-sec-5700"><label>P-176</label><title>Clinical Outcomes of Children with Wilms Tumor Treated on a Modified SIOP WT 2001 PROTOCOL and Comparison with A Historic Cohort Treated with Upfront Surgery</title><p><underline underline-style="single">R. John</underline><sup>1</sup>, J. Kurian<sup>2</sup>, L.G. Mathew<sup>1</sup>, S. Sen<sup>2</sup></p><p><italic><sup>1</sup>Christian Medical College, Pediatric Hematology Oncology, Vellore, India; <sup>2</sup>Christian Medical College, Pediatric Surgery, Vellore, India</italic></p><p><bold>Background/Objectives</bold>: To analyze the clinical profile of children with Wilms tumor treated by the modified SIOP protocol and compare with historical patients treated on the NWTS protocol</p><p><bold>Design/Methods</bold>: Clinical, radiological and biopsy data of 59 children diagnosed to have Wilms tumor from 2004 to 2014 and treated using the SIOP WT 2001 protocol, with a minor modification of pre‐operative posterior flank core biopsy, were collected from their medical records. The outcome of this cohort was compared with 62 children treated from 1985 – 1995 on the NWTS protocol from two centres, including our centre and reported by Sen et al.</p><p><bold>Results</bold>: The median age at diagnosis was 36 months. M: F was1:0.7. 31% had metastatic disease, 18% had renal vein/IVC thrombosis and 10% had bilateral tumour. 97% had favourable histology. Mean tumour volume reduced from 523ml to 315ml following neoadjuvant chemotherapy. 55 children underwent surgery and 52 completed treatment. 2 children had tumour spill and one had recurrence at biopsy site.</p><p>After a mean follow up of 42 months, 43 are in CR1 and 4 in CR2. The OS was 80% and EFS was 73%. Comparing this data with the historical cohort: OS 80 vs 55%, stage I‐ 100 vs 81%, II‐90 vs 75%, III‐ 80 vs 42% IV‐ 53 vs 14%, V‐ 67 vs 50%. OS for localized disease 97 vs 80% and metastatic disease 50 vs 18%.</p><p><bold>Conclusions</bold>: There is significant improvement in OS of all stages of Wilms tumour treated on SIOP‐WT‐2001 protocol compared to historic cohort treated with upfront surgery followed by chemotherapy. In centres where patients present with large tumours, use of neoadjuvant chemotherapy followed by surgery is preferable. The outcome of the cohort treated on SIOP‐WT‐2001 protocol for localised disease is comparable with data from developed countries, however it is less for metastatic disease.</p></sec><sec id="pbc26772-sec-5710"><label>P-177</label><title>Bilateral Wilms Tumor, Demographic Characteristics, Treatment and Outcome: A Multicenter Study</title><p><underline underline-style="single">R. Kebudi</underline><sup>1</sup>, D. Tugcu<sup>2</sup>, F. Akici<sup>3</sup>, T. Celkan<sup>4</sup>, S. Vural<sup>5</sup>, G. Tokuc<sup>6</sup>, G. Aydogan<sup>3</sup>, Z. Karakas<sup>2</sup>, B. Zulfikar<sup>1</sup>, S. Bay<sup>7</sup>, S. Yilmaz<sup>8</sup>, A. Irıbas<sup>9</sup>, A. Celik<sup>10</sup>, C. Buyukunal<sup>11</sup>, F. Gun Soysal<sup>10</sup>, S. Kuroglu<sup>12</sup>, I. Adaletli<sup>12</sup>, B. Bilgic<sup>13</sup>, E. Darendeliler<sup>9</sup></p><p><italic><sup>1</sup>Istanbul University Cerrahpasa Medical Faculty & Oncology Institute, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>2</sup>Istanbul University‐ Istanbul Medical Faculty, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>3</sup>Kanuni Sultan Suleyman Education and Research Hospital, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>4</sup>Istanbul University‐ Cerrahpasa Medical Faculty, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>5</sup>Sisli Etfal Education and Research Hospital, Pediatric Oncology, Istanbul, Turkey; <sup>6</sup>Marmara University‐ Pendik Education and Research Hospital, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>7</sup>Istanbul University Oncology Institute, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>8</sup>Yeditepe University, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>9</sup>Istanbul University‐ Oncology Institute, Radiation Oncology, Istanbul, Turkey; <sup>10</sup>Istanbul University‐ Istanbul Medical Faculty, Pediatric Surgery, Istanbul, Turkey; <sup>11</sup>Istanbul University Cerrahpasa Medical Faculty, Pediatric Surgery, Istanbul, Turkey; <sup>12</sup>Istanbul University‐ Cerrahpasa Medical Faculty, Radiology, Istanbul, Turkey; <sup>13</sup>Istanbul University‐ Istanbul Medical Faculty, Pathology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Bilateral Wilms tumor (BWT) comprise 5% of all Wilms tumor in children. The outcomes of children with BWT are reported to be inferior than for children with unilateral tumors at diagnosis.</p><p><bold>Design/Methods</bold>: In this multicentric study, patients with BWT treated in seven centers in Istanbul were retrospectively evaluated for demographic characteristics, treatment and outcome.</p><p><bold>Results</bold>: Thirty one patients (19 female, 12 male) with a median age of 22.5 months (4‐63) treated between 1990‐2017 were evaluated. Nine patients had various congenital conditions. Eight patients (26%) had metastasis (lung, liver) at diagnosis. Eighteen patients had a biopsy (58%), 8 patients unilateral nephrectomy (26%) at diagnosis. Five (16%) patients were diagnosed as BWT only radiologically. Anaplasia was found in 4 patients. All received chemotherapy (vincristine, actinomycine D±adriamycine (VAD) initially). Radiologic response to VAD given the same day was better. Twenty five patients underwent surgery (8 unilateral nephrectomy; 8 unilateral nephrectomy+partial contralateral nephrectomy; 4 unilateral nephrectomy+contralateral tumor excision; 2 bilateral partial nephrectomy; 1 unilateral partial nephrectomy+ contralateral tumor excision; 1 bilateral tumor excision; 1 unilateral tumor excision). Fifteen patients (48%) received radiotherapy. Three patients (9.6%) who never had surgery are alive with no disease (14‐36 months from diagnosis). Two patients (6.5%) developed chronic renal failure. Four patients died due to progressive disease. Overall survival was 79% and event free survival 73%, at a median follow up of 57 months (3‐322). Survival was significantly lower in metastatic patients (95 vs 48%) (p=0.04) and in those with anaplasia in histopathology (95 vs 0%) (p=0.001).</p><p><bold>Conclusions</bold>: Treatment of BWT is a challenge and the goal is to have a good survival and to spare normal renal parenchyma from unnecessary surgical resection, when possible. In this series, the survival in nonmetastatic patients with favorable histology is quite high with most of the surviving patients having adequate renal function.</p></sec><sec id="pbc26772-sec-5720"><label>P-178</label><title>Outcomes of Nephroblastoma (Wilms Tumor) Treatment in Western Ukraine, A 10 Year Report from a Retrospective Cohort Analysis</title><p><underline underline-style="single">R. Kizyma</underline><sup>1</sup>, Z. Kizyma<sup>1</sup>, I. Lukavetskyi<sup>1</sup>, B. Romanyshyn<sup>1</sup>, B. Kotsay<sup>2</sup>, A. Kuzyk<sup>2</sup>, A. Synyuta<sup>1</sup>, M. Zakharus<sup>1</sup>, I. Shchurovska<sup>3</sup>, R. Sobko<sup>3</sup></p><p><italic><sup>1</sup>Western Ukrainian Specialized Children's Medical Centre, Surgery/Pediatric Oncology, Lviv, Ukraine; <sup>2</sup>Lviv National Medical University, Pediatrics, Lviv, Ukraine; <sup>3</sup>Western Ukrainian Specialized Children's Medical Centre, Intensive Care Department, Lviv, Ukraine</italic></p><p><bold>Background/Objectives</bold>: The objectives of the analyses study were to review the clinical presentation and management of children with Wilms tumor and the factors influencing the outcome in Lviv region. Despite the good overall prognosis in patients with nephroblastoma, most children in the developing country present with advanced stage of disease at diagnosis.</p><p><bold>Design/Methods</bold>: A retrospective chart review of 46 children with renal tumours mostly from western part of Ukraine treated and observed at surgery department of our institution from 2005 to 2015 was performed. Diagnosis was confirmed by conventional CT, MRI and sonography, that were performed according to the site of involvement. The treatment protocol was based on SIOP recommendations.</p><p><bold>Results</bold>: More than a half of patients presented with large primary tumour or metastatic spread of disease: 17 cases (37%) were diagnosed as stage III, 10 cases (21.7%) as stage IV. Stage I was diagnosed in 5 patients (10.9%) and stage II in 10 children (21.7%). Four cases with bilateral disease (stage V) were observed with dominant tumour referring to stage III. The neoadjuvant vincristin‐dactinomycin chemotherapy regimen was used as standart with no upfront surgeries (nephrectomy or biopsy) performed in majority of cases. Unfavourable histological type (including clear cell sarcoma) was revealed in 17.4%. Adjuvant high risk chemotherapy and use of radiotherapy was considered in 43.5% of children mostly due to massive tumour spread at diagnosis. The 3‐year overall survival (OS) and event free survival (EFS) rates were 87% and 83%, respectively. Primary tumour stage was the most statistically significant factor that influenced the overall survival.</p><p><bold>Conclusions</bold>: The approach of neoadjuvant chemotherapy of nephroblastoma is more feasible compared to upfront surgery in the realms of developing country, considering statistically larger amount of advanced stage tumours at presentation.</p></sec><sec id="pbc26772-sec-5730"><label>P-179</label><title>Wilms Tumor: A Retrospective Study of a Single Institute</title><p><underline underline-style="single">T. Mehmood</underline><sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Memorial Cancer Hospital and Research Centre, Radiation Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: To compare our results to SIOP 9 study.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed 45 children with Wilms Tumor (WT) treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre Lahore, Pakistan from January 2001 to December 2010. Kaplan Meier method with Log‐Rank testing was employed for survival analysis.</p><p><bold>Results</bold>: The mean age was 3.5 years old, with a sex ratio 0.48. Eighty percent of the children presented a painless abdominal tumor as a first sign. The tumor was mainly unilateral (93%), right for 56% of them. Ultrasounds, computed tomography showed a heterogeneous tumor in 52%, with a medium size of 16.5 cm, developed in 48% in the lower pole of the kidney. Venous thrombosis was diagnosed in 6.5% of the patients. 23% of the patients had metastatic disease at presentation. Most of the patients received preoperative chemotherapy (98.3%) followed by nephrectomy. Postoperative stage I, II, III were respectively 39%, 41%, 20% and according to SIOP 9 risk classification, there were 28%, 62%, 10% of low, intermediate and high histological risk. Postoperative chemotherapy was received in 84% while adjuvant radiotherapy was given to 16% of the patients. The five‐year overall survival was 68%, 80% in localized stages and 46% in metastatic stages. Thirty‐four percent relapsed in an average of 9 months. No late treatment related side effects were seen.</p><p><bold>Conclusions</bold>: This study shows less overall survival then the SIOP 9, due to a bigger rate of metastatic forms and late diagnosis.</p></sec><sec id="pbc26772-sec-5740"><label>P-180</label><title>Renal Tumors in Children: A 25‐Year Single Center Experience</title><p><underline underline-style="single">M. Moschovi</underline><sup>1</sup>, A. Zampogiannis<sup>1</sup>, A. Athanasiadou<sup>1</sup>, I. Nikas<sup>2</sup>, K. Stefanaki<sup>3</sup>, G. Chrousos<sup>1</sup></p><p><italic><sup>1</sup>University of Athens Medical School, 1st Pediatric Dept‐ Hematology/Oncology Unit, Athens, Greece; <sup>2</sup>University of Athens Medical School, Imaging Department‐ “AGIA SOPHIA” Children's Hospital, Athens, Greece; <sup>3</sup>University of Athens Medical School, Pathology Department‐ “AGIA SOPHIA” Children's Hospital, Athens, Greece</italic></p><p><bold>Background/Objectives</bold>: Nephroblastoma, or Wilms’ tumor, is the most common renal malignancy in childhood. The median age at diagnosis is approximately 3.5 years. The occurrence in infancy and adolescence is quite rare. Other less frequent tumors include mesoblastic nephroma, clear cell sarcoma, rhabdoid tumor and adenocarcinoma.</p><p><bold>Design/Methods</bold>: We reviewed all children with renal tumors treated in our center in the last 25 years and evaluated demographic features, histopathologic results and outcome.</p><p><bold>Results</bold>: Out of a total of 91 cases with renal tumor, there were 85 cases of nephroblastoma (34M, 51F), three cases of mesoblastic nephroma, one of clear cell sarcoma, one of rhabdoid tumor, and one of anaplastic sarcoma. Specifically regarding nephroblastoma, the age at diagnosis ranged from 4mo‐14yrs (mean: 4.2yrs): 2 children (2,5%) were <6mo, 35 children (41%) were 6mo–3yrs, 41 children (48%) were 3‐10yrs and 7 children (8,5%) were >10yrs old. In three cases, nephroblastoma developed in the context of a genetic syndrome, specifically two cases of Denys‐Drash syndrome and one of WAGR syndrome. 35 patients resided in large urban centers and 48 resided in the province. Relapse was observed in two cases, 12 (M) and 17 (F) years after the initial diagnosis, respectively, with the relapse in the second case occurring two years after pregnancy. Now, both cases are in second remission. One case with Denys‐Drash syndrome remains in remission ten years after diagnosis. Three cases died: two with nephroblastoma‐one from the disease and the other with Denys‐Drash syndrome from renal failure‐ and one with rhabdoid tumor.</p><p><bold>Conclusions</bold>: Nephroblastoma is nowadays a curable disease. We observed a higher mean age at diagnosis than those recorded in international data. This may denote a delay in diagnosis and thus a need for a higher level of awareness. Since relapse can occur decades after the initial diagnosis, a long‐term follow‐up is required.</p></sec><sec id="pbc26772-sec-5750"><label>P-181</label><title>Single and Tandem High‐Dose Chemotherapy Followed by Autologous Stem Cell Rescue in Wilms Tumors: A Single‐Institution Report on Feasibility and Toxicity Profile</title><p><underline underline-style="single">M. Delafoy</underline><sup>1</sup>, C. Pasqualini<sup>1</sup>, C. Dufour<sup>1</sup>, I. Hezam<sup>2</sup>, G. Goma<sup>3</sup>, V. Lapierre<sup>4</sup>, D. Valteau‐Couanet<sup>1</sup></p><p><italic><sup>1</sup>Gustave Roussy, Children and Adolescent Oncology Unit, Villejuif, France; <sup>2</sup>Gustave Roussy, Clinical Research Operations Department, Villejuif, France; <sup>3</sup>Gustave Roussy, Biostatistic and Epidemiology Unit, Villejuif, France; <sup>4</sup>Gustave Roussy, Cell Therapy Unit, Villejuif, France</italic></p><p><bold>Background/Objectives</bold>: Very few data have been reported yet on high‐dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) in Wilms tumors (WT). We aim to define the feasibility and the safety profile of HDC with ASCR in a pediatric cohort of WT.</p><p><bold>Design/Methods</bold>: We analysed data from patients with WT treated with HDC and ASCR from 2000 to 2016 in the Children and Adolescent Oncology Unit at Gustave Roussy. Toxicity is reported according to CTCAE v4.0.</p><p><bold>Results</bold>: Ten patients received HDC with ASCR, 5 as single (Melphalan‐Etoposide Carboplatine (MEC), n=4; Thiotepa 900mg/m<sup>2</sup>, n=1), and 5 as a tandem HDC (Thiotepa 720mg/m<sup>2</sup> with ASCR, followed after 6 weeks by Etoposide 1.8g/m²‐Melphalan 140mg/m<sup>2</sup>, n=4; tandem Thiotepa 900 mg/m², n=1). The median age at ASCR was 5.6 years (2.6‐21.2). HDC was performed at relapse for 9 patients and as first‐line in 1 patient with stage 4 high‐risk WT. Most observed toxicity was digestive with grade ≥ 3 mucositis and diarrhoea in 6 and 3 patients, respectively. One grade 3 renal toxicity was displayed after MEC. No neurological toxicity was observed nor sinusoidal obstruction syndrome. The median duration of neutrophil recovery and hospitalisation was 10 (2‐13) and 24 days (21‐36), respectively. No toxicity‐related death was observed. Toxicity profile was similar in single and tandem HDC. Whenever needed, the treatment could be completed by lung and/or liver radiotherapy, with no significant delay. At the last follow‐up, 4 patients were alive in complete remission (CR1 n=1; CR2 n=3), while 6 patients died of progressive disease.</p><p><bold>Conclusions</bold>: Single and tandem HDC seems to be feasible and with an acceptable toxicity profile in WT. Prospective national and international studies are needed to define the best condition regimens and to evaluate the role of HDC in this setting.</p></sec><sec id="pbc26772-sec-5760"><label>P-182</label><title>Consolidation Therapy with Autologous Hematopoietic Stem Cell Transplant in Patients with Relapsed Wilms Tumour. Experience of A Single Mexican Pediatric Hospital</title><p>A. Castellanos<sup>1</sup>, <underline underline-style="single">H.</underline><underline underline-style="single">Pena</underline><sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Pediatría, Oncology, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: To determine the experience of a therapeutic arm with autologous hematopoietic stem cell rescue in wilms tumour's patients at National Institute of Pediatrics (INP) in Mexico City</p><p><bold>Design/Methods</bold>: We performed a retrospective study with the analysis of 10 years of experience at INP of patients with Wilms Tumour. We only analized patients with relapse</p><p><bold>Results</bold>: A total of 9 relapses (8%) were diagnosed, including 5 patients (55%) with wilms tumour relapse who received treatment with intense chemotherapy, radiation therapy and autologous hematopoietic stem cell transplantation. The mean age at diagnosis was 38 months with a mean relapse time from diagnosis of 18 months. Favorable histology was reported in 2 patients, and all the cases were metastatic at diagnosis, all cases with lung metastasis and one patient also liver. All patients received intense chemotherapy with ifosfamide 1.8grm2scdose / 5 days, etoposide 100mgm2scdose / 5 days and carboplatin 450mgm2scdose / 1 day (ICE) as well as abdominal/pulmonary radiation therapy for the treatment of relapse.The 5‐year overall survival is 57% (95% CI 2.46‐9.00). The cause of death was progression of disease in both cases. No transplant‐related mortality was reported</p><p><bold>Conclusions</bold>: Treatment of relapse in wilms tumor with combination therapy (radiation, chemotherapy and stem cell transplant) is effective. Morbi‐mortality related to intensive treatment was no reported in our cases</p></sec><sec id="pbc26772-sec-5770"><label>P-183</label><title>Association Between Long Interspersed Nuclear Element‐1 Methylation Levels and Relapse in Blastemal Component of Wilms Tumors</title><p><underline underline-style="single">B. Pereira</underline><sup>1</sup>, R. Montalvao‐de‐Azevedo<sup>1</sup>, P. Faria<sup>2</sup>, P. Nicolau Neto<sup>3</sup>, M. Maschietto<sup>4</sup>, B. de Camargo<sup>1</sup>, S. Coelho Soares Lima<sup>3</sup></p><p><italic><sup>1</sup>Instituto Nacional de Cancer, Pediatric Hematology Oncology Programa, Rio de Janeiro, Brazil; <sup>2</sup>Instituto Nacional de Cancer, Patholgy Division, Rio de Janeiro, Brazil; <sup>3</sup>Instituto Nacional de Cancer, Carcinogenesis molecular Program, Rio de Janeiro, Brazil; <sup>4</sup>Brazilian Biosciences National Laboratory LNBio‐, Brazilian Center for Research in Energy and Materials CNPEM‐, Campinas, Brazil</italic></p><p><bold>Background/Objectives</bold>: Risk stratification of Wilms tumors (WTs) is largely based on tumor stage and histology, with the blastemal component predominance in chemotherapy pretreated WT classifying patiets as high risk. WTs present an hypomethylation profile compared to matched normal kidney. We aimed to explore the relation between global DNA methylation, represented by LINE‐1 (17% of the human genome) in WT blastemal component and prognostic factors</p><p><bold>Design/Methods</bold>: Samples from 47 FFPE sporadic unilateral WTs from patients treated according to the SIOP WT 2001 protocol at INCA (Brazil) were reviewed by pathologist who defined areas of blastema and normal renal cortex tissues. Prognostic factors (age, gender and risk classificaion) and relapse were explored regarding LINE‐1 methylation as defined by pyrosequencing. Average methylation of 5 CpG sites located in LINE‐1 were used for analyzes.</p><p><bold>Results</bold>: Comparing WT blastemal (median of 65%, 47.4‐73.2%) to normal kidney (median of 71.8%, 51.5‐77.5%) samples revealed that LINE‐1 is hypomethylated in WT (p<0.0001). Age, gender, stage and risk classification showed no relation with methylation levels within WT samples. Nevertheless, tumors from patients who relapsed (60.5%, 47.4‐71.30%) presented lower methylation levens than those patients without relapse (66.5%, 52.8‐73.30%, p=0.0005). A ROC curve analysis using a cut‐off value of 62.71% for LINE‐1 methylation levels showed that the area under the curve (AUC) was 0.80, with a sensitivity of 76.5% and a specificity of 83.3% (p=0.0005).</p><p><bold>Conclusions</bold>: We suggest that LINE‐1 methylation levels evaluated in the blastemal component of WT can be used as a marker for patients, with WT that presented relapse reporting hypomethylation compared to patients without relapse</p></sec><sec id="pbc26772-sec-5780"><label>P-184</label><title>Challenges and Implications of Histopathology Diagnosis of ‘Non‐Wilm's’ Tumours of Kidney in Children</title><p><underline underline-style="single">M. Ramadwar</underline><sup>1</sup>, A. Sali<sup>1</sup>, B. Rekhi<sup>1</sup>, S. Qureshi<sup>2</sup>, G. Chinnaswamy<sup>3</sup>, T. Vora<sup>3</sup>, N. Khanna<sup>4</sup>, S. Medhi<sup>5</sup></p><p><italic><sup>1</sup>TATA Memorial Hospital, Pathology, Mumbai, India; <sup>2</sup>TATA Memorial Hospital, Paediatric Surgery, Mumbai, India; <sup>3</sup>TATA Memorial Hospital, Medical Oncology, Mumbai, India; <sup>4</sup>TATA Memorial Hospital, radiation oncology, Mumbai, India; <sup>5</sup>TATA Memorial Hospital, Radiolgy, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: ‘Non‐Wilm's’ tumour category constitutes several rare benign and highly aggressive tumours of kidney in children. We aim to review histopathology of ‘non‐Wilm's’ tumours with emphasis on diagnostic challenges and clinical relevance of the precise diagnosis.</p><p><bold>Design/Methods</bold>: We reviewed histopathology and immunohistochemistry (IHC) of 55 patients diagnosed with ‘non‐Wilm's’ renal tumours from period 2011‐ 2016. Clinical details were noted from electronic medical records.</p><p><bold>Results</bold>: Various non‐Wilm's renal tumours in our series of 55 patients were rhabdoid tumour (20), clear cell sarcoma (11), congenital mesoblastic nephroma (4), Ewing's sarcoma/ PNET (3), Translocation associated renal cell carcinoma (5), cystic partially differentiated nephroblastoma (2), Papillary RCC (1),Burkitt's lymphoma (1), granulocytic sarcoma (1). All rhabdoid tumours showed loss of INI1 on IHC. Remaining 8 tumours posed diagnostic problems. Distinction between clear cell sarcoma and Wlim's tumour could not be resolved (2). Undifferentiated round cell tumours posed a problem of differentiation between PNET, Wilm's tumour and synovial sarcoma respectively (5), Teratoid Wilm's and teratoma could not be distinguished.</p><p>11 of 20 patients with rhabdoid tumour underwent resection post‐chemotherapy. 3 patients presented with extensive brain and lung metastasis. Rest were inoperable tumours. 7 of 11 patients with clear cell sarcoma could undergo resection. Relapses were in the form of bone and brain metastasis.</p><p><bold>Conclusions</bold>: Rhabdoid tumour and clear cell sarcoma were commonest ‘non‐Wilm's‘ tumours in our series (31/55). CMN represented benign tumours. Rhabdoid tumours were the most aggressive tumours. Tumours with undifferentiated round cell morphology posed diagnostic problem. Clear cell sarcoma also posed a diagnostic problem due to its non‐discrete morphology and lack of specific immunoprofile. Diagnosis of rhabdoid tumours was facilitated by its distinctive morphology and loss of INI‐1 expression on IHC. Thus our study emphasises the need of precise diagnosis on biopsy due to its impact on treatment decisions of wide variety of different tumour entities.</p></sec><sec id="pbc26772-sec-5790"><label>P-185</label><title>Tumor Inferior VENA CAVA (IVC) Thrombosis in Children with Nephroblastoma</title><p>M. Rubanskaya<sup>1</sup>, K. Anatoliy<sup>1</sup>, <underline underline-style="single">K. Polad</underline><sup>1</sup>, R. Mikhail<sup>1</sup></p><p><italic><sup>1</sup>Cancer research instutute N.N. Blokhin RAMS, children oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Nephroblastoma is one of the most common solid tumors in childhood (about 7%). The incidence of tumor thrombosis in nephroblastoma according to various large studies is 3 to 6%. In the literature there are rare individual descriptions of cases of thrombosis of children with nephroblastoma with the spread of thrombus to the atrium.</p><p><bold>Design/Methods</bold>: In our clinic from 1990 to 2016 were treated 24 children with nephroblastoma, with IVC thrombosis. Age of children ranged from 1 year to 15 years. In 2 of these, the thrombus reached the right atrium. Treatment included preoperative chemotherapy, surgery (nephrectomy, thrombectomy) and postoperative radiation therapy and chemotherapy.</p><p><bold>Results</bold>: Survival in stage III nephroblastoma does not differ from survival in nephroblastoma with tumor IVC thrombosis. With preoperative chemotherapy, complete regression of the tumor thrombus can be achieved in 57.9% of cases, partial regression in 21.1%. Preoperative chemotherapy reduces intraoperative blood loss and the frequency of surgical complications. Under the condition of radical operation, the localization of lesions of different sections of the IVC does not affect survival. Currently, 22 children were alive without evidence of recurrence and disease progression.</p><p><bold>Conclusions</bold>: Complex therapy allows to achieve a good overall survival of children with nephroblastoma with IVC thrombosis.</p></sec><sec id="pbc26772-sec-5800"><label>P-186</label><title>The Outcome of Ruptured Wilms Tumor: Single Institution Experience</title><p><underline underline-style="single">T. sarrawi</underline><sup>1</sup>, T. ISMAEEL<sup>1</sup>, H. HALALSHEH<sup>1</sup>, R. DEEBAJAH<sup>1</sup>, K. ghandoUr<sup>1</sup>, F. AJLOUNI<sup>1</sup>, I. SULTAN<sup>1</sup></p><p><italic><sup>1</sup>King Hussein Cancer Center, Pediatric, Amman, Jordan</italic></p><p><bold>Background/Objectives</bold>: Patients with Wilms tumor (WT) can present with ruptured tumors with no specific symptoms. Radiologic diagnosis, pathological confirmation and optimal management are necessary to improve the outcome of these patients.</p><p><bold>Design/Methods</bold>: We conducted a retrospective chart‐review of all pediatric patients who were diagnosed with WT between 2003‐2016. Ruptured Wilms Tumor was diagnosed based on radiological and/or pathological findings</p><p><bold>Results</bold>: Twenty seven patients (Males, 52%) were analysed. Median age at diagnosis was 4.5 years (range, 1.6‐15.8). Pathological local stages, irrespective of rupture, were as follows: I (n=3, 11%), II (n=7, 26%), III (n=17, 63%). The median duration of symptoms before presentation was 2 weeks (range, 0‐17). Twenty three (85%) patients had favorable histology. Distant metastasis was found in 8(29.6%) patients at presentation. Upfront nephrectomy was done for 9(33.3%) of patients. Ruptured WT was identified radiologically in 21(78%) patients and intraoperatively in 6 patients (22%). Rupture was pathologically confirmed in 13 patients (48%). Twenty five (93%) patients received postoperative radiotherapy, whether flank or whole abdomen. Relapse developed in 8(30%) patients, and 6 of them died. One of the relapsed patients was not upstaged and 2 of them did not receive radiotherapy. The 3‐year OS and EFS were 69±11% and 66±9.9%, respectively. Univariate analysis showed relatively worse EFS for patients with age less than 4 years (p=0.059). In further analysis, no difference in outcome was observed according to duration of symptoms, use of radiotherapy or upfront nephrectomy.</p><p><bold>Conclusions</bold>: Similar to previous reports, we showed that majority of patients with rupture can be cured with a 3‐drug regimen and abdominal radiation. Clinico‐radiological‐pathological correlation is important to diagnose these patients. The current staging system is not optimal to capture these patients and needs to be revised.</p></sec><sec id="pbc26772-sec-5810"><label>P-187</label><title>Presentation and Outcomes of Wilms Tumour in a Paediatric Oncology Unit in Ghana</title><p><underline underline-style="single">L.G. Tagoe</underline><sup>1</sup>, E. Nyarko<sup>1</sup></p><p><italic><sup>1</sup>Korle Bu Teaching Hospital, Child Health, Accra, Ghana</italic></p><p><bold>Background/Objectives</bold>: Wilms tumour is the fourth commonest childhood malignancy in Ghana. The survival of Wilms tumour in sub‐Saharan Africa is reported to be below 50%. The objective of this study is to describe the presentation of Wilms tumour, extent of spread at presentation and patient outcomes.</p><p><bold>Design/Methods</bold>: In this retrospective study, clinical notes, including results of investigations of children diagnosed with Wilms tumour at the Paediatric Oncology Unit of the Korle‐bu Teaching Hospital, Accra, from January 2011 to December 2015 were reviewed. Data was then analysed for time lag between symptom onset, presentation and start of treatment, evidence of metastases, histopathological features and patient outcomes.</p><p><bold>Results</bold>: Fifty‐one case notes (54%) were retrieved out of the ninety‐four cases seen over the period. Majority of the patients (37%) were between three to five years old with a male: female ratio 1:1.7. Five (10%) had bilateral disease. The commonest presenting complaint was a painless abdominal mass (47%). Most patients delayed in seeking medical help with 53% presenting after a month. In majority (98%) of the patients, maximum tumour diameter was >8cm by imaging. 11 cases (22%) had metastases at presentation, to the lungs and/or liver. 96% of patients received treatment, which in all cases, except two, involved neoadjuvant chemotherapy prior to nephrectomy. 35% of cases were found to be Stage III at surgery. 57% were classified as intermediate risk at histopathology and 20% high risk. 33% received adjuvant radiotherapy. 9 patients (18%) abandoned treatment, whilst 55% completed treatment and are currently alive. 8 patients (16%) relapsed after treatment completion. 7 patients (14%) died either before, during treatment or after relapse.</p><p><bold>Conclusions</bold>: Although most children with Wilms tumour in our setting present with advanced stage disease (stages III to V), with the appropriate treatment including radiotherapy, the outcomes are encouraging.</p></sec><sec id="pbc26772-sec-5820"><label>P-188</label><title>Intussusception After Renal Tumor Surgery in Children: Two Cases and an Overview of Literature</title><p><underline underline-style="single">S. van Peer</underline><sup>1</sup>, C. van de Ven<sup>1</sup>, S. Terwisscha van Scheltinga<sup>1</sup>, J. Hol<sup>1</sup>, M. van Grotel<sup>1</sup>, M. van den Heuvel‐Eibrink<sup>1</sup></p><p><italic><sup>1</sup>Princess Máxima Center for Pediatric Oncology, Pediatric Oncology, Utrecht, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: To further optimize survival rates as well as quality of cure for pediatric kidney tumors, attention for treatment related morbidity and mortality has become increasingly important. Intussusception is a rare but important complication after tumornephrectomy in children, causing morbidity, mortality and prolonged hospitalization. In this study, we describe two recent cases in our institute and provide a comprehensive review of the literature.</p><p><bold>Design/Methods</bold>: For our narrative review, we searched for all reported cases of post tumornephrectomy intussusception published until November 2016, using Pubmed and Embase libraries.</p><p><bold>Results</bold>: A total of 52 pediatric renal tumor cases who developed intussusception after tumornephrectomy were identified. Median age was 23 months (range 5‐84). Median time of onset was postoperative day 6 (range 3‐37). Of 41 patients described in detail, 37 suffered from a ileoileal intussusception, 4/41 were ileocolic. Most frequent presenting symptom was bilious vomiting. Preceding treatment approach could was documented in 45 cases; i.e. preoperative chemotherapy was administered to 10/45 patients. In 29 of 30 well documented cases successful manually reduction through re‐laparotomy was described and only 1 patient needed resection. All patients survived without recurrence of intussusception.</p><p><bold>Conclusions</bold>: In pediatric renal tumor patients small bowel obstruction seems to reflect most postnephrectomy intussusception cases in contrast to the ileocolic idiopathic intussusceptions that are observed in healthy children. Symptoms of intussusception mimic chemotherapy related toxicity and general post‐surgical symptoms, thereby initiating a significant delay in diagnosis. Awareness of intussusception after renal tumor surgery is warranted.</p></sec><sec id="pbc26772-sec-5830"><label>P-189</label><title>Evaluation of Preoperative Tace in Children with Advanced Wilm's Tumor</title><p><underline underline-style="single">C. Lai</underline><sup>1</sup>, J. Wang<sup>2</sup>, Q. Shu<sup>2</sup>, M. Li<sup>2</sup></p><p><italic><sup>1</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Radiology, Hangzhou, China; <sup>2</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Surgical Oncology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: To evaluate the efficacy of preoperative TACE in children with advanced Wilm's tumor.</p><p><bold>Design/Methods</bold>: In the late 62 cases of advanced Wilms tumor, inclusion criteria: ① tumor diameter> 10cm or medial border over midline;② imaging studies suggest tumor invasion of adjacent organs, have abdominal aortic lymph node metastasis or ascites;③ inferior vena cava tumor thrombosis; ④ the lung, liver, bone and other distant metastases; ⑤ bilateral Wilms tumor. Study groups:① Preoperative arterial chemoembolization group (31 cases), ② Preoperative intravenous chemotherapy group (20 cases), ③ Early surgery group (11 cases).</p><p><bold>Results</bold>: Preoperative TACE group average reduction of 32.4% of tumor, preoperative chemotherapy tumor shrinkage of 20.3%, the tumor volume reduction rate between the two groups was statistically significant.Three groups of patients with complete resection rate was 87.1%, 70.0% and 18.2%, preoperative TACE group with preoperative chemotherapy group, the difference was statistically significant.</p><p><bold>Conclusions</bold>: Preoperative TACE has higher tumor shrinkage rate, shorter peroperatin treatment time, less systemic toxicity, higher rate of complete tumor resection. TACE is safe and effective in advanced Wilm's tumor.</p></sec><sec id="pbc26772-sec-5840"><label>P-190</label><title>Evaluation of Preoperative Transarterial Chemoembolization in Wilms’ Tumor</title><p>Z. Sun<sup>1</sup>, <underline underline-style="single">D. Hu</underline><sup>1</sup>, J. Chen<sup>1</sup>, H. Jin<sup>1</sup>, X. Guo<sup>1</sup>, X. Fang<sup>1</sup>, J. Wang<sup>2</sup></p><p><italic><sup>1</sup>Jinhua Municipal central hospital, Department of pediatric surgery, Jinhua, China; <sup>2</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Surgical Oncology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: To evaluate the efficacy of transarterial chemoembolization (TACE) combining with surgery in the treatment of Wilms’ tumor in children.</p><p><bold>Design/Methods</bold>: Twenty‐four cases of wilms’ tumor were admitted to the department of pediatric surgery in Jinhua municipal central hospital between January 2010 and December 2016. Three cases of bilateral tumor and 1 case of solitary tumor were excluded, 20 cases of unilateral wilms’ tumor were randomly allocated to preoperative TACE group ( preoperative TACE + surgery, n = 10) and control group (preoperative chemotherapy + surgery, n = 10). The shrinkage volume of tumor between pre‐ and post‐chemotherapy, blood loss during surgery, intra‐operative tumor spillage, operative time and postoperative complications were analyzed.</p><p><bold>Results</bold>: Comparing with control group, the shrinkage volume of tumor is higher in the preoperative TACE group (476.9±156.75cm<sup>3</sup> vs. 577.5±138.35cm<sup>3</sup>, <italic>P<0.05</italic>), blood loss during surgery was less (97.5±21.63ml vs. 119±26.23ml, <italic>P<0.05</italic>), myelosuppression rate was lower (0 vs. 5, <italic>P<0.05</italic>). The number of Less intra‐operative tumor spillage in TACE group, but there was statistical diffence between two groups. The mean follow‐up time was 34.15 months, no tumor recurrence or distant metastasis was observed.</p><p><bold>Conclusions</bold>: Preoperative TACE combining with surgery is a safe and effective modality in the treatment of wilms’ tumor in children.</p></sec><sec id="pbc26772-sec-5850"><label>P-191</label><title>Clinical Characteristics of Renal Cell Carcinoma Associated with XP11.2 Translocation/TFE Gene Fusion in Children: An Experience of A Single Institution</title><p><underline underline-style="single">W. Yao</underline><sup>1</sup>, K. Li<sup>1</sup>, K. Dong<sup>1</sup>, X. Xiao<sup>1</sup>, S. Zheng<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital of Fudan University, Pediatric Surgery, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: To investigate the clinical features, prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion in children.</p><p><bold>Design/Methods</bold>: A retrospective review of 10 cases between Jan 2010 and Dec 2016 were evaluated and the clinical data were collected and analyzed.</p><p><bold>Results</bold>: Xp 11.2 translocation RCCs were identified in 7 males and 3 females with a mean age of 5.2 years (range: 1.2‐12.9 years). The clinical symptom included painless hematuria in 3 cases, abdominal pain with microscopic hematuria in 3 cases and as an incidental finding in 4 patients. According to the TNM staging system, there were 3 patients in stage I, 2 patients in stage II, 4 patients in stage III and 1 patients in stage IV with lumber metastasis. The tumor side is between 5.11‐ 745.05 cm<sup>3</sup> (mean 197.17cm<sup>3</sup>). Radical nephrectomy and lymphadenectomy were performed in 8 patients and lymphatic invasion was confirmed in 4 cases, while tumor biopsy was performed in 2 patients. Only one patient received postoperative chemotherapy, while 7 patients just observed after surgery and of the 2 patients with biopsy, one received radiotherapy and the other one gave up treatment. All patients were followed up for an average of 24.2 months (range: 2‐ 74 months), and 7 were still alive and 3 had died after surgery.</p><p><bold>Conclusions</bold>: Xp 11.2 translocation RCC is rare subtype of renal tumor in children associated with poor prognosis and lymphatic metastasis. Radical nephrectomy and lymphadenectomy is the main treatment for these patients.</p></sec></sec><sec id="pbc26772-sec-5860"><title>Solid Non Brain Tumours ‐ Bone Tumours</title><sec id="pbc26772-sec-5870"><label>P-192</label><title>In Vivo Prevention Local Effect of Cadmium of Local Recurrence in Xenograft Model of Osteosarcoma</title><p>D. Demirkiran<sup>1</sup>, <underline underline-style="single">S. Aktas</underline><sup>1</sup>, P. Ercetin<sup>1</sup>, E. Kolatan<sup>1</sup>, O. Yilmaz<sup>2</sup>, H. Havitcioglu<sup>3</sup>, N. Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University, Institute of Oncology, Izmir, Turkey; <sup>2</sup>Dokuz Eylul University, Experimental Animal Sciences, Izmir, Turkey; <sup>3</sup>Dokuz Eylul University, Orthopedics, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: Osteosarcoma usually occurs in childhood and young adulthood and is very aggressive. These tumors were achieved great success in limb salvage surgery. However, residual tumor may remain at the microscopic level increases the likelihood of recurrence. Apart from surgery, the residual tumor is observed despite the high‐dose methotrexate, cisplatin chemotherapy regimens, therefore, new approaches are needed for the treatment of osteosarcoma. In this study, the cadmium in cement was placed locally after surgical resection to evaluate its preventive efficacy on residual tumor and recurrence in in vivo animal model.</p><p><bold>Design/Methods</bold>: K7M2 tumorigenic osteosarcoma cell line was cultivated in vitro. Then, the xenograft tumor model was formed by giving the tumor cells subcucateously to athymic nude mice. After the tumor growth, control tumor, near total resected tumor group, near total resected group with serum in cement and near total resected group with cadmium in cement group was conducted randomly with 7 animals in each group. Animals were observed for 15 days for recurrences in tumor site. After the sacrification, the presence of residue was checked histopathologically in each group.</p><p><bold>Results</bold>: Tumor was formed within one month after subcutanous injection. REcurrent tumor was formed in all animals in near total resected group, near total resected group with serum in cement. No or small tumor formation was observed in cadmium group. No systemic toxic effect was observed.</p><p><bold>Conclusions</bold>: Our data suggest that local application of cadmium in cement might help local therapy of osteosarcoma after surgery. Postoperative local treatment with agents within orthopedic biyomechanic substances might be an option of additive treatment to overcome the recurrences in osteosarcoma. Our next step is to test chemotherapoetic agents (methotrexate, cispatin) in cemnent in vivo animal model.</p></sec><sec id="pbc26772-sec-5880"><label>P-193</label><title>Successful Re‐Treatment of an Unresectable Sacral Giant Cell Tumour of Bone with Denosumab after a Pregnancy‐Induced Hiatus</title><p>S. Wilson<sup>1</sup>, S. Pratap<sup>2</sup>, <underline underline-style="single">E. Blanco</underline><sup>1</sup>, B. Hassan<sup>3</sup></p><p><italic><sup>1</sup>Oxford University Hospitals NHS Foundation Trust, Paediatric Haematology/Oncology, Oxford, United Kingdom; <sup>2</sup>Oxford University Hospitals NHS Foundation Trust, Oxford Sarcoma Service, Oxford, United Kingdom; <sup>3</sup>University of Oxford, Oxford Sarcoma Service, Oxford, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Giant cell tumours of bone (GCTB) are benign, locally aggressive tumours predominantly treated surgically. More recently, neoadjuvant treatment with the RANK‐L monoclonal antibody Denosumab has enabled surgery in unresectable cases to be considered. Denosumab disturbs the RANK‐RANKL interaction, inhibiting osteoclastic‐induced bone lysis and promotes osteogenesis. RANK‐L is overexpressed on GCTB stromal cells driving bony destruction associated with the tumour.</p><p>The Oxford Sarcoma Service selectively utilises Denosumab to optimise operability and reduce surgical – associated morbidity.</p><p><bold>Design/Methods</bold>: We present the case of a patient undergoing Denosumab treatment for an unresectable sacral GCTB who became pregnant on treatment.</p><p><bold>Results</bold>: The patient presented with cauda equina syndrome. Biopsy of an extensive S2‐S5 vertebral lesion confirmed a sacral GCTB. Resection would require sacrifice of S2‐3 nerve roots and the loss of bowel and bladder function. Denosumab was commenced with an excellent metabolic, radiological and neurological response after 1 cycle. PET/CT demonstrated a reduction in SUVmax from 16.3 to 4.4, with resolution of the presacral soft tissue mass and sacral ossification. Complete metabolic response was seen after 6 cycles of Denosumab.</p><p>After 17 cycles, treatment was stopped because of pregnancy. During this time the patient's symptoms were stable despite the tumour increasing by greater than 15mm in the sagittal axis. A normal baby was born by elective Cesarean section, without skeletal or metabolic abnormalities.</p><p>Denosumab was recommenced with a rapid radiological response after 1 cycle, peaking at cycle 13 when dose frequency was reduced to 6‐weekly. Alterations in bone mineralisation density has necessitated planning definitive local therapy with proton beam therapy.</p><p><bold>Conclusions</bold>: Denosumab provides excellent tumour control for unresectable GCTB. We report objective evidence that re‐treatment is effective after an hiatus and the risk of resistance is low. Consideration of long‐term toxicity and definitive management remain important considerations.</p></sec><sec id="pbc26772-sec-5890"><label>P-194</label><title>A DNA Methylation‐Based Classifier for Accurate Molecular Diagnosis of Bone Sarcomas</title><p>P. Wu<sup>1</sup>, B. Cooper<sup>1</sup>, F. Bu<sup>2</sup>, C. Bowman<sup>2</sup>, K. Jonathan<sup>3</sup>, J. Serrano<sup>2</sup>, S. Wang<sup>4</sup>, T. Jackson<sup>4</sup>, D. Gorovets<sup>2</sup>, R. Gorlick<sup>5</sup>, M. Ladanyi<sup>3</sup>, K. Thomas<sup>2</sup>, M. Snuderl<sup>2</sup>, <underline underline-style="single">M. Karajannis</underline><sup>6</sup></p><p><italic><sup>1</sup>NYU Langone Medical Center, Radiation Oncology, New York, USA; <sup>2</sup>NYU Langone Medical Center, Pathology, New York, USA; <sup>3</sup>Memorial Sloan Kettering Cancer Center, Pathology, New York, USA; <sup>4</sup>NYU Langone Medical Center, Pediatrics, New York, USA; <sup>5</sup>Montefiore Medical Center, Pediatrics, New York, USA; <sup>6</sup>Memorial Sloan Kettering Cancer Center, Pediatrics, New York, USA</italic></p><p><bold>Background/Objectives</bold>: Pediatric bone sarcomas present a unique diagnostic challenge because of the considerable morphologic overlap between different entities. The choice of optimal treatment, however, is dependent upon accurate diagnosis. Genome‐wide DNA methylation profiling has emerged as a powerful new diagnostic tool in brain tumors, with diagnostic accuracy exceeding standard histopathology. We developed and validated a methylation based classifier to differentiate between osteosarcoma (OS), Ewing's sarcoma (ES), and synovial sarcoma (SS).</p><p><bold>Design/Methods</bold>: DNA methylation status of 482,421 CpG sites in 15 OS, 10 ES, and 11 SS samples were measured using the Illumina HumanMethylation450 array. From this training set of 36 sarcoma samples we developed a random forest classifier from the 400 most differentially methylated CpG sites (FDR q value < 0.001). This classifier was then validated in 10 SS samples from The Cancer Genome Atlas (TCGA), 86 OS samples from TARGET‐OS, and 15 ES samples from a recently published series (Huertas‐Martinez et al., Cancer Lett. 2016).</p><p><bold>Results</bold>: DNA methylation profiling revealed three distinct molecular clusters, each enriched with a single sarcoma subtype. Within the validation cohorts, all samples from TCGA were accurately classified as synovial sarcoma (10/10, sensitivity and specificity 100%). All but one sample from TARGET‐OS were classified as OS (85/86, sensitivity 98%, specificity 100%) and all but one sample from the ES series was classified as ES (14/15, sensitivity 93%, specificity 100%). The single mismatch, an osteosarcoma sample which was classified as a ES, was later determined to be a misdiagnosed ES based on RNA‐seq data demonstrating high EWRS1 and ETV1 expression. An additional clinical sample that was misdiagnosed as a SS based on initial histolopathology, was accurately recognized as OS by the methylation classifier.</p><p><bold>Conclusions</bold>: OS, ES and SS have distinct epigenetic profiles. Our validated methylation‐based classifier provides increased diagnostic accuracy, including in cases where standard histopathology is inconclusive.</p></sec><sec id="pbc26772-sec-5900"><label>P-195</label><title>Extrapulmonary Metastasis is an Important Prognostic Factor in Patients with Osteosarcoma Accompanied by Pulmonary Metastasis</title><p><underline underline-style="single">N. Kitagawa</underline><sup>1</sup>, M. Shinkai<sup>1</sup>, K. Mochizuki<sup>1</sup>, H. Usui<sup>1</sup>, E. Osawa<sup>1</sup>, K. Yoshizawa<sup>1</sup>, J. Machida<sup>2</sup>, H. Goto<sup>3</sup>, K. Nozawa<sup>4</sup>, M. Tanaka<sup>5</sup>, Y. Tanaka<sup>5</sup></p><p><italic><sup>1</sup>Kanagawa Children's Medical Center, Department of Surgery, Yokohama, Japan; <sup>2</sup>Kanagawa Children's Medical Center, Department of Orthopedic Surgery, Yokohama, Japan; <sup>3</sup>Kanagawa Children's Medical Center, Department of Hematology / Oncology and regenerative medicine, Yokohama, Japan; <sup>4</sup>Kanagawa Children's Medical Center, Department of Radiology, Yokohama, Japan; <sup>5</sup>Kanagawa Children's Medical Center, Department of Pathology, Yokohama, Japan</italic></p><p><bold>Background/Objectives</bold>: Distant metastasis is one of the most important prognostic factors in osteosarcoma. Metastases usually occur in the lung. We have performed aggressive pulmonary metastasecomy, but prognosis of these patients are still unsatisfactory. The aim of this study is to find prognostic factors in patients with osteosarcoma accompanied by pulmonary metastasis.</p><p><bold>Design/Methods</bold>: Retrospective chart reviews of 50 patients with osteosarcoma were performed. All patients underwent neoadjuvant, adjuvant chemotherapy and surgery for the primary lesion. Each metastatic lung lesion was removed mainly by wedge resection through an open thoracotomy, sometimes lobectomy if tumor was too large.</p><p><bold>Results</bold>: Twenty‐eight patients had lung metastases. Thirteen out of these 28 patients had extrapulmonary metastasis(EPM). Metastatic sites were bones, soft tissue, the diaphragm and brain. The 5‐year survival rate was 96% in patients without metastasis, compared to 50% with pulmonary metastasis. In 28 patients with pulmonary metastasis, the 5‐year survival rate of patients without EPM was 76%, 15% in patients with EPM. In patients without EPM, 90% of 5‐year survival rate was achieved by surgical metastasectomy compared to 60% without metastasectomy. In patients with EPM, the 5‐years survival rate achieved by surgical metastasectomy was 25% compared to 0% without.</p><p><bold>Conclusions</bold>: Our results suggested that pulmonary metastasis was the most important prognostic factor in patients with osteosarcoma, and EPM was also a contributing factor. In patients without EPM, pulmonary metastasectomy is recommended. However, in patients with EPM, the prognosis was still poor even when metastasectomy was performed. Some form of new strategy is needed.</p></sec><sec id="pbc26772-sec-5910"><label>P-196</label><title>Mechanical Damage of Knee Endoprosthesis in Children with Malignant Bone Tumors</title><p><underline underline-style="single">V. Kobys</underline><sup>1</sup>, V. Konovalenko<sup>2</sup></p><p><italic><sup>1</sup>Kiev City Oncology Center, Pediatric Oncology, Kiev, Ukraine; <sup>2</sup>Institute of Experimental Oncology, Department of Osteology, Kiev, Ukraine</italic></p><p><bold>Background/Objectives</bold>: Due to the growth of the child and the increase of body mass, the mechanical load on the endoprothesis significantly increases, and extension of the prosthesis increases the arm of force on the endoprosthesis stem. Over time this leads to fracture of the femoral endoprosthesis stem and the need for reoperation to replace the endoprosthesis.</p><p><bold>Design/Methods</bold>: During the period from 2000 to 2016, we operated 50 patients with malignant femur bone tumors aged 7 to 18 years, the average age was 11.5 years. 16 (31%) of them had a fracture of the femoral bone endoprosthesis stem in the period from 3 to 10 years after the arthroplasty. The material was titanium endoprosthesis or kobal‐chromium‐molybdenum alloy. Rod diameter femoral stem was 10 to 12 mm.</p><p><bold>Results</bold>: All patients with a fracture of the femoral endoprosthesis stem had reimplantation of the stem, mostly with a stem of a larger diameter. There was no deterioration of limb function. In cement endoprosthesis the stems were removed without cutting the bone containing the fragments of the stem. In the cement‐free prosthesis, longitudinal osteotomy was performed to extract fragments of the endoprothesis stem.</p><p><bold>Conclusions</bold>: When implanting knee endoprotheses in children, preference should be given to cement endoprosthesis because of the high risk of fracture endoprosthesis legs. They are much less traumatically removed when replacing endoprosthesis stems. Later, when the patient stops growing, cement‐free endoprosthesis can be implanted.</p></sec><sec id="pbc26772-sec-5920"><label>P-197</label><title>Serum Adhesion Molecules Levels in Bone and Soft Tissue Sarcoma and Prognostic Significance</title><p><underline underline-style="single">N. Kurucu</underline><sup>1</sup>, C. Sonmez<sup>2</sup>, N. Sarı<sup>3</sup>, M. Yıldırım<sup>3</sup>, İ. Ilhan<sup>3</sup></p><p><italic><sup>1</sup>Hacettepe University Faculty of Medicine, Department of Pedatric Oncology, Ankara, Turkey; <sup>2</sup>A.Y Ankara Oncology Research and Traning Hospital, Department of Biochemistry, Ankara, Turkey; <sup>3</sup>A.Y Ankara Oncology Research and Traning Hospital, Department of Pediatric Oncology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: Adhesion molecules are involved in carcinogenesis and metastases. The aim of this study is to analysis the serum levels of some adhesion molecules and their relationship with clinical, laboratory and prognostic factors.</p><p><bold>Design/Methods</bold>: Forty‐four patients diagnosed with bone and soft tissue sarcomas and 31 healthy controls were included in the study. Serum CD44, ICAM‐1, VCAM‐1, selectin and cadherin levels were analyzed with ELISA method at diagnosis, after induction and at the end of treatment. The mean AM levels of patients at different time were compared with each other and those of control groups. The relationship between serum AM levels and presence of metastases, percentage of necrosis and course of disease were evaluated.</p><p><bold>Results</bold>: There were 19 males, 21 females with a median age of 13 (1‐21) years. The diagnoses were osteosarcoma in 21, Ewing sarcoma in 15, rhabdomyosarcoma in six, synovial sarcoma in two. Tumor location was long bones in 70% of patients. Twenty patients (45.5%) had metastatic disease at diagnosis. The mean CD44, selectin and cadherin levels of patients at diagnosis were significantly (p<0.001) higher than those of control group. Patients’ CD44 and selectin levels were higher compared to controls in each diagnostic group. In osteosarcoma and Ewing sarcoma, significant decrease inCD44 and cadherin levels were observed at the end of treatment as compared to levels at diagnosis. The CD44 levels of patients with pulmonary metastasis had higher levels of CD44 than non‐metastatic patients (p:0.020). VCAM‐1 levels were significantly higher in relapsed disease (p:0.017). There was no relationship between adhesion molecules levels and mean percentage of necrosis.</p><p><bold>Conclusions</bold>: CD44, selectin levels were observed in bone and soft tissue sarcoma and they may be used as markers for diagnosis and follow‐up. Our findings suggest that elevated levels of CD44 and VCAM‐1 were associated with metastatic and relapsed disease, respectively.</p></sec><sec id="pbc26772-sec-5930"><label>P-198</label><title>An Economical Analysis for the Care of Pediatric Osteosarcoma Patients</title><p><underline underline-style="single">T. Kutluk</underline><sup>1</sup>, C. Akyüz<sup>1</sup>, A. Varan<sup>1</sup>, B. Yalçın<sup>1</sup>, N. Kurucu<sup>1</sup>, B. Aydın<sup>1</sup></p><p><italic><sup>1</sup>Hacettepe University Cancer Institute & Faculty of Medicine, Department of Pediatric Oncology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: Survival rates in childhood cancer improved significantly during the last several decades. For further improvement at global level, economical analysis are critically important. The cost of diagnosis, treatment and follow‐up of patients with osteosarcoma was investigated on this study.</p><p><bold>Design/Methods</bold>: Thirty‐two pediatric osteosarcoma cases sequentially diagnosed in 2009‐2014 were included. The direct costs of ambulatory and inpatient care starting from diagnosis to December 2016 for each patient were analyzed in detail including examination, imaging, laboratory, operation, pathology, medicines, medical supplies, hospital accommodation and other service costs both for inpatient and outpatient care.</p><p><bold>Results</bold>: Thirty‐two patients (with a mean, median, minimum, maximum age, M/F ratio was 13.01, 13.58, 6.17, 17.83 years, M/F=17/15 respectively) were included. 22 patients had local and 10 had metastatic diseases at diagnosis. Three‐year overall survival (OS) was 58% for 32 patients. Three‐year OS was 75% for 22 patients with local disease and 20% for 10 patients with metastatic diseases. Median follow‐up time was 40 months. Total costs for 32 patients 1.257.549,74 USD including 1.176.401,53 USD for inpatient costs (%93.5) and 81.148,21 USD for outpatient costs (% 6.5) with an average cost of 39.298,43 USD per patient. The distribution of costs (as USD) to different groups were; operation 68.766,64 (%5.47), services 115.947,44 (%9.22), medicine 223.672,80 (%17.79), laboratory examinations 41.464,84 (%3.30), examination 13.157,17 (%1.05), pathology 2635,27 (%0.21), supplies 688.401,48 (%54,74), imaging 46.478,02 (%3.70), hospital accommodation‐bed fees 57.026,08 (%4.53).</p><p><bold>Conclusions</bold>: To better understand the cost of care in pediatric cancers for investment purposes, detailed economical analysis are needed. As an example, the cost of care for pediatric osteosarcoma patients were calculated in this study. The average cost per patient found in this study seems reasonable for a middle‐income country. These kinds of analysis will help to plan the childhood cancer care for countries, which are planning to invest on the childhood cancer control.</p></sec><sec id="pbc26772-sec-5940"><label>P-199</label><title>Mechanisms of Drug Resistance to Like‐EURAMOS1 Chemotherapy in Childhood Osteosarcoma: Preliminary Results</title><p>A. Levashov<sup>1</sup>, <underline underline-style="single">E. Senzhapova</underline><sup>1</sup>, D. Khochenkov<sup>2</sup></p><p><italic><sup>1</sup>Pediatric Hematology and Oncology Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Pediatric Hematology and Oncology Institution, Moscow, Russia; <sup>2</sup>Experimental Diagnostic and Treatment of Tumor Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Experimental Diagnostic and Treatment of Tumor Institution, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The aim of this study was to estimate ERCC1, TOP2a, RFC1 and MGMT proteins expression in 27 biopsy specimens and 38 tumor tissue samples with poor response (grade I and II of tumor cells necrosis rate) to neoadjuvant chemotherapy after surgery of the primary site.</p><p><bold>Design/Methods</bold>: Proteins expression was assessed by immunohistochemical method using anti‐ERCC1 (clone 8F1, Abcam), anti‐TOP2a (Ki‐S1, Dako), anti‐RFC1 (SCL19A1ab, Genetex), anti‐MGMT (MT3.1, Thermo). ERCC1 and MGMT positive specimen was defined as weak (+), moderate (++), strong (+++) colouring of the tumor nuclei and cytoplasm (for ERCC1 and MGMT) with number of positive tumor cells above 10% (for ERCC1), 25% (for MGMT). TOP2a and RFC1 positive specimen was defined as moderate (++), strong (+++) colouring of the tumor nuclei and cytoplasm (for TOP2a), membrane (for RFC1) with number of positive tumor cells above 25%.</p><p>All 38 patients were treated according to like‐EURAMOS1 chemotherapy. Primary metastatic osteosarcoma was diagnosed in 15 out of 38 patients and localized disease in 23.</p><p><bold>Results</bold>: TOP2a positive samples were revealed in 70.4% of biopsy specimens, in 26% of postoperative specimens (6.7% for group with metastases, 39.1% for group without metastases, p = 0.026), ERCC1 in 51.9% and 34.2%, RFC1 in 55% and 23.1%, MGMT in 85.7% and 88.5%, ERCC1 positive / TOP2a negative variant in 11.1% and 28.9%, ERCC1 positive / TOP2a negative / RFC1 negative variant in 0% and 26.9%, TOP2a negative / RFC1 negative variant in 10% and 65.4% (p < 0.05).</p><p><bold>Conclusions</bold>: These data suggest that basic mechanisms of drug resistance were presented by decreased TOP2a and RFC1 expression and constant MGMT expression, increased number of ERCC1 positive / TOP2a negative variant, ERCC1 positive / TOP2a negative / RFC1 negative variant and TOP2a negative / RFC1 negative variant in postoperative specimens.</p></sec><sec id="pbc26772-sec-5950"><label>P-200</label><title>Challenges in the Nursing Care for Children with Cancer: Report of Experience from Nigeria</title><p><underline underline-style="single">N. Mary</underline><sup>1</sup></p><p><italic><sup>1</sup>National Hospital Abuja, nursing serivces, Abuja, Nigeria</italic></p><p><bold>Background/Objectives</bold>: Cancer is one the major causes of death in children and adolescents, accounting for about 4% of deaths in children below 5years in Nigeria. The nursing care of these patients often does not receive adequate attention. This report highlights challenges in nursing care of these children in a low resource setting and is aimed at raising awareness to influence advocacy and action.</p><p><bold>Design/Methods</bold>: A retrospective review of 38 children treated for cancers in an inpatient children's ward over a one‐year period (November 2015 – November 2016). In the same period, a total of 992 children were admitted into the same ward. The nursing care of the patients has been reviewed</p><p><bold>Results</bold>: Children with cancers accounted for 3.8% of admissions on the ward. In addition to the nursing workload of these patients, several important challenges and limitations were encountered requiring attention and efforts of the nursing staff, including; financial burden on parents and their inability to cope with costs, psychological issues involving parents and patients (aggression, anxiety, depression, withdrawal) and difficulties with communicating disease course, treatment and complications of treatment. These challenges significantly increased the nursing burden of the patients, which were often not part of patient treatment plan.</p><p><bold>Conclusions</bold>: It's important to include these identified challenges in the counseling and treatment plan of children with cancers, particularly in low resource settings where the burden of nursing care is enormous. Development and implementation of a careful multidisciplinary care plan should help in addressing these challenges</p></sec><sec id="pbc26772-sec-5960"><label>P-201</label><title>Retinoblastoma, Osteosarcoma and Unusual Sites of Tumor Recurrence: A Case Report</title><p><underline underline-style="single">K. O'Halloran</underline><sup>1</sup>, M.R. Wollman<sup>2</sup></p><p><italic><sup>1</sup>Childrens Hospital of UPMC, Pediatrics Residency Program, Pittsburgh, USA; <sup>2</sup>Childrens Hospital of UPMC, Pediatric Hematology/Oncology, Pittsburgh, USA</italic></p><p><bold>Background/Objectives</bold>: Osteosarcoma following retinoblastoma is known to occur, however, patterns of osteosarcoma recurrence in this subset of patients are not well described. We report the case of a patient with a history of bilateral germline retinoblastoma and osteosarcoma with unusual sites of soft tissue osteosarcoma recurrence.</p><p><bold>Design/Methods</bold>: Case Report.</p><p><bold>Results</bold>: At 6 months of age the patient was diagnosed with bilateral germline retinoblastoma despite no family history. He underwent chemotherapy with vincristine, carboplatin and etoposide. Given disease progression, however, he underwent enucleation of the right eye. He remained in remission for 12 years at which time he developed knee pain found to be an osteosarcoma tumor. No metastatic disease was noted on chest CT. He underwent 29 weeks of doxorubicin, cisplatin and methotrexate as per AOST0331. Less than 1 year later pulmonary metastases were found and following metastasectomy he was started on dinutuximab (phase II trial). Two weeks following initiation of dinutuximab he presented with an antebcubital fossa mass found on biopsy to represent soft tissue recurrence of osteosarcoma. PET scan subsequently revealed T12 vertebral, left popliteal soft tissue and right lower lobe lung lesion. Genetic testing was positive for TP53 mutation and CSF1R. He was subsequently started on ifosfamide. Due to mixed response and poor prognosis, however, he is now undergoing palliative radiation therapy and oral sorafenib.</p><p><bold>Conclusions</bold>: This case suggests survivors of germline retinoblastoma who develop a second primary malignancy and subsequent relapse may have more unusual sites and patterns of recurrence. This case furthermore illustrates that underlying genetic mutations such as Rb gene mutations may impact response to therapies including chemotherapy.</p></sec><sec id="pbc26772-sec-5970"><label>P-202</label><title>Dose Intensity of Neoadjuvant Chemotherapy in the Treatment of Paediatric Patients with Osteosarcoma at Hospital Infantil De Mexico</title><p><underline underline-style="single">M.A.</underline><underline underline-style="single">Palomo</underline><underline underline-style="single">Colli</underline><sup>1</sup>, A. Perez Bañuelos<sup>2</sup>, M. Mier‐Cabrera<sup>3</sup>, J.F. Gaytan Morales<sup>1</sup>, C. Cicero Oneto<sup>1</sup>, I. Castorena Villa<sup>1</sup></p><p><italic><sup>1</sup>Hospital Infantil de México, Oncology, México, Mexico; <sup>2</sup>Hospital de Especialidades del Niño y la Mujer, Pediatrics, Queretaro, Mexico; <sup>3</sup>Hospital Regional de Alta Especialidad Ixtapaluca, Pediatrics, Ixtapaluca, Mexico</italic></p><p><bold>Background/Objectives</bold>: Osteosarcoma is the most common bone malignancy, which is more frequent in children and adolescents. Neoadjuvant chemotherapy for osteosarcoma offers a series of advantages, such as treatment of microscopic metastases or shrinking the primary tumor with possibility of limb‐sparing surgery. Preoperative treatment allows <italic>in vivo</italic> evaluation of the treatment and postoperative treatment adjustment according to histological response.</p><p><bold>Design/Methods</bold>: We conducted a retrospective study based in medical records of all patients with osteosarcoma who had received neoadjuvant treatment at Hospital Infantil de México Federico Gómez (HIMFG) between 2009‐2014. The aim of this study was to evaluate the dose intensity (DI), which is calculated as dose per unit of time. For the purpose of this analysis, “time” was set as “days”, starting at “Day 1” of chemotherapy according to 2 different treatments. The MAP treatment consisted of pre‐operative administration of two 5‐week cycles of cisplatin (120 mg/m<sup>2</sup>), doxorubicin (75mg/m<sup>2</sup>) and methotrexate(2x 12g/m<sup>2</sup>). The second one consisted of four cycles of cisplatin(120mg/m<sup>2</sup>), and doxorubicin(75mg/m<sup>2</sup>) administrated every three weeks. The neoadjuvant DI was calculated for each drug administrated.</p><p><bold>Results</bold>: Thirty‐four medical records were collected during this period of time. However, eleven of them were eliminated since chemotherapy information was incomplete or treatment‐related death prior to day and follow‐up ended before day 70‐84. The information from the remaining 23 medical records was analyzed. The study population were 12 females and 22 males. Regarding the age at diagnosis, the median was 11.5 years(4‐17y). Metastases at diagnosis was observed in 15 patients(44.1%). The average time between diagnosis and surgery was 14.08± 1.2 weeks for MAP protocol and 23.21± 1.96 weeks for Cisplatin/Doxorubicin.</p><p>The relative DI was 0.65 for doxorubicin, 0.68 for Cisplatin and 0.75 for Methotrexate.</p><p><bold>Conclusions</bold>: DI is inadequate in many cases because of toxicity and the lack of sufficient beds in hospital, which results in delay on surgery.</p></sec><sec id="pbc26772-sec-5980"><label>P-203</label><title>Clinical Outcome of Osteosarcoma in Children: Experience from a Developing Country</title><p><underline underline-style="single">A.S.B. Syed</underline><sup>1</sup>, H. Saeed<sup>1</sup>, A.A. Arshad<sup>1</sup>, R. Mohammad Wali<sup>1</sup>, S. Javed Khan<sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Memorial Cancer Hospital & Research Center, Pediatric Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Osteosarcoma is the most common bone tumor in children. There is limited information about outcome for pediatric osteosarcoma in Pakistan. We conducted this study to determine the outcome of children with osteosarcoma who were diagnosed and treated in our institution over 10 years.</p><p><bold>Design/Methods</bold>: We conducted a retrospective chart review of patients with osteosarcoma who received treatment at our institution between January 2005 and December 2014. Kaplan‐Meier analysis was used for survival analysis using SPSS version 19.</p><p><bold>Results</bold>: Osteosarcoma was diagnosed in 225 patients out of which 77 patients (34.2%) abandoned treatment within first 3 months of diagnosis. The final study population was 147. All patients received treatment with Cisplatin, Doxorubicin and Methotrexate as per Euromos 1 protocol. Mean age at diagnosis was 13.6 years (SD +/‐ 3.2). Male to female ratio was 1.7:1. 120 patients (81.6%) had non‐metastatic disease. 131 (89%) had lower extremity, 14 (9.5%) upper extremity and 2 (1.4%) had axial involvement. There were 28 (19%) mortalities (16 from disease progression, 8 from infectious complications and 4 from cardiac complications). 29 patients (19.7%) had disease progression during treatment while 24(16.3%) relapsed after end of treatment.</p><p>The overall survival (OS) and event free survival (EFS) for entire population at eight years was 70% and 40% respectively with median follow‐up of 43 months. For metastatic and non‐metastatic cases the OS and EFS were 57% and 72% and 19% and 52% respectively. None of the patients with axial tumor survived. For upper extremity and lower extremity tumors OS and EFS were 92% and 68% and 59% and 41 % respectively. There was no difference in survival based on gender.</p><p><bold>Conclusions</bold>: Survival for osteosarcoma is about 70% but EFS is lower than expected. Measures to improve care for infections and cardiac complications can improve these outcomes. Efforts to reduce abandonment are also needed.</p></sec><sec id="pbc26772-sec-5990"><label>P-204</label><title>Treatment Abandonment in Patients with Osteosarcoma: Experience from a Developing Country</title><p>H. Saeed<sup>1</sup>, S.A.S. Baqari<sup>1</sup>, A.A. Arshad<sup>1</sup>, <underline underline-style="single">R. Mohammad Wali</underline><sup>1</sup>, S. Javed Khan<sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Memorial Cancer Hospital & Research Center, Pediatric Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Treatment abandonment is a common cause of cancer related mortality in developing countries especially in conditions that require mutilating surgery. We conducted this study to determine the patterns of treatment abandonment in patients of Osteosarcoma treated at our institution over 10 years.</p><p><bold>Design/Methods</bold>: We conducted a retrospective chart review of patients diagnosed with Osteosarcoma at our institution between January 2005 and December 2014. We compared characteristic of patients that continued treatment and that abandoned. SPSS version 19 was used for analysis.</p><p><bold>Results</bold>: Osteosarcoma was diagnosed in 225 patients out of which 77 patients (34.2%) abandoned treatment. Thus, about 8 patients a year did not complete treatment. About half of these (38 patients) abandoned prior to start of chemotherapy while the remaining 39 left following neo‐adjuvant chemotherapy.</p><p>The mean age of treated group was 13.6 (SD+/‐3.2) and abandonment group was 14.4(SD+/‐2.6). Of the total 134 male patients 40 (30%) abandoned while 37 of 90 females (41%) abandoned. The likelihood ratio for abandonment for females was 3 (p= 0.056). None of the patients from Afghanistan abandoned, while 25% from Sindh and Baluchistan, 32.7% from KPK and 37.4 from Punjab abandoned treatment. 34% of patients with non‐metastatic and 37% with metastatic disease abandoned. Follow‐up information was only available for 8 (10%) patients. 3 patients died of disease progression and 5 patients came back with progressive disease and were lost to follow‐up again.</p><p><bold>Conclusions</bold>: There is high rate of treatment abandonment in Osteosarcoma patients at our institution. Half of the cases occur at time of surgery so better counseling and preparation of patients for amputation may reduce abandonment rates. Females also show a higher trend for abandonment. Disease prognosis and geographic distance from institution don't affect abandonment. There is need for better follow‐up of patients who abandoned to know their outcomes.</p></sec><sec id="pbc26772-sec-6000"><label>P-205</label><title>Epiphysis Growth after Epiphyseal‐Preservation Surgery for Childhood Osteosarcoma Around the Knee Joint</title><p><underline underline-style="single">A. Takeuchi</underline><sup>1</sup>, N. Yamamoto<sup>1</sup>, K. Hayashi<sup>1</sup>, T. Higuchi<sup>1</sup>, K. Abe<sup>1</sup>, Y. Taniguchi<sup>1</sup>, H. Aiba<sup>1</sup>, Y. Araki<sup>1</sup>, H. Tsuchiya<sup>1</sup></p><p><italic><sup>1</sup>Kanazawa University Graduate School of Medical Sciences, Orthopaedic Surgery, Kanazawa, Japan</italic></p><p><bold>Background/Objectives</bold>: Osteosarcoma usually occurs in metaphyseal locations and must be excised with the adjacent joint and replaced by an endoprosthesis. Recently, advanced imaging, accurate tumor excision and rigid fixation using a locking plate have been used in epiphysis‐preserved tumor excision for selected patients. To reconstruct the defect after epiphysis‐preserved tumor excision, various methods, including allograft, distraction osteogenesis, tumor‐devitalised autograft, vascularised fibular graft and custom‐made implants, have been applied. Tumor‐devitalised autograft treated with liquid nitrogen procedure was introduced in 1999 and its usefulness has since been reported. The advantages of frozen autografts include simplicity and the possibility of preserving proteins, including bone morphogenetic protein (BMP). We investigated postoperative epiphysis growth following epiphyseal‐preservation surgery for childhood osteosarcoma around the knee joint.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed 13 patients with osteosarcoma who underwent epiphysis‐preserved tumor excision (transmetaphyseal, transphyseal and transepiphyseal excision) and reconstructed by using tumor‐devitalized autograft treated with liquid nitrogen. The mean patient age was 11 (range, 6 to 15) years. The mean follow‐up periods were 59 (range, 30 to 93) months. Nine tumors were in the distal femur, and four were in the proximal tibia. Epiphysis transverse growth rate, epiphysis‐width discrepancy (EWD) and collapse of epiphysis were evaluated by using pre‐ and post‐operative whole standing leg radiographs. Functional outcome, complications and oncological status were also investigated.</p><p><bold>Results</bold>: The mean epiphysis growth rate was 9.7% (range, 0.5 to 28.0 %), mean EWD was 0.1mm (range, –1.7 to 3.2 mm), mean LLD was–29mm (range, –1 to –48 mm) and two patients underwent limb lengthening. There was no apparent collapse of the residual epiphysis. The mean MSTS score was 27.7 (range, 18 to 30).</p><p><bold>Conclusions</bold>: Epiphysis transverse growth continued after epiphyseal‐preservation surgery in childhood osteosarcoma. Epiphyseal‐preservation surgery in children should be considered.</p></sec><sec id="pbc26772-sec-6010"><label>P-206</label><title>Prognostic Impact of Diagnostic and Treatment Delay in Children with Osteosarcoma</title><p><underline underline-style="single">L. Vasquez</underline><sup>1</sup>, A. Zapata<sup>2</sup>, S. Chavez<sup>2</sup>, R. Diaz<sup>2</sup>, F. Tarrillo<sup>1</sup>, M. Oscanoa<sup>1</sup>, I. Maza<sup>1</sup>, J. Geronimo<sup>1</sup></p><p><italic><sup>1</sup>Rebagliati Hospital, Pediatric Oncology, Lima, Peru; <sup>2</sup>National Institute of Neoplastic Diseases INEN, Pediatric Oncology, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: The aim of this study is to evaluate the relationship between latency to diagnosis (LD) and medical/non‐medical treatment delay (TD) and survival outcomes in children with osteosarcoma.</p><p><bold>Design/Methods</bold>: A retrospective analysis of all consecutively treated patients at the two major tertiary centers in childhood cancer of Peru (between January 2008 and December 2015) with diagnosis of osteosarcoma was performed. LD was measured as the time between start of symptoms and definitive diagnosis. TD was defined as any delay in weeks of the frontline treatment protocol. All causes of TD were evaluated as medical (neutropenia or severe infection) and extra‐medical (lack of available beds, surgical prosthesis or social problems). Overall survival (OS) and event‐free survival (EFS) were estimated and compared according to LD, TD and known prognostic factors.</p><p><bold>Results</bold>: A total of 113 patients were included in the study. Median LD was 17 weeks (range, 3‐53.3). No association between clinical stage, tumor size and LD were detected. Children of parents without a formal job had significantly longer LD (p=0.018). Delayed LD was not associated to worse outcome. Multivariate analysis confirmed that OS and EFS were significantly worse for a TD longer than 4 weeks with a hazard ratio of 2.70 (95%CI, 1.11‐6.76, p=0.003) and 1.13 (95%CI, 1.00‐1.26, p=0.016) respectively. Only 15% of patients completed the treatment protocol in the initially established time. Most TD (85%) was caused by extra‐medical reasons, with no differences in survival rates between both groups (p=0.081).</p><p><bold>Conclusions</bold>: Longer LD in children with osteosarcoma did not seem to influence OS and EFS. A delay from any cause in the oncological treatment is independently associated with poor prognosis. Based on these results, further efforts are needed to decrease treatment delay in our country.</p></sec></sec><sec id="pbc26772-sec-6020"><title>Solid Non Brain Tumours ‐ Soft Tissue Sarcomas</title><sec id="pbc26772-sec-6030"><label>P-207</label><title>Treatment Outcome in Patients with Orbital Rhabdomyosarcoma‐ Clinical Experience from a Regional Cancer Centre in North India</title><p><underline underline-style="single">A. Biswas</underline><sup>1</sup>, N. Adhikari<sup>1</sup>, S. Bakhshi<sup>2</sup>, S. Sen<sup>3</sup>, S. Kashyap<sup>3</sup>, R. Meel<sup>4</sup>, B. Mohanti<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Radiation Oncology, New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences, Medical Oncology, New Delhi, India; <sup>3</sup>All India Institute of Medical Sciences, Ocular Pathology, New Delhi, India; <sup>4</sup>All India Institute of Medical Sciences, Ophthalmology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Orbital Rhabdomyosarcoma(RMS) is a favourable prognostic tumour, where cure rates of more than 90% can be achieved with combination chemotherapy and local radiotherapy in trial setting. We intend to report the treatment outcome of patients with orbital RMS treated at our institute.</p><p><bold>Design/Methods</bold>: The treatment plan for patients diagnosed with orbital RMS was induction chemotherapy (VAC regimen‐Vincristine,Actinomycin D, Cyclophosphamide) for 3 courses followed by orbital radiotherapy (45Gray/25fractions/5weeks) followed by further chemotherapy (VAC regimen) up to a total of 12 courses. Clinical data was collected by retrospective chart review from 2010‐17. Overall survival (OS) and progression free survival (PFS) were analyzed by Kaplan‐Meier method.</p><p><bold>Results</bold>: Twenty five patients met the study criterion (male: female=13:12). Median age at presentation was 13 years. The common symptoms (median duration 4 months) were proptosis, visual disturbance, ocular pain, eyelid swelling and ptosis in 80%,64%,28%,28% and 20% patients respectively. Orbital biopsy revealed embryonal and alveolar RMS in 21(84%) and 4(16%) patients respectively. After staging work‐up, 5(20%),17(68%) and 3(12%) patients had IRS clinical group II, III and IV disease respectively. Systemic chemotherapy(VAC) was administered in all patients (median‐6 courses). Orbital radiotherapy was given in 19(76%) patients(median dose 45 Gray;18‐curative;1‐palliative). After a mean follow‐up of 18.11 months, 10(40%) patients had disease progression(local‐8,regional‐1,distant‐1). Two patients could be successfully salvaged with chemotherapy(ICE regimen‐Ifosfamide,Carboplatin,Etoposide) and orbital exenteration. At last follow‐up, 8(32%) patients had died‐ 4 due to progressive disease and 4 due to chemotherapy related toxicity. Median PFS was 20.03 months and median OS was not reached. The actuarial rate of PFS and OS were respectively 46.9% and 64.6%(at 2 years) and 46.9% and 53.8%(at 3 years).</p><p><bold>Conclusions</bold>: Combination chemotherapy (VAC) and orbital radiotherapy (45Gy) led to modest clinical outcome in patients with orbital RMS at our centre possibly due to high incidence of alveolar RMS(16%), metastatic disease(12%), poor treatment compliance(20%) and toxic death(16%).</p></sec><sec id="pbc26772-sec-6040"><label>P-208</label><title>Rhabdomyosarcoma in Infants Under 6 Months: A Clinical, Histological and Molecular Analysis of the French Cohorts SIOP MMT 89‐95, RMS 2005 and National Cancer Registry</title><p><underline underline-style="single">T. Butler</underline><sup>1</sup>, D. Ranchère‐Vince<sup>2</sup>, G. Pierron<sup>3</sup>, D. Orbach<sup>4</sup>, L. Galmiche<sup>5</sup>, B. Lacour<sup>6</sup>, C. Bergeron<sup>7</sup>, A. Coulomb<sup>8</sup>, H. Martelli<sup>9</sup>, D. Anne‐Sophie<sup>10</sup>, D. Cecile<sup>11</sup>, J.C. Gentet<sup>12</sup>, C. Vérité<sup>13</sup>, D. Sophie<sup>14</sup>, L. Mansuy<sup>15</sup>, N. Cozic<sup>16</sup>, M.P. Castex<sup>17</sup>, H. Brisse<sup>18</sup>, V. Minard‐Colin<sup>1</sup></p><p><italic><sup>1</sup>Institut Gustave Roussy, Pediatric, Villejuif, France; <sup>2</sup>Centre Léon Bérard, Biopathology, Lyon, France; <sup>3</sup>Institut Curie, Biopathology, Paris, France; <sup>4</sup>Institut Curie, Pediatric, Paris, France; <sup>5</sup>Necker Hospital, Biopathology, Paris, France; <sup>6</sup>Nancy Hospital, French National Registry Center, Nancy, France; <sup>7</sup>Centre Léon Bérard, Pediatric, Lyon, France; <sup>8</sup>Trousseau Hospital, Biopathology, Paris, France; <sup>9</sup>Bicêtre Hospital, Pediatric Surgery, Kremlin‐Bicêtre, France; <sup>10</sup>Centre Oscar Lambert, Pediatric, Lille, France; <sup>11</sup>Rouen Hospital, Pediatric, Rouen, France; <sup>12</sup>Hôpital de la Timone, Pediatric, Marseille, France; <sup>13</sup>Bordeaux Hospital, Pediatric, Bordeaux, France; <sup>14</sup>Nantes Hospital, Pediatric, Nantes, France; <sup>15</sup>Nancy Hospital, Pediatric, Nancy, France; <sup>16</sup>Institut Gustave Roussy, Biostatistics, Villejuif, France; <sup>17</sup>Hôpital des enfants, Pediatric, Toulouse, France; <sup>18</sup>Institut Curie, Radiology, Paris, France</italic></p><p><bold>Background/Objectives</bold>: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in childhood with 2 major subtypes: alveolar and embryonal tumors. RMS in infants, ∼4‐10% of RMS, is a particular entity with specific clinical presentation and outcome. Recently, molecular rearrangement involving <italic>NCOA2</italic> or <italic>VGGL2</italic> genes have been described in congenital spindle cell RMS (S/ScRMS).</p><p><bold>Design/Methods</bold>: Our retrospective study reviewed all clinical, histological and molecular data from infants aged less than 6 months at diagnosis and treated in France for a RMS (registered in MMT89, MMT95, RMS2005 or recorded in the French National Cancer Registry). A histological centralized review and molecular analysis were performed on tumoral tissue of each patient.</p><p><bold>Results</bold>: 45 infants were included with a median age of 2.4 months at diagnosis. 6(13%) were metastatic and 7 patients (16%) had congenital malformations. Considering only survivors, the median follow‐up was 6.2 years. OS and EFS rates for all patients were 59.8% (95%CI, 47‐77) and 47% (95%CI, 34‐65). 24 infants (53%) experienced treatment failures: 14 relapsed (31%), mostly loco‐regional, and 9 (20%) progressed early. a <italic>PAX‐FOXO1</italic> translocation was identified in 2 patients. 2 VGLL2‐related RMS were recorded, both localized and with a common spindle cell histologic appearance. The two are alive in first CR. Molecular analysis for the 25 remaining patients are ongoing (CGH array, FISH, RT‐PCR and if all negatives RNAseq). 29(81%) infants did not present any grade III or IV toxicities. 31 infants received ifosfamide, among (24 with aged less than 6 months). One tubular toxicity and 3 neurologic toxicities were recorded for infants treated with ifosfamide.</p><p><bold>Conclusions</bold>: Our results suggest that a subtype of neonatal RMS does exist, with specific a clinical, histological (S/ScRMS) and/or molecular presentation (<italic>VGLL2</italic>, <italic>NCOA2</italic> fusions).</p></sec><sec id="pbc26772-sec-6050"><label>P-209</label><title>Role of PET‐CT in Evaluation of Therapy Response for Pediatric Rhabdomyosarcoma</title><p><underline underline-style="single">E. Elnadi</underline><sup>1</sup>, M. Mohamed S Zaghlol<sup>1,2</sup>, G. Taha<sup>3</sup>, H. Hafez<sup>4</sup>, S. Abdel Hamid<sup>5</sup>, E. Elkholy<sup>6</sup>, A. Younes<sup>7</sup>, N. Elkinaai<sup>8</sup>, M. Khalaf<sup>9</sup>, E. Khaled<sup>10</sup></p><p><italic><sup>1</sup>Benisuif University ‐ Egypt And Children's Cancer Hospital Egypt, Children Cancer Hospital Of Egypt, Cairo, Egypt; <sup>2</sup>Nci‐ Egypt And Children's Cancer Hospital Egypt, Radiotherapy, Cairo, Egypt; <sup>3</sup>Helwan University‐ Children Cancer Hospital Of Egypt, Surgical Oncology, Cairo, Egypt; <sup>4</sup>National Cancer Institute‐ Children Cancer Hospital, Pediatric Oncology, Cairo, Egypt; <sup>5</sup>National Cancer Institute ‐ Children Cancer Hospital, Pediatric Oncology, Cairo, Egypt; <sup>6</sup>Nci‐ Children Cancer Hospitl, Nuclear Medicine, Cairo, Egypt; <sup>7</sup>Nci‐ Children Cancer Hospital, Surgical Oncology, Cairo, Egypt; <sup>8</sup>National Cancer Institute‐ Children Cancer Hospital, Pathology, Cairo, Egypt; <sup>9</sup>National Cancer Institute‐ Children Cancer Hospital, Radiology, Cairo, Egypt; <sup>10</sup>Children Cancer Hospital Of Egypt, Research, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: PET‐CT has been used to evaluate RMS and other sarcomas in adults and children. Role of PET‐CT in staging pediatric RMS has not been clearly established, this study aimed to investigate the role PET in evaluation of response to treatment and its correlation with survival in pediatric patients with RMS.</p><p><bold>Design/Methods</bold>: A retrospective study included children with intermediate risk RMS presented to CCHE period from Jan, 2010 to June, 2016. They were stratified and treated based on COG protocol study ARST0531. The patients did initial PET scan and then at w 4 and at w 15.</p><p><bold>Results</bold>: We reported 138 patients who had initial PET, 18 excluded with negative PET and 120 patients were analyzed. Age ranged from 0.02 years to 14 years old with median 4.095. Eighty seven cases had embryonal pathology and 33 were of alveolar type. Fifty one patients did PET CT on week 4, 36 patients were negative and 15 patients were positive. Sixty six patients did PET CT at W 15, 58 patients were negative PET and 8 patients were still positive. OS% for negative patients at W4 was 86.6% ± 0.143 at 5 years in comparison to 33.8% ± 0.509 IN PET positive cases(P Value: 0.089). EFS% for negative patients was 69% ± 0.199 and positive patients was 33% ± 0.407 (P Value: 0.357). OS% for negative patients at W15 was 60.7% ± 0.186 and was 66.7% ± 0.533 in PET positive patients at W15 (P Value: 0.604). EFS% for negative patients at W15 was 52.9% ± 0.152 and EFS% for positive patients was 41.7% ± 0.401 (P Value: 0.452).</p><p><bold>Conclusions</bold>: Patients with negative PET at W4 had better outcome. Results was insignificant due to small number of pet negative patients. PET scan can be a tool to predict outcome in RMS</p></sec><sec id="pbc26772-sec-6060"><label>P-210</label><title>Outcome of Vaginal Tumors in Pediatric Age Group; Children's Cancer Hospital Egypt (CCHE) 57357 Experience</title><p><underline underline-style="single">M. Elsherif</underline><sup>1</sup>, E. Mohsen<sup>2</sup>, S. Ahmed<sup>3</sup>, M. Elwakeel<sup>4</sup>, H. Taha<sup>5</sup>, M. Elshafiey<sup>6</sup>, G. Taha<sup>6</sup>, M. Saad<sup>7</sup>, D. Elgalaly<sup>8</sup>, E. Khaled<sup>8</sup>, A. Elhaddad<sup>9</sup></p><p><italic><sup>1</sup>Pediatric Oncology Fellow at CCHE‐57357, pediatric oncology, Cairo, Egypt; <sup>2</sup>Assistant professor of pediatrics at faculty of medicine beni‐souef university‐ consultant of pediatric oncology at CCHE‐57357, pediatric oncology, Cairo, Egypt; <sup>3</sup>Lecturer of pediatric oncology at NCI ‐ consultant of pediatric oncology at CCHE‐57357, pediatric oncology, Cairo, Egypt; <sup>4</sup>Professor of radiology at NCI‐ consultant of radiology at CCHE‐57357, Radio‐diagnosis, Cairo, Egypt; <sup>5</sup>Professor of clinical pathology at NCI‐ head of clinical pathology department at CCHE‐57357, Clinical pathology, Cairo, Egypt; <sup>6</sup>Consultant of surgery at CCHE‐57357, surgical oncology, Cairo, Egypt; <sup>7</sup>Professor of Radiotherapy at NCI‐ Consultant of radiotherapy at CCHE‐57357, Radiation‐Oncology, Cairo, Egypt; <sup>8</sup>Clinical Research Specialist at CCHE‐57357, Clinical Research, Cairo, Egypt; <sup>9</sup>Professor of Pediatric Oncology at NCI ‐ Head of pediatric oncology department at CCHE‐57357, Pediatric Oncology, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Childhood vaginal tumors are rare comprising less than 5% of all pediatric cancers. Rhabdomyosarcoma (RMS), germ cell tumors and adenocarcinoma are the most common malignancies of the vagina.</p><p>To analyze the outcome of children with vaginal tumors who were treated at a single institution.</p><p><bold>Design/Methods</bold>: A Retrospective chart review of all pediatric patients with vaginal tumors treated at CCHE‐57357 from June 2007 till June 2016.</p><p><bold>Results</bold>: Nineteen patients (median age, 2.7 years; range, 0.72 ‐ 12.15 years) were studied. Three different histological subtypes were identified; RMS in 11 patients, germ cell tumor in 7 cases, and clear cell adenocarcinoma in one patient. Vaginal Bleeding was the most common clinical presentation, reported in (65%) of the patients. Surgery was done for 6 patients (33%) (4 with uterine salvage and 2 underwent hysterectomy).Thirteen patients (72.2%) remain disease‐free with median follow‐up of 36 months. Only one patient with RMS died out of disease progression. The 3‐ year OS and EFS for patients with RMS were 88.9% and 80% respectively, while for those with germ cell tumors the OS was 100% and EFS was 66.7%.</p><p><bold>Conclusions</bold>: Vaginal tumors are rare in the pediatric population and generally have a good prognosis. Treatment with chemotherapy only or with either conservative surgery or brachytherapy may achieve an excellent outcome in germ cell tumors and rhabdomyosarcoma.</p></sec><sec id="pbc26772-sec-6070"><label>P-211</label><title>Radiotherapy in the Local Management of Aggressive Fibromatosis: Efficacy is Inversely Proportional to Age</title><p>J. Bates<sup>1</sup>, C. Morris<sup>1</sup>, N. Iovino<sup>1</sup>, M. Rutenberg<sup>2</sup>, R. Zlotecki<sup>1</sup>, C.P. Gibbs<sup>3</sup>, M. Scarborough<sup>3</sup>, <underline underline-style="single">D. Indelicato</underline><sup>2</sup></p><p><italic><sup>1</sup>University of Florida College of Medicine, Radiation Oncology, Gainesville, USA; <sup>2</sup>University of Florida College of Medicine, Radiation Oncology, Jacksonville, USA; <sup>3</sup>University of Florida College of Medicine, Orthopaedics and Rehabilition, Gainesville, USA</italic></p><p><bold>Background/Objectives</bold>: Aggressive fibromatosis, also called desmoid tumor, is a locally aggressive non‐malignant disease affecting patients across all ages. Although radiotherapy has an established role in disease management, cross‐study comparison suggests effectiveness is inversely proportional to patient age. Our goal was to comprehensively describe local control across all ages using a large single‐institution cohort.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed all patients treated with radiotherapy for desmoid tumor at a single institution from 1975–2015. Demographic, tumor‐related, and treatment‐related information was abstracted from patient charts. Kaplan‐Meier analysis, logistic regression, and Cox proportional hazards models were used to analyze the effect of various factors on local control following radiotherapy.</p><p><bold>Results</bold>: A total of 101 patients were identified with a median follow‐up of 14.3 years (range, 0.3–41.5). At 5 and 10 years, the overall survival rates were 98% and 94% and overall local control rates were 82% and 78%. Most patients were female (66%) and white (66%); 15% were <20 years old at diagnosis, 47% were 20 to <40, and 39% were 40 years or older. The cohorts were split evenly between patients with initial versus recurrent disease at the time of radiotherapy. On univariate analysis, the only factors predicting for increased risk of local recurrence was young age at diagnosis (<20, 72% 5‐year local control; 20‐<40, 73% 5‐year local control; ≥40, 97% 5‐year local control; p = 0.008) and use of twice‐daily fractionation as compared to once‐daily radiotherapy fractionation (73% versus 90% 5‐year local control; p = 0.008). Logistic regression confirmed a relationship between increasing age and increasing probability of local control (p = 0.004).</p><p><bold>Conclusions</bold>: Younger patients with aggressive fibromatosis exhibit more frequent local failures than older patients, suggesting that tumor biology and radio‐responsiveness may differ with age. Younger patients may benefit from alternate approaches to local therapy or radiation‐dose escalation.</p></sec><sec id="pbc26772-sec-6080"><label>P-212</label><title>Kaposi Sarcoma, Oral Malformations, Mitral Dysplasia, and Scoliosis (KOMS Syndrome) Associated with 7Q34‐Q36.3 Heterozygous Terminal Deletion</title><p><underline underline-style="single">C. Jackson</underline><sup>1,2,3</sup>, A. Lefèvre‐Utile<sup>4</sup>, A. Guimier<sup>5</sup>, V. Malan<sup>5</sup>, J. Bruneau<sup>6</sup>, A. Gessain<sup>7</sup>, O. Cassar<sup>7</sup>, J. Amiel<sup>5</sup>, A. Cobat<sup>8,9</sup>, V. Rattina<sup>8,9</sup>, L. Abel<sup>1,8,9</sup>, J.L. Casanova<sup>1,4,8,9,10</sup>, S. Blanche<sup>4</sup></p><p><italic><sup>1</sup>The Rockefeller University, St. Giles Laboratory of Human Genetics of Infectious Diseases‐ Rockefeller Branch, New York, USA; <sup>2</sup>Weill Cornell Medical Center, Division of Pediatric Hematology‐Oncology, New York, USA; <sup>3</sup>Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, USA; <sup>4</sup>Necker‐Enfants Malades Hospital, Pediatric Immunology‐Hematology‐Rheumatology Unit, Paris, France; <sup>5</sup>Necker‐Enfants Malades Hospital, Genetics Department, Paris, France; <sup>6</sup>Necker‐Enfants Malades Hospital, Pathology Unit, Paris, France; <sup>7</sup>Institut Pasteur, Unit of Epidemiology and Physiopathology of Oncogenic Viruses, Paris, France; <sup>8</sup>Necker‐Enfants Malades Hospital, Laboratory of Human Genetics of Infectious Diseases‐ Necker Branch‐ INSERM U1163, Paris, France; <sup>9</sup>Paris Descartes University, Imagine Institute, Paris, France; <sup>10</sup>Howard Hughes Medical Institute, Howard Hughes Medical Institute, New York, USA</italic></p><p><bold>Background/Objectives</bold>: The meiotic pathway is conserved in humans and chromosomal crossover errors during meiosis can cause chromosomal deletions. Chromosome 7 germline terminal macrodeletions have been implicated in human congenital malformations and developmental delays. We herein decipher a novel cancer predisposition phenotype (endemic Kaposi sarcoma) attributable to a heterozygous macrodeletion of 7q34‐q36.3 in a 16‐year‐old girl originally from West Indies.</p><p><bold>Design/Methods</bold>: Comparative genomic hybridization (CGH) array in the patient was significant for 7q34‐q36.3 macrodeletion of 16 megabase pairs (Mbp). To investigate the mode of inheritance, Affymetrix Genome‐Wide Human SNP (single nucleotide polymorphism) Array 6.0 was performed in the patient and her mother (father not available), and data were analyzed using PennCNV Software. Human herpesvirus‐8 (HHV‐8) genotype was performed by nested polymerase chain reaction (PCR), and comparative sequence analysis was utilized to demonstrate the origin of HHV‐8 viral strain.</p><p><bold>Results</bold>: We herein describe a novel <italic>de novo</italic> heterozygous macrodeletion of 7q34‐q36.3 (7:142,883,341‐159,127,004; Reference genome b37/hg19) associated with endemic Kaposi sarcoma predisposition. The HHV‐8 viral strain belongs to the Sub‐Saharan African B subtype, and clustered with strains previously characterized from Cameroon and Uganda. Similar to previously reported cases of germline chromosome 7q terminal deletions, our patient has dental malposition, and developmental (growth and intellectual) delay. Novel phenotypic features include Kaposi sarcoma, oral malformations (furrowed tongue), scoliosis (thoracolumbar), and mitral valve dysplasia (KOMS).</p><p><bold>Conclusions</bold>: The occurrence of HHV‐8‐driven Kaposi sarcoma, in a child otherwise normally resistant to other infectious agents and without any other tumoral lesion, points to a very selective immunodeficiency. While defects in organogenesis have been described with chromosome 7 terminal macrodeletions, this is the first report of immunodeficiency and cancer predisposition syndrome (KOMS Syndrome) associated with this chromosomal region.</p></sec><sec id="pbc26772-sec-6090"><label>P-213</label><title>Local Control for Non Metastatic Genito‐Urinary Rhabdomyosarcoma (RMS). A Single Centre Experience</title><p><underline underline-style="single">J. Lopes</underline><sup>1</sup>, K. Parashar<sup>1</sup>, L. McCarthy<sup>1</sup>, A. Robb<sup>1</sup>, M. Pachl<sup>1</sup>, P. Kearns<sup>2</sup>, D. Ford<sup>2</sup>, S. Arul<sup>1</sup></p><p><italic><sup>1</sup>Birmingham Children's Hospital, Paediatric Surgery and Urology, Birmingham, United Kingdom; <sup>2</sup>Birmingham Children's Hospital, Paediatric Oncology, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Recent studies show 5‐year survival of localized genito‐urinary RMS patients of 77%. Though recent publications have advocated more conservative surgery, in our surgical centre emphasis is placed on achieving complete local control of disease with surgery if at all possible. Our principle behind considering radical surgery was the belief of the importance of clear margins and avoidance of radiotherapy.</p><p><bold>Design/Methods</bold>: We reviewed the notes of all patients identified by the pathology database with RMS treated at our center over the last 15 years.</p><p><bold>Results</bold>: From 2001 to 2016 we treated 12 patients for localized genito‐urinary RMS. 7:5 M:F, median age 1.7y (2mo to 6.7 yrs), with origin in uterus(1), vagina(2), bladder/ prostate(9).</p><p>All patients had pre‐operative chemotherapy. Surgery decisions were based on pre‐operative imaging, examination under anaesthesia, laparoscopy and cystoscopy. One team of two surgeons performed: radical hysterectomy (2), vaginectomy (1), pelvic exenteration (1), partial cystectomy (2), total cystectomy (1), cysto‐prostatectomy (4). 3/6 patients have had urinary undiversion. Two patients did not have surgery ‐ 1 with an unresectable tumour; 1 with near total resolution of his bladder neck tumour. Four patients had radiotherapy ‐ 1 with an unresectable tumour and 3 with positive resection margins.</p><p>Mean follow up is 6 years (9mo – 13.3 years) with 100% survival. Two patients suffered local recurrence. A patient post partial vaginectomy, later required pelvic exenteration and post‐operative radiotherapy, and is now 10 years recurrence free. A patient post partial cystectomy, had chemotherapy post relapse, and is now 4.5 years recurrence free.</p><p><bold>Conclusions</bold>: In our series survival was 100%. The 2 local recurrences had conservative surgery initially. Radical surgery was performed in 8/10 patients.</p><p>Although there is a trend for conservative surgery we believe this should be judged against the high survival rates that come with good surgical local control. We reserve radiotherapy for those with incomplete resections.</p></sec><sec id="pbc26772-sec-6100"><label>P-214</label><title>Alveolar Soft Part Sarcoma of Paediatric Orbit</title><p><underline underline-style="single">N. Pushker</underline><sup>1</sup>, R. Meel<sup>1</sup>, S. Kashyap<sup>2</sup>, S. Sen<sup>2</sup>, M. Bajaj<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences, Dept of Ocular Pathology‐ Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Alveolar soft‐part sarcoma (ASPS) is a translocation‐associated sarcoma that constitutes 1% of all sarcomas. It occurs most commonly in the lower extremities and rarely in orbit. It is commonly misdiagnosed due to its rarity and nonspecific clinical findings</p><p><bold>Design/Methods</bold>: Retrospective review of medical records, histopathology and imaging findings of all cases of ASPS of paediatric orbit that were treated at our centre between Jan 2001 and Dec 2016 (16 years).</p><p><bold>Results</bold>: Four cases of ASPS of orbit presenting in childhood were analysed. The median age of presentation was 8.5 months (range 3.5 ‐12 years). There were 2 male and 2 female patients. All 4 patients presented with proptosis of left eye. The median duration of symptoms was 8 months (range 3 months – 1 year). The initial clinical and imaging diagnosis was low flow vascular malformation (capillary haemangioma) in 3 cases and pseudotumor in 1 case. Imaging revealed a well defined lesion in all 4 cases. There was no bone erosion or extraorbital extension in any case. The lesion involved lateral orbit in 2, superior orbit in 1 and inferior orbit in 1 case. Ultrasound revealed a homogeneous lesion with regular internal architecture. One case underwent exenteration, while 3 underwent orbitotomy for tumor excision.</p><p><bold>Conclusions</bold>: Orbital ASPS is a rare malignancy of childhood, and may masquerade other benign tumors of orbit.</p></sec><sec id="pbc26772-sec-6110"><label>P-215</label><title>Treatment Outcome of Four‐Drug Versus Three‐Drug Regimen for Osteosarcoma: A Single Institute Experience</title><p>H.Y. Ju<sup>1</sup>, P. Byung‐Kiu<sup>1</sup>, P. Seog Yun<sup>2</sup>, K. June Hyuk<sup>3</sup>, K. Hyun Guy<sup>3</sup>, Y. Jong Hyung<sup>4</sup>, K. Mimi<sup>1</sup>, <underline underline-style="single">P. Hyeon Jin</underline><sup>1</sup></p><p><italic><sup>1</sup>National Cancer Center, Pediatric Oncology Center, Goyang‐si, Republic of Korea; <sup>2</sup>National Cancer Center, Department of Pathology, Goyang‐si, Republic of Korea; <sup>3</sup>National Cancer Center, Orthopaedic Oncology Clinic, Goyang‐si, Republic of Korea; <sup>4</sup>Hallym University Chuncheon Sacred Heart Hospital, Department of Pediatrics, Chuncheon, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: In osteosarcoma treatment, extent of tumor necrosis at the time of surgery following preoperative chemotherapy is known to be strongly associated with survival rate. We conducted a retrospective study to see if difference in tumor necrosis and treatment outcome comes from addition of ifosfamide to conventional three‐drug regimen.</p><p><bold>Design/Methods</bold>: Patients who had been treated at the National Cancer Center from 2002 to 2015 were evaluated. As a four‐drug regimen, 2 courses of neoadjuvant chemotherapy included intravenous methotrexate 12 g/m², cisplatin 120 mg/m², doxorubicin 75 mg/m², and ifosfamide 9g/m². Adjuvant chemotherapy was tailored according to tumor necrosis: good responders received 2 courses of doxorubicin 90 mg/m², ifosfamide 9g/m², methotrexate 12 g/m², and cisplatin 120 mg/m²; poor responders received an additional course of ifosfamide 9g/m², methotrexate 12 g/m², cisplatin 120 mg/m². As a three‐drug regimen, 7921 or AOST 0331 regimen was performed.</p><p><bold>Results</bold>: Total 26 patients were included in the study. Median age at the time of diagnosis was 15.9 (10.3‐36.7) years. Twelve (46.2%) patients were treated with three drugs from 2002 to 2012. Remaining 14 (53.8%) patients were treated with 4 drugs from 2009 to 2015. Four‐drug regimen yielded higher proportion of good responder when compared to three‐drug‐regimen (71.4% vs. 41.7%) (OR 3.5, <italic>P</italic>=0.233). 5 year survival rate of the former group was 76.2%, and that of latter group was 50% (<italic>P</italic>=0.64). Event‐free survival of the former group was 64.3%, and that of latter group was 33.3% (P=0.348).</p><p><bold>Conclusions</bold>: There was no difference between four‐ and three‐drug regimens with regard to necrosis rate, overall survival, and event‐free survival. However, small sample size could have precluded statistical difference, considering the apparent difference in treatment results between two groups. Further study in a larger scale is warranted to reach a solid conclusion.</p></sec><sec id="pbc26772-sec-6120"><label>P-216</label><title>Prognostic Value of Molecular Alterations in Infantile Spindle Cell Rhabdomyosarcoma</title><p><underline underline-style="single">E. Pozzo</underline><sup>1</sup>, M. Debiec‐Rychter<sup>2</sup>, R. Sciot<sup>3</sup>, M. Renard<sup>4</sup>, A. Uyttebroeck<sup>4</sup>, H. Segers<sup>4</sup></p><p><italic><sup>1</sup>KU Leuven, Department of Development and Regeneration, Leuven, Belgium; <sup>2</sup>KU Leuven and University Hospitals Leuven, Department of Human Genetics, Leuven, Belgium; <sup>3</sup>KU Leuven and University Hospitals Leuven, Department of Pathology, Leuven, Belgium; <sup>4</sup>University Hospitals Leuven, Department of Paediatric Hemato‐Oncology, Leuven, Belgium</italic></p><p><bold>Background/Objectives</bold>: Childhood rhabdomyosarcoma (RMS) is classified as embryonal (ERMS), alveolar (ARMS), or spindle cell (SRMS). SRMS is an uncommon subtype of RMS with age‐dependent genetic characteristics. Recent molecular analyses have described <italic>NCOA2</italic> and/or <italic>VGLL2</italic> rearrangements in the majority of infantile SRMS and their overall good prognosis. Here, we sought to identify the presence of these molecular aberrations in infantile SRMS patients and investigate their correlation with observed clinical outcome.</p><p><bold>Design/Methods</bold>: The samples from children diagnosed with RMS between 1990 and 2016 at our hospital (n=84) were analyzed with fluorescence in situ hybridization (FISH), array‐CGH and assessed for clinicopathological characteristics and survival. Patients who were diagnosed with RMS before 12 months of age were considered for this study.</p><p><bold>Results</bold>: Nine patients were diagnosed with infantile RMS, and three of them were histologically identified as infantile SRMS. Sites of primary disease of infantile SRMS patients included paravertebral, gluteal and periscapular muscles, with FISH analysis revealing absence of <italic>NCOA2</italic> and/or <italic>VGGL2</italic> rearrangements. Patients were allocated to RMS 2005 subgroup D treatment; following chemotherapeutic course, 2/3 patients underwent surgical removal with 0/3 patients requiring radiotherapy and one patient receiving 4 months of maintenance therapy (cyclophosphamide and vinorelbine) to avoid mutilating effects of radiotherapy. Two patients out of three had treatment‐related toxicities including nephrotoxicity and temporary neurotoxicity. Compared to infantile ERMS and ARMS patients (66.7% survival, 54.3 months median follow‐up), all patients with SRMS at follow‐up were alive and well, with one long‐term follow‐up of 55 months. To date, no patients developed local recurrence nor distant metastases.</p><p><bold>Conclusions</bold>: Although patients with infantile SRMS were negative for <italic>NCOA2</italic> or <italic>VGGL2</italic> rearrangements, the good prognosis and event‐free survival were not affected. Further studies are needed to identify novel molecular aberrations in infantile SRMS that could correlate with prognosis and event‐free survival.</p></sec><sec id="pbc26772-sec-6130"><label>P-217</label><title>Promising use of Rapamycin in an INFANT with Rare Smooth Muscle Cell Tumor of Nose and Upper LIP</title><p><underline underline-style="single">M. Ramzan</underline><sup>1</sup>, S. Katewa<sup>1</sup></p><p><italic><sup>1</sup>Manipal Hospital, Pediatric Hematology Oncology & BMT, Jaipur, India</italic></p><p><bold>Background/Objectives</bold>: Smooth muscle tumor (SMT) are rare in children and very difficult to treat. mTOR inhibitors like rapamycin (sirolimus) are a type of targeted therapy that stops the protein that helps cells divide and survive. mTOR inhibitors are being studied to treat perivascular epithelioid cell tumors (PEComas) and epithelioid hemangioendothelioma. Use of rapamycin has not been mentioned in literature for treatment of SMT.</p><p><bold>Design/Methods</bold>: We report a 5 month old infant first product of non‐consanguineous marriage who had swelling over tip of nose and face since birth.</p><p><bold>Results</bold>: CT scan showed lobulated soft tissue mass of 22x39mm. PET CT revealed localized FDG avid lobulated, heterogeneous, enhancing mass of 34x37x41.6mm involving right side of nose, upper lip and adjoining cheek in the pre maxillary region with calcification. Histopathology showed of spindle cell with fusiform nuclei and indistinct eosinophilic cytoplasm arranged in fascicles, was suggestive of spindle cell sarcoma, likely to be embryonal rhabdomyosarcoma. However, immunohistochemistry was strongly positive for SMA and negative for desmin, myogenin, caldesmon, S‐100, CD34 with Ki 67 of 5% (low to intermediate grade smooth muscle tumor). He was started on vincristine, actinomycin and cyclophosphamide (VAC) chemotherapy. At 6 weeks, mass reduced in size clinically so another 6 weeks of VAC given. After 12 weeks of chemo CT scan still showed mass of 31x21x26 mm. He was then started on only rapamycin 0.5 mg daily. After 8 weeks his facial swelling has significantly reduced clinically. CT showed residual mass of 21×12×21mm. Currently this infant is on rapamycin and doing well.</p><p><bold>Conclusions</bold>: Rapamycin treatment was promising in this case of SMT. Further role of this drug has to be investigated in large clinical trial in SMT.</p></sec><sec id="pbc26772-sec-6140"><label>P-218</label><title>Does Extent of Surgery Affect Fibrosarcoma Outcomes?</title><p><underline underline-style="single">K. Rao</underline><sup>1</sup>, J. Sola<sup>1</sup>, O. Picado<sup>1</sup>, E. Perez<sup>1</sup></p><p><italic><sup>1</sup>University of Miami Miller School of Medicine/Jackson Memorial Hospital, Pediatric Surgery, miami, USA</italic></p><p><bold>Background/Objectives</bold>: To determine whether surgery type has any prognostic indications for survival in fibrosarcomas.</p><p><bold>Design/Methods</bold>: We reviewed patients <20 years of age diagnosed with fibrosarcomas from 1973‐2013, who had any type of surgery, in the Surveillance Epidemiology and End Results (SEER) database. Kaplan‐Meier analyses demonstrated disease‐specific survival (DSS) for clinical and pathologic variables. Significant covariate predictors of DSS as determined by univariate analysis were analyzed using Cox regression.</p><p><bold>Results</bold>: We identified 1,163 pediatric patients. The mean age at diagnosis was 12 ± 6 years. There was no gender predilection, with a male‐female ratio of 1:1. Most (54%) were White and 18% were Black. The majority (59%) were classified as localized tumors, 28% had regional involvement, and 3% had distant metastases. The majority of patients required surgery (93%), and only 8% required radiation. Overall DSS was 91% at 5 years, 90% at 10 years, and 89% at 15 years. Of the 639 patients who had surgery, site of tumor, grade, SEER stage, and radiation were all significant using univariate Kaplan‐Meier survival analyses. Multivariate Cox regression showed that tumor stage was an independent determinant of survival, however surgical procedure type (local versus aggressive resections) showed no significance.</p><p><bold>Conclusions</bold>: Fibrosarcomas are rare in pediatric populations. Although stage is an independent determinant of survival, surgical procedure type (local versus more aggressive resections) did not show significance in a multivariate model. Aggressive surgical resection of fibrosarcomas is not associated with increased survival.</p></sec><sec id="pbc26772-sec-6150"><label>P-219</label><title>Lymph Node Ratios Predict Disease‐Specific Mortality in Pediatric Rhabdomyosarcoma</title><p><underline underline-style="single">K. Rao</underline><sup>1</sup>, J. Tashiro<sup>1</sup>, J. Sola<sup>1</sup>, H. Neville<sup>1</sup>, A. Hogan<sup>1</sup>, E. Perez<sup>1</sup></p><p><italic><sup>1</sup>University of Miami Miller School of Medicine/Jackson Memorial Hospital, Pediatric Surgery, miami, USA</italic></p><p><bold>Background/Objectives</bold>: Lymph node involvement is associated with increased local recurrence rates and decreased survival rates in pediatric rhabdomyosarcoma. We sought to determine whether lymph node ratio (LNR) predicts disease‐specific mortality (DSM).</p><p><bold>Design/Methods</bold>: We identified patients <20 years of age diagnosed with rhabdomyosarcoma from 1988‐2013 in the Surveillance Epidemiology and End Results (SEER) database. We calculated LNR's by taking the number of nodes positive/ total number of nodes examined. We used Kaplan‐Meier estimates to plot DSM for clinical and pathologic variables and Cox regression to evaluate LNR in models.</p><p><bold>Results</bold>: Our study presented 188 cases with both lymph node data and greater than three nodes examined. Median age at diagnosis was 9.5 years (2‐15), 64% were male and 74% were White. The stage at presentation was 36% localized, 42% regional, and 16% distantly metastasized. Forty‐eight percent of patients received radiation therapy after surgery. The median number of nodes examined was 7 (4‐14) and mean LNR was 0.13 ± 0.26. The mean survival was 89 ± 76 months. Overall 5‐year DSM was 13% for 5 years, and 18%, for 10, 15, and 20 years. The largest threshold for LNR associated with DSM was 0.75. Five‐year survival was 82% for LNR < 0.75 versus 15% for LNR ≥ 0.75 (p<0.003). Lymph node status, stage and LNR were significant determinants of DSM on univariate analysis. Using Cox regression with all significant covariates, LNR and stage remained independent determinants of DSM.</p><p><bold>Conclusions</bold>: Pediatric rhabdomyosarcomas are rare. LNR is an independent determinant of DSM. Using 0.75 as a threshold may offer further value in DSM prognostication.</p></sec><sec id="pbc26772-sec-6160"><label>P-220</label><title>Clinicopathologic Spectrum of a Series of Rhabdomyosarcomas Diagnosed at a Tertiary Cancer Referral Centre, Mumbai, India</title><p><underline underline-style="single">B. Rekhi</underline><sup>1</sup>, C. Gupta<sup>1</sup>, S. Qureshi<sup>2</sup>, G. Chinnaswamy<sup>3</sup>, T. Vora<sup>3</sup>, J. Bajpai<sup>3</sup>, N. Khanna<sup>4</sup>, S. Laskar<sup>4</sup></p><p><italic><sup>1</sup>tata memorial hospital, Surgical Pathology, mumbai, India; <sup>2</sup>tata memorial hospital, Surgical Oncology, mumbai, India; <sup>3</sup>tata memorial hospital, Medical Oncology, mumbai, India; <sup>4</sup>tata memorial hospital, Radiation Oncology, mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Spindle cell/sclerosing rhabdomyosarcoma (RMS) is a relatively newly recognized subtype of RMS. Immunohistochemically; high myogenin expression is associated with alveolar RMS (ARMS) and an aggressive clinical course.</p><p><bold>Design/Methods</bold>: This study was aimed at evaluating clinicopathologic and immunohistochemical features of 300 cases of RMS. Immunohistochemical expression of myogenin and MyoD1 was graded, based on percentage of tumor cells displaying positive intranuclear immunostaining, such as grade 1(1‐25%); grade 2(26‐50%); grade 3(51‐76%) and grade 4(76‐100%). Follow‐up details were available in 272(90.7%) patients. Various clinicopathologic parameters were correlated with 3‐year disease‐free and overall survival.</p><p><bold>Results</bold>: Most cases, including various subtypes, except pleomorphic RMS, occurred in the first two decades (228 cases)(76%), in males and in the head and neck region (126)(42%), followed by extremities (59)(19.7%). The most common subtype was ARMS (140 cases)(46.7%), followed by embryonal RMS (90)(30%); spindle cell/ sclerosing RMS (61)(20.3%) and pleomorphic RMS (9)(3%). Immunohistochemically, desmin was expressed in 292/299(97.6%) tumors, myogenin in 238/267(89.1%) and MyoD1 in 192/266(72.2%) tumors. High myogenin expression (more than, equal to 51% positive tumor cells) was significantly associated with cases of ARMS (95/121,78.5%), as compared to other subtypes(48/117, 41%).(p<0.001). High MyoD1 expression was seen in more cases of pure sclerosing, combined with spindle cell/ sclerosing RMSs(10/10, 100%), as compared to the other subtypes(91/141, 67.4%)(<italic>p</italic>=0.032) There was no significant difference between high myogenin expression and disease‐free survival and/ or 3 year overall survival. Children, especially in first decade; patients with tumor sizes less than 5cm; without metastasis and at an early tumor stage, showed significantly better survival outcomes.</p><p><bold>Conclusions</bold>: There was significant association between high myogenin expression and cases of ARMSs and high MyoD1 expression and cases of spindle cell/sclerosing RMS. Children in first decade, with smaller sized tumors, presenting at early stage had relatively better outcomes. High myogenin expression was not found to be related with aggressive clinical outcomes.</p></sec><sec id="pbc26772-sec-6170"><label>P-221</label><title>Radachlorin‐Based Photodynamic Therapy of Soft Tissue Sarcoma in Children</title><p><underline underline-style="single">N. Rostovtsev</underline><sup>1</sup>, S. Kovalenko<sup>1</sup></p><p><italic><sup>1</sup>Regional Children Hospital, Surgery department, Chelyabinsk, Russia</italic></p><p><bold>Background/Objectives</bold>: The aim of our research was to assess the effectiveness and the period of intraoperative phototoxicity of radachlorin mediated photodynamic therapy (PDT). To treat malignant tumors characterized by far and near infrared absorption band (650‐800 nm) in children we used the second‐generation photosensitizer radachlorin (654‐662 nm absorption band). This agent is non‐toxic, shows a high photodynamic activity, and has a good contrast ratio (to 10:1) and a fine clearance.</p><p><bold>Design/Methods</bold>: During a ten‐year period (2007‐2017), seventeen patients with primary soft tissue sarcoma (10 cases of embryonal rhabdomyosarcoma, 3 cases of mixed rhabdomyosarcoma, and 4 cases of alveolar fibrosarcoma) were treated. PDT was predominantly inpatient (intraoperative). In one case of alveolar fibrosarcoma, PDT was performed on an outpatient basis. All children were admitted to hospital with an advanced stage of disease (tumors ranged from 10 to 20 cm in diameter and were mainly T3‐4, sometimes T2).</p><p><bold>Results</bold>: Treatment based on chlorin photosensitizer mediated PDT did not cause systemic or local events and was well tolerated by all patients including children with a concomitant disease. Due to fast accumulation of radachlorin in tumor, it was possible to use laser in 1‐4 hours after intravenous administration of the agent. Therapeutic effect was observed in all patients including complete tumor resorption in 19 cases (58.8%) and partial resorption in 7 cases (41.2%).</p><p><bold>Conclusions</bold>: Chlorin photosensitizers have a high photodynamic activity and fine therapeutic effects; they are quickly excreted from the body and, due to a fast clearance, do not induce the prolonged light sensitivity. This erases the problem of the long‐term cutaneous phototoxicity. Thanks to a fast accumulation in tumor with a high contrast gradient between tumor and normal tissues, chlorin photosensitizers make it possible to reduce the number of PDT sessions and to achieve positive therapeutic outcomes.</p></sec><sec id="pbc26772-sec-6180"><label>P-222</label><title>Prognostic Impact of Circulating Endothelial Cells and Endothelial Progenitor Cells on Treatment Response and Survival of Pediatric Patients with Solid Tumors</title><p><underline underline-style="single">H. Sayed</underline><sup>1</sup>, A. Zahran<sup>2</sup></p><p><italic><sup>1</sup>South Egypt Cancer Institute, Pediatric Oncology, Assiut, Egypt; <sup>2</sup>South Egypt Cancer Institute, Clinical Pathology, Assiut, Egypt</italic></p><p><bold>Background/Objectives</bold>: Neoangiogenesis plays an important role in growth and spread of pediatric solid tumors. The levels of circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) have been documented as indicators of the vascular function in cancer. Here, we evaluated the role of these cells in pediatric solid tumors and their prognostic impact.</p><p><bold>Design/Methods</bold>: A prospective study included 70 patients with different pediatric solid tumors treated with different types of chemotherapy in addition to 20 age and sex matched healthy children as controls. Blood samples collected at diagnosis then at day 7 and day 21 after chemotherapy. Samples assessed for CECs and EPCs using the flowcytometry.</p><p><bold>Results</bold>: The mean levels of CECs and EPCs of patients at diagnosis were significantly higher than controls (85.29±24.78 and 26.1±9.11 versus 20.08±6.65; and EPCs; 2.78±1.48 respectively; p < 0.001 for both). The highest levels of CECs was observed in patients with rhabdomyosarcoma (RMS). An overall increase was reported in CECs and after the first cycle of chemotherapy, that was significantly correlated to treatment response and overall survival.</p><p><bold>Conclusions</bold>: As the highest levels of CECs was observed in our patients who respond to therapy, the magnitude of increase of CECs at day 7 after chemotherapy might be used as very early predictor of response to therapy and outcome but further study on larger population is necessary to confirm that.</p></sec><sec id="pbc26772-sec-6190"><label>P-223</label><title>Alveolar Soft Part Sarcoma in Children and Adolescents: Treatment Results of the Five Cooperative Weichteilsarkom Studiengruppe Trials (CWS)</title><p><underline underline-style="single">M. Sparber‐Sauer</underline><sup>1</sup>, G. Seitz<sup>2</sup>, T. von Kalle<sup>3</sup>, C. Vokuhl<sup>4</sup>, I. Leuschner<sup>4</sup>, M. Scheer<sup>1</sup>, M. Münter<sup>5</sup>, S.S. Bielack<sup>1,6</sup>, B. Kazanowska<sup>7</sup>, R. Ladenstein<sup>8</sup>, F. Niggli<sup>9</sup>, T. Klingebiel<sup>10</sup>, J. Fuchs<sup>11</sup>, E. Koscielniak<sup>1,12</sup></p><p><italic><sup>1</sup>Stuttgart ‐ Olgahospital‐ Stuttgart Cancer Center‐ Zentrum für Kinder– Jugend‐ und Frauenmedizin, Pediatrics 5 Oncology‐ Hematology‐ Immunology, Stuttgart, Germany; <sup>2</sup>University Children´s Hospital Marburg, Department of Pediatric Surgery, Marburg, Germany; <sup>3</sup>Klinikum Stuttgart‐ Zentrum für Kinder– Jugend‐ und Frauenmedizin‐ Olgahospital, Institute of Radiology, Stuttgart, Germany; <sup>4</sup>University of Kiel, Institute of Paidopathology, Kiel, Germany; <sup>5</sup>Klinikum Stuttgart, Institute of Radiotherapy, Stuttgart, Germany; <sup>6</sup>University of Muenster, Department of Pediatric Hematology and Oncology, Münster, Germany; <sup>7</sup>University of Wroclaw, Department of Pediatric Hematology/Oncology and BMT, Wroclaw, Poland; <sup>8</sup>St. Anna Kinderspital, Pediatric Oncology, Wien, Austria; <sup>9</sup>University of Zurich, Department of Pediatric Oncology, Zürich, Switzerland; <sup>10</sup>University of Frankfurt, Hospital for Children and Adolescents, Frankfurt, Germany; <sup>11</sup>University Children´s Hospital, Department of Pediatric Surgery and Urology, Tuebingen, Germany; <sup>12</sup>University Children´s Hospital‐, Department of Pediatric Hematology and Oncology, Tübingen, Germany</italic></p><p><bold>Background/Objectives</bold>: Alveolar soft part sarcomas (ASPS) are mesenchymal tumours characterized by t(X;17)(p11;q25) leading to ASPSL‐TFE3.</p><p><bold>Design/Methods</bold>: The clinical data of 61 children and adolescents with ASPS, treated according to recommendations for “adult type” NRSTS in five prospective trials of the Cooperative Weichteilsarkom Studiengruppe (CWS) (1987‐2015), were analyzed.</p><p><bold>Results</bold>: Median age was 14 years [range: 3–20]. The tumour was mainly located in the extremities (75%). 46 patients had localized (LD) and 15 metastatic disease (MD). 34/46 patients with LD and 3/15 with MD received primary resection (LD: RO n=37, R1 n=6, R2 n=2 and MD, primary tumour: R0 n=8, R1 n=1, R2 n=3), 7 of the LD patients received RT additionally. All 37 patients are alive, 30/37 patients in complete remission (CR). CHT after primary resection (n=17) or biopsy (n=7) was given in 12/46 patients with LD and 12/15 MD. In 7 patients response was assessable: 2 partial, 4 stable disease and 1 progression. In 12/24 patients a secondary resection was performed, in 3 RT was added: 8/12 patients were in CR in comparison to 4/12 patients without secondary resection. After a median follow‐up of 6 years (range: 0.2– 16.5), 45/46 patients with localized and 8/15 patients with MD were alive: 36/45 and 2/8 in complete remission, the others mostly in stable disease. 10 yr overall survival (OS) and event free survival (EFS) were 88% and 65% respectively. Age<10 years, IRS I‐III, size ≤5cm, T1 and R0 or R1 (primary or delayed) resection correlated with favorable prognosis concerning EFS and OS.</p><p><bold>Conclusions</bold>: Prognosis of patients with ASPS when treated in prospective trials is comparable to prognosis of patients with rhabdomyosarcoma. Primary or delayed complete tumour resection correlates with long term survival.</p></sec><sec id="pbc26772-sec-6200"><label>P-224</label><title>Family History of MPNST Among Individuals with NF‐1 IS Associated with Increased Incidence and Earlier Development of MPNST</title><p><underline underline-style="single">M. Spira</underline><sup>1</sup>, <underline underline-style="single">F. Malbari</underline><sup>2</sup>, P. Knight<sup>3</sup>, C. Zhu<sup>4</sup>, M. Roth<sup>4</sup>, J. Gill<sup>4</sup>, I. Abbott<sup>5</sup>, A. Levy<sup>4</sup></p><p><italic><sup>1</sup>Albert Einstein College of Medicine, Bronx, USA; <sup>2</sup>Children's Hospital at Montefiore, Department of Neurology, Bronx, USA; <sup>3</sup>Children's Tumor Foundation, Research & Medical Programs, New York, USA; <sup>4</sup>Children's Hospital at Montefiore, Department of Pediatric Hematology/Oncology and Marrow and Blood Cell Transplantation, Bronx, USA; <sup>5</sup>Children's Hospital at Montefiore, Department of Neurosurgery, Bronx, USA</italic></p><p><bold>Background/Objectives</bold>: Neurofibromatosis type 1 (NF‐1) is a relatively common autosomal dominant tumor predisposition syndrome. Malignant peripheral nerve sheath tumors (MPNST) are the leading cause of death in young adults with NF‐1. The reported incidence of MPNST among individuals with NF‐1 varies, and there is little information regarding the risk factors for developing MPNST in this patient population.</p><p><bold>Design/Methods</bold>: Individuals with NF‐1 registered with the Children's Tumor Foundation's Neurofibromatosis Registry were emailed an anonymous 15‐minute survey regarding personal and family history of NF‐1 and MPNST, ages of onset, and symptomatology. Participation was voluntary and information was self‐reported and not verified by individual health records.</p><p><bold>Results</bold>: The survey was sent to 4801 registrants and had 878 responses (18.3% response rate). Among all respondents having at least one blood relative diagnosed with MPNST, 19.4% developed MPNST themselves. This was significantly higher than the incidence of MPNST among respondents who reported a negative family history of MPNST (7.5%, <italic>p</italic>=0.021). The presence of a positive family history for MPNST was found to be a risk factor for development of MPNST (OR‐2.975; 95% CI 1.232‐7.187). In addition, NF1 patients with MPNST and a positive family history of MPNST were significantly more likely to have developed the disease prior to age 10 than those with a negative family history of MPNST (42.9% vs 7.0%, <italic>p</italic>=0.029), These patients were also more likely to develop MPNST before age 20, however the difference was not significant (71.4% vs 32.6%, <italic>p</italic>=0.089).</p><p><bold>Conclusions</bold>: These results suggest that a positive family history of MPNST represents a risk factor for the development of MPNST. This data supports consideration for implementing enhanced screening for this at‐risk population. Furthermore, since the results also suggest an earlier onset of disease in individuals with a positive family history of MPNST, screening should be carefully considered particularly for patients less than 10 years.</p></sec><sec id="pbc26772-sec-6210"><label>P-225</label><title>Prognostic Factors and Survival in Children with Rhabdomyosarcoma: Experience at the Instituto Nacional De Enfermedades Neoplasicas and Hospital Rebagliati</title><p><underline underline-style="single">C. Ugaz Olivares</underline><sup>1</sup>, J. Montoya<sup>1</sup>, C. Perez<sup>1</sup>, L. Vasquez<sup>2</sup>, L. Rios<sup>2</sup></p><p><italic><sup>1</sup>Instituto Nacional de Enfermedades Neoplásicas, Lima, Lima, Peru; <sup>2</sup>Hospital Rebagliati, Lima, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Rhabdomyosarcoma (RMS) is still one of the neoplasms with poor prognosis in our country despite the improvement in the worldwide cure rate. The aim of this study is to determine survival and associated prognostic factors of this entity.</p><p><bold>Design/Methods</bold>: Retrospective cohort study. All infants and children younger than 14 years with RMS treated at the Instituto Nacional de Enfermedades Neoplasicas (INEN) and Hospital Rebagliati between May 1990 and December 2016 were reviewed.</p><p><bold>Results</bold>: A total of 252 children were identified, 124 patients (49.2%) were male and 128 (50.8%) female. The median age was 5 years (range, 1 month ‐ 14 years). The most frequent histological type was embryonal (76.9%) and 41.5% of patients had metastatic disease at onset. With a median follow‐up of 26 months, the 5‐year overall survival (OS) rate for localized and metastatic RMS was 69.3% (standard error, SE 5.32%) and 21.8% (SE 6.29 %) respectively. Five‐year event‐free survival (EFS) for localized and metastatic RMS was 48.0% (SE 5.45%) and 12.3% (SE 4.32%), respectively. Eleven patients had no survival data. In the multivariate analysis, the presence of metastases (P=0.001), histological type (P=0.014), positive surgical margins (P=0.046), risk group (P=0.001), clinical‐surgical group (P=0.001) and stage (P=0.001) significantly affected OS. There was a significant improvement in 5‐year OS according to decades (30.5% in 1990 ‐ 1999, 40.0% in 2000 ‐ 2009 and 54.5% in 2010 ‐ 2016, P=0.001). Age, gender, provenance, tumor size and histological subtype did not affect significantly OS.</p><p><bold>Conclusions</bold>: Survival rates in patients with RMS are lower than those reported in developed countries, although there is evidence of improvement in recent years. It is necessary to optimize the multidisciplinary management of this disease.</p></sec><sec id="pbc26772-sec-6220"><label>P-226</label><title>Pencil‐Beam Scanned Protons for the Treatment of Ewing's Sarcoma Patients: Results from the Paul Scherrer Institute</title><p><underline underline-style="single">D.C. Weber</underline><sup>1</sup>, F. Murray<sup>1</sup>, D. Antunes Correia<sup>1</sup>, U. Kliebsch<sup>1</sup>, M. Walser<sup>1</sup>, A. Bolsi<sup>1</sup>, A. Lomax<sup>1</sup>, R. Schneider<sup>1</sup></p><p><italic><sup>1</sup>Paul Scherrer Institute, Center for Proton Therapy, Villigen, Switzerland</italic></p><p><bold>Background/Objectives</bold>: Few data exist regarding the clinical outcome of patients with Ewing's sarcoma (EWS) treated with pencil‐beam scanning proton therapy (PT). We report the local/distant control rates, survivorship and late toxicity of children, adolescents and young adults (AYA) treated at the Paul Scherrer Institute.</p><p><bold>Design/Methods</bold>: Thirty‐eight patients (median age, 9.9 years) were identified. A total of 24 male and 14 female patients received a median dose of 54.9 GyRBE (range, 45.0‐69.6). Size of the tumor ranged from 1.7 to 24 cm (median, 6.7). Most common primary site was axial/pelvic (n=27; 71%). Four patients (11%) presented with metastasis at diagnosis. Twenty (53%) patients had chemo‐PT only. Median follow up was 49.6 months (range, 9.2‐131.7).</p><p><bold>Results</bold>: The 5‐year actuarial rate of local control (LC), metastasis‐free survival (MFS) and overall survival (OS) were 81.5%, 76.4% and 83.0%, respectively. All local recurrences occurred in field and in patients with non‐extremity primaries. Six patients died, all of tumor progression. Age < 10 years was a favorable factor for LC (p=0.05) and OS (p=0.05) of borderline significance but was significant for MFS (p=0.003). Tumor volume < 200 ml were favorable prognostic factors for DFS (p=0.03) and OS (p=0.07). Acute toxicity was limited to grade 1‐2 skin erythema or mucositis. Only 2 (6.9%) grade 3 late toxicities were observed. The 5‐year actuarial rate of grade 3 toxicity‐free survival was 90.9%.</p><p><bold>Conclusions</bold>: These preliminary data suggests that the outcomes of children and AYA with EWS were good and PT was well tolerated with very few late adverse events. The local and distant tumor control for older patients with large pre‐PT tumor volumes remains problematic in these challenging patients.</p></sec><sec id="pbc26772-sec-6230"><label>P-227</label><title>Clinical Characteristics and Prognosis of Pediatric Rhabdomyosarcoma in SCMC</title><p><underline underline-style="single">H. yali</underline><sup>1</sup>, G. yijin<sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center SCMC Affiliated to Shanghai Jiaotong University School of Medicine, Hematology/Oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: The objective of this study was to determine treatment outcomes in pediatric patients with rhabdomyosarcoma treated at the Shanghai Children's Medical Center (SCMC).</p><p><bold>Design/Methods</bold>: A retrospective chart review of 108 pediatric patients (< 19 y old) with Rhabdomyosarcoma(RMS) diagnosed between 2005 and 2014 was performed. According to the pathological subtype, TNM stage and postoperative pathologic staging, the patients were divided into four groups: low‐risk group, intermediate‐risk group, high‐risk group and distant metastatic group. The Kaplan‐Meier survival analysis and Cox regression multivariate analysis were used to assess prognostic factors for overall survival (OS) and event‐free survival (EFS).</p><p><bold>Results</bold>: The median age at diagnosis was 65.5 months. The median follow‐up for living patients was 44.3 months and the median follow‐up for all patients was 36.9 months. The most common primary sites arose in the others (includes abdomen, trunk, retroperitoneum, etc.) (32.4%). The 5‐year OS and EFS for all patients were 86.1% and 72.2% and for metastatic disease were 58.8% and 29.4%, respectively. On multivariate analysis, metastatic disease at presentation, ≤1y or≧10y, tumor size ≧ 5cm were associated with worse EFS (P < 0.05). Metastatic disease at presentation was associated with worse OS (P < 0.05). The estimated 5‐years EFS rate for four groups (low‐risk group, intermediate‐risk group, high‐risk group and distant metastatic group) were 71.4%, 85.1%, 75.7%, and 29.4%, respectively (P < 0.001). The estimated 5‐years OS rate for four groups was 85.7%, 95.7%, 86.5% and 58.8%, respectively (P < 0.001).</p><p><bold>Conclusions</bold>: RMS patients with distinct groups have different outcomes in the SCMC, which is quite similarly to the worldwide data. However, this study need for long‐term follow‐up of RMS survivors for analysis of prognosis factors.</p></sec></sec><sec id="pbc26772-sec-6240"><title>Solid Non Brain Tumours ‐ Retinoblastoma</title><sec id="pbc26772-sec-6250"><label>P-228</label><title>Clinico‐Demographic Profile of Retinoblastoma Patients Seen in Tertiary Referral Centers in MANILA, Philippines (2014‐2016)</title><p><underline underline-style="single">A.P. Alcasabas</underline><sup>1</sup>, B. Gepte<sup>2</sup>, G. Mercado<sup>3</sup>, A. Goleta‐Dy<sup>4</sup>, E. Domingo<sup>3</sup>, P. Fajardo<sup>1</sup>, J. Lecciones<sup>2</sup></p><p><italic><sup>1</sup>University of the Philippines ‐ Philippine General Hospital, Paediatrics, Manila, Philippines; <sup>2</sup>Philippine Children's Medical Center, Pediatrics, Manila, Philippines; <sup>3</sup>University of the Philippines ‐ Philippine General Hospital, Opthalmology, Manila, Philippines; <sup>4</sup>St. Luke's Medical Center, Pediatrics, Quezon City, Philippines</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma has a high incidence in the Philippines (16.5 per million children 0‐4 years). In Luzon, the country's largest island, 90 cases are expected annually. Two government pediatric cancer units in Manila started a retinoblastoma program in October 2013 involving adoption of a uniform stage‐based protocol, patient navigation, data management and community‐based health worker education on early warning signs. We report the clinico‐demographic profiles of children diagnosed from January 1, 2014 – December 31, 2016.</p><p><bold>Design/Methods</bold>: Prospective data collection of all consecutive patients and review</p><p><bold>Results</bold>: A total of 119 cases were seen. Eighty‐two had unilateral retinoblastoma, 35 bilateral, and 2 trilateral. Mean age (months) at diagnosis: unilateral 29 (3‐108); bilateral: 19 (2‐51); and trilateral 13 (12‐14). M:F ratio 1.4:1. Average lag time from initial symptoms to diagnosis was 12 months (1 ‐ 46). Reasons for delay include financial constraints (N=67, 56%), ignorance of disease (N=27; 23%), misdiagnosis (N=11; 9%), multiple referrals (N=4; 3%) and fear (N=4; 3%). Only 16 % (N=19) of patients came from Metro Manila, with most 40% (N=47) from Southern Luzon (16,700 km<sup>2</sup> area). Chief complaints were leukocoria in 42% (n=50), orbital mass 37% (n=44), buphthalmos 10% (N=12), post enucleation in 8% (N=9), strabismus 1% (N=1), blindness 1% (N=1), no data 2% (N=2). Majority had extra‐ocular disease (50%) with International Retinoblastoma Staging System Stage 0: N=1; Stage 1: N=45; Stage II: N=2, Stages III N=33; Stage 4: N=24; and unknown: N=13.</p><p><bold>Conclusions</bold>: To address delayed diagnosis and low detection rates, a nationwide educational campaign should tackle both the early warning signs of retinoblastoma and the availability of government financial aid, including the national health insurance coverage for enucleation, chemotherapy and radiation. A patient referral system from communities and local hospitals to retinoblastoma treatment centers should be established.</p></sec><sec id="pbc26772-sec-6260"><label>P-229</label><title>Impact of Simple Lifestyle Intervention Yoga/Meditation on Improvement in the Quality of Life and Semen Quality in Fathers of Children Affected with Retinoblastoma</title><p><underline underline-style="single">S. Bisht</underline><sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, ANATOMY, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma (RB) is the most common childhood intraocular malignancy and its incidences has increased by 30% in the past 5 years which is believed to be due to the effect of environmental factors causing oxidative stress (OS). Sperm DNA integrity is essential for fertilization, proper embryonic development and birth of healthy offspring. Sperm is highly vulnerable to oxidative damage to both nuclear and mitochondrial DNA due to minimal cytosolic anti‐oxidants and deficient DNA damage repair mechanism. Yoga/meditation are being increasingly used as adjunct to modern medicine in treatment of several clinical conditions. In the present study, we analyzed the effects of yoga/meditation on seminal OS and sperm DNA integrity in fathers of children affected with RB.</p><p><bold>Design/Methods</bold>: A total of 50 men were recruited for the study. Semen samples were collected at base line (day 0), 1 month, 3 months and after 6 months of yoga/meditation intervention. Reactive oxygen species (ROS), DNA fragmentation index (DFI) and 8‐hydroxy‐2’‐deoxyguanosine (8‐OHdG) levels were estimated at day 0, 1 month, 3 months and 6 months.</p><p><bold>Results</bold>: There was reduction in mean DFI levels at 1 month (p=0.63), 3 months (p=0.046) and 6 months (p=0.032), seminal mean ROS levels at 1 month (p=0.74), 3 months (p=0.039) and 6 months (p=0.006), 8‐OHdG levels at 1 month (p=0.68), 3 months (p=0.043) and 6 months (p=0.022) with respect to the base line levels (day 0) of yoga/meditation intervention.</p><p><bold>Conclusions</bold>: Yoga/meditation may significantly lower OS and oxidative DNA damage, and levels of mutagenic base 8‐OHdG in the sperm DNA. Thus yoga/meditation are simple lifestyle interventions which are therapeutic for maintaining/restoring sperm DNA integrity and hence, can reduce the prevalence of childhood cancers where poor sperm DNA integrity could be one of the reason.</p></sec><sec id="pbc26772-sec-6270"><label>P-230</label><title>“Where does this Come From?” Understanding How Survivors and Parents of Children with Retinoblastoma Conceptualize Genetics</title><p><underline underline-style="single">H. Dimaras</underline><sup>1</sup>, A. Gedleh<sup>1</sup>, A. Lee<sup>1</sup>, J. Hill<sup>1</sup>, K. Hougham<sup>1</sup>, J. Kabiru<sup>2</sup>, K. Kimani<sup>3</sup>, L. Njambi<sup>3</sup></p><p><italic><sup>1</sup>Hospital for Sick Children, Ophthalmology & Vision Sciences, Toronto, Canada; <sup>2</sup>Kikuyu Eye Unit, Ophthalmology, Kikuyu, Kenya; <sup>3</sup>The University of Nairobi, Ophthalmology, Nairobi, Kenya</italic></p><p><bold>Background/Objectives</bold>: Genetic testing and counselling have become integral parts in the management of heritable cancers, like the childhood eye cancer retinoblastoma. This study aimed to determine the attitudes, knowledge and experiences ‐ concerning retinoblastoma genetics ‐ among survivors and parents of children with retinoblastoma in Canada and Kenya.</p><p><bold>Design/Methods</bold>: Data was collected through focus groups and a brief demographic questionnaire. Study settings were in Canada (The Hospital for Sick Children) and Kenya (Kenyatta National Hospital and Kikuyu Eye Unit). Thematic analysis was used to identify key themes from discussions in each setting.</p><p><bold>Results</bold>: Three focus groups were conducted in Toronto (n = 15) and five in Kenya (n = 31). Themes that were common to both Canadian and Kenyan populations included: (a) there is significant confusion about the genetics and heritability of retinoblastoma; (b) there is a need for improved communication from healthcare teams about genetics; and (c) there is a need for improved access to psychosocial support to help with coping. Unique themes included: (a) genetic diagnosis can cause significant interruption to family relationships (Kenya); and (b) genetic testing and counselling are valued by families (Canada).</p><p><bold>Conclusions</bold>: Even in Canada, where genetic testing and counselling are well established, retinoblastoma survivors and parents were found to have significant gaps in their knowledge of genetics. Similarly in Kenya, participants were confused about the genetics and heritability of retinoblastoma. Improving communication from healthcare teams, and providing psychosocial support, could help enhance information uptake and understanding by families in both Canada and Kenya. The patient perspective from each population also revealed context‐specific issues that are useful for the refinement of cancer genetic services in each setting.</p></sec><sec id="pbc26772-sec-6280"><label>P-231</label><title>Enhancing Communication about Retinoblastoma Clinical Encounters Using a Novel Global Data Repository</title><p><underline underline-style="single">B. Gallie</underline><sup>1</sup>, K. Houghham<sup>1</sup>, T. Truong<sup>2</sup>, L. Justin<sup>2</sup>, T. Viet<sup>2</sup>, Y. Gavrylyuk<sup>2</sup>, S. Soliman<sup>1</sup>, C. Zhang<sup>3</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Ophthalmology and Vision Science, Toronto, Canada; <sup>2</sup>Techna Institute‐ University Health Network, Health Informatics Research, Toronto, Canada; <sup>3</sup>Beijing Children's Hospital, Ophthalmology, Beijing, China</italic></p><p><bold>Background/Objectives</bold>: Communication plays a critical role in effective retinoblastoma care. Yet communication of details from clinical encounters to all members of a patient's circle of care (individuals that provide or support retinoblastoma patient care including parents / legal guardians) remains complex and onerous. Despite best intentions, poor communication (i) wastes time and money, (ii) results in misunderstandings about the retinoblastoma treatments and prognosis, and (iii) contributes to family stress in the face of devastating diagnoses and difficult choices.</p><p><bold>Design/Methods</bold>: We set out to develop an innovative IT solution to enhance retinoblastoma circle of care communication. The prototype point‐of‐care retinoblastoma data repository, developed by 2005, has been tested extensively by care providers and iteratively refined for more than a decade at SickKids. We showed in 2009, 2015 that the cornerstone of this database, a language‐independent timeline, enhances understanding by parents of children with retinoblastoma concerning purposes and quality of care.</p><p><bold>Results</bold>: The Internet version of the repository, now called <bold>D</bold>isease‐specific <italic>e</italic>lectronic <bold>P</bold>atient <bold>I</bold>llustrated <bold>C</bold>linical <bold>T</bold>imeline for <bold><italic>R</italic></bold><italic>etino</italic><bold><italic>B</italic></bold><italic>lastoma</italic> (D<italic>e</italic>PICT<italic>RB</italic>), is ready for global deployment. With consent, at diagnosis a new retinoblastoma patient is given a D<italic>e</italic>PICT<italic>RB</italic> account by their treatment centre. Identifiable disease‐specific summary data about each clinical encounter is entered at the point of care, into the patient's D<italic>e</italic>PICT<italic>RB</italic> account on a secure Telus server. Included in D<italic>e</italic>PICT<italic>RB</italic> are drawings mapping the tumours and treatments in each eye, selected images key to understanding and cancer prognostic staging based on algorithms. “Write access” is securely assigned to clinical members of the circle of care; parents and others have “read access”, supporting effective dialogue with care‐givers.</p><p><bold>Conclusions</bold>: Anecdotal feedback suggests that D<italic>e</italic>PICT<italic>RB</italic> enhances communication. By modulating communication within retinoblastoma circles of care, D<italic>e</italic>PICT<italic>RB</italic>has potential to reduce waste, improve understanding of the retinoblastoma treatment course and empower parents/legal guardians to be informed decision makers.</p></sec><sec id="pbc26772-sec-6290"><label>P-232</label><title>The Canadian Retinoblastoma Research Registry</title><p><underline underline-style="single">K. Hougham</underline><sup>1</sup>, H. Dimaras<sup>1</sup>, C. Moses<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Ophthalmology and Vision Sciences, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma is an aggressive childhood eye cancer. Retinoblastoma patients (individuals affected by retinoblastoma, including parents/legal guardians) indicate they are deeply incentivized to keep abreast of research and help co‐create it.</p><p><bold>Design/Methods</bold>: We initiated the Canadian Retinoblastoma Patient Engagement Strategy, in response to the keen interest of the patient community to be involved in research. As part of this strategy, we created the Canadian Retinoblastoma Research eRegistry. The purpose of the eRegistry is to engage Canadian retinoblastoma patients with the research community. Registrants are invited to give permission to (Part A – Passive Participation) receive general information about retinoblastoma (e.g., lay summaries); and (Part B – Active Participation) be contacted about specific research studies for which they (or their children) might be a suitable subject or team member (e.g., research assistant).</p><p><bold>Results</bold>: Since it launched (November, 2016), 35 people have agreed to participate in the Canadian Retinoblastoma Research Registry. All registrants enrolled in Parts A and B of the registry. Thirty‐seven percent (n = 13) of the registrants are retinoblastoma survivors and 74% (n=26) of the registrants are the parent/legal guardian of someone diagnosed with retinoblastoma. All of the registrants are 30 years of age and older. Forty‐five percent (n =16) of the registrants are from large urban centers. As part of enrollment, registrants are invited to share research topics of interest. A quarter (n = 9) of the registrants provided suggested research topic(s), including second cancers, genetics and psychological side effects.</p><p><bold>Conclusions</bold>: These initial data indicate: (i) registrants are keen to receive both general information as well as invitations for specific research studies; (ii) targeted recruitment efforts may be required to reach younger people affected by retinoblastoma and retinoblastoma survivors; and (iii) although interested in retinoblastoma research, some retinoblastoma patients do not have specific research priorities.</p></sec><sec id="pbc26772-sec-6300"><label>P-233</label><title>Development of Beagle Retinoblastoma Model: Mimicking Tumor Microenvironment Surrounding Vitreous Seeds</title><p><underline underline-style="single">D.H. Jo</underline><sup>1</sup>, J.H. Kim<sup>2</sup>, H.O. Jun<sup>2</sup>, C.S. Cho<sup>2</sup>, E. Bak<sup>1</sup>, J.H. Kim<sup>1</sup></p><p><italic><sup>1</sup>Seoul National University College of Medicine, Department of Ophthalmology, Seoul, Republic of Korea; <sup>2</sup>Seoul National University Hospital, Fight against Angiogenesis‐Related Blindness FARB Laboratory‐ Clinical Research Institute, Seoul, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: This study aims to develop a novel orthotopic transplantation model of retinoblastoma model in beagles which mimics vitreous seeds. In patients with retinoblastoma, there is no definite method to investigate the characteristics of vitreous seeds because biopsy is absolutely prohibited.</p><p><bold>Design/Methods</bold>: SNUOT‐Rb1 and Y79 cells (2 x 10<sup>7</sup> cells) from 2 different retinoblastoma cell lines were intravitreally injected into the eyes of beagles. At 6 weeks after the injection, the enucleated eyes were processed for further analyses. Retinoblastoma cells isolated from the vitreous cavity were evaluated for proliferation and characteristics as retinoblastoma cells. Furthermore, RNA sequencing was performed to investigate the overall patterns of gene expression in retinoblastoma cells isolated from the vitreous cavity.</p><p><bold>Results</bold>: At 6 weeks after the injection of retinoblastoma cells, the clumps of retinoblastoma cells were observed in the vitreous cavity of beagles. The isolated cells from the clumps demonstrated similar shapes to their parental cells and the viability was over 98%. Further analyses also showed that isolated cells possessed their characteristics as retinoblastoma cells. In addition, differentially expressed genes which could be valuable therapeutic targets were identified by comparison of gene expression between retinoblastoma cells isolated from the vitreous cavity and their parental cells.</p><p><bold>Conclusions</bold>: This beagle retinoblastoma model mimics vitreous seeds in patients with retinoblastoma. Because there is no method to identify the characteristics of vitreous seeds, this model will be valuable to investigate them.</p></sec><sec id="pbc26772-sec-6310"><label>P-234</label><title>Mitochondrial Complex V (ATP 6 and ATP 8) in Retinoblastoma Tumor and ITS Association with Clinicopathological Parameters</title><p><underline underline-style="single">S. Kashyap</underline><sup>1</sup>, L. Singh<sup>1</sup>, M. Singh<sup>2</sup>, N. Pushker<sup>3</sup>, S. Sen<sup>1</sup>, B. Chawla<sup>3</sup>, R. Meel<sup>3</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Ocular Pathology, Delhi, India; <sup>2</sup>AII India Institute of Medical Sciences, Ocular pathology, New delhi, India; <sup>3</sup>All India Institute of Medical Sciences, Ophthalmology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Mitochondrial defects play an important role in the development and progression of cancer. Genetic defects of OXPHOS have been recognized as an important cause of human disease. The objective of this study is to elucidate the role of ATP 6 and ATP 8 proteins and its prognostic significance in retinoblastoma (Rb).</p><p><bold>Design/Methods</bold>: Immunohistochemistry was performed with primary antibodies against ATP 6 and ATP 8 on 45 formalin‐fixed retinoblastoma tissues and their expression were confirmed by western blotting on fresh tissues. Expression were then correlated with clinical, histopathological parameters and tumor staging.</p><p><bold>Results</bold>: ATP6 and ATP8 proteins were expressed in 35% and 45% cases of primary retinoblastoma cases by immunohistochemistry. Histopathological high risk factors including massive choroidal invasion, scleral invasion and optic nerve cut end were identified in 42.2% cases. Expression of ATP 6 and ATP 8 were statistically significant with various histopathological high risk factors and tumor invasion (>1 HRFs)(p<0.05).</p><p><bold>Conclusions</bold>: This is the first study predicting a relevant role of ATP 6 and ATP 8 protein and might be used as a therapeutic marker in retinoblastoma. This may be used as an attractive future anticancer target in primary retinoblastoma tumors.</p></sec><sec id="pbc26772-sec-6320"><label>P-235</label><title>Changing Strategies in the Approach to Treatment of Bilateral Retinoblastoma, Demographics, Genetics, Outcome: 26‐Years Experience</title><p><underline underline-style="single">R. Kebudi</underline><sup>1</sup>, S. Tuncer<sup>2</sup>, S. Bay Buyukkapu<sup>3</sup>, S. Sencer<sup>4</sup>, O. Gorgun<sup>1</sup>, H. Yazıcı<sup>5</sup>, D. Akdeniz Odemis<sup>5</sup>, B. Tuncer<sup>5</sup>, F. Yaman Agaoglu<sup>6</sup>, I. Ayan<sup>3</sup>, E. Darendeliler<sup>6</sup></p><p><italic><sup>1</sup>Istanbul University Cerrahpasa Medical Faculty and Oncology Institute, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>2</sup>Istanbul University‐ Istanbul Faculty of Medicine, Department of Ophthalmology‐ Ocular Oncology Service‐, ISTANBUL, Turkey; <sup>3</sup>Istanbul University‐ Oncology Institute, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>4</sup>Istanbul University‐ Istanbul Faculty of Medicine, Department of Radiology, ISTANBUL, Turkey; <sup>5</sup>Istanbul University‐ Oncology Institute, Cancer Genetics, Istanbul, Turkey; <sup>6</sup>Istanbul University‐ Oncology Institute, Radiation Oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Treatment decision in bilateral retinoblastomas (BRB) depends on tumor burden, potential for vision, status of the contralateral eye. Ocular salvage and late effects are important issues. This study evaluates demographic features, genetics, treatment modalities, late effects in BRB.</p><p><bold>Design/Methods</bold>: Patients with BRB treated in the Istanbul University, Oncology Institute and Opthalmology Department between 1990‐2016 were retrospectively assessed. All patients were multidisciplinarily evaluated for chemotherapy (CT‐chemoreduction /adjuvant), local opthalmic therapies (transpupillary thermotherapy, cryotherapy, plaque), radiotherapy, enucleation. The chemotherapy protocol used had vincristine, cisplatin, etoposide, cyclophosphamide until 2009; vincristine, etoposide, carboplatin since then. Since 2011, intraarterial, intravitreal CT was used. Genetic testing was done by Sanger DNA sequencing and MLPA analysis.</p><p><bold>Results</bold>: 114 BRB (56 male, 58 female) (228 eyes) with a median age of 9 months (0,5‐42) were evaluated. Three had extraocular disease, two trilateral RB. Seventeen had a family history of retinoblastoma. The kind of mutations most observed were nonsense, frameshift, splice site. According to ICRB classification, 67 eyes were in group E, 43 group D, 27 group C, 45 group B, and 19 group A. Enucleation was done in 68 eyes, mostly group E. Radiotherapy was used for 30 eyes, most before 2000. Bone‐soft tissue deformities, cataracts were observed in irradiated patients. Five developed a second cancer (4 sarcomas, 1 meningioma) at a median of 11 years, four in irradiated sites. The 5 yr survival was 93.5%.</p><p><bold>Conclusions</bold>: Chemoreduction (systemic, intraarterial) and local ophtalmic therapies enable preservation of vision in most group A, B, C tumors and some D tumors. Most group E tumors require enucleation. Radiotherapy can be avoided in most cases. Intra‐arterial chemotherapy is promising in maintaining ocular salvage. Patients should be followed up for late effects, genetic counseling should be done.</p><p>The genetic work was supported by Scientific Research Projects Coordination Unit, Istanbul University, Project numbers BYP20546/2016 and 23070”.</p></sec><sec id="pbc26772-sec-6330"><label>P-236</label><title>Intraarterial Chemotherapy (IAC) for Patients with Retinoblastoma (RB) Treated in One Center</title><p><underline underline-style="single">B. Dembowska‐Baginska</underline><sup>1</sup>, O. Rutynowska‐Pronicka<sup>1</sup>, A. Kolodziejczyk‐Gietka<sup>1</sup>, K. Cieslik<sup>2</sup>, A. Olechowski<sup>2</sup>, W. Hautz<sup>2</sup>, M. Pedich<sup>3</sup>, E. Jurkiewicz<sup>3</sup>, U. Pasik<sup>3</sup></p><p><italic><sup>1</sup>The Children's Memorial Health Institute, Oncology, Warsaw, Poland; <sup>2</sup>The Children's Memorial Health Institute, Ophthalmology, Warsaw, Poland; <sup>3</sup>The Children's Memorial Health Institute, Radiology, Warsaw, Poland</italic></p><p><bold>Background/Objectives</bold>: Intraarterial chemotherapy for retinoblastoma is accepted as an effective treatment method. Since 2015 this method has been introduced in our center. Aim: to present tumor control and complications following IAC for Retinoblastoma.</p><p><bold>Design/Methods</bold>: Material and methods: 37 patients with intraocular RB (unilateral ‐ 29, bilateral‐8) were treated with IAC, 4 as primary treatment and 33 after systemic chemotherapy. In general all patients with bilateral disease and group E unilateral disease received systemic chemotherapy prior IAC. Patients who did not achieve complete tumor control after both treatments underwent laser therapy and intravitrous melphalan injections when needed. A total of 43 eyes were treated. IAC consisted of melphalan as a single agent or with topotecan or carboplatin. Doses of drugs were determined by the patients’ age and angioanatomy. Success of treatment was defined as tumor inactivation and ocular survival.</p><p><bold>Results</bold>: Results; catherization was successful in 90% of procedures. There were 122 injections of chemotherapy (melphalan alone‐ 17, with topotecan ‐ 13, with topotecan and carboplatin‐ 89, topotecan and carboplatin ‐ 3). Each eye received a median of 3 intaarterial chemotherapy courses. Eye preservation was feasible in 41 out of 43 eyes. There were no hematological toxicities. One cerebro ‐ vascular event and 3 episodes of optic neuritis were observed. One patient with tumor progression on systemic chemotherapy and IAC developed distant metastases.</p><p><bold>Conclusions</bold>: Conclusions IAC allowed eye globe preservation in our RB patients’ series.</p></sec><sec id="pbc26772-sec-6340"><label>P-237</label><title>Retinoblastoma: A Curable Childhood Malignancy‐ Experience in a Tertiary Care Hospital of Bangladesh</title><p><underline underline-style="single">B. Mamtaz</underline><sup>1</sup>, J. Islam<sup>2</sup>, F. Begum<sup>1</sup>, S. karim<sup>3</sup></p><p><italic><sup>1</sup>National institute of cancer research & hospital, Paediatric Oncology, Dhaka, Bangladesh; <sup>2</sup>National institute of cancer research & hospital, Cancer Epidemiology, Dhaka, Bangladesh; <sup>3</sup>Bangabandhu Sheikh Mujib Medical University, Paediatric Haematology and Oncology, Dhaka, Bangladesh</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma (RB) is the most common intraocular malignancy of childhood. It accounts for 3% of all childhood malignancies and 11% of malignancies develop in the first year of life. RB is curable if diagnosed early and treated appropriately. But in Bangladesh many children with RB die due to delayed diagnosis and treatment. National Institute of Cancer Research and Hospital (NICRH) is the only tertiary care specialized cancer hospital in government sector in Bangladesh. Most of the children with RB are referred here for management from all parts of the country.The aims of the study were to see the prevalence of RB among the children attended the out patient department of Paediatric Oncology of NICRH and also the proportion of patients those were able to take treatment.</p><p><bold>Design/Methods</bold>: It was an observational study conducted from January 2008 to December 2016 in Paediatric Oncology Department of NICRH, Mohakhali, Dhaka, Bangladesh. Children with RB, age less than18 yrs of both sexes were included in the study. Data were collected from patients’ registry.</p><p><bold>Results</bold>: Total patients attended the outpatient department of Pediatric Oncology during the study period were 2,687 and among them 537 (20%) were cases of RB. Male were 66%, female were 34% and most common age group was 1.5 to 3.0 years. Unilateral cases were 422(79%) and Bilateral were 115(21%). Only 236 (43% ) patient of RB took treatment. Most (95%) of attended children with RB were in advanced stage.</p><p><bold>Conclusions</bold>: Awareness about the importance of early diagnosis and treatment of RB is very important. This awareness can save valuable lives as well as vision of many children.</p></sec><sec id="pbc26772-sec-6350"><label>P-238</label><title>Sunlight Exposure Prior to Diagnosis of Sporadic Retinoblastoma, Risk and Extent of Intraocular Disease</title><p><underline underline-style="single">M. Orjuela‐Grimm</underline><sup>1</sup>, M. Ramírez‐Ortiz<sup>2</sup>, A. Medina‐Sanson<sup>3</sup>, X. Liu<sup>4</sup>, M.L. Cabrera<sup>5</sup>, J.P. Medina‐Paez<sup>6</sup>, J. Romero‐Rendón<sup>7</sup>, S. Bhatt‐Carreño<sup>6</sup>, A. Ruiz<sup>6</sup>, V. Ponce‐Castañeda<sup>7</sup></p><p><italic><sup>1</sup>Columbia University‐ Mailman School of Public Health, Epidemiology & Pediatric Oncology, New York, USA; <sup>2</sup>Hospital Infantil de Mexico, Ophthalmology, Mexico City‐DF, Mexico; <sup>3</sup>Hospital Infantil de Mexico, Oncology, Mexico City‐DF, Mexico; <sup>4</sup>Columbia University‐ Mailman School of Public Health, Biostatistics, New York, USA; <sup>5</sup>Hospital Infantil de Mexico, Pathology, Mexico City‐DF, Mexico; <sup>6</sup>Columbia University‐ Mailman School of Public Health, Epidemiology, New York, USA; <sup>7</sup>Hospital de Pediatría IMSS Siglo XXI, Unidad de Investigación, Mexico City‐ DF, Mexico</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma is one of few pediatric malignancies whose incidence varies geographically. Prior ecologic studies suggested that UV exposure through sunlight might contribute to increased incidence, though individual level exposure was never examined. Previously sunlight in infancy was recommended to prevent Vitamin D (VitD) deficiency. Rodent models of retinoblastoma suggest VitD inhibits angiogenesis.</p><p><bold>Design/Methods</bold>: In EpiRbMx, mothers of children with retinoblastoma are interviewed at diagnosis and report their child's daily & weekly sunlight exposure during 3 age periods (0‐6 months, 6.1‐12 months, 12.1‐23 months). We examined whether duration of sunlight exposure varied between 216 unilateral and 101 bilateral retinoblastoma cases,and 152 similarly aged healthy controls. In 158 unilateral ('unilaterals') and 75 bilateral ('bilaterals') cases we examined whether extent of disease varied with reported duration of sun exposure ('sun').</p><p><bold>Results</bold>: Sun increased with age in cases and controls. Within each age group, cases had less sun than controls. Greater maternal education was associated with less sun, particularly after age 6 months (p<0.05). Controlling for maternal education, cases had less sun than controls. Compared with controls, Unilaterals had less sun at each age (p<.05), while Bilaterals had less sun after age 12 months (p<.0001), and at earlier ages (p=0.08). Controlling for maternal education, unilaterals had more sun than bilaterals, especially at age >12 months (p<0.01).</p><p>In u<bold>nilaterals</bold>, maternal education was inversely associated with International <bold>Intraocular Retinoblastoma Classification</bold> (IIRC), and St. Jude stage, and Sun. Sun was positively associated with IIRC in unilaterals >12 months (p=0.03), though less so after adjusting for maternal education (p=0.06); there was no association with St Jude stage. In bilaterals, sun was unrelated to extent of intra or extraocular disease.</p><p><bold>Conclusions</bold>: In central Mexico, sun exposure is inversely associated with incidence of retinoblastoma. In unilateral retinoblastoma, sun exposure in the 2nd year of life appears positively associated with extent of intraocular disease.</p></sec><sec id="pbc26772-sec-6360"><label>P-239</label><title>Clinical‐Epidemiological Characteristics of Bilateral Retinoblastoma in Children at the Edgardo Rebagliati Martins Hospital (HNERM) and Oncosalud ‐ Clinic in Lima‐Peru During the Period 1999‐2016</title><p><underline underline-style="single">C. alvarez</underline><sup>1,2</sup>, G. paredes<sup>2,3</sup></p><p><italic><sup>1</sup>rebagliati hospital, oncology pediatric, lima, Peru; <sup>2</sup>oncosalud clinic, oncology pediatric, lima, Peru; <sup>3</sup>rebagliati hospital, oncology pediatric, lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Bilateral Retinoblastoma: current multimodal treatment reduces the tumor to the maximum and prevents blindness.</p><p><bold>Design/Methods</bold>: Descriptive, retrospective study of children with bilateral retinoblastoma Rebagliati Hospital‐Oncosalud Clinic.</p><p><bold>Results</bold>: Twenty‐five cases in a population of 3263 oncological children of Rebagliti Hospital and 30,000 early detection cancer children program in Oncosalud Clinic. Mean age was 16.8 months ( newborn – fortyeigth months ), Male / Female sex ratio 1.08, boys thirteen and twelve girls. Pre‐school 52%, infants 44% and schoolers 4%. One case with family history of bilateral Retinoblastoma and RB1 gene (+). Clinical: leukocoria 100%, proptosis 12.5%, headache 12.5%, seizures 4.1%. Three cases (12.5%) had metastasis: bone marrow; brain and a sphenoid case and cervical nodes. International stage of the right eye: A (4%), D (44%), E (52%) and left eye: B (8%), C (12%), D (8%), E (72%). Reese's clasification of the right eye: I (4%), IV (36%), V (60%) and left eye: I (4%), III (12%), IV (8%), V (76%). Enucleation at debut was in 3 cases (12.5%), and 24 cases (96%) received systemic chemotherapy. From 2003 onwards, focal therapy was added, preserving unilateral vision in 11 (44%) of 25 cases, of whom 10 (90.9%) received chemotherapy more focal therapy (four cryotherapy (16%), three received laser (12%);one received brachytherapy (4%), one thermotherapy and one intraarterial‐ chemotherapy melphalan); one thermotherapy alone (9.09%). At the time of this report, twenty one cases in remission (84%) and four deaths (16%) due to denial of bilateral enucleation by persistent post‐systemic chemotherapy. Overall survival of 104.29 months and disease free survival of 119.25 months.</p><p><bold>Conclusions</bold>: Bilateral Retinoblastoma was more prevalent in preschoolers and males, leukocoria was the most frequent sign. The introduction of focal treatment from 2003 together with surgery and systemic chemotherapy has helped to preserve vision in the less compromised eye, avoiding blindness.</p></sec><sec id="pbc26772-sec-6370"><label>P-240</label><title>Efficacy of Intrathecal Topotecan in Patients with Advanced Retinoblastoma. Preliminary Report</title><p>C. Leal<sup>1</sup>, A. Perez<sup>1</sup>, <underline underline-style="single">H.</underline><underline underline-style="single">Pena</underline><sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional de Pediatría, Oncology, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma (Rb) is the most commun intraocular neoplasia, with high mortality in advanced disease. Topotecan is a topoisomerase I with anti‐tumor activity against a variety of adult and childhood solid tumors. The CSF penetration of the active lactone form of topotecan and no significant neurologic toxicity was observed.</p><p>To determine the efficacy of intrathecal topotecan in patients with advanced Rb.</p><p><bold>Design/Methods</bold>: Patients newly diagnosed for orbitary and CNS metastatic Rb were enrolled in this study. Treatment was based on ifosfamide 1.8grm2scdose/5 days, etoposide 100mgm2scdose/5 days and carboplatin (AUC 6 or 450mgm2scdose/day 1) each 21 days concomitant with intrathecal topotecan (0.4mg/dose) administered twice weekly during the 6 cycles of intense chemotherapy.</p><p><bold>Results</bold>: We enrolled 6 patients with unilateral extraocular Rb with mean age of 32 months, with a metastasic CNS disease by cerebral magnetic resonance (MR) in 3 of them and non‐metastatic patient with advanced orbital disease. 2 patients were found to have positive CFS for neoplasic cells, achieving CSF response (negativization on patology study) after one and two cycles with intrathecal topotecan and chemotherapy. All were submitted to enucleation after 2 cycles of treatment. 2 patients (33%) presented progression to CNS confirmed by MRI, both died with tumor activity. Four of them are free of disease mesured clinically and by imagen and CSF. No one presented any sign of neurological toxicity. One patient presented hematological and infectious grade IV toxicity.</p><p><bold>Conclusions</bold>: Remission of the disease was achieved in four patients, without severe or irreversible adverse events. Complete response, measured by imaging and CSF negativization, were confirmed after two cycles of treatment. Topotecan must be evaluated in a large study to prove the efficacy.</p></sec><sec id="pbc26772-sec-6380"><label>P-241</label><title>Associations of RB1 Genetic Variants with Clinical Traits in Retinoblastoma Patients from a Brazilian Service (INCA ‐ Rio de Janeiro)</title><p><underline underline-style="single">B.</underline><underline underline-style="single">Pinto</underline><underline underline-style="single">Nasr</underline><sup>1</sup>, M.C. Silva de Miranda Gomes<sup>1</sup>, B. Palma Matta<sup>1</sup>, V. Lima<sup>1</sup>, M.A. Moraes Moreira<sup>1</sup>, C. Rodrigues Bonvicino<sup>1</sup>, L. Leontina Couto<sup>1</sup>, V. Mendonça<sup>1</sup>, M.A. Faria Domingues de Lima<sup>2</sup>, F. Regla Vargas<sup>3</sup>, A.C. Evangelista dos Santos<sup>1</sup></p><p><italic><sup>1</sup>Instituto Nacional do Cancer INCA, Oncogenetic, Rio de Janeiro, Brazil; <sup>2</sup>Universidade do Grande Rio, Oncogenetic, Rio de Janeiro, Brazil; <sup>3</sup>Hospital Universitário Gafrée‐Guinle HUGG, Oncogenetic, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: Estimate frequency of variants in <italic>RB1</italic> gene and test associations with different clinical traits in patients with Retinoblastoma (RB).</p><p><bold>Design/Methods</bold>: Retrospective chart review of 206 patients was performed. We reviewed three continuous traits – age of diagnosis (DX), age of first symptom (1S), lag‐time between 1S and DX (LAG) – and the categorical traits: laterality, survival, family history, intra/extraocular tumors, treatment, secondary tumors. We performed complete Sanger sequencing and Multiplex Ligation‐dependent Probe Amplification (MLPA) of <italic>RB1</italic> gene from blood samples of 127 patients. <italic>RB1</italic> molecular diagnosis was defined as Positive or Inconclusive. To test effects of <italic>RB1</italic> molecular diagnosis, laterality and survival on square root (SQRT) of each continuous trait we used three‐way ANOVA. Chi‐square tests were used to test associations between pairs of categorical traits</p><p><bold>Results</bold>: ANOVA of SQRT age data showed patients with bilateral RB have significant earlier diagnosis (DX = 11.5m ± 0.3) and first symptom (1S = 4.7m ± 0.3) than unilateral (DX = 26.4m ± 0.2; 1S = 15.7m ± 0.4); <italic>P</italic> < 0.01. Patients with pathogenic variants presented earlier DX average (11.0m ± 0.3) than inconclusive ones (23.2m ± 0.3); <italic>P</italic> < 0.05. Significant effect of survival was found for LAG time (<italic>P</italic> < 0.01), which deceased patients had greater LAG average (10.3m ± 0.4) than living/non‐determined (4.7m ± 0.1). Chi‐square tests were non‐significant for all pairs of categorical traits (alpha = 0.01), except for: <italic>RB1</italic> molecular diagnosis (M) × laterality; M × family history of RB; survival × intra/extraocular tumors. Pathogenic variants were associated with higher frequency of bilateral (31) than unilateral (18). Most frequent types of pathogenic <italic>RB1</italic> variants were nonsense (20) and splicing (9). All patients with splicing variants had bilateral tumors.</p><p><bold>Conclusions</bold>: Frequencies of <italic>RB1</italic> variants were similar to literature. A possible trend which patients with splicing variants develop bilateral RB was detected.</p></sec><sec id="pbc26772-sec-6390"><label>P-242</label><title>Retinoblastoma Screening Practices Among Physicians in Botswana</title><p><underline underline-style="single">H. Reed</underline><sup>1</sup>, P. Mehta<sup>1</sup>, J. Slone<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma is a rare but highly treatable childhood malignancy with cure rates >90% in high‐income countries. Since 2007, the sole childhood cancer treatment center in Botswana, located at Princess Marina Hospital (PMH) in Gaborone, has been operated by Baylor College of Medicine and Texas Children's Cancer and Hematology Centers. PMH records indicate that 16 patients were diagnosed with retinoblastoma with only 10 (62.5%) surviving despite the availability of many appropriate treatment options. The study assessed retinoblastoma screening practices among physicians in Botswana in order to identify opportunities for improving early detection.</p><p><bold>Design/Methods</bold>: A questionnaire assessing demographics, retinoblastoma screening knowledge, and barriers to performing the red reflex exam was distributed to physicians practicing in Botswana using REDCap online data‐capture software.</p><p><bold>Results</bold>: Thirty‐six of 266 physicians submitted responses. Pediatricians were more likely than non‐pediatricians to correctly identify the red reflex exam technique (odds ratio (OR)=6.0, 95% confidence interval (CI)=1.0‐34.8, p=0.029) and to report being very confident in performing the red reflex exam (OR=11.3, CI=1.9‐68.1, p=0.003). Only 6 respondents reported performing the red reflex exam all/most of the time in children <6 years. More than half of respondents reported having access to a working ophthalmoscope only some of the time or never. Physicians working in the private/mission sector were more likely than Ministry of Health (MOH) physicians to have reliable access to a working ophthalmoscope (OR=6.6, CI=1.1‐39.3, p=0.026). The most frequently self‐reported barriers to performing the red reflex exam included time constraints, no access to an ophthalmoscope, and no training/lack of confidence in performing the red reflex exam.</p><p><bold>Conclusions</bold>: Although the disparity in survival is likely multifactorial, improved screening may lead to better outcomes by increasing early detection. Multiple opportunities for intervention to improve retinoblastoma screening in Botswana were identified, including physician education, particularly among non‐pediatricians with pediatric patients, and access to ophthalmoscopes among MOH physicians.</p></sec><sec id="pbc26772-sec-6400"><label>P-243</label><title>First Prospective National Registry for Pediatric Eye Cancer in Germany and Austria</title><p><underline underline-style="single">M. Reschke</underline><sup>1</sup>, M. Borowski<sup>2</sup>, S. Johannes<sup>3</sup>, P. Sovinz ‐ Ritter<sup>4</sup>, W. Sauerwein<sup>5</sup>, S. Goerike<sup>6</sup>, A. Eggert<sup>3</sup>, N. Bornfeld<sup>7</sup>, D. Lohmann<sup>8</sup>, P. Temming<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Essen, Department of Pediatric Hematology and Oncology, Essen, Germany; <sup>2</sup>University of Muenster, Institute of Biostatistics and Clinical Research, Muenster, Germany; <sup>3</sup>Charité‐University Hospital Berlin, Department of Pediatric Hematology and Oncology, Berlin, Germany; <sup>4</sup>University Hospital Graz, Department of pediatric Hematology and Oncology, Graz, Austria; <sup>5</sup>University Hospital Essen, Department of Radiotherapy, Essen, Germany; <sup>6</sup>University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen, Germany; <sup>7</sup>University Hospital Essen, Department of Ophthalmology, Essen, Germany; <sup>8</sup>University Hospital Essen, Institute of Human Genetics, Essen, Germany</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma is the most frequent malignant, intraocular tumor in childhood. Five year overall survival rate is high in developed countries; however, secondary primary malignancies and compromised vision still complicate follow‐up. Clinical trials and multicenter prospective data are rare.</p><p><bold>Design/Methods</bold>: RB‐registry is a prospective multicenter observational clinical study for patients with newly diagnosed pediatric eye cancer in Germany and Austria. It collects data about the results of genetic analysis, stage of disease at first diagnosis (TNM, IRSS and ICRB staging systems), choice of therapy and outcome. Reference evaluations for neuroradiology, genetics, cytology, radiotherapy, and histopathology were established to improve the comparability of the investigations performed at different participating centers.</p><p><bold>Results</bold>: The recruitment rate exceeded the expected registration. In 3 years, 154 patients with 146 retinoblastoma (91 unilateral, 52 bilateral), three uveal melanomas, two medulloepithelioma of the ciliary body, two retinal astrocytoma, and one heritable retinoblastoma predisposition with non‐penetrance for retinoblastoma were included. In total, 193 eyes were affected by retinoblastoma. Most frequent ICRB group was E (n=66, 34.2%), and most frequent IRSS stages were IRSS 0 (n=64, 44.1%) and I (n=69, 47.6%). Most ICRB E eyes were primarily enucleated (n=59, 90.8%), whereas all 16 ICRB A eyes were treated focally. Overall eye survival remained at 48.2% after 16 months and was associated with ICRB grouping (p<0.001, logrank test); 100 of 193 eyes were enucleated.</p><p><bold>Conclusions</bold>: RB registry is a well‐established clinical registry appropriate to improve patient counseling and to provide a basis for the development of interventional clinical trials. In the long‐term, the data will help to improve therapy protocols and thus conserve vision, reduce late term side effects, and increase quality of life.</p></sec><sec id="pbc26772-sec-6410"><label>P-244</label><title>Histopathologic Risk Characteristics of Retinoblastoma After Secondary Enucleation in Patients Undergoing Organ‐Saving Treatment</title><p>T. Ushakova<sup>1</sup>, <underline underline-style="single">Y. Serov</underline><sup>1</sup>, O. Gorovtsova<sup>1</sup>, N. Ivanova<sup>1</sup>, I. Trofimov<sup>2</sup>, A. Yarovoy<sup>3</sup>, V. Yarovaya<sup>3</sup>, A. Pavlovskaya<sup>4</sup>, B. Dolgushin<sup>2</sup>, V. Polyakov<sup>1</sup></p><p><italic><sup>1</sup>SR Institute of pediatric oncology and heamatology N.N. Blokhin Russian Cancer R, HEAD AND NECK TUMORS, Moscow, Russia; <sup>2</sup>SRI of clinical and experimental radiology of N. N. Blokhin Cancer Research Center, laboratory of interventional radiology, Moscow, Russia; <sup>3</sup>S.Fyodorov Eye Microsurgery Complex, ocular oncology, Moscow, Russia; <sup>4</sup>SRI clinical oncology of N. N. Blokhin Cancer Research Center, pathology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The development of metastasis in retinoblastoma (RB) depends on histopathologic risk characteristics such as tumor invasion of the optic nerve with retrolaminar proliferation, massive invasion of choroid, sclera and structures of anterior chamber. To demonstrate histopatholgic features of retinoblastoma eyes enucleated after organ‐saving treatment, including intra‐arterial melphalan with special focus the type of tumor recurrence if present.</p><p><bold>Design/Methods</bold>: From 01.2011 to 10.2016, 16 eyes (16 patients) were enucleated after prior combined organ‐saving treatment, including selective intra‐arterial chemotherapy at our institute.</p><p><bold>Results</bold>: 10 of 16 eyes had insufficiency or minimum tumor invasion choroid and/or prelaminar invasion of the optic nerve and/or massive vitreous tumor spread. The adjuvant therapy was not administrated for patients of this group. 4 of 16 eyes had massive tumor invasion choroid and/or including anterior segment and/or a beginning optic nerve of the eye. The second line of chemotherapy was administrated for patients of this group. 2 of 16 eyes had a type IV regression. These eyes were enucleated in connection with the development of secondary complications as glaucoma, hemophthalmus and subatrophy of eye. So far none of our patients developed metastatic disease.</p><p><bold>Conclusions</bold>: The most common reason for secondary enucleation of the eye was intraocular tumor progression, including anterior segment of the eye. Recurrent tumors in 4 cases with massive tumor invasion choroid and/or including anterior segment and/or a beginning optic nerve of the eye had the potential risk to develop metastatic disease.</p></sec><sec id="pbc26772-sec-6420"><label>P-245</label><title>Long Term Follow Up of Retinoblastoma Survivors: Experience from India</title><p><underline underline-style="single">R. Seth</underline><sup>1</sup>, A. Singh<sup>1</sup>, V. Guru<sup>1</sup>, B. Chawla<sup>2</sup>, S. Pathy<sup>3</sup>, S. Sapra<sup>1</sup></p><p><italic><sup>1</sup>ALl India Institute of Medical Sciences, Pediatrics, Delhi, India; <sup>2</sup>ALl India Institute of Medical Sciences, Ophthalmology, Delhi, India; <sup>3</sup>ALl India Institute of Medical Sciences, Radiation Oncology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma (Rb) is the most common primary intraocular tumor of infancy and childhood. Survivors’ ocular and visual problems and increased risk for subsequent malignancy are well documented but data on long term health status of Rb survivors are limited: this being particularly true for India</p><p><bold>Design/Methods</bold>: Children who had completed treatment for retinoblastoma at least 2 years ago before and were under follow up at the after cancer treatment clinic were evaluated.</p><p><bold>Results</bold>: In our series of 213 patients, the median age was 29 months, there was a male preponderance, and majority had unilateral disease. Enucleation was done in almost three fourth and 3% underwent bilateral enucleation. Majority of the patients received chemotherapy, and few received radiation.. Growth was affected in about one third and majority were those who had received radiation. Diminished vision was noticed in about one‐sixth. Orbital hypoplasia and contracted socket was seen in 14.1% cases. 2.7% were hearing impaired. About one‐sixth had a global intelligence delay. Second neoplasms were seen in 0.01%. No other abnormalities seen.</p><p><bold>Conclusions</bold>: Common late effects in our Rb survivors include diminished vision in the salvage eye,Intellectual disability and contracted socket; there is a need for timely institution of prosthesis to avoid late effects like hypoplasia, contracted sockets and better cosmesis and enhanced self esteem. Second neoplasm is a concern. Lifelong follow up and counseling of a healthy lifestyle is needed for Rb survivors.</p></sec><sec id="pbc26772-sec-6430"><label>P-246</label><title>Expression Pattern of Immune Checkpoints PD‐1 and PD‐L1 in Retinoblastoma and ITS Prognostic Significance</title><p><underline underline-style="single">L. Singh</underline><sup>1</sup>, S. Kashyap<sup>2</sup>, S. Sen<sup>2</sup>, M.A. Rizvi<sup>3</sup></p><p><italic><sup>1</sup>Jamia Millia Islamia and AIIMS, Ocular Pathology and Biosciences, New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences, Ocular Pathology, New Delhi, India; <sup>3</sup>Jamia Millia Islamia, Biosciences, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma (RB), malignant tumor of the sensory retina, is the most common eye cancer of childhood due to the defect of RB gene. The immune system plays an important role in controlling and eradicating cancer. Recent studies suggest that programmed death‐1/programmed death ligand (PD‐1/PD‐L1) pathway in T‐cell activation plays a major role in tumor escape mechanism from host immunity. Therefore, we investigated the expression of PD‐1 and PD‐L1 in human retinoblastoma cancer to define their clinical significance in patient's prognosis after surgery.</p><p><bold>Design/Methods</bold>: PD‐1 and PD‐L1 protein expression was evaluated in 60 prospective cases of primary enucleated retinoblastoma specimens by immunohistochemistry and validated by western blotting. PD‐1 and PD‐L1 mRNA expression was investigated by quantitative real time PCR (qPCR). Expression of PD‐1 and PD‐L1 were then correlated with clinical, histopathological parameters and patient survival.</p><p><bold>Results</bold>: Immunohistochemistry showed cytoplasmic PD‐1 expression in (9/60) 15 % cases, whereas PD‐L1 showed nuclear expression in (31/60) 51.6% cases. Western blotting confirmed the immunoreactivity results on representative cases. The protein and the mRNA levels of determination by IHC and real time qPCR were closely correlated. Expression of PD‐L1 showed significant correlation with poor tumour differentiation and tumor invasion (p<0.05). There was a significant difference in the overall survival of patients with PD‐L1 expression.</p><p><bold>Conclusions</bold>: These data suggest that PD‐L1 expression may be a new biomarker for patients with retinoblastoma in tumor originating from sensory retinal cells. This study provides first data for the role of immune checkpoints in retinoblastoma patients. Further studies are necessary to confirm this observation and to evaluate the predictive value of PD‐1 and PD‐L1 in retinoblastoma in the context of PD‐1 inhibition.</p></sec><sec id="pbc26772-sec-6440"><label>P-247</label><title>Correlation of p65/RelA Expression with Tumour Invasion in Primary Retinoblastoma</title><p><underline underline-style="single">M.K. Singh</underline><sup>1</sup>, S. Kashyap<sup>1</sup>, S. Sen<sup>1</sup>, N. Pushker<sup>2</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Ocular Pathology, Delhi, India; <sup>2</sup>All India Institute of Medical Sciences, Ophthalmology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma (Rb) is a malignant tumor of developing retina of children which occur before the age of five years. Nuclear factor kappa B (NFκB) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The nuclear factor‐κB (NF‐κB) transcription factors family is thought to play an important role in the development of certain cancers. Therefore, the aim of this study was to investigate the localisation and expression of p65/RelA protein in retinoblastoma.</p><p><bold>Design/Methods</bold>: Prospective analysis of 55 primary retinoblastoma cases over a period of one year. Expression of RelA was analyzed by Immunohistochemistry (IHC) in formalin fixed retinoblastoma specimens. Their mRNA expressions were analyzed on 25 fresh primary enucleated retinoblastoma tissues by real time polymerase chain reaction (qPCR). Results were then correlated with clinical and pathological parameters.</p><p><bold>Results</bold>: Expression of p65/RelA proteins was found to be 30% in retinoblastoma cases but not in normal retina. This protein was more frequently detected in poorly‐differentiated and invasive tumours than in well‐differentiated and non‐invasive tumours. Increased expression of p65/RelA was statistically significant with choroidal invasion and invasive tumors (>1 HRFs). mRNA expressions of p65/RelA was found to be upregulated in 35% of cases. mRNA expressions were correlated well with immunostaining.</p><p><bold>Conclusions</bold>: This study demonstrated that expression of p65/RelA protein represent a reliable prognostic marker of retinoblastoma and might be related to retinoblastoma tumorigenesis and progression through a non‐canonical pathway. Targeting NFκB combined with other therapies may represent a novel approach to retinoblastoma.</p></sec><sec id="pbc26772-sec-6450"><label>P-248</label><title>Intra‐Arterial Melphalan and Topotecan Therapy for Retinoblastoma: Hacettepe Experience</title><p><underline underline-style="single">A. Varan</underline><sup>1</sup>, H. Kiratli<sup>2</sup>, I. Bajin<sup>1</sup>, A. Akgoz<sup>3</sup>, C. Akyuz<sup>1</sup></p><p><italic><sup>1</sup>Hacettepe University‐ Institute of Oncology, Dept. of Pediatric Oncology, ANKARA, Turkey; <sup>2</sup>Hacettepe University‐ Faculty of Medicine, Dept. of Ocular Oncology, Ankara, Turkey; <sup>3</sup>Hacettepe University‐ Faculty of Medicine, Dept. of Radiology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma is the most common intraocular malignancy in children. Here we present our results of intra‐arterial chemotherapy (IAC) with melphalan and topotecan (IAC‐MT) in the treatment of newly diagnosed or relapsed‐refractory retinoblastoma patients.</p><p><bold>Design/Methods</bold>: In this study we retrospectively analysed the clinical features and outcomes of the 37 patients and 41 eyes treated with IAC‐MT between October 2015 and February 2017. Tumor control and globe salvage with IAC‐MT were analyzed. Complete blood counts were examined 7 and 15 days after the IACT for systemic toxicity.</p><p><bold>Results</bold>: The median age at diagnosis was 13 months (range 1‐101 months). There were 18 girls and 19 boys. Intra‐arterial chemotherapy with melphalan and topotecan was the primary treatment in 21 eyes and secondary in 20 eyes. The eyes who received IAC‐MT as a first‐line therapy were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 2), B (n = 1), C (n =3), D (n = 14), or E (n = 2). After IAC with a mean follow‐up of 6 months (range 2‐16 months), complete regression was achieved for tumor in 22 eyes (53%). Four of 41 eyes were enucleated (10%), 1 from 21 first‐line treated group and 3 from 20 second‐line treated group. Globe salvage was achieved in 95% of primary‐treated cases and in 85% of secondary‐treated cases.The 1‐year enucleation‐free survival rate was 70%. The further treatment requirements after IACT were as follows: enucleation in 4 eyes, and local therapy in 11 eyes. No severe systemic side effect observed.</p><p><bold>Conclusions</bold>: Our preliminary results supported that globe salvage and avoidance of toxicity related with systemic chemotherapy may be achieved by IAC‐MT. Given its safety and high efficacy, it is expected that IAC‐MT will replace conventional strategies.</p></sec><sec id="pbc26772-sec-6460"><label>P-249</label><title>Identification of RB1 Germline Mutations and the Inheritance Pattern of Retinoblastoma in Jordan</title><p><underline underline-style="single">Y. Yousef</underline><sup>1</sup>, M. Mehyar<sup>1</sup>, I. Nawaiseh<sup>1</sup>, I. Sultan<sup>2</sup>, R. Deebajah<sup>2</sup>, A. Tbakhi<sup>3</sup></p><p><italic><sup>1</sup>King Hussein Cancer Center, Department of Surgery Ophthalmology, Amman, Jordan; <sup>2</sup>King Hussein Cancer Center, Pediatric Oncology, Amman, Jordan; <sup>3</sup>King Hussein Cancer Center, Cell Therapy and Applied Genomics, Amman, Jordan</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma (RB) is a childhood cancer developing in the retina due to mutations in the RB1 gene. Herein we are trying to identify the oncogenic mutations in the RB1 gene and the inheritance pattern of RB in the Jordanian RB patients.</p><p><bold>Design/Methods</bold>: The peripheral blood of 50 Retinoblastoma patients was collected, and genomic DNA was extracted. DNA sequencing was conducted by Next Generation Sequencing analysis, Sanger sequencing, Quantitative multiplex PCR (QM‐PCR), and Allele‐specific PCR.</p><p><bold>Results</bold>: In this cohort, 50 affected patients were studied. Twenty (40%) patients had unilateral RB, and 30(60%) had bilateral RB. Overall, 36(72%) patients had germline disease, 17(47%) of them had the same mutation detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease, and 13(43%) had inherited mutation, and in the unilateral group, 6(30%) had germline disease and 4(20%) had inherited mutation. Of interest, in the inherited cases, paternal mutation was seen in 88% of the affected patients. Only one (2%) of the patients had mosaic mutation detected, and in one(2%) of the inherited cases the mother had mosaic mutation. Over the 17 inherited cases, 16(94%) of them had unaffected carrier parent.</p><p><bold>Conclusions</bold>: Even all bilateral RB patients in our cohort had germline disease, 30% of unilateral disease were germline, and 47% of patients with germline disease had inherited disease from affected(6%) or unaffected carrier(94%). Therefore molecular screening is very important for the genetic counseling regarding the risk for inherited Retinoblastoma in both unilateral and bilateral cases.</p></sec></sec><sec id="pbc26772-sec-6470"><title>Solid Non Brain Tumours ‐ Liver Tumours</title><sec id="pbc26772-sec-6480"><label>P-250</label><title>Genomic Studies in Hepatoblastoma: Insight into Somatic Mutations Using Array‐CGH Analysis and Whole‐Exome Sequencing</title><p><underline underline-style="single">T. Aguiar</underline><sup>1</sup>, T. Rodrigues<sup>2</sup>, F.A. dos Santos<sup>3</sup>, J. Sobral<sup>2</sup>, S.S. da Costa<sup>2</sup>, C.M.L. da Costa<sup>3</sup>, I.W. da Cunha<sup>4</sup>, M. Cypriano<sup>5</sup>, S.R.C. de Toledo<sup>5</sup>, J.E.S. de Souza<sup>6</sup>, E. Valadares<sup>7</sup>, R. Borges<sup>8</sup>, V. Odone<sup>9</sup>, I. Tojal<sup>6</sup>, D.M. Carraro<sup>6</sup>, C. Rosenberg<sup>2</sup>, A. Krepischi<sup>2</sup></p><p><italic><sup>1</sup>A.C.CAMARGO CANCER CENTER, CIPE, são paulo, Brazil; <sup>2</sup>University of Sao Paulo, Genetic, Sao Paulo, Brazil; <sup>3</sup>A.C.CAMARGO CANCER CENTER, Pediatric Oncology, Sao Paulo, Brazil; <sup>4</sup>A.C.CAMARGO CANCER CENTER, Pathology Department, Sao Paulo, Brazil; <sup>5</sup>GRAACC, Pediatric Oncology, Sao Paulo, Brazil; <sup>6</sup>A.C.CAMARGO CANCER CENTER, CIPE, Sao Paulo, Brazil; <sup>7</sup>Baleia's Hospital, Pediatric Department, Belo Horizonte, Brazil; <sup>8</sup>Conceição Children's Hospital, Pediatric Department, Xangri‐Lá, Brazil; <sup>9</sup>ITACI, Pediatric Oncology, Sao Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Hepatoblastoma is the most common primary liver tumor in children, accounting for over 1% of pediatric cancers. Although molecular data on HB tumorigenesis is still scarce because of its rarity, recently new insights have been gained into their molecular biology. The main objective of this study was to investigate the mutational burden of HBs.</p><p><bold>Design/Methods</bold>: A whole‐exome sequencing was performed in a discovery cohort of 6 HBs and their matched non‐tumoral liver tissues (<italic>244K Agilent SureSelect Target Enrichment</italic>). Bioinformatic analysis of exome data identified somatic variants in 69 genes which were chosen for validation using a target sequencing panel (<italic>SureSelectXT Target Enrichment System for Illumina Paired‐End Sequencing Library</italic>). The gene panel was composed of the detected 69 genes and other 48 genes related with HB or cancer, and it was used to investigated additional 13 HB samples as a validation group. To complement the screening of somatic mutations, we performed an array‐CGH analysis (Agilent 180K) in twelve HB samples to screen for copy number alterations.</p><p><bold>Results</bold>: A total of 71 somatic mutations were validated in 53 genes considering the entire HB group. The somatic analysis reveals pathogenic mutations in the <italic>CTNNB1</italic> gene and a recurrent missense mutation in the <italic>CX3CL1</italic> gene; the role of these mutations was explored by IHQ studies of their proteins as well as by gene expression analysis by RT‐PCR. Array‐CGH analysis showed mainly whole‐chromosome and chromosome‐arm aneuploidies, and a few focal aberrations could be also mapped.</p><p><bold>Conclusions</bold>: Our data highlighted a relatively stable tumoral genome in this type of pediatric liver tumor, which present a low mutational burden regarding potentially pathogenic mutations and copy number alterations.</p><p><bold>Grants</bold>: FAPESP (2016/04785‐0), FAPESP (2013/08028‐1), CNPq (141625/2016‐3).</p></sec><sec id="pbc26772-sec-6490"><label>P-251</label><title>Investigations of Gankyrin as a Potential Target for Liver Cancer</title><p><underline underline-style="single">A. D'Souza</underline><sup>1</sup>, L. Valanejad Keifer<sup>2</sup>, K. Lewis<sup>2</sup>, A. Cast<sup>2</sup>, M. Wright<sup>2</sup>, R. Karns<sup>3</sup>, N. Timchenko<sup>2</sup></p><p><italic><sup>1</sup>Cincinnati Children's Hospital Medical Center, Cancer and Blood Disease Institute, 45229, USA; <sup>2</sup>Cincinnati Children's Hospital Medical Center, Pediatric Surgery, Cincinnati, USA; <sup>3</sup>Cincinnati Children's Hospital Medical Center, Gastroenterology, Cincinnati, USA</italic></p><p><bold>Background/Objectives</bold>: One of the critical steps in development of hepatoblastoma (HBL) is the loss of control of proliferation of hepatocytes. Our examination of a large bank of HBL samples found that an oncogene Gankyrin is elevated in all examined HBL patients with high rate of proliferation. The goal of this project was to examine the role of Gankyrin in activation of liver proliferation.</p><p><bold>Design/Methods</bold>: To test the role of Gankyrin in liver proliferation, we generated liver‐specific Gankyrin knockout mice (Gank LKO) and examined liver proliferation using two models: proliferation after surgery and after liver injury. Liver proliferation was monitored using a combination of approaches including measuring DNA replication, mitosis and expression of cell cycle genes and oncogenes. Immunostaining, QRT‐PCR and Western blotting assays were used.</p><p><bold>Results</bold>: Gank LKO mice had normal livers by gross examination and serum hepatic function testing. However, RNA‐Seq analyses showed that Gank LKO mice have reduced expression of genes that are involved in liver regeneration and liver cancer. Consistent with these findings, we found that liver proliferation after partial hepatectomy (PH) is dramatically inhibited in Gank LKO mice. Looking for underlying mechanisms, we found that tumor suppressor proteins (TSPs) are reduced by Gankyrin in control mice after PH, but are elevated in Gank LKO mice. These elevated TSPs in Gank LKO mice inhibit liver proliferation. Similar inhibition of liver proliferation was observed in Gank LKO mice after liver injury mediated by carbon tetrachloride.</p><p><bold>Conclusions</bold>: Gankyrin is a powerful oncogene in HBL. Our study demonstrates that deletion of Gankyrin is sufficient to inhibit liver proliferation in animal models, which is an important mechanism behind carcinogenesis. These results strongly suggest that inhibitors of Gankyrin should be investigated as potential targeted therapy for HBL.</p></sec><sec id="pbc26772-sec-6500"><label>P-252</label><title>Liver Transplantation for Hepatoblastoma</title><p><underline underline-style="single">B. Dembowska‐Bagińska</underline><sup>1</sup>, E. Swieszkowska<sup>1</sup>, H. Ismail<sup>2</sup>, D. Broniszczak<sup>2</sup>, M. Markiewicz<sup>2</sup>, J. Teisseyre<sup>2</sup>, M. Drogosiewicz<sup>1</sup>, A. Brozyna<sup>1</sup>, W. Grajkowska<sup>3</sup>, M. Pyzlak<sup>3</sup>, P. Kaliciński<sup>2</sup></p><p><italic><sup>1</sup>The Children's Memorial Health Institute, Oncology, Warsaw, Poland; <sup>2</sup>The Children's Memorial Health Institute, Pediatric Surgery and Organ Transplantation, Warsaw, Poland; <sup>3</sup>The Children's Memorial Health Institute, Patology, Warsaw, Poland</italic></p><p><bold>Background/Objectives</bold>: Liver transplantation (LTX) has its established role in the treatment of children with hepatoblastoma.</p><p>Aim; presentation of treatment results and complications of LTX for hepatoblastoma.</p><p><bold>Design/Methods</bold>: Between 2002 and 2017, 22 children underwent liver transplantation for unresectable hepatoblastoma. Age at transplantation ranged from 8/12 to 13 and 8/12 (median‐ 2 and 2/12 years). There were 10 patients with POSTEXT III, 9 with POSTEXT IV. Six patients were stage IV disease, bilateral lung metastases. All patients received preoperative chemotherapy according to SIOPEL recommendations. All six patients had no evidence of metastatic disease before LTX. Twenty children received grafts from related donors, 2 cadaveric grafts. All patients received chemotherapy after transplantation (median 2 courses – cisplatin, vincristine, 5 FU).</p><p><bold>Results</bold>: 18 out of 22 patients are alive with a median follow‐up of 3 years. Patients survival is 100%, 81,6 %, 61,2 % at 1, 5 and 10 years. Four patients died; one 10 years from LTX of bone marrow aplasia of unknown etiology, 3 patients from relapses refractory to chemotherapy 4, 7, 11 months from LTX. Relapses occurred in the lungs of 3 patients, in 1 of them bone metastases were also observed. Post‐transplantation chemotherapy was well tolerated. One patient underwent 2 re‐transplantations 2 years then 1 month from primary and second LTX.</p><p><bold>Conclusions</bold>: Our data confirm that LTX is a treatment option for children with unresectable Hepatoblastoma.</p></sec><sec id="pbc26772-sec-6510"><label>P-253</label><title>Characteristics and Outcome of Hepatoblastoma: Experience at the Instituto Nacional De Enfermedades Neoplasicas (INEN) ‐ Peru</title><p>R. Diaz<sup>1</sup>, E. Ruiz<sup>2</sup>, S. Chavez<sup>1</sup>, V. Caloretti<sup>1</sup>, E. Maradiegue<sup>1</sup>, <underline underline-style="single">A.</underline><underline underline-style="single">Wachtel</underline><sup>3</sup></p><p><italic><sup>1</sup>Instituto Nacional de Enfermedades Neoplásicas, Pediatric Oncology, Lima, Peru; <sup>2</sup>Instituto Nacional de Enfermedades Neoplásicas, Chief Abdominal Surgical Department, Lima, Peru; <sup>3</sup>Instituto Nacional de Enfermedades Neoplásicas, Pediatric Oncology, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Hepatoblastoma (HB) represents 6% of solid pediatric malignancies at the INEN. The purpose of this study was to evaluate the clinical features and outcome of these patients between 1999 and 2014.</p><p><bold>Design/Methods</bold>: This is a retrospective and descriptive study. Between January 1999 and December 2014, 145 patients under 15 years of age were diagnosed having HB, 14 patients were excluded. Survival analysis was performed using Kaplan‐Meier method.</p><p><bold>Results</bold>: The median age was 3.3 years (range 0.08 to 14 years), M/F ratio 2/1. Fifty patients (38.1%) had complete remission, 22 had progressive disease (16.7%). 49 patients recurred (37.4%) and 37 died (28.2%) Staging according to PRETEXT was: I 10.6% (14), II 38.9 %( 51), III 35.8 %(47), IV 10.6 %( 14). Nineteen patients (14.5%) had pulmonary metastases at diagnosis. The 5 year overall survival (OS) was 65.8% and Event Free Survival (EFS) 61%. OS in the non‐metastatic group was 71.9% and 42.8% in the metastatic group. The OS for Pretext I 90.9%, II 66.9%, III 57.6%, IV 38.1% OS according to initial treatment neoadjuvant chemotherapy or surgery was SIOPEL 79%, carboplatin/doxorubicin 64.1%, VCR/5FU/cisplatin 35% and 67.1% for those with initial surgery. The EFS for these patients was 60%, 56%, 25% and 62% respectively</p><p><bold>Conclusions</bold>: HB is not a rare tumor at our Institution and a multidisciplinary team approach is crucial for the improvement on survivorship. The lung metastases conditions a worse prognosis and there has been improved survival since 2008 with SIOPEL treatment.</p></sec><sec id="pbc26772-sec-6520"><label>P-254</label><title>Epigenetic Mechanisms in Liver Tumors: Gene Expression Analysis of the Epigenetic Machinery in Hepatoblastomas</title><p>M.P. Rivas<sup>1</sup>, E. Goulart<sup>1</sup>, L. Caires<sup>1</sup>, T. Aguiar<sup>2</sup>, S.S. Costa<sup>1</sup>, I.W. da Cunha<sup>3</sup>, C.M.L. Costa<sup>4</sup>, M. Cypriano<sup>5</sup>, S.R.C. de Toledo<sup>5</sup>, M. Maschietto<sup>6</sup>, D.M. Carraro<sup>2</sup>, C. Rosenberg<sup>1</sup>, <underline underline-style="single">A. Krepischi</underline><sup>1</sup></p><p><italic><sup>1</sup>Institute of Biosciences ‐ University of São Paulo, Genetics and Evolutionary Biology, Sâo Paulo, Brazil; <sup>2</sup>AC Camargo Cancer Center, International Research Center, São Paulo, Brazil; <sup>3</sup>AC Camargo Cancer Center, Department of Pathology, São Paulo, Brazil; <sup>4</sup>AC Camargo Cancer Center, Department of Pediatric Oncology, São Paulo, Brazil; <sup>5</sup>Pediatric Oncology Institute GRAACC‐ Federal University of São Paulo, Department of Pediatrics, São Paulo, Brazil; <sup>6</sup>National Center for Research in Energy and Materials, CNPEM, Campinas, Brazil</italic></p><p><bold>Background/Objectives</bold>: Liver tumors in children account for 1‐4% of all pediatric solid tumors. While hepatocellular carcinoma is predominant in adults, the most common liver cancer in children is hepatoblastoma. Mechanisms underlying hepatoblastoma development are still poorly explored, and prognosis in advanced tumor stages remains poor. It is suggested that this embryonal tumor is associated with a blockage in hepatocyte differentiation. These tumors carry a low mutational burden, and the impairment of epigenetic mechanisms, which are the core of embryogenesis and development, stands out as an alternative route for tumorigenesis. The main objective of this study was to explore the role of genes associated with methylation and hydroxymethylation in hepatoblastomas.</p><p><bold>Design/Methods</bold>: The cohort of tumors consisted of 29 hepatoblastomas and a control group of 8 non‐tumoral liver tissues.The expression of genes of the epigenetic machinery (<italic>DNMT1, DNMT3A, DNMT3L, UHRF1, TET1, TET2</italic> and <italic>TET3</italic>) was analyzed by qPCR (Taqman). A 5hmC quantification assay (Quest 5‐hmC™ DNA ELISA Kit) was applied to assess the level of 5hmC in tumors compared to controls.</p><p><bold>Results</bold>: <italic>TET1</italic> and <italic>TET2</italic> genes were found to be up‐regulated in tumors. A significant increase in the 5hmC levels was also evident in hepatoblastoma samples when compared to non‐tumoral tissues. These data suggested that hepatoblastomas could present a pluripotency pattern of gene expression; to address this issue, the expression levels of three genes associated with pluripotency (<italic>POU5F1, SOX2</italic> and<italic>NANOG</italic>) were evaluated, and no alteration was detected.</p><p><bold>Conclusions</bold>: The upregulation of DNA methylation genes, such as <italic>TETs</italic>, and an increased level of 5hmC, support the hypothesis that hepatoblastomas exhibit an epigenetic signature of immature cells, suggesting a blockage during hepatic cells differentiation in their genesis. However, the absence of pluripotency markers showed commitment with the differentiation process. Our hypothesis is that hepatoblastomas are in a transitional stage of hepatic differentiation, probably hepatoblasts.</p><p><italic>Funding</italic>: FAPESP; CAPES</p></sec><sec id="pbc26772-sec-6530"><label>P-255</label><title>Development of Hepatoblastoma During Growth Hormone Therapy</title><p><underline underline-style="single">T. Oue</underline><sup>1</sup>, T. Sasaki<sup>1</sup>, M. Zenitani<sup>1</sup>, N. Tanaka<sup>1</sup></p><p><italic><sup>1</sup>Hyogo College Of Medicine, Pediatric Surgery, Nishinomiya‐shi‐ Hyogo, Japan</italic></p><p><bold>Background/Objectives</bold>: Growth hormone (GH) is reported to affect tumor growth and increases the risk of neoplasia such as leukemia. However, the association between GH and hepatoblastoma (HB) has been rarely reported. Here we present two cases of HB that developed during GH therapy.</p><p><bold>Design/Methods</bold>: Patient medical records were collected and retrospectively reviewed.</p><p><bold>Results</bold>: Patient 1 was a 2‐year‐old boy and patient 2 was a 13‐year‐old boy. Both were administered with GH therapy for growth retardation due to poor GH secretion, as shown by tolerance tests. Abdominal distention of the right upper quadrant was observed 2 month and 2 years after GH therapy initiation in patients 1 and 2, respectively. Imaging studies including abdominal computed tomography (CT) revealed a huge tumor in the left hepatic lobe, and serum alpha‐fetoprotein was markedly elevated in both cases. GH therapy was discontinued and tumor biopsy was immediately performed to confirm the diagnosis of HB. The tumor was completely resected after several courses of chemotherapy using cisplatin and doxorubicin, according to the protocol of the Japan Pediatric Liver Tumor Study Group. After additional chemotherapy, the patients are alive without disease for 4 years and 1 year, respectively. GH secretions normalized and catch‐up growth was observed in both cases after the treatment of HB.</p><p><bold>Conclusions</bold>: In patient 1, as HB was noticed soon after the initiation of GH therapy, GH may have accelerated the growth of an already present HB. In patient 2, HB developed during the 2 years of GH therapy; therefore, GH may have initiated HB tumorigenesis. In both cases, GH therapy was immediately discontinued because GH likely accelerated tumor growth. Normalized GH secretion after tumor resection may indicate that HB tumors secrete a type of GH antagonist.</p></sec><sec id="pbc26772-sec-6540"><label>P-256</label><title>What is the Role of Aneuploidy in Embryonal Tumors? Cytogenomic Analysis of Hepatoblastomas</title><p><underline underline-style="single">M. Rivas</underline><sup>1</sup>, J. Barros<sup>1</sup>, T. Aguiar<sup>2</sup>, S. Costa<sup>1</sup>, C. Costa<sup>2</sup>, I. Werneck<sup>2</sup>, D. Carraro<sup>2</sup>, S. Toledo<sup>3</sup>, M. Cypriano<sup>3</sup>, C. Rosenberg<sup>1</sup>, E. Novak<sup>4</sup>, V. Odone‐Filho<sup>4</sup>, A. Krepischi<sup>1</sup></p><p><italic><sup>1</sup>Institute of Biosciences ‐ University of São Paulo, Genetics and Evolutionary Biology, Sâo Paulo, Brazil; <sup>2</sup>AC Camargo Cancer Center, Department of Pediatric Oncology, São Paulo, Brazil; <sup>3</sup>Pediatric Oncology Institute GRAACC, Department of Pediatrics, São Paulo, Brazil; <sup>4</sup>Instituto de Tratamento de Câncer Infantil ITACI, Pediatric Department at São Paulo University Medical School, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Cytogenetic alterations leading to changes in chromosome copy number (aneuploidy) are hallmarks of cancer cells. Hepatoblastoma (HB) is an uncommon embryonal liver tumor accounting for approximately 80% of childhood hepatic cancer and is mostly diagnosed in children under the age of 18 months. Currently, there are no validated prognostic or therapeutic biomarkers for HB patients. Most HBs are sporadic cases, although its incidence is elevated in certain genetic syndromes, including Beckwith–Wiedemann and familial adenomatous polyposis. To explore the cytogenomic profile of HBs, we investigated a cohort of 10 hepatoblastomas by microarrays aiming to identify relevant chromosome regions and genes.</p><p><bold>Design/Methods</bold>: An array‐CGH 180K platform was performed, and we have characterized the copy number profile of two different commercial HB cell lines as well as two hepatocellular carcinoma lineages.</p><p><bold>Results</bold>: The array‐CGH analysis revealed quite stable genomes in this kind of embryonal tumor. Four HBs presented with no detectable chromosomal imbalances, whereas four of them exhibited mainly whole‐chromosome and arm aneuploidies, with a prevalence of gains affecting 1q and the entire chromosomes 2 and 8. Few focal alterations could be delimitated, including a 2q24.3 amplification in two tumors sharing a minimum common region of 5,3 Mb that harbors 20 genes; a complex rearrangement of non‐contiguous deletions at 3p26.1‐p25.2; and a large 55 Mb segment deleted at 4q31‐4q25. Two HBs presented a higher load of chromosomal rearrangements compared to the HB group.</p><p><bold>Conclusions</bold>: The characterization of the liver tumor cell lines highlighted the quiet chromosomal landscape of the embryonal liver tumors compared to their adult counterpart, hepatocellular carcinomas, which carry several cytogenetic changes in a complex genome. Our data suggested that aneuploidy possibly plays a limited role in HB tumorigenesis, rather linked to the process of acquisition of entire chromosomes than to the amplification of oncogenes and tumor suppressors losses. Funding: CAPES (1671499); FAPESP (2013/08028‐1)</p></sec><sec id="pbc26772-sec-6550"><label>P-257</label><title>Contributions of Propranolol for the Treatment of Infantile Hepatic Hemangioendothelioma: The Mexico Experience at the National Institute of Pediatrics</title><p>J. Palacios<sup>1</sup>, S. Solórzano<sup>2</sup>, <underline underline-style="single">J. Shalkow</underline><sup>3</sup>, R. Rodríguez<sup>4</sup>, A. León<sup>5</sup>, E. Cruz<sup>1</sup>, D. Hernández<sup>1</sup></p><p><italic><sup>1</sup>National Institute of Pediatrics, Surgical Oncology, Mexico, Mexico; <sup>2</sup>National Institute of Pediatrics, Radiology, Mexico, Mexico; <sup>3</sup>Ministry Of Health, Childhood Cancer, Mexico, Mexico; <sup>4</sup>National Institute of Pediatrics, Pathology, Mexico, Mexico; <sup>5</sup>Ministry Of Health, Oncology, Mexico, Mexico</italic></p><p><bold>Background/Objectives</bold>: Infantile hepatic hemangioendothelioma (IHEE) is the most common benign liver tumor in infancy. Presenting symptoms may include abdominal distention, hepatomegaly, associated cutaneous hemangiomas, congestive heart failure (CHF), anemia, and thrombocytopenia. Recently, propranolol has proven a good therapeutic alternative.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed 10 cases of IHEE treated with propranolol at the Surgical Oncology Department of the National Institute of Pediatrics in Mexico between 2007 and 2016. Demographic, clinical data and outcomes were collected.</p><p><bold>Results</bold>: There were 7 girls and 3 boys. All were diagnosed after birth, except one by prenatal ultrasound. All presented with a palpable abdominal mass, 7 had CHF, 6 had associated cutaneous hemangiomas and bi‐lobar liver involvement. One developed thrombocytopenia. No case presented hypothyroidism. Diagnosis was confirmed by Doppler US and angio‐CT‐scan. All were treated first‐line with propranolol at 2.5 mg/Kg/day after cardiac evaluation, with no adverse reactions to treatment. Response was seen at 3 months. After radiographic response, propranolol was gradually waned. Nine patients are alive without recurrence between 3 and 8 years follow‐up. Eight showed complete response, one did not respond and required hepatic embolization. One patient died due to severe coagulopathy (Kasabach‐Merrit syndrome).</p><p><bold>Conclusions</bold>: Propranolol offers an excellent therapeutic alternative to IHEE, probably due to its anti‐angiogenic properties (vasoconstriction, decreased expression of VEGF, and apoptosis of capillary endothelial cells), with 90% survival and no recurrence in this series. 80% of our patients had complete clinical and radiographic response without adverse reactions to treatment.</p></sec><sec id="pbc26772-sec-6560"><label>P-258</label><title>Aggressive Hepatoblastoma is Associated with C/EBPA Mediated De‐Differentiation of Hepatocytes into Cells Expressing Stem Cell Markers</title><p><underline underline-style="single">N. Timchenko</underline><sup>1</sup>, A. Cast<sup>1</sup>, L. Valanejad<sup>1</sup>, M. Wright<sup>1</sup>, A. Gupta<sup>2</sup>, L. Zhu<sup>3</sup>, S. Shin<sup>1</sup></p><p><italic><sup>1</sup>Cincinnati Children's Hospital Medical Center, Division of Pediatric General and Thoracic Surgery, Cincinnati, USA; <sup>2</sup>Cincinnati Children's Hospital Medical Center, Division of Pathology, Cincinnati, USA; <sup>3</sup>St. Jude Children's Research Hospital, Department of Pharmaceutical Sciences, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Aggressive form of Hepatoblastoma, HBL, is associated with a poor prognosis. Tumor suppressor proteins (TSPs) are usually eliminated in HBL. While examining a large cohort of HBL patients, we have identified a group of aggressive HBL samples which express high levels of TSPs. One of these TSPs, C/EBPα, is de‐phosphorylated at Ser190. The goal of this work was to determine the role of post‐translationally modified C/EBPα in aggressive liver cancer and determine molecular mechanisms by which de‐ph‐C/EBPα causes development of liver cancer.</p><p><bold>Design/Methods</bold>: To test the role of Ser190‐de‐ph C/EBPα in liver cancer, we generated a mouse model, C/EBPα‐S193A, and investigated development of spontaneous liver cancer. These mice were also treated with Diethylnitrosamine (DEN); and liver cancer was examined by state‐of‐the‐art approaches. Liver cancer was also investigated in additional models of aggressive liver cancer such as Pten/p53 DKO mice.</p><p><bold>Results</bold>: We found that de‐phosphorylation of C/EBPα converts this protein from a TSP into an oncogene. Using C/EBPα‐S193A mice and liver samples from patients (HBL and HCC), we found that mouse and human C/EBPα, dephosphorylated at Ser193/Ser190 correspondingly, causes de‐differentiation of hepatocytes into cells which express markers of stem cells (tumor initiating hepatocytes, TIH). The S193‐de‐ph‐C/EBPα‐dependent pathway of transformation of hepatocytes into TIH includes increased hepatocyte proliferation, multi‐nucleation of hepatocytes, and enlarged hepatocytes with intra‐nuclear inclusions expressing DLK1 and containing glycogen. The molecular mechanisms of this transformation are associated with epigenetic alteration and formation of high MW multi‐protein complexes.</p><p><bold>Conclusions</bold>: In patients with aggressive HBL, de‐phosphorylation of C/EBPα at Ser 190 converts this tumor suppressor into protein with oncogenic activities. The tumor promotion activity of oncogenic form of C/EBPα includes the transformation of hepatocytes into tumor initiating cells that express markers of stem cells. These findings provide molecular basis for development of a therapy to treat aggressive liver cancer.</p></sec><sec id="pbc26772-sec-6570"><label>P-259</label><title>Role of Hepatic Artery Blockage in the Treatment of High Risk Infantile Hepatic Hemangioma</title><p><underline underline-style="single">J. Wang</underline><sup>1</sup>, Q. Shu<sup>1</sup>, M. Li<sup>1</sup>, M. He<sup>1</sup>, J. Cai<sup>1</sup>, J. Mao<sup>1</sup>, X. Chen<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Surgical Oncology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: Infantile Hepatic hemangioma (IHH) is the most common tumor of the liver during infancy. Children with diffuse lesions are more likely to have a greater risk of death, especially in cases with severe congestive heart failure (CHF) and abdominal compartment syndrome (ACS). Aggressive treatment is crucial to improve mortality. In this study, the efficacy of hepatic artery blockage in the treatment of high risk IHH was evaluated.</p><p><bold>Design/Methods</bold>: Nineteen patients with diffuse IHH aged from 12d to 37d admitted to our center between Jan. 2014 and Sep. 2016 were included in this study. Clinical data were retrospectively analyzed. Glucocorticoid (methylprednisolone, 4mg/kg/day) plus propranolol (1mg/kg/day) were administrated as the first‐line treatment. Symptoms including CHF or ACS could not relieve or even deteriorated 48 hours after drug administration in 8 patients (high risk group). Hepatic artery blockage was suggested in high risk group. Five cases underwent surgery (4 cases by hepatic artery ligation and one case blocked by micro‐coil embolization). Other 3 cases refused hepatic artery blockage method kept glucocorticoid plus propranolol treatment.</p><p><bold>Results</bold>: In cases underwent hepatic artery blockage, CHF and ACS relieved promptly after surgery in 4 cases (including 3 cases of hepatic artery ligation and 1 case of hepatic artery embolization), 1 case had deteriorated heart failure and died eventually. Other 3 cases in high risk group refused hepatic artery blockage all died from deteriorated CHF and ACS.</p><p><bold>Conclusions</bold>: Severe congestive heart failure and abdominal compartment syndrome are high risk factors in children with diffuse infantile hepatic hemangioma. Blockage blood flow of hepatic artery is a simple method to relieve CHF and ACS. Hepatic artery blockage combined with drug therapy may improve mortality of high risk IHH.</p></sec><sec id="pbc26772-sec-6580"><label>P-260</label><title>Report of Childhood Hepatoblastoma: 74 Cases from a Single Center</title><p><underline underline-style="single">T. Wang</underline><sup>1</sup>, C. Pan<sup>1</sup>, J. Tang<sup>1</sup>, Q. Ye<sup>1</sup>, M. Zhou<sup>1</sup>, Y. Gao<sup>1</sup>, W. Hu<sup>1</sup></p><p><italic><sup>1</sup>Shanghai children's medical center, Hematology/Oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: To investigate the efficacy of the protocol for pediatric hepatoblastoma and the prognostic factors.</p><p><bold>Design/Methods</bold>: All consecutive cases were divided into either low risk group or high risk group according to grouping criteria. Complete remission was defined as both negative for imaging and α fetoprotein. Retrospective analysis was performed for clinical features, short and long‐term outcomes and prognostic factors.</p><p><bold>Results</bold>: 74 cases including 45 males and 29 females were enrolled. The median age at diagnosis was 1.7 years old. According to PRETEXT staging, 18 cases were in stage I‐II and 56 in stage III‐IV. 19 of 74 cases existed distant metastasis at first presentation including 13 with lungs and/or pleura metastasis. The median cycles of chemotherapy were 5 in low risk group and 8 in high risk group. AFP was back to normal after median 5 cycles of chemotherapy in total plus surgery and 2 cycles post total tumor resection. Untill August 30, 2016, the median follow‐up time was 24.17 months. 59 cases achieved complete remission. 1 case did not reach remission, 3 progressed, another 5 relapsed, and total 6 cases already died. The estimated five years EFS were 72.4% and OS were 90%. The five years EFS and OS in low risk group were both 100%, and those in high risk group were 68% and 87.6%, respectively. The five years OS rates were 75.3% and 94.9% respectively for with and without distant metastasis (<italic>P</italic>=0.016). After 3 cycles of chemotherapy post tumor resection, AFP returned to normal in 43 and still high in 26 cases, with five years OS rates were 100% and 80.9%, respectively (<italic>P</italic> = 0.011).</p><p><bold>Conclusions</bold>: The result of this protocol is reasonable when comparing with worldwide researchs. Besides staging, metastasis, pathological subtypes, postoperative AFP after 3 cycles of chemotherapy back to normal or not is also a prognostic factor.</p></sec></sec><sec id="pbc26772-sec-6590"><title>Solid Non Brain Tumours ‐ Germ Cell Tumours</title><sec id="pbc26772-sec-6600"><label>P-261</label><title>Experience of Low and Intermediate Risk Malignant Extra‐Cranial Pediatric Germ Cell Tumors at CCHE</title><p>S. Ahmed<sup>1,2</sup>, <underline underline-style="single">O. Arafah</underline><sup>1,2</sup>, G. Taha<sup>3</sup>, N. elkinaai<sup>4</sup>, M. Elwakeel<sup>5</sup>, W. Rashed<sup>6</sup>, D. Elgalaly<sup>7</sup>, M. Essam<sup>7</sup></p><p><italic><sup>1</sup>57357hospital, Pediatric Oncology, Cairo, Egypt; <sup>2</sup>National Cancer Institute. Cairo university, Pediatric Oncology, Cairo, Egypt; <sup>3</sup>57357hospital, Surgical Oncology, Cairo, Egypt; <sup>4</sup>57357hospital, Pathology, Cairo, Egypt; <sup>5</sup>57357hospital, Radiodiagnosis, Cairo, Egypt; <sup>6</sup>57357hospital, Clinical trial unit, Cairo, Egypt; <sup>7</sup>57357hospital, Clinical research, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Survival rates for children with malignant extra cranial germ cell tumors (MGCTs) have increased significantly. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of stage, histologic features, and primary tumor site. Sustained favorable outcome with therapy reduction in low and intermediate risk encourages lesser toxic therapy to decrease long term side effects.</p><p><bold>Design/Methods</bold>: Out of 122 eligible patients with MGCTs, a retrospective analysis was done for 47 cases, stratified and treated at CCHE according to AGCT0132 protocol adopted for low and intermediate risk MGCTs, from July 2007 till end of December 2015. All cases were followed up until June 2016.</p><p><bold>Results</bold>: For low and intermediate risk MGCTs, mean age was 4.3 years. Low risk (LR) patients were 23 (19 testicular and 4 ovarian). Yolk sac tumor predominates in male cases while main histological types in female cases were Mixed GCT, followed by Dysgerminoma. Intermediate risk (IR) were 24 cases with male to female ratio 1.7:1, with two extragonadal cases (2 males with sacrococcygeal tumors) and 22 gonadal cases (13 males and 9 females). Yolk sac tumor predominates in male cases while main histological types in female cases were Yolk sac tumors, Mixed GCT, and Dysgerminoma. Five years OS were 100% and 95.7% for LR and IR respectively, while five years EFS were 88 % and 91.3 % for LR and IR respectively.</p><p><bold>Conclusions</bold>: Reduction of therapy did not compromise the favorable outcome in the low and intermediate risk groups with excellent salvage potential. Long term survival raises concerns about late side effects encouraging more therapy reduction.</p></sec><sec id="pbc26772-sec-6610"><label>P-262</label><title>Outcome of the Sacrococcygeal Teratoma: A Single Institutional Study</title><p><underline underline-style="single">T.T. Nguyen</underline><sup>1</sup></p><p><italic><sup>1</sup>Dr Nguyen Thanh Truc, Children Hospital N 2, HoChiMinh city, Vietnam</italic></p><p><bold>Background/Objectives</bold>: To report our initial experience with Sacrococcygeal Tumors (SCT) treated at our hospital over a 5 year period with reference to clinical presentations, surgical attentions and short outcomes like: urinary and defecation functions, and tumor recurrence.</p><p><italic>Background</italic>: statement of the problem e.g. incidence, difficulty with diagnosis, poor antenatal diagnosis, late referral or difficulties with referral. The rarity of SCT indicates the need for concentration in a specialist center and the need for long term follow up.</p><p><bold>Design/Methods</bold>: All infants with Sacrococcygeal tumors who had surgery in our hospital from 1/2010 till 12/2015 were selected. Details of gender, prenatal investigation, presentation,preoperative investigations, initial surgical outcome and short term follow up were noted. Only patients with a follow up greater than one year were included.</p><p><bold>Results</bold>: Of 44 cases of Sacrococcygeal tumors 16 (36%) were male and 28 (64%) were female. Chief complaint was Sacrococcygeal mass. A prenatal diagnosis was established in 23 (53), among these 21 cases had cesarean. The remaining 21 cases without prenatal diagnosis were delivered normally. Most, 42 cases, were delivered at term. Preoperative investigation included Ultrasound (22) CT scan (20) and MRI in 12. AFP and BHCG were done in 79.5%( and 77.3 %. The mean age at diagnosis was 1.2 day and surgery was complete resection with coccycgectomy (35) or without coccycgectomy(9). Mean length of stay was 18 days. Complications included: wound infection (6 cases), wound dehiscence (3 cases), rectal perforation in need of temporary stoma (2cases). In the short term (1‐5 year) constipation was noted in 5 patients, 1 local benign and 2 malignant recurrences with an average time to recurrence of 12 moths (benign and malignancy is defined as AFP high associated recurrent institut tumor )</p><p><bold>Conclusions</bold>: Sacrococcygeal tumor surgery in infants is a relatively safe procedure not without potential complications.</p></sec><sec id="pbc26772-sec-6620"><label>P-263</label><title>Sacrococcygeal Teratoma: Analysis of Surgical Outcome</title><p><underline underline-style="single">N. Peters</underline><sup>1</sup>, J.K. Mahajan<sup>2</sup></p><p><italic><sup>1</sup>PGIMER‐ Chandigarh India, Pediatric Surgery, Chandigarh, India; <sup>2</sup>PGIMER‐ Chandigarh, Pediatric Surgery, Chandigarh, India</italic></p><p><bold>Background/Objectives</bold>: We reviewed our experience with presentation and treatment of sacrococcygeal teratoma (SCT).</p><p><bold>Design/Methods</bold>: From July 2000 – May 2016, charts of 14 patients of SCT were retrospectively reviewed.</p><p><bold>Results</bold>: There were 11 females and 3 males. Age at time of surgery ranged from 1 day to 8 years (median 58 days). Seven patients underwent surgery within 1<sup>st</sup> week of life and 4 were antenatally diagnosed. 6 patients underwent surgery between 1.5 to 8 years, neoadjuvant chemotherapy (3) and non resolving perianal abscess (1) being the reason for delayed surgery. Ten patients were of Altman type I, 3 were type II and 1 patient was of type III. Eight patients underwent CT scan and 4 had preop ultrasound. Two patients had giant SCT (>10cm). Serum AFP levels ranged from 4.36 – 48400 ng/ml. Levels were raised for all cases of malignancy and 6 of the 8 others. Levels fell to normal within 1 year for all patients. One patient with normal AFP and mature histology developed recurrence after 1 year. Two patients, 1 each with giant benign and malignant tumor developed neurogenic bowel and bladder. Ten patients had mature histology, 1 had immature and remaining 3 had malignant histology. There was no postoperative mortality. One patient (mature histology and type III morphology) died at 5 months post operative due to unrelated causes. The median follow up was 3 years (range 1‐17 years), most recent being a telephonic follow up. All survivors are disease free and had a good quality of life.</p><p><bold>Conclusions</bold>: Surgical excision of SCT is associated with good outcome. Serum AFP levels may take up to 1 year to normalize. Recurrence can occur even with mature histology; hence long term follow up is required. Neurogenic bladder and bowel incontinence may be associated with large benign and malignant tumors.</p></sec><sec id="pbc26772-sec-6630"><label>P-264</label><title>Profile of Paediatric Orbital and Periorbital Tumors‐ A Report from a Tertiary Eye Care Centre in India</title><p><underline underline-style="single">N. Pushker</underline><sup>1</sup>, R. Meel<sup>1</sup>, A. shashni<sup>1</sup>, N. Gupta<sup>1</sup>, S. Modaboyina<sup>1</sup>, S. Kashyap<sup>2</sup>, S. Sen<sup>2</sup>, M.S. Bajaj<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences‐ New Delhi, ophthalmology, Ansari Nagar‐ New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences‐ New Delhi, ocular pathology, Ansari Nagar‐ New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: To assess the frequency of occurrence of orbital and periorbital tumors in paediatric age group operated at our centre.</p><p><bold>Design/Methods</bold>: This was a retrospective study in which all the patients of age less than 16 years who were operated for orbital and periorbital tumor at our centre from 2015 to 2016 were included.</p><p><bold>Results</bold>: A total of 109 patients were included in this study. The mean age of presentation was 7.82 ± 5.03 years. Among these 57 % were male and 43 % were female. 44 cases (40.4%) were dermoid. Other tumors were conjunctival nevus (11%), capillary hemangioma (9%), neurofibromas (7%), rhabdomyosarcoma(5.5%), inclusion cyst (4.5%), lymphangioma (3.6%), pyogenic granuloma(3.6%), sebaceous cyst (2.7%), basal cell carcinoma(1.8%), pilomatrixoma (1.8%) with 1 case each (0.9%) of neuroblastoma, reactive follicular lymphoma, squamous cell carcinoma, apocrine cyst, inflammatory pseudotumor, lymphoblastic lymphoma, follicular conjunctival hyperplasia, chalazion.</p><p><bold>Conclusions</bold>: In paediatric patients who were operated for orbital and periorbital tumor at our centre, dermoid was found to be the most common tumor requiring surgical intervention.</p></sec><sec id="pbc26772-sec-6640"><label>P-265</label><title>Dermoids in Paediatric Orbit‐ A Retrospective Case Series</title><p><underline underline-style="single">R. Meel</underline><sup>1</sup>, A. Shashni<sup>1</sup>, N. Pushker<sup>1</sup>, S. Modaboyina<sup>1</sup>, N. Gupta<sup>1</sup>, S. Sen<sup>2</sup>, S. Kashyap<sup>2</sup>, M.S. Bajaj<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences‐ New Delhi, ophthalmology, Ansari Nagar‐ New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences‐ New Delhi, ocular pathology, Ansari Nagar‐ New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: To study the clinical and radiological features of ocular and orbital dermoid in paediatric age group</p><p><bold>Design/Methods</bold>: A retrospective case series analysing the clinical and radiological features of ocular and orbital dermoid in patients less than 16 years of age who were operated at our centre were included in this study</p><p><bold>Results</bold>: Total 33 patient were included in this study. The mean age of the patient was 6.71 ± 5.53 years. Of all the patients 70 % were male and 30% were female. 51.5% (17/33) cases had limbal dermoid, 24.2% (8/33) cases had an internal angular dermoid (located at frontonasal suture line), 15% (5/33) cases had an external angular dermoid (located at frontozygomatic suture line), 9% (3/33) cases had an epibulbar dermoid (lipodermoid). 9% (3/33) cases of limbal dermoid were bilateral. 24.2% (8/33) cases were associated with Goldenhar syndrome. Majority of the cases showed cystic lesion with fat density on imaging (Ultrasound biomicroscopy and Computed tomography). None of the patients had an intracranial extension</p><p><bold>Conclusions</bold>: Dermoid is the most common benign tumor of paediatric eye and orbit and may present as ocular surface mass or periocular tumor. Most cases can be successfully managed with surgical excision.</p></sec><sec id="pbc26772-sec-6650"><label>P-266</label><title>Pediatric Testicular Tumors in Poland. A Report from the Polish Pediatric Solid Tumors Group (2008‐2016)</title><p><underline underline-style="single">J. Stefanowicz</underline><sup>1</sup>, M. Jezierska<sup>2</sup>, E. Adamkiewicz‐Drożynska<sup>2</sup>, K. Połczyńska<sup>2</sup>, E. Iżycka‐Świeszewska<sup>3</sup>, M. Rąpała<sup>4</sup>, K. Bilska<sup>5</sup>, L. Chełmecka‐Wiktorczyk<sup>6</sup>, R. Dębski<sup>7</sup>, B. Dembowska‐Bagińska<sup>8</sup>, G. Karolczyk<sup>9</sup>, I. Karpińska‐Derda<sup>10</sup>, B. Kazanowska<sup>11</sup>, E. Leszczyńska<sup>12</sup>, M. Matysiak<sup>13</sup>, A. Mizia‐Malarz<sup>14</sup>, J. Nurzyńska‐Flak<sup>15</sup>, G. Sobol‐Milejska<sup>16</sup>, J. Peregud‐Pogorzelski<sup>17</sup>, K. Wachowiak‐Szajdak<sup>18</sup></p><p><italic><sup>1</sup>Gdansk Medical University, Department of Pediatrics‐ Hematology and Oncology, Gdańsk, Poland; <sup>2</sup>Medical University of Gdansk, Department of Paediatrics‐ Haematology and Oncology, Gdańsk, Poland; <sup>3</sup>Medical University of Gdansk, Department of Pathology and Neuropathology, Gdańsk, Poland; <sup>4</sup>Marciniak Hospital, Department of Pediatric Surgery, Wrocław, Poland; <sup>5</sup>Institute of Mother and Child, Clinic of Oncological Surgery of Children and Adolescents, Warsaw, Poland; <sup>6</sup>Children's University Hospital, Department of Pediatric Hematology and Oncology‐, Cracow, Poland; <sup>7</sup>Nicolaus Copernicus University, Department of Pediatrics‐ Hematology and Oncology, Bydgoszcz, Poland; <sup>8</sup>Children's Memorial Health Institute, Department of Oncology, Warsaw, Poland; <sup>9</sup>Children Hospital, Division of Pediatric Hematology and Oncology, Kielce, Poland; <sup>10</sup>Chorzow Pediatrics and Oncology Center, Department of Pediatric Hematology and Oncology, Chorzów, Poland; <sup>11</sup>Wroclaw Medical University‐, Department and Clinic of Pediatric Oncology‐ Hematology and Bone Marrow Transplantation, Wroclaw, Poland; <sup>12</sup>Medical University of Bialystok, Department of Pediatric Oncology and Hematology, Bialystok, Poland; <sup>13</sup>Medical University, Department of Pediatric Hematology and Oncology, Warsaw, Poland; <sup>14</sup>Upper Silesia Children's Care Health Centre‐ Medical University of Silesia, Department of Pediatric Oncology‐ Haematology and Chemotherapy, Katowice, Poland; <sup>15</sup>Medical University of Lublin‐, Department of Pediatric Oncology and Hematology, Lublin, Poland; <sup>16</sup>Medical University of Silesia, Department of Pediatric Oncology‐ Hematology and Chemotherapy, Katowice, Poland; <sup>17</sup>Pomeranian Medical University in Szczecin, Department of Oncology and Hematology‐, Szczecin, Poland; <sup>18</sup>Medical University of Poznań, Department of Pediatric Oncology‐ Hematology and Transplantology‐, Poznań, Poland</italic></p><p><bold>Background/Objectives</bold>: The aim of the study was to evaluate the results of the treatment children and adolescents with testicular tumors in Poland.</p><p><bold>Design/Methods</bold>: A statistical analysis was performed on the clinical data and the results of treatment of patients with testicular tumors reported to the database of extracranial germ cell tumors of the Polish Pediatric Solid Tumours Group in the years 2008‐2016.</p><p><bold>Results</bold>: The study included 138 patients aged 0 to 18 years old who were treated according to TGM 95 protocol. The mean age of respondents was 13.8 years, the median 16.3. For the whole group, 5YOS was 95.6±2.2%, 5YEFS 88.1±3.3%. Children over 10 yr formed the majority (84%), while 16% were patients ≤10 yr. The results of treatment were comparable in both age groups (5‐year OS in the group of children ≤10 yr. 100% vs. children >10 yr. 95.9±2.4%, p=0.419, 5‐year EFS 88.2±7.8% vs. 89.1±3.5%, p=0.794). Most of these were secretory tumors (84%). It was found that the results of treatment did not differ in the groups of non‐secretory and secretory tumors (5YOS 100% vs. 94.8±2.6%, p=0.461, 5YEFS 83.3±10.8% vs. 88.03±3.6%, p=0.54). The mean AFP concentration was 2670.7 ±4966, a median 792, range 11.0 – 30 000, IU/ml. The other prognostic factors were analysed: histological structure ‐ mixed tumors 70%, yolk sack tumor 8%, embryonal carcinoma 5%, other 17%; the stage of disease: 5YOS for stages I, II, III ‐ 100%, for stage IV – 84.7±7.2%, p=0.0173, and the risk group: in the high risk group 5YOS was 90±4.8%, in the standard risk group 100%, p=0.0234.</p><p><bold>Conclusions</bold>: The results of treatment of patients in the developmental age with testicular tumors in Poland are very good. The most significant prognostic factors are the stage and the risk group.</p></sec></sec><sec id="pbc26772-sec-6660"><title>Solid Non Brain Tumours ‐ Rare Tumours</title><sec id="pbc26772-sec-6670"><label>P-267</label><title>Multiple Mutations in Genes Associated with Colon Carcinoma: Analysis of Whole Exome Sequencing and Array Comparative Genome Hybridization (ACGH) Data in 15‐Year‐Old Patient</title><p><underline underline-style="single">S. Cardellicchio</underline><sup>1</sup>, C. Cecchi<sup>1</sup>, P. Scalini<sup>1</sup>, S. Giglio<sup>1</sup>, A. Tamburini<sup>1</sup></p><p><italic><sup>1</sup>Meyer Children's Hospital, Oncology/Hematology Unit, Firenze, Italy</italic></p><p><bold>Background/Objectives</bold>: Colon carcinoma is a rare disease in the pediatric population. A 15‐year‐old male, without a strong family history of cancer, presented with metastatic colon‐adenocarcinoma, medium grade of differentiation, methylation of MGMT gene, amplification of HER2 and MET without ROS1, ALK, TRKA, BRAF genes’ rearrangements. He died in 16 months after five treatment lines. Whole exome sequencing was employed to identify single‐nucleotide variants, small insertion/deletions, and copy number abnormalities in the patient's and parent's germline.</p><p><bold>Design/Methods</bold>: DNA was extracted from the patient's and parent's blood. DNA libraries were constructed and sequenced on Illumina HiSeq1000. aCGH was performed.</p><p><bold>Results</bold>: Whole exome sequencing highlighted: in exon 1 of BCL2A1 gene a variant inherited from both parents (c.245G> A); in exon 33 of POLE gene a variant (c4187A> G) inherited from his father and in exon 19 a variant (c.2083T > A) inherited from the mother; in exon 22 of the ATM gene a variant (c3161C> G) inherited from both parents.</p><p>Using array CGH analysis we found: an interstitial deletion of 4q32.3 MARCH‐1 gene, inherited from the mother and an interstitial deletion of 7q11.22 AUTS2 gene inherited from his father.</p><p><bold>Conclusions</bold>: The mutation identified in homozygosity of BCL2‐A1 gene, involved in embryogenesis and tumorigenesis processes, is shown in Human Gene Mutation Database as associated with an increased risk of colorectal carcinoma.</p><p>The variants of the POLE and ATM genes, expressed in heterozygous, present an uncertain pathogenic role; they are not reported in the literature but in ClinVar (archive which shows the correlations between clinically significant variations and phenotypes) are related with increased susceptibility to colon cancer.</p><p>The POLE gene variants identified in our patient, may correlate with an early onset and a more aggressive course, instead it is hard to speculate on the role of the deletions found in MARCH‐1 and AUTS2 genes in absence of protein expression studies.</p></sec><sec id="pbc26772-sec-6680"><label>P-268</label><title>Long‐Term Survivorship for Children and Adolescents With HIV‐Related Kaposi Sarcoma in Lilongwe, Malawi</title><p><underline underline-style="single">W. Kamiyango</underline><sup>1</sup>, J. Villiera<sup>1</sup>, J. Kamwagha<sup>1</sup>, P. Mehta<sup>2</sup>, M. Scheurer<sup>2</sup>, P. Kazembe<sup>1</sup>, N. El‐Mallawany<sup>2</sup></p><p><italic><sup>1</sup>Baylor College of Medicine Children's Foundation Malawi, Pediatrics, Lilongwe, Malawi; <sup>2</sup>Texas Children's Hospital, Pediatrics, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Kaposi sarcoma (KS) is among the most common childhood cancers in sub‐Saharan Africa and continues to occur at high numbers despite the increased availability of antiretroviral therapy (ART). Although one‐two year survival estimates for pediatric KS have been reported throughout the region, longer‐term outcomes have not been described.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed the pediatric KS database of HIV‐infected children and adolescents diagnosed with KS at a pediatric HIV referral center in Lilongwe, Malawi. Long‐term survivorship was determined in patients diagnosed between 2006‐2013 that were still alive at last follow‐up. All but two survivors were treated with chemotherapy plus ART according to Malawian national guidelines; the two exceptions received ART alone. Typically, patients received 8 cycles of bleomycin and vincristine over 6 months. Evaluating characteristics of survivors only, demographics, duration of survival, time off of chemotherapy, and need for 2<sup>nd</sup> line chemotherapy or ART were described.</p><p><bold>Results</bold>: There were 50 (31%) long‐term survivors among 161 HIV‐related cases of pediatric KS. The median age at time of KS diagnosis among survivors was 8 years (interquartile range [IQR] 4.6‐13); there were 22 females (44%). Median overall survival was 4.8 years (IQR 3.6‐6.8), with the longest survivor alive 10.5 years from date of KS diagnosis. Fourteen (28%) patients experienced relapse requiring additional doses of chemotherapy and remained alive at time of data collection. The median time off of chemotherapy was 3.5 years (IQR 2.1‐5.3) with the longest duration reaching 10 years. In total, 28 (56%) patients were still on 1<sup>st</sup> line ART, with 22 (44%) receiving 2<sup>nd</sup> line ART.</p><p><bold>Conclusions</bold>: Long‐term survival is possible for HIV‐infected children and adolescents with KS in Malawi despite myriad limitations. The majority of patients were able to achieve long‐term disease control with up‐front chemotherapy and life‐long ART, with over half of children still on 1<sup>st</sup> line ART regimens.</p></sec><sec id="pbc26772-sec-6690"><label>P-269</label><title>Potential for Improved Survival Outcomes after Treatment with Intensified Chemotherapy and Antiretroviral Therapy in Children with Pulmonary Kaposi Sarcoma Presenting with Severe Pleural Effusions</title><p><underline underline-style="single">J. Villiera</underline><sup>1</sup>, W. Kamiyango<sup>1</sup>, P. Mehta<sup>2</sup>, P. Kazembe<sup>1</sup>, N. El‐Mallawany<sup>2</sup></p><p><italic><sup>1</sup>Baylor College of Medicine Children's Foundation Malawi, Pediatrics, Lilongwe, Malawi; <sup>2</sup>Texas Children's Hospital, Pediatrics, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: In the initial eight years of the pediatric Kaposi sarcoma (KS) program in Lilongwe, Malawi, there has never been a survivor of pulmonary KS (n>10) after up‐front treatment with bleomycin and vincristine. With all but two patients dying within 6 months, and the longest duration of survival being 9 months, a programmatic shift was implemented to initiate patients with pulmonary KS on a chemotherapy regimen intensified by adding doxorubicin. We report a case series of pulmonary KS patients with improved survival.</p><p><bold>Design/Methods</bold>: We evaluated a series of HIV‐infected children presenting with pulmonary KS manifested by large serosanguineous pleural effusions in addition to characteristic hyperpigmented KS skin lesions or woody edema. Patients were treated with an intensified chemotherapy regimen of doxorubicin, bleomycin, and vincristine (8 cycles total, given every 3 weeks) plus protease‐inhibitor based antiretroviral therapy. Clinical characteristics and treatment response were described.</p><p><bold>Results</bold>: There were three patients (one female) with pulmonary KS that achieved disease control and prolonged survival. Patient ages at presentation were 7, 8, and 14 years. All presented with large serosanguineous pleural effusions and severe respiratory distress requiring supplemental oxygen via nasal cannula (for duration ranging 2‐5 weeks) and multiple thoracentesis procedures (range 2‐15 taps), but ultimately achieved resolution of hypoxia and effusions. One patient had concurrent skin and lymph node KS lesions and the other two both had characteristic woody edema. All had pleural fluid cytology evaluation performed; as anticipated, none yielded malignant KS cells. All three children are alive in partial remission with stable disease achieving overall survival duration of 7, 10, and 22 months, off of chemotherapy for respective durations of 1, 4, and 16 months.</p><p><bold>Conclusions</bold>: Improved survival may be achievable for pediatric pulmonary KS patients receiving intensified chemotherapy and antiretroviral therapy. Longer follow‐up is required to determine definitive long‐term outcomes.</p></sec><sec id="pbc26772-sec-6700"><label>P-270</label><title>Secondary Malignancies After Chilhood Cancers: A Single Center Experience</title><p><underline underline-style="single">F. Akici</underline><sup>1</sup>, G. Aydogan<sup>1</sup>, Z. Salcioglu<sup>1</sup>, G. Ersoy<sup>1</sup>, A. Akçay<sup>2</sup>, D. Tugcu<sup>3</sup>, S. Sander<sup>4</sup>, E. Darendeliler<sup>5</sup></p><p><italic><sup>1</sup>Kanuni Sultan Suleyman Training and Research Hospital ‐, Pediatric Hematology Oncology, Istanbul, Turkey; <sup>2</sup>Acibadem University Atakent Hospital, Department of Pediatric Bone Marrow Transplantation, Istanbul, Turkey; <sup>3</sup>Istanbul University School of Medicine, Pediatric Hematology Oncology, Istanbul, Turkey; <sup>4</sup>Kanuni Sultan Suleyman Training and Research Hospital ‐, Pediatric Surgery, Istanbul, Turkey; <sup>5</sup>Istanbul University School of Medicine, Radiation Oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: The occurrence of second malignancies (SM) is an important late event following the treatment of childhood cancers. It is 3 folds greater thn the normal population, the incidence is about 3% in the first 20 years after pirmary diagnosis.</p><p><bold>Design/Methods</bold>: The incidence of SMs is studied in a population of 1678 patients with minumum 3 years follow up after cessation of chemoradiotherapy or radiotherapy for childhood cancers between June 1990 and January 2017. The study included the patients treated in inpatient and outpatient clinics of Kanuni Sultan Süleyman Research and Training Hospital.</p><p><bold>Results</bold>: SMs were found in 6 (0,5%) patients. The mean time for the occurence of SM was 8 years (3‐14 years). Case 1: A girl 9 years old with diagnosis of Nodular Sclerosing Hodgkin Lymphoma stage 3 treated with both radiotherapy and chemotherapy developed thyroid papillary carcinoma 7 years 3months after primary diagnosis. Case 2: A boy 8 years old diagnosed as non‐ Hodgkin Lymhoma developed hepatocellular carcinoma 10 years after treatment. Case 3: B cell non‐Hodgkin lymphoma patient 3 years old was diagnosed as epidermoid carcinoma of external ear 12 years after. Case 4: 8 years old male patient developed adrenal cortex carcinoma 7 years after treated successfully for Burkitt Lymphoma. Case 5: A female patient was diagnosed as breast carcinoma after 14 years of acute lymphoblastic leukemia (ALL) treatment. Case 6: Mucoepidermoid Carcinoma of parotid gland was seen 3 years after completition of ALL chemotherapy at age of 8.</p><p><bold>Conclusions</bold>: All of the SM s were solid neoplasms. One patient has thyroid carcinoma which could depend on thyroid irradiation, the alkalyting agents could be the cause of the other neoplasms. Continued follow‐up is mandatory after treatment for childhood cancers. Since the prognosis of most SM is unfavorable, early recognition and prevention are important.</p></sec><sec id="pbc26772-sec-6710"><label>P-271</label><title>Clinical Characterization of Malignant Rhabdoid Tumors – The Sick Kids Experience</title><p><underline underline-style="single">A. Fonseca</underline><sup>1</sup>, A. Gupta<sup>1</sup>, R. Grant<sup>1</sup>, A. Huang<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Paediatric Haematology Oncology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Rhabdoid Tumors (RTs) are rare cancers defined by bi‐allelic loss of function alterations of <italic>SMARCB1</italic>, which encodes a critical component of the SWI/SNF chromatin‐remodeling complex. They can arise in the brain where they are called Atypical Teratoid/Rhabdoid Tumors (ATRTs) and in various extra‐cranial locations where they are called Malignant Rhabdoid Tumors (MRTs). Both ATRTs and MRTs are frequently lethal diseases for which best therapeutic approaches remains to be determined. Herein, we describe the Sick Kids experience.</p><p><bold>Design/Methods</bold>: Patients diagnosed with MRT at the hospital for Sick Children between 1996‐2016 were identified and charts reviewed. Demographic data, treatment details and survival information was collected.</p><p><bold>Results</bold>: We identified twenty‐five patients diagnosed with MRTs between 1996 and 2016. Median age at diagnosis was 3.2 years (1 month ‐16.6 years), 64%(n=14) were female and 36%(n=8) were male. Thirty‐two percent of the tumors were intra‐abdominal (n=8), 24% (n=6) para‐spinal, 16% in extremities (n=4), 8% nasopharyngeal (n=2), 8% multifocal (n=2), 4% Skull base (n=1), 4%Chest wall (n=1) and 4% neck (n=1). Most of the patients, 56% presented with advanced disease (stage III and IV), 8% (n=2) of the patients presented with multifocal disease and correspond to patients diagnosed with rhabdoid tumor predisposition syndrome. The median time to progression was 6 months (ranging from 1 month to 25 months). Most of the patients (n=20) were treated with multimodal therapy including chemotherapy in 18 patients, radiation therapy in 11 patients and surgery in 14 patients. Only 20% of patients are alive and free of disease, 64% of patients succumbed to the disease.</p><p><bold>Conclusions</bold>: MRTs continues to be a disease with poor outcomes. Young patients and patients presenting with metastatic disease have a dismal prognosis. Insights in the biology of this entity are urgently needed to guide therapeutic approaches and the development of clinical trials.</p></sec><sec id="pbc26772-sec-6720"><label>P-272</label><title>Paratestitular Rhabdomyosarcoma in Children: Surgical Analysis</title><p><underline underline-style="single">R.</underline><underline underline-style="single">Vianna</underline><sup>1</sup>, E. Lopes<sup>1</sup>, V. Nascimento<sup>1</sup>, S. Coelho<sup>1</sup>, F.N. Gutierrez<sup>1</sup>, J. Oliveira<sup>1</sup>, F. Lima<sup>2</sup>, S. Ferman<sup>3</sup>, A. Ikeda<sup>3</sup>, P. Faria<sup>4</sup></p><p><italic><sup>1</sup>Instituto Nacional de Câncer, Pediatric Surgery, Rio de Janeiro, Brazil; <sup>2</sup>Instituto Nacional de Câncer, Pediatric Research Nurse, Rio de Janeiro, Brazil; <sup>3</sup>Instituto Nacional de Câncer, Pediatric Oncology, Rio de Janeiro, Brazil; <sup>4</sup>Instituto Nacional de Câncer, Pathology, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: In children, about 7% of all cases of genitourinary rhabdomyosarcoma are paratesticular in origin. Prognosis for paratesticular rhabdomyosarcoma (RMS) is favorable; approximately 60% to 80% of patients have localized disease at diagnosis. The purpose of this study was to report a retrospective review of paratesticular RMS in children treated at the Pediatric Oncology Department at one institution in Brazil. The prognostic, surgical and histopathologic aspects were analyzed.</p><p><bold>Design/Methods</bold>: From 1987 to 2017, a total of twenty five patients with ages ranging from 10 months to 16 years old with pathologically confirmed diagnosis of paratesticular RMS treated at our institution.</p><p><bold>Results</bold>: The median age at presentation was 12 years (range 10 months – 16 years). Sixteen patients were ≥10 years old (76%). Eighteen patients had initial surgery at non‐oncologic hospital and seven needed a second surgery. One third of patients who underwent initial surgery outside our institution required second surgery (three hemiscrotectomy and four lymphadenectomy). Partial cystectomy was performed in one patient due to vesical metastasis. The histopathological classification of RMS was: embryonal in 19, alveolar in four and not classified RMS in two. The patients were treated following the International Rhabdomyosarcoma Study Group from 1987 to 2008 (88%) and European Pediatric Soft Sarcoma Group protocol since 2009 (12%). All patients received chemotherapy and only seven received radiotherapy. The 5‐year overall survival (OS) was 76%, with follow up from 6 months to 20 years (median 4 years). The mortality among patients ≥10 years of age was 37,5%, while all patients < 10 years are alive.</p><p><bold>Conclusions</bold>: The 5‐year OS was worse in patients ≥10 years old, confirming current data. The patients who underwent initial surgery at non‐oncologic hospital needed second surgery more frequently, including hemiscrotectomy. Continued effort is required to educate providers on appropriate workup of scrotal masses to avoid scrotal violation.</p></sec><sec id="pbc26772-sec-6730"><label>P-273</label><title>Our Experience with Primary Total Thyroidectomy and Lymph Node Biopsy in Papillary Thyroid Carcinoma</title><p><underline underline-style="single">Z. Jenovari</underline><sup>1</sup>, P. Hauser<sup>2</sup>, M. Garami<sup>2</sup>, E. Varga<sup>2</sup>, Z. Karady<sup>2</sup>, A. Sallai<sup>2</sup>, E. Hosszu<sup>2</sup>, T. Budi<sup>2</sup>, T. Prokopp<sup>2</sup></p><p><italic><sup>1</sup>Semmelweis University, 2nd. Department of Pediatrics, Budapest, Hungary; <sup>2</sup>Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary</italic></p><p><bold>Background/Objectives</bold>: There are concerns about the optimal primer surgery in case of papillary thyroid carcinoma. From 2006 we moved on the total thyroidectomy and regional lymph node biopsy as the first attempted procedures in all cases, to provide opportunity for postoperative iodine isotope therapy. There are few evidences about the results of this procedure.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed the data of the children underwent primary total thyroidectomy in our unit from 2006‐2016.</p><p><bold>Results</bold>: 29 patients were found, the mean age 15.3 year (7‐20), M/F ratio 8/21. All had papillary thyroid carcinoma proven by FNAB and histology postoperatively. US and MRI were done for all. There was not pulmonary metastasis detected. 12 patients had regional lymph node enlargement on radiology. 13 patients underwent lymph node biopsy of the intraoperatively suspected nodules, central neck lymph node dissection done in 5 cases. Lateral neck dissection never attempted as primer procedure. The recurrent laryngeal nerve and the parathyroid glands (at least 1) were identified and preserved.</p><p>None of the patients had recurrent nerve lesion, or permanent hypocalcemia, or residual thyroid tissue.</p><p>13 out of 29 patients received postoperative iodine isotope therapy. Only 5 out of the 13 had pathologic lymph node enlargement postoperatively (>1cm, positive scan or MRI). 4 out of this 5 patients had isotope treatment twice, one patient 3 times. Finally 4 out of 5 underwent extended regional lymph node dissection.</p><p>The average follow up was 59 months (6‐131 months).</p><p><bold>Conclusions</bold>: The primary total thyroidectomy in papillary thyroid carcinoma is effective and safe procedure, the complications, (recurrent nerve injury or hypocalcemia) can be minimised by experienced surgeon. The postoperative iodine isotope therapy seems less effective for pathologic enlarged lymph nodes, in this cases the primer regional lymph node dissection of the affected region should be prior to the isotope therapy.</p></sec><sec id="pbc26772-sec-6740"><label>P-274</label><title>Immunotherapy of Metastatic Pediatric Melanoma with Checkpoint Inhibitors</title><p><underline underline-style="single">E. Kabickova</underline><sup>1</sup>, M. Kyncl<sup>2</sup>, R. Kodet<sup>3</sup>, M. Kalinova<sup>3</sup>, L. Krskova<sup>3</sup>, O. Belohlavek<sup>4</sup>, D. Sumerauer<sup>1</sup></p><p><italic><sup>1</sup>2nd Faculty of Medicine‐ Charles University and University Hospital Motol, Pediatric Hematology and Oncology, Prague 5, Czech Republic; <sup>2</sup>2nd Faculty of Medicine‐ Charles University and University Hospital Motol, radiology, Prague 5, Czech Republic; <sup>3</sup>2nd Faculty of Medicine‐ Charles University and University Hospital Motol, Pathology and Molecular Medicine, Prague 5, Czech Republic; <sup>4</sup>Na Homolce Hospital, PET Centre, Prague 5, Czech Republic</italic></p><p><bold>Background/Objectives</bold>: Metastatic melanoma in children is rare, fatal disease. The introduction of immune checkpoint inhibitor antibodies has dramatically improved the clinical outcomes for adult patients with advanced melanoma. Data on checkpoint inhibitors treatment in children with melanoma is limited.</p><p><bold>Design/Methods</bold>: We present two cases of primary metastatic melanoma in uncommon locations in children treated with immune checkpoint inhibitors. Both patients were diagnosed and treated at our centre within the last 2 years.</p><p><bold>Results</bold>: The first patient was a 16‐year‐old girl with metastatic melanoma of unknown primary site (MUP) with multifocal visceral infiltrates. The second patient was an 8‐year‐old boy with primary leptomeningeal melanoma in neurocutaneous melanosis. In both BRAF mutations were absent.</p><p>Due to the significant melanoma dissemination urgent control of the disease was required. Both patients started with chemotherapy CVD (cisplatin, vinblastine, dacarbazine). The girl with MUP reached partial response (PR) after 2 cycles of CVD and continued with ipilimumab monotherapy (3 mg/kg every 3 weeks for 4 doses) with prolonged stable disease (SD). Five weeks after the last ipilimumab administration disease progression (DP) was documented. After further 4 CVD cycles second PR was observed. One month after the last CVD course pembrolizumab monotherapy (2 mg/kg) started. The girl expired from rapidly progressive disease within 37 days of the initial dose of pembrolizumab.</p><p>The boy with CNS melanoma had only SD after 3 courses of CVD. That's why we decided to continue with palliative craniospinal irradiation (36 Gy). Monotherapy with pembrolizumab (2 mg/kg every 3 weeks) was started during radiotherapy. No objective response was observed after radiotherapy and during immunotherapy. He died 23 days after the 3<sup>rd</sup> dose of pembrolizumab from CNS melanoma progression.</p><p><bold>Conclusions</bold>: Immunotherapy with checkpoint inhibitors in our patients was well tolerated, but did not change their disease course.</p></sec><sec id="pbc26772-sec-6750"><label>P-275</label><title>Inflammatory Myofibroblastic Tumor in Children: Morphological and Molecular Characterization</title><p>A. Suleymanova<sup>1</sup>, E. Imyanitov<sup>2</sup>, V. Roschin<sup>3</sup>, <underline underline-style="single">T. Shamanskaya</underline><sup>1</sup>, Y. Olshanskaya<sup>4</sup>, A. Kazakova<sup>4</sup>, S. Talypov<sup>5</sup>, D. Konovalov<sup>3</sup>, D. Kachanov<sup>1</sup>, N. Mitiushkina<sup>2</sup>, S. Varfolomeeva<sup>1</sup></p><p><italic><sup>1</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Clinical Oncology, Moscow, Russia; <sup>2</sup>N.N. Petrov Institute of Oncology, Laboratory of Molecular Oncology, Saint‐Petersburg, Russia; <sup>3</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Pathology, Moscow, Russia; <sup>4</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Cytogenetics, Moscow, Russia; <sup>5</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Surgery, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Inflammatory myofibroblastic tumor (IMT) is a rare type of childhood malignancies with intermediate biological behavior. The aim of the study was to analyze clinical, morphological and molecular features of IMT in a cohort of patients treated in Russian federal center.</p><p><bold>Design/Methods</bold>: Nine patients with IMT during the period from 01.2012 to 12.2016 were included in the analyses. The diagnosis was established by histological examination. ALK immunostaining was done with two different antibodies: ALK (ultra) and ALK (D5F3). Rearrangement of the ALK gene was detected by FISH. ALK, ROS1, PDGFRB fusion genes were analyzed by PCR.</p><p><bold>Results</bold>: Median age at diagnosis was 61.9 months (range 5.9 ‐ 102.5 months). In most cases the tumor was located in the abdominal cavity ‐ 4/9 (44.4%). The histological type of the tumor was represented by a compact/spindle cell variant in 5/9 (55.5%), myxoid/vascular in 2/9 (22.2%) and hypocellular fibrous in 2/9 (22.2%). Expression of ALK protein was observed in 6/9 (66.6%) cases, in 5/6 cases expression was detected by two antibodies. In 1 case, the expression of ALK antibody (D5F3) was positive, while the reaction with ALK antibody (ultra) was negative. In ALK‐positive tumors the following translocations were detected: TPM4ex7/ALKex20 in 2/6 (33.3%) cases, TPM3ex6/ALKex20 in 1/6 (16.6%), CLTCex31/ALKex20 in 1/6 (16.6%). In 1/4 (25%) of ALK‐negative tumors translocation TFGex4/ROS1ex35 was detected. In 4/9 (44.4%) tumors translocations were not detected, of which 2/4 (50%) were cases with positive expression of ALK protein. All patients are alive. The median follow up was 24.3 months (range 15.2‐34.6 months).</p><p><bold>Conclusions</bold>: This work allowed to conduct an in‐depth study of the clinical, morphological and molecular‐genetic characteristics of IMT in a cohort of children in Russia. It was shown that in some cases expression of ALK protein does not correlate with the presence of gene rearrangements.</p></sec><sec id="pbc26772-sec-6760"><label>P-276</label><title>Childhood Lung Adenocarcinoma Treated with Crizotinib</title><p>C. Akyüz<sup>1</sup>, <underline underline-style="single">N. Kalkan</underline><sup>2</sup>, N. Kurucu<sup>1</sup>, M. Haliloğlu<sup>3</sup>, D. Orhan<sup>4</sup>, A. Üner<sup>5</sup></p><p><italic><sup>1</sup>Hacettepe Univercity Oncology İnstitude, Pediatric Oncology, Ankara, Turkey; <sup>2</sup>Hacettepe Univercity Medical Faculty, Pediatric Oncology, Ankara, Turkey; <sup>3</sup>Hacettepe Univercity Medical Faculty, Radiology, Ankara, Turkey; <sup>4</sup>Hacettepe Univercity Medical Faculty, Pediatric Pathology, Ankara, Turkey; <sup>5</sup>Hacettepe Univercity Medical Faculty, Pathology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: Although lung cancer is the most common invasive type of cancer worldwide, it is a rare in children. Goal directed treatment besides chemotherapy has become popular in the last decade. Crizotinib is a tyrosine kinase inhibitor and has been shown to affect survival in NSCLC patients with anaplastic lymphoma kinase (ALK) or c‐ros oncogene 1 (ROS‐1) translocation.</p><p><bold>Design/Methods</bold>: Here an adolescent case of adenocarcinoma with crizotinib treatment was reported.</p><p><bold>Results</bold>: The patient had complaints of night fever, lymph node enlargement and weight loss for six months of duration. Chemotherapy was started after epithelial neoplasm thymoma type B3 was diagnosed from supraclavicular lymph node metastasis and biopsy from lung nodules. The patient was referred to our hospital due to no‐ response to the treatment. Histopathologic evaluation of the lymph node biopsy in our hospital revealed lung adenocarcinoma metastasis. A mass of 4x5 cm in the right lung middle lobe, bilateral parenchymal, subpleural nodular lesions, focal areas of consolidation and signs of lymphangitis carcinomatosis was detected. Two courses of docetaxel and gemcitabine was administered initially and crizotinib of 250 mg/dose bid started since immunohistochemistry for ROS1 was positive. First assessment after the treatment showed excellent clinical and radiologic response. Although primary mass lesion regressed after 7 ½ month of crizotinib treatment, 36 Gy of cranial radiotherapy was administered due to brain metastasis. Subsequently, cisplatin and pemetrexed treatments were started.</p><p><bold>Conclusions</bold>: Lung cancer is a rare tumor of childhood and constitutes 0.2% of all childhood cancers. This illustrative case reminds adenocarcinoma when there is lack of clinical and pathological correlation and emphasizes the assessment for monoclonal antibody therapy by checking the presence of oncogenes as ROS‐1 and ALK. Although treatment is challenging in patients presented with advanced stage disease, currently survival rates were significantly improved with such goal directed therapies.</p></sec><sec id="pbc26772-sec-6770"><label>P-277</label><title>Pediatric Nasopharyngeal Carcinoma: A Single Institute Experience from Developing Country</title><p><underline underline-style="single">P. Khullar</underline><sup>1</sup>, A. Thakwani<sup>1</sup>, K. Chufal<sup>1</sup>, K. Medi<sup>1</sup></p><p><italic><sup>1</sup>Batra Hospital And Medical Research Centre, Radiation Oncology, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Pediatric nasopharyngeal carcinomas (NPCs) accounts < 1% of all pediatric tumors. There is limited data on clinical features, treatment results, prognostic factors, outcome and late toxicities of pediatric NPC from India</p><p><bold>Design/Methods</bold>: This analysis was carried out in consecutive 47 patients of pediatric NPCs, who were registered at our center in between 1<sup>st</sup> May 2006 to 30<sup>th</sup> April 2016 ( 10 years). Patients’ records were retrospective reviewed and data obtained from case records files. Patients were treated with Neoadjuvant chemoradiotherapy (CTRT) with cisplatin and followed by cisplatin and 5‐fluorouracil (5‐FU) or concurrent CTRT with cisplatin.</p><p><bold>Results</bold>: The median age was 15 years (range 10‐18 years) and male:female ratio was 1.5:1. The median duration of symptoms was 6 months (range 0.5‐2 years). AJCC stage distribution was stage II‐ 15%, stage III‐ 40%, and stage IV‐ 45%. Distant metastasis at presentation was seen in 5 patients. Complete response was seen in 65% and overall response was observed in 90% of cases. With a median follow‐up time of 36 months, the 3‐year overall survival (OS) rate, local‐regional control (LRC) rate and distant metastasis‐free survival (DMFS) rate were 42%, 56% and 38% respectively. In multivariate analysis, T4 (<italic>p</italic> = 0.01) and stage IV (<italic>p</italic> = 0.001) were the independent adverse prognostic factors for OS. Significant reduction in trismus and xerostomia were observed in patients treated by intense modulated radiotherapy ( IMRT).</p><p><bold>Conclusions</bold>: Most of patients with pediatric NPC present with advanced stage disease at our center. No difference in response rate and outcomes were seen with the two schedules of CTRT ( Neoadjuvant <italic>vs</italic> concurrent). Local control could be achieved in majority of patients; however, distant metastasis was the most common reason for relapse. Reducing late toxicities with IMRT might be the future direction for the management of pediatric NPC</p></sec><sec id="pbc26772-sec-6780"><label>P-278</label><title>Solid Pseudopapillary Tumor of the Pancreas in a Patient with a Diagnosis of Tuberous Sclerosis Complex</title><p><underline underline-style="single">S.S. Kilic</underline><sup>1</sup>, M. Alkan<sup>1</sup>, O. Ozden<sup>1</sup></p><p><italic><sup>1</sup>Cukurova University Faculty Of Medicine, Pediatric Surgery, Adana, Turkey</italic></p><p><bold>Background/Objectives</bold>: Tuberous Sclerosis Complex (TSC) is a genetic disease that effects to cell development. Epilepsy, mental retardation, development of hamartomas in the different part of body could sign of the TSC. Renal, brain basis tumors and neuroendocrine tumor of the pancreas could develope in TSC patients. Solid Pseudopapillary Tumor of The Pancrease (SPTP) is the low grade malign tumor of the adolescent age.</p><p><bold>Design/Methods</bold>: Cukurova University Medical Faculty Hospital record of a patient who was operated for pancreatic mass investigated.</p><p><bold>Results</bold>: In 2012, Abdominal Magnetic Resonance investigation has made to a 15 years old male TSC patient and a nodulary lesion, measuring 2,5 cm, has found in the tail of pancreas. Nodulary lesion was supposed as hamartoma of pancreas that developed secondary to TSC. Patient was followed up. In 2016, a hypoechoic and sharp edges lesion, measuring 4 cm, was found with Ultrasound (US) investigation in the tail of pancreas. Lesion has solid feature was found by Computed Tomography. Cause of increase in lesion measurements, operation decision was maked. A solid lesion, measuring 5x5x4 cm, in the tail of pancreas has found during operation. Tail of pancreas was detached from side. Splenic artery and vein was tried to detach from lesion, but it was not able. Than, Distal pancreatectomy including lesion was made by using surgical stapler with containing splenic artery and vein. Spleen appeared normal and preserved. Pathology report of lesion was SPTP with tumor free surgical board. One month later an US was made and blood flow of spleen was found normal. There was not residual tumor tissue. Patient is following with no treatment by pediatric oncology.</p><p><bold>Conclusions</bold>: Pathologies of pancreas could develop in TSC patients but SPTP is seen rarely. Lesions in the TSC patients which followed as hamartoma in pancreas should remember that it could be SPTP.</p></sec><sec id="pbc26772-sec-6790"><label>P-279</label><title>Head and Neck Hemangiomas of Childhood: A Single Center Experience</title><p><underline underline-style="single">D. Kizmazoglu</underline><sup>1</sup>, D. Ince<sup>1</sup>, N. Agrali<sup>2</sup>, E. Erkoc<sup>3</sup>, M. Erdem<sup>1</sup>, T. Erdag<sup>3</sup>, K. Mutafoglu<sup>1</sup>, and N.Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University Institute of Oncology, Pediatric Oncology, İZMİR, Turkey; <sup>2</sup>Dokuz Eylul University Faculty of Medicine, Pediatrics, İZMİR, Turkey; <sup>3</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Otorhinolaryngology, İZMİR, Turkey</italic></p><p><bold>Background/Objectives</bold>: Aim of this study is to analize clinical characteristics and treatment responses of our patients with head/neck hemangiomas.</p><p><bold>Design/Methods</bold>: Medical records of 121 patients with head/neck hemangiomas between 2006 to 2016 were evaluated retrospectively.</p><p><bold>Results</bold>: The median age of diagnosis was 12mos (10days‐16yrs), F/M:2.0. The localization of lesions were only at head and neck in 85(70.2%) patients, remaining patients have also hemangiomas on other parts of body.Localization of hemangiomas were as follows; periorbital 35.5% (n=43), cheek 19.8%(n=24), cervical 14% (n=17), scalp 13.2% (n=16), periauricular 9.9% (n=12), mouth and lip 9.9% (n=12) forehead 8.2% (n=10), subglottic 7.4% (n=9), nasal 5%(n=6), parotis 3.3% (n=4). Sixtysix patients (54.5%) have been followed up without medical treatment.Treatment indications were local complications (haemorrhage, ulceration,infection) (6.7%), life threating organ dysfunction (73.0%) and cosmetic (20.3%). The median follow‐up period was 8 mos (0 mos‐7yrs). Remaining 55 patients required medical treatment (propranolol in 45, corticosteroids in two cases, both of them in 8 cases). Chemotherapeutics (vincristine, vinblastine and cyclophosphamide) were used in one case. Majority of our cases received propranolol, and there was no observed propranolol related side effects. The median duration of propranolol treatment was 10 mos (10 days – 35 mos).Twenty‐one patients have still receiving propranolol.Treatment cessation was done in 32 cases.Complete regression was achieved in 13 patients,and partial regression was achieved in 19 cases with propranolol. The patients who had subglottic hemangioma were the most problematic cases because of respiratory and feeding difficulties.Two of them required tracheostomy.Complete regression occured in all subglottic hemangiomas with medical treatment.Ocular complications (ambylopia, strabismus etc) occured in 15 patients with periorbital hemangioma despite medical treatment.</p><p><bold>Conclusions</bold>: Although childhood hemangiomas can regress spontaneously, head/neck hemangiomas are usually required medical treatment because the risk of ocular, feeding and respiratory complications. Novadays propranolol is a well tolerated, effective and safe drug option for treatment of childhood hemangiomas.</p></sec><sec id="pbc26772-sec-6800"><label>P-280</label><title>Primary Peripheral Neuroectodermal Tumor of Orbit‐ Case Series of a Rare Childhood Malignancy</title><p><underline underline-style="single">R. Meel</underline><sup>1</sup>, S. Kashyap<sup>2</sup>, N. Pushker<sup>1</sup>, S. Sen<sup>2</sup>, M. Bajaj<sup>1</sup>, S. Bakhshi<sup>3</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India; <sup>2</sup>All India Institute of Medical Sciences, Dept of Ocular Pathology‐ Dr Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India; <sup>3</sup>All India Institute of Medical Sciences, Dept of Medical Oncology‐ Dr BRA IRCH, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Peripheral primitive neuroectodermal tumor (pPNET) belongs to the Ewing sarcoma family of tumors. Primary PNET constitutes 4% of all childhood soft tissue tumors. Primary PNET of orbit is rare with only a handful of cases reported in literature.</p><p><bold>Design/Methods</bold>: Retrospective review of clinical records, imaging and histopathology of all primary orbital pPNET presenting in childhood that were treated at our center between Jan 2004‐ Dec 2016 (13 years).</p><p><bold>Results</bold>: Clinical, imaging and histopathology details of nine pediatric patients with primary orbital pPNET were analyzed. The median age of presentation was 6 years (age range ‐1.5 months – 13 years). One case presented with congenital PNET of Orbit. 5/9(55.5%) were male and 4/9(44.4%) were female children. Duration of symptoms ranged from 5 days – 8 months (median‐1.75 months). The most common presenting complaint was proptosis followed by eyelid swelling. Imaging showed variable enhancing mass lesions with heterogeneous attenuation in all, with calcific densities in 2 cases. Calcified tumor matrix was seen as radiating spicules in one case. Bone erosion and extra‐orbital extension was seen in 8/9 (88.8%) cases. Metastasis to foot was present in one case at presentation. Diagnosis was made on histopathological examination of incision/ excision biopsy specimen in 7 cases, while 2 cases were diagnosed on fine needle aspiration biopsy. All cases showed positivity for MIC2 and S100 protein on immunohistochemistry, and were negative for PAS.</p><p><bold>Conclusions</bold>: Primary PNET is a rare malignancy to occur in pediatric orbit. Majority of the patients in our series presented with large tumors that had extraorbital extension of disease at the time of presentation.</p></sec><sec id="pbc26772-sec-6810"><label>P-281</label><title>Lipoblastoma and Lipoblastomatosis. 5 Years´ Experience in a Pediatric Institution</title><p><underline underline-style="single">M.E.</underline><underline underline-style="single">Nana</underline><sup>1</sup>, M. Garcia Lombardi<sup>1</sup>, E. De Matteo<sup>2</sup>, M. Medin<sup>2</sup></p><p><italic><sup>1</sup>Hospital de Niños R. Gutierrez, Oncology, Ciudad Autónoma de Buenos Aire, Argentina; <sup>2</sup>Hospital de Niños Ricardo Gutierrez, Pathology, Buenos Aires, Argentina</italic></p><p><bold>Background/Objectives</bold>: Lipoblastoma and lipoblastomatosis are rare benign mesenchymal tumors. They occur in infancy and early childhood, generally in boys. The aim of this study is to report clinical characteristics, diagnostic strategy, type of treatment and outcome of pediatric patients (p) with lipoblastoma/lipoblastomatosis (LL). We will compare our results with other published reports.</p><p><bold>Design/Methods</bold>: Retrospective and descriptive study. We reviewed the clinical reports of p with LL admitted at the Oncology Unit of Hospital de Niños Ricardo Gutierrez between January 2012 and January 2017.</p><p><bold>Results</bold>: Six p with LL were admitted in 5 years. They represent 0.8% of all the p treated in this Unit. Boys 4/Girls2. Age range: 5 ‐ 24 months. Clinical presentation: fast growing and painless mass in all cases. Localization: paravertebral 3p, suprapubic 2p and gluteal 1p. Inicial diagnostic methods: ultrasound 5p, computed tomography 3p and magnetic nuclear resonance 1p. Maximum tumor diameter range: 2 to 9 cm. In 4/6p a fine needle aspiration (FNA) was performed with compatible cytology. Pathological diagnosis: lipoblastoma 5p and diffuse lipoblastomatosis 1p. Treatment: surgery (complete resection all p and 1p without margins). Median follow‐up time: 20 months (R: 4 ‐ 61 months). None p relapsed and all remained alive.</p><p><bold>Conclusions</bold>: LL represented a small percentage of all the diagnosis in our Unit, All p were younger than 3 years and most of them boys. We used ultrasound and FNA for inicial diagnosis approach and biopsy for confirmation. Surgery was the treatment strategy. No p relapsed. However, the follow‐up time was short. Our results were similar to the published reports. Although LL are rare tumors, they should be considered in infants and children with painless fast growing soft‐tissue tumors.</p></sec><sec id="pbc26772-sec-6820"><label>P-282</label><title>Congenital Metastatic Ewing's Sarcoma / Primitive Neuroectodermal Tumor Presenting as “Blueberry Muffin”Cutaneous Lesions: A Case Report</title><p><underline underline-style="single">W.E. Oliveira Júnior</underline><sup>1</sup>, M.C. Angelini<sup>2</sup>, G.T. Comes<sup>2</sup>, D.R. Jozala<sup>2</sup>, B.K. Takegawa<sup>2</sup>, R.G. Marques<sup>2</sup>, A.M. Rodrigues<sup>2</sup>, R.C. Ribeiro<sup>1</sup>, V. Kremer<sup>1</sup>, P.L.T.A. Lourençao<sup>2</sup>, E.V.P. Ortolan<sup>2</sup></p><p><italic><sup>1</sup>Barretos Childrens Cancer Hospital, Pediatric Surgery Department, Barretos, Brazil; <sup>2</sup>Botucatu Medical School, Surgery and Orthopedics Department‐ Pediatric Surgery, Botucatu, Brazil</italic></p><p><bold>Background/Objectives</bold>: Ewing's Sarcoma/Primitive Neuroectodermal Tumors (EWS/PNET) are extremely rare in newborns. Less than 20 newborns (28 days) with congenital EWS/PNET of soft tissue have been reported in the English literature. The prognosis generally is poor, and most of the babies not survive more than 24 months of life.</p><p><bold>Design/Methods</bold>: To describe a 14‐day‐old newborn diagnosed with metastatic retroperitoneal EWS/PNET with “blueberry‐muffin”cutaneous lesions.</p><p><bold>Results</bold>: A 14‐day‐old newborn female was admitted due to multiple and progressive skin nodules, associated with hemothorax and signs of central nervous system involvement. She was a full‐term cesarean neonate without a family history of genetic diseases. A physical examination revealed multiple erythema‐violaceous nodules, with firm constancy characterized as “blueberry muffin” lesions, also were found bilateral ocular proptosis and a posterior thoracic‐abdominal mass, hard, with poorly defined limits. Computed tomography (CT) detected a massive solid retroperitoneal mass, measuring 6.2 cm x 5 cm, hypodense, with calcifications, involving the Aorta at an angle higher than 180 degrees, invading the superior mediastinum and left pleural cavity, widening the posterior intercostal spaces to the left, encompassing the costal arches, extending to the posterior wall invading left paravertebral musculature reaching the skin; also hypodense solid nodules with contrast enhancement distributed in the liver, spleen, adrenal, and pancreas areas, compatible with hematogenous and lymphatic metastases. Since the mass was unresectable, she was submitted to biopsy of skin lesions and initiated empirical chemotherapy protocol for Neuroblastoma. A pathologic examination found histological evidence of malignant, small round tumor cells. The tumor cells were immunohistochemically positive for CD99 and CD56, compatible with Ewing's Sarcoma / Primitive Neuroectodermal Tumor. Given the aggressiveness of the disease, two days after the diagnosis the newborn died.</p><p><bold>Conclusions</bold>: Our report illustrates the extreme difficulties in managing a newborn with a congenital metastatic EWS/PNET. Since these tumors are highly aggressive, prognosis is terrible, and treatment challenging.</p></sec><sec id="pbc26772-sec-6830"><label>P-283</label><title>Germline DICER1 Mutations in Twelve Chinese Patients with Pleuropulmonary Blastoma</title><p><underline underline-style="single">X. Peng</underline><sup>1</sup>, S. Cai<sup>2</sup>, X. Ma<sup>3</sup></p><p><italic><sup>1</sup>Capital Medical University, School of Public Health, Beijing, China; <sup>2</sup>Beijing Children's Hospital‐ Capital Medical University, Center for Clinical Epidemiology and Evidence‐based Medicine, Beijing, China; <sup>3</sup>Beijing Children's Hospital‐ Capital Medical University, Hematology Oncology Center, Beijing, China</italic></p><p><bold>Background/Objectives</bold>: A growing number of studies committed themselves to explore the role of <italic>DICER1</italic> mutation in development of PPB. However, the majority of reported cases were Caucasian. Therefore, 12 consecutive cases of sporadic PPB from Beijing Children's Hospital were tested in order to describe the <italic>DICER1</italic> mutation status and clinical characteristics of Chinese patients with PPB, which will add more evidence for further understanding of pathogenesis of PPB.</p><p><bold>Design/Methods</bold>: Medical history and family history of 12 children with PPB were collected. Blood samples from children with PPB and their first degree relative were tested for <italic>DICER1</italic> mutations by Next‐Gen sequencing. Whole genome sequencing of peripheral blood of the proband, the proband's parents and twin sister, and FFPE of the proband tumor tissue was performed. All participants’ parents signed a consent form to genetic testing and medical history collection.</p><p><bold>Results</bold>: Twelve patients with pleuropulmonary blastoma (6 patients suffering from type II pleuropulmonary blastoma and 6 patients suffering from type III pleuropulmonary blastoma, respectively) were evaluated for germline <italic>DICER1</italic> mutations. Seven patients were identified deleterious <italic>DICER1</italic> mutation, among which 6 mutations lead to premature protein truncation as a result of frameshift mutation or nonsense mutations. Another one case carried a germline<italic>DICER1</italic> mutation which was suspected to deleteriously affect splice site. Case 02 have a total of 135,109 somatic mutations, consisting of a nonsense mutation located within TDG and missense mutations of <italic>DICER1</italic>. Two <italic>DICER1</italic> mutation positive cases were found to have lung cysts preceding the diagnosis of PPB. Furthermore, only one child was found a remarkable family history of thyroid diseases.</p><p><bold>Conclusions</bold>: Germline mutation frequency of Chinese patients with PPB is similar with published studies. Routine germline<italic>DICER1</italic> test might be benefit to improve the accuracy and awareness of differential diagnosis type I PPB from other diseases, especially lung cysts.</p></sec><sec id="pbc26772-sec-6840"><label>P-284</label><title>Granulosa Cell Tumors: A Study of Nine Rare Cases Over a Period of Fifteen Years in a Single Institute</title><p><underline underline-style="single">Y. Saad‐eldin Sadek</underline><sup>1</sup></p><p><italic><sup>1</sup>Faculty of Medicine‐University of Alexandria, Pediatric Surgery, Alexandria, Egypt</italic></p><p><bold>Background/Objectives</bold>: Ovarian tumors in children are rare, comprising 1% of all childhood tumors.Juvenile granulosa cell tumors are rare subtypes the sex cord‐stromal cell tumors.</p><p>The study aimed at reporting and studying cases of juvenile granulosa cell tumors over a period of 15 years</p><p><bold>Design/Methods</bold>: All cases of juvenile granulosa cell tumors treated over a period of 15 years in the Main University Hospital were reported.They were studied concerning: the age, the ways of clinical presentation and the tumor markers: Alpha Phetoprotein (AFP) and Human Chorionic Gonadotrophic Hormone (HCG),The imaging done for diagnosis, the treatment procedures and follow up were also reported.</p><p><bold>Results</bold>: Nine cases of granulosa cell tumors were reported: 5 cases were retrospective and 4 cases were prospective. Eight cases with an age range 4‐6 years and only one case was 7 months old.</p><p>All cases presented with pseudo‐ precocious puberty in the form of: breast hypertrophy with extensive suprapubic hair in 6 cases,suprapubic hair with enlarged clitoris in one case, suprapubic hair with huge intra‐abdominal swelling in one case and vaginal bleeding in one case.</p><p>Tumor markers: AFP and HCG were negative in all cases.ultra‐sonography revealed unilateral solid ovarian tumors in 7 cases,huge ovarian swelling with mixed solid and cystic elements in one case and a small ovarian cyst in one case.</p><p>Cases were treated as follows: unilateral oophorectomy in 8 cases and partial oophorectomy in one case.The histopathological study revealed benign granulosa cell tumors in all cases.Follow‐up revealed regression of signs of pseudo‐precocious puberty over a period ranged from 10 to 120 days.</p><p><bold>Conclusions</bold>:</p><p>*Juvenile granulosa cell tumors should be considered in prepubertal girls with pseudo‐precocious puberty and negative tumor markers (AFP & HCG), and differentiated from functioning germ cell tumors including ovarian carcinoma.</p><p>*Unilateral oophorectomy is the curative treatment because they are mostly benign.</p></sec><sec id="pbc26772-sec-6850"><label>P-285</label><title>Uveal Melanoma in Young Patients</title><p><underline underline-style="single">S. Saakyan</underline><sup>1</sup></p><p><italic><sup>1</sup>Moscow Helmholtz Research Institute of Eye Disease, Ocular Oncology and Radiology, Moscow, Russia</italic></p><p><bold>Background/Objectives: Purpose</bold> To analyze the clinical profile and survivability of young patients with uveal melanoma.</p><p><bold>Design/Methods</bold>: Retrospective case‐control series. Out of 1224 patients with uveal melanoma treated in 2005‐2015 there were 21 patients (1,7%) aged 20 and younger (15 male, 6 female). The mean age of those patients was 15,7±0,5 years. In all cases the tumor was unilateral. All patients were examined with standard ophthalmological procedures, and also ultrasound Color Doppler Imaging, OCT and Fluorescein angiography. The tumors were treated by ruthenium plaque brachyterapy (11 cases), transpupillary thermotherapy (2cases), proton beam therapy (2 cases) and enucleation (6 cases).</p><p><bold>Results</bold>: All patients were divided into 2 groups: with organ preservation treatment (71%) and without (29%). In the first group the mean tumor height was 4.8±0.4 mm. In the second group 9.9±0.4 mm, enucleation was performed in all cases. Case monitoring in the 1 group demonstrated the 100% 2‐year survivability and 90.9% 5‐year survivability vs 100% 1‐year survivability and 83.3% 2‐year survivability in the 2 group.</p><p><bold>Conclusions</bold>: There was no increasing the incidence of uveal melanoma at young patients during the last years and the most common there were the medium and large tumor's sizes and they demonstrated good results of the local treatment.</p></sec><sec id="pbc26772-sec-6860"><label>P-286</label><title>Overexpression of MIR‐483‐3P and MIR‐149‐3P IS Associated with Clinical Characteristics of Pediatric Adrenocortical Tumors</title><p>C.A.P. Corrêa<sup>1</sup>, R.C.P. Lira<sup>1</sup>, A.F. Andrade<sup>1</sup>, J.A. Yunes<sup>2</sup>, S.R. Brandalise<sup>2</sup>, M.J. Mastellaro<sup>2</sup>, L.F. Leal<sup>1</sup>, S.R.R. Antonini<sup>1</sup>, L.G. Tone<sup>1</sup>, <underline underline-style="single">C.A. Scrideli</underline><sup>1</sup></p><p><italic><sup>1</sup>Ribeirão Preto School of Medicine ‐ University of São Paulo, Pediatrics, Ribeirão Preto, Brazil; <sup>2</sup>Boldrini Children Center, Pediatrics, Campinas, Brazil</italic></p><p><bold>Background/Objectives</bold>: Although childhood adrenocortical tumors (ACT) are rare neoplasms, its incidence in Brazil is particularly higher. Currently, there are no reliable biomarkers, which predict diagnosis or prognosis of ACT in children. Aiming to find potential biomarkers of ACT prognosis, we validated the expression of two miRNAs that were found differentially expressed in a microarray‐based miRNA profiling conducted with 37 pediatric ACT samples</p><p><bold>Design/Methods</bold>: The validation of miR‐149‐3p and miR‐483‐3p expressions was evaluated by RT‐qPCR in 47 ACT pediatric tumors and 8 non‐neoplastic adrenal pediatric samples. The comparison between miRNA profiles and clinical/biological features were performed by Mann‐Whitney test and Kaplan‐Meier curves with log‐rank test for Event‐free survival (EFS) analysis and relative risk (RR) and multivariate analysis by Cox Regression Model</p><p><bold>Results</bold>: The miR‐483‐3p was overexpressed in tumor samples (P<0.0001), which also showed significant association with virilizing tumors (P=0.002) and <italic>TP53</italic> mutation p.R337H (P=0.042). The miR‐149‐3p expression was significantly higher in patients classified as Sandrini's stage IV (P=0.008), relapse/metastasis (P=0.006) and unfavorable event (P=0.021). Patients with expression levels higher than median of miR‐149 showed a lower 5‐years EFS (66.5.7%±9.9% <italic>versus</italic> 91.3%±0.59%; P=0.028; RR: 4.7, 95% IC: 1.028‐21.489). Multivariate analysis showed that this overexpression was an independent prognostic factor (P = 0.042) when analyzed in association with tumor size and advanced stage. Moreover, miR‐483 presented negative correlations with inhibitors of Wnt pathway: <italic>DKK3</italic> (Rho=‐0.48; P=0.003) and <italic>SFRP1</italic> (Rho=‐0.033; P=0.05). Contrary to this, miR‐149 showed positive correlation with <italic>MYCC</italic> (Rho=0.47; P=0.005), an important target‐gene of Wnt pathway</p><p><bold>Conclusions</bold>: We observed overexpression of miR‐483‐3p in ACT when compared to non‐neoplastic samples. The higher expression of miR‐149‐3p in tumors seems to be related with poor prognosis of pediatric ACTs. Interestingly, both miRNAs showed significant and opposite correlations with genes of Wnt signaling, ptahway suggesting a possible relationship of these miRNAs with an essential pathway for adrenal development</p></sec><sec id="pbc26772-sec-6870"><label>P-287</label><title>Aberrant PDGFR Signaling as a Target for Treatment of the Infantile Myofibromatosis with Sunitinib</title><p><underline underline-style="single">R. Veselska</underline><sup>1,2,3</sup>, M. Sramek<sup>2,3,4</sup>, J. Neradil<sup>2,3,4</sup>, P. Macigova<sup>3,4</sup>, P. Mudry<sup>1,4</sup>, K. Melicharkova<sup>1,2</sup>, O. Slaby<sup>1,5</sup>, J. Vanackova<sup>5</sup>, J. Sterba<sup>1,2,4</sup></p><p><italic><sup>1</sup>University Hospital Brno, Department of Pediatric Oncology, Brno, Czech Republic; <sup>2</sup>St. Anne's University Hospital, International Clinical Research Center, Brno, Czech Republic; <sup>3</sup>Masaryk University‐ School of Sciences, Department of Experimental Biology, Brno, Czech Republic; <sup>4</sup>Masaryk University‐ School of Medicine, Department of Pediatric Oncology, Brno, Czech Republic; <sup>5</sup>Masaryk University, CEITEC MU ‐ Center of Molecular Medicine, Brno, Czech Republic</italic></p><p><bold>Background/Objectives</bold>: Infantile myofibromatosis (IM) belongs to the family of soft tissue tumors. Majority of them shows a benign behavior but resistant and malignant forms are also known. Although molecular mechanisms of the IM pathogenesis are not completely explained, some studies suggest the association of mutations in platelet‐derived growth factor receptor beta (PDGFRb) gene and other related genes with this disease.</p><p><bold>Design/Methods</bold>: We analyzed in detail a primary IM cell line as well as fresh frozen tumor tissues from two siblings suffering with IM. Human phospho‐protein arrays were employed for detection of the phosphorylation status of 49 receptor tyrosine kinases (RTKs) and of 24 mitogen‐activated protein kinases (MAPKs) and other important downstream signaling proteins. Expression and phosphorylation of selected candidate proteins involved in PDGFR signaling was determined using immunoblotting. The whole‐exome sequencing was used to uncover germinal and tumor‐specific mutations in the signaling‐related genes.</p><p><bold>Results</bold>: Tumor samples from both siblings showed a relatively highest phosphorylation level of PDGFRb and ERK1/2 implicated over‐activation of the PDGFRbeta/MAPK signaling axis. Subsequent sequencing revealed germ‐line heterozygous c.1681C>A missense mutation of <italic>PDGFRB</italic> gene. Furthermore, the same germinal mutation in <italic>PTPRJ</italic> gene, which product specifically binds and dephosphorylates ERK1/2 kinases, were detected in both of siblings. Subsequent <italic>in vitro</italic> experiments using primary tumor‐derived cell line were focused on testing of different low‐molecular‐weight inhibitors to examine the cell viability and the responsiveness of the PDGFRb/MAPK signaling axis. The results showed that sunitinib, i.e. multi‐targeted RTK inhibitor, was able to inhibit PDGFRb but its effect on downstream MAPKs was a marginal only.</p><p><bold>Conclusions</bold>: According to the <italic>in vitro</italic> experiments, sunitinib represents a suitable treatment of IM. Up‐to‐date, these results were verified by positive therapeutic response to the administration of sunitinib in both siblings.</p><p><bold>Acknowledgement</bold>: Study was supported by grants 16‐34083A and 16‐33209A from AZV MZCR.</p></sec><sec id="pbc26772-sec-6880"><label>P-288</label><title>Efficacy of Combined Transperineal (TP) and Transabdominal (TA) Ultrasonography in Diagnosis and Follow‐Up of Vaginal Malignancies</title><p><underline underline-style="single">X. Yang</underline><sup>1</sup>, J. Ye<sup>1</sup>, J. Yu<sup>1</sup>, Q. Shu<sup>2</sup>, J. Wang<sup>2</sup></p><p><italic><sup>1</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Ultrasound, Hangzhou, China; <sup>2</sup>Children's Hospital ‐ Zhejiang University School of Medicine, Department of Surgical Oncology, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: This study investigated the sonographic features of vaginal malignancies in girls and the efficacy of transperineal(TP) in conjunction with transabdominal (TA) ultrasonography in the diagnosis and follow‐up of vaginal malignancies in girls.</p><p><bold>Design/Methods</bold>: Imaging data of 16 cases of vaginal malignancies in our center from January 2000 to December 2016 were retrospectively analyzed. Characteristics of ultrasonography, CT and MR were summarized. All cases confirmed by pathology. Patients aged form 3m7d to 6y. In this group, 10 cases were vaginal endodermal sinus tumors, 4 cases were embryonal rhabdomyosarcomas, one was nephroblastoma and one was metastatic neuroblastoma. All patients underwent transperineal(TP) in conjunction with transabdominal(TA) ultrasonography, some underwent CT and MR.</p><p><bold>Results</bold>: The results of transperineal and transabdominal ultrasonography. In the 16 cases, the pelvic hypoechoic masses could be shown by transabdominal ultrasonography. 4 cases combined intrauterine hematocele. However, it could be clearly display the size, border, blood flow of the vaginal hypoechoic occupancy, and the relationship of the occupancy and vagina by transperineal ultrasonography. There were no obvious necrotic liquefaction and calcification in the mass. During the follow‐up process of 14 cases after chemotherapy, the vaginal tumor could not be clearly shown by transabdominal ultrasonography after the tumor shrinkage, while it still be clearly shown by transperineal ultrasonography. <bold>Ten</bold> cases underwent CT examination. Lesions appeared as similar‐circular soft tissue masses with heterogeneous density, variable necrosis and cystic degeneration on unenhanced CT. Twelve cases underwent MR examination. Masses were uniformly isointense on T1‐weighted images, heterogeneously hyperintense on T2‐weighted images. Heterogeneous enhancement especially peripherally was noted on both CT and MRI contrast‐enhanced images.</p><p><bold>Conclusions</bold>: Vaginal malignancies often have characteristic echo pattens. Transperineal in conjunction with transabdominal ultrasonography are helpful in diagnosing and following up of vaginal malignancies.Therefore,ultrasound may be preferred as the initial investigation for cases of vaginal malignancy as it is a non‐invasive,radiation‐free,inexpensive technique.</p></sec></sec><sec id="pbc26772-sec-6890"><title>Solid Non Brain Tumours ‐ Histiocytosis</title><sec id="pbc26772-sec-6900"><label>P-289</label><title>Reduced Doses of Cladribine Plus Cytarabine for Refractory or Reactivated Langerhans Cell Histiocytosis (LCH)</title><p><underline underline-style="single">M.F. Gutierrez</underline><sup>1</sup>, M. Urbieta<sup>1</sup>, M. Garcia Lombardi<sup>1</sup>, R. Ramirez<sup>1</sup>, S. Acosta<sup>1</sup>, A. Oller<sup>1</sup></p><p><italic><sup>1</sup>Hospital de Niños Ricardo Gutierrez, Pediatric Oncology, Capital federal, Argentina</italic></p><p><bold>Background/Objectives</bold>: Treatment with Cladibrine (2CDA) as single drug or with Cytarabine at higt doses (9 mg/m2/d and 1000 mg/m2/d for 5 days) has been effective in children with refractory or reactivated LCH after 2 or 3 previous treatment regimens</p><p>OBJECTIVES: To describe our experience in reduced doses 2CDA plus Cytarabine scheme in refractory or reactivated patients(p) with LCH, follow up and acute toxicity.</p><p><bold>Design/Methods</bold>: Retrospective analysis of patients records treated between January 2008 and February 2017 with refractory o reactivated LCH after standard therapy. Patients received 2cda (5 mg / M2 daily for 5 days) +/‐ cytarabine (100 mg / m2 / day for 4 days). Courses were repeated every 3‐4 weeks.</p><p><bold>Results</bold>: Fifty one patients with LCH were admitted during the indicated period, 7p were treated with 2‐CDA plus Ara‐C, 1p with 2‐CDA alone. The median age at diagnosis was 24.57 months (range 3 to 180 months). All patients had multisystemic LCH at diagnosis. Four patients had risk organ involvement and 2 had SNC tumorous lesions. Median of previus chemotherapy schemes:2 (1‐3). Seven of 8 patients were evaluables. One patient was excluded because of severe liver toxicity the first day of infusion (grade 3).</p><p>A total 42 were performed. All patients received 6 courses. There were 7 admissions due to febrile neutropenia and 17 episodes of grade 3‐4 haematological toxicity. Seven of seven patients present no active disease (NAD) after median follow up of 4,16 month (range 1.9 to 86.1 month).</p><p><bold>Conclusions</bold>: In our experience the treatment with reduced doses of cladribine +/‐ cytarabin for refractory or reactivated LCH patients was usefull to obtain and sustain NAD, with very tolerable toxicity.</p></sec><sec id="pbc26772-sec-6910"><label>P-290</label><title>Multifocal Histiocytic Sarcoma in A 2 Year Old Child, Successfully Treated with Acute Myeloid Leukaemia Based Chemotherapy</title><p><underline underline-style="single">M. Madni</underline><sup>1</sup>, M. Velangi<sup>1</sup>, I. Colmenero<sup>2</sup>, R. Zbigniew<sup>3</sup></p><p><italic><sup>1</sup>Birmingham Children's Hospital, Hematology and Oncology, Birmingham, United Kingdom; <sup>2</sup>Birmingham Children's Hospital, Histopathology, Birmingham, United Kingdom; <sup>3</sup>Birmingham Heartlands Hospital, histopathology, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Histiocytic and dendritic cell neoplasms are rare malignant disorders originating from tissue macrophages/ histiocytes. The incidence is estimated as 0.05 per 100,000 per year in Europe. In the past, most of these disorders were misdiagnosed as lymphomas, especially diffuse large B cell lymphoma or anaplastic large cell lymphoma. However, after the WHO 2008 classification the diagnosis has been simplified. Historically, histiocytic sarcoma (HS) is associated with an unfavourable prognosis with no consensus on treatment strategy and most of the literature is available in the form of case reports with variable treatment protocols used with variable success. In most of the cases these tumours respond poorly to the treatment commonly used in Langerhan cell histiocytosis.</p><p><bold>Design/Methods</bold>: Case Report</p><p><bold>Results</bold>: We describe a 2 years old patient with multifocal HS. She presented with multiple soft tissue and bony lesions involving the maxilla and mandible with disease also present in abdomen, tibia and femur. Initial impression on histopathology favoured a myeloid malignancy and she was commenced on treatment according to AML 15 protocol. On‐going Immunohistochemical investigation concluded the diagnosis of HS on the basis of positivity of CD68, CD163, and Lysozyme. After a good response to initial AML therapy and, in the knowledge that there is no optimum treatment strategy for HS we continued the same chemotherapy regimen. She is currently 23 months off treatment and maintaining clinical and radiological remission.</p><p><bold>Conclusions</bold>: We conclude that HS can be successfully treated with chemotherapy alone commonly used for Acute Myeloid Leukaemia without significant toxicity.</p></sec><sec id="pbc26772-sec-6920"><label>P-291</label><title>Spectrum of Presentation, Management and Late–Effects of Langerhans Cell Histocytosis Over A 10‐Year Period, in a UK Tertiary Paediatric Oncology Centre</title><p><underline underline-style="single">A. Mitchell</underline><sup>1</sup>, U. Uparkar<sup>1</sup>, R. Ramanujachar<sup>1</sup>, G. Nicolin<sup>1</sup>, A. Cooke<sup>1</sup>, J. Gray<sup>2</sup></p><p><italic><sup>1</sup>Department of Paediatric Oncology, Southampton Children's Hospital, Southampton, United Kingdom; <sup>2</sup>University of Southampton, Child Health, Southampton, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Langerhans Cell Histiocytosis (LCH) describes a clinical spectrum of disease caused by clonal proliferation of pathological Langerhan's cells infiltrating tissues. We aimed to characterise the disease presentations in the South of England to the Southampton Principal treatment centre (PTC) over the past 10 years due to clinical concern regarding increased incidence and complexity of clinical LCH presenting over recent years.</p><p><bold>Design/Methods</bold>: Retrospective data was collected on demographics, disease sites, treatment modalities at diagnosis/relapses, remission free periods and outcome at latest evaluation at follow‐up.</p><p><bold>Results</bold>: 1041 children were treated for cancer at Southampton PTC over the past 10 years (1/1/2006‐31/12/2016). 46 cases of LCH were identified, median age of 2 yrs 6 months accounting for 4.3% of our patients. Male:female ratio 1.2:1. 62% (28) presented with single‐system disease and 38% (16) multi‐system disease. 4 children were identified as having diabetes insipidus 8.7%. 78% of cases were biopsied. 2 cases of neuro‐degenerative LCH were identified.</p><p>Majority (88%, 23/26) of children with single system disease had uncomplicated course, no further disease recurrence at last follow up. Uni‐focal bone disease was treated by curettage except one who was already resolving at time of review and therefore observed. multi‐system (34%, 16 cases) patients had a more complicated course with 64% suffering a relapse (10/16) and 2/16 patients had at least 4 relapses needing salvage therapy. 15% of our overall cases had risk organ + disease.</p><p><bold>Conclusions</bold>: We present our centres experience with LCH over the past 10 years. We witnessed a spike in incidence of LCH in 2016 however further data is required to delineate a clear trend of increasing incidence. Novel strategies to evaluate and monitor BRAF in blood and urine such as those being employed in the latest international LCH IV trial offer the opportunity to better understand the risk factors for disease severity.</p></sec><sec id="pbc26772-sec-6930"><label>P-292</label><title>Mortality Risk Factors of Children with Hemophagocytic Lymphohistiocytosis: A Prospective Study at Children's Hospital 1, HO CHI MINH, Vietnam</title><p><underline underline-style="single">T. Nguyen</underline><sup>1</sup>, A. Phan<sup>1</sup>, D. Tran<sup>1</sup>, C. Cao<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital 1, Hematology‐Oncology, Ho Chi Minh, Vietnam</italic></p><p><bold>Background/Objectives</bold>: Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory condition. Whether primary or secondary, prompt initiation of HLH therapy is mandatory to prevent irreversible tissue damage. We identify risk factors of mortality of Vietnamese children with HLH who were treated by the HLH‐2004 protocol.</p><p><bold>Design/Methods</bold>: We conducted a prospective study between Jan 2009 to Dec 2011. The diagnosis of HLH at the Children's Hospital 1 in Ho Chi Minh city, Vietnam was compatible with the diagnostic criteria of the HLH‐2004 proposed by the HLH Study Group of the Histiocyte Society, and patients who fulfilled at least five of the following signs or laboratory findings were enrolled: fever (higher than 38°C for more than 7 days), splenomegaly or hepatomegaly, cytopenia (affecting ≥2 of three lineages in the peripheral blood: hemoglobin (<90 g/l), leucopenia (<5x10<sup>9</sup>/l), neutropenia (<1x10<sup>9</sup>/l), thrombocytopenia (<100x10<sup>9</sup>/l), hypertriglyceridemia (≥3 mmol/l) or hypofibrinogenemia (≤1 g/l), hyperferritinemia (≥500 mg/l) and hemophagocytosis in bone marrow or lymph nodes.</p><p><bold>Results</bold>: A total of 144 patients, median age 2.5 years (range 0.1‐15 years) with a male:female ratio of 1.6:1 were enrolled into the study. All patients were treated with the HLH‐2004 protocol and had a median time from diagnosis to treatment of 2 days (range 0‐6days). The overall 5‐years survival rate was 70.1±5.3% with a median follow‐up of 5.4 years. Of all patients, 64 (44.4%) achieved complete resolution, 16 (11.1%) had active disease, 21 (14.6%) developed reactivation and 43 (29.9%) died. Factors independently associated with mortality included persistent elevated ferritin levels (OR=5.5, 95% CI=4.3‐6.2), central nervous system involvement (OR=4.5, 95% CI=2.7‐6.3), severe liver failure (OR=2.4, 95% CI=2.1‐2.9), gastrointestinal bleeding (OR=4.1, 95% CI=3.7‐4.6), persistent fever > 1 week of induction therapy (OR=2.8, 95% CI=2.2‐3.4).</p><p><bold>Conclusions</bold>: Early diagnosis and prompt management of HLH in children with a close follow‐up of mortality risks factors can improve patient survival.</p></sec><sec id="pbc26772-sec-6940"><label>P-293</label><title>Langerhans Cell Histiocytosis: A Single Center Experience of 92 Cases</title><p><underline underline-style="single">A. Raj</underline><sup>1</sup>, A. Batra<sup>1</sup>, S. Bakhshi<sup>1</sup>, B. Biswas<sup>1</sup></p><p><italic><sup>1</sup>MRO Ward‐ Institute Rotary Cancer Hospital‐ AIIMS, Medical Onology Department, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Langerhans cell histiocytosis (LCH) is a rare disease. Limited data has been published from India regarding long‐term outcomes.</p><p><bold>Design/Methods</bold>: We performed a retrospective analysis of patients with LCH treated at Institute Rotary Cancer Hospital, New Delhi from August 2002‐January 2017.</p><p><bold>Results</bold>: Ninety‐two patients were registered during August 2002‐January 2017. Median age was 3 years, with male: female ratio of 7:3. Median time from symptoms to diagnosis was 6 months. Bony swellings (61.5%), fever (37.3%) and skin rash (27.8%) were most common presenting complaints. Bony lytic lesions, anemia, lung involvement, jaundice, bone marrow involvement were seen in 84%, 52%, 11.2%, 8.9% and 6.7% of patients, respectively. Patients were divided into three risk categories [A – multifocal/unifocal bone only (28.7%) B – Soft tissue involvement with no organ dysfunction (42.5%), C – Organ Dysfunction (28.8%)]. The patients were treated with DALHX‐83 protocol (prednisolone, vinblastine, etoposide, 6‐Mercaptopurine). Response assessment was done at 12 week, end of treatment and suspected disease progression. Eighty‐nine of 92 patients received first‐line treatment. Complete response (CR) was observed in 15.3%, partial response or stable disease (PR/SD) 72.1%, whereas 12.6% had disease progression at 12 weeks of therapy. Thirty‐three patients progressed among whom 29 took second‐line treatment. Prednisolone, vinblastine and etoposide or cladribine were used in second‐line treatment. The CR to 2<sup>nd</sup> line therapy was 23%. Progression free survival (PFS) at 60 months was 59.1% [95% CI: 0.46‐0.70] and overall survival (OS) at 10 years was 92.8% [95% CI: 0.8 –0.97]. On multivariate analysis, total bilirubin >3 g/dl (<italic>p</italic>=0.03), 12 week response (<italic>p</italic><0.001) and DALHX‐83 risk category (<italic>p</italic>=0.03) were significant predictors of PFS.</p><p><bold>Conclusions</bold>: This is the largest Indian series of LCH with outcome results comparable to western population with a 5‐year PFS of 59.1% and 10 year OS of 92.8%.</p></sec><sec id="pbc26772-sec-6950"><label>P-294</label><title>BRAF V600E Mutation in Pediatric Cranial Juvenile Xanthogranuloma</title><p><underline underline-style="single">P. Techavichit</underline><sup>1</sup>, D. Sosothikul<sup>1</sup>, K. Chiengthong<sup>1</sup>, C. Teerapakpinyo<sup>2</sup>, P. Thorner<sup>3</sup>, S. Shuangshot<sup>2</sup></p><p><italic><sup>1</sup>Chulalongkorn University, Pediatrics, Bangkok, Thailand; <sup>2</sup>Chulalongkorn University, Pathology, Bangkok, Thailand; <sup>3</sup>Hospital for Sick Children and University of Toronto, Laboratory Medicine, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Juvenile xanthogranuloma (JXG) is a rare primarily pediatric non‐Langerhans cell histiocytosis (non‐LCH). <italic>BRAF</italic> V600E mutation is observed in approximately 60% of LCH. In addition, the mutation has recently been identified in 54 % of Erdheim‐Chester disease (ECD) but none in other non‐LCH lesions.</p><p><bold>Design/Methods</bold>: Retrospectively reviewed.</p><p><bold>Results</bold>: Patient # 1 presented with headache and recurrent vomiting. MRI of the brain revealed multiple intracranial extra‐axial masses. A biopsy of the right temporal lesion was originally reported as JXG. The lesion was found to have a BRAF mutation by BRAF immunohistochemistry, with subsequent confirmation by molecular methods.</p><p>Patient #2 developed intractable seizures at the time of diagnosis. A cerebellar lesion was identified and a biopsy of this was originally diagnosed as Rosai‐Dorfman disease (RDD) on the basis of the immunohistochemical profile, although the lesion did not show all the typical features of RDD.</p><p>Patient #3 was brought to medical attention due to bilateral proptosis and multiple cranial lesions. A biopsy of the right parietal bone lesion was reported as JXG.</p><p>Bone marrow study, bone scintigraphy and imaging of the chest and abdomen were performed in all patients and there was no evidence of extracranial disease involvement in any of the patients.</p><p>Patients #2 and #3 received intuitional chemotherapy regimen for LCH that consisted of vinblastine, prednisolone, cytarabine, 6‐mercaptopurine and methotrexate for a total of 46 weeks. All three patients underwent radiotherapy to the primary affected site with varying doses of radiation. At the median follow up time of 20 months, all patients are alive with partial to complete disease response.</p><p><bold>Conclusions</bold>: In our report, we detected BRAF V600E mutation in all 3 JXG patients with indolent presentation. Targeted <italic>BRAF</italic> inhibitor may have a potential role in refractory JXG cases with this mutation. Further study of <italic>BRAF</italic> status in a lager series of JXG is warranted.</p></sec></sec><sec id="pbc26772-sec-6960"><title>Brain Tumours</title><sec id="pbc26772-sec-6970"><label>P-295</label><title>Medulloblastoma, Treatment Outcome and Prognostic Factors at National Cancer Institute, Egypt “2008 – 2013”</title><p><underline underline-style="single">A. Mustafa</underline><sup>1,2</sup>, N. Ali<sup>1,2</sup>, R. Emad<sup>1</sup>, E. Ebeid<sup>1</sup></p><p><italic><sup>1</sup>National Cancer Institute, Pediatric Oncology, Cairo, Egypt; <sup>2</sup>Nci ‐Children Cancer Hospital Egypt, Pediatric Oncology, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma (MB) is the most common malignant brain tumor of childhood. It occurs at all ages, peaking in incidence between 4 and 7 years. Our aim was to assess the outcome and prognostic factors among MB pediatric patients at the National Cancer Institute, Cairo University.</p><p><bold>Design/Methods</bold>: This is a retrospective study included 53 eligible patients with established diagnosis of medulloblastoma during the period from January 2008 to December 2013.</p><p><bold>Results</bold>: Among the 53 patients, 31 were males (58.5%). Median age at diagnosis was 6 years (range 0.6‐18 years). Vomiting was the most frequent presenting symptom followed by headache detected in 90.6% and 86.8% of patients, respectively. The majority of our patients were high risk 45 patients (84.9%) (15% of them infantile ≤3 years), while 8 patients (15.1%) were standard risk. Median follow up period was 38.6 months (range 13.3 to 81.9). The 5‐year overall survival (OS) and progression‐free survival (PFS) rates were 54.6% and 74.8%, respectively. The presence of postoperative residual, spinal seedling, M staging, and completing chemotherapy protocol had a significant difference regarding survival rate <italic>(p=0.045, p<0.001, p=0.021 & p<0.001, respectively)</italic>. There was no significant difference between patients presented at age ≤ 3 years versus >3 years old regarding survival rate (5‐year OS 50.0% versus 55.2%, respectively), also histopathological sub‐types had no impact on survival (p=0.099). At the end of this study 29 patients (54.7%) were alive, 22 patients (41.5%) were dead and 2 patients (3.8%) lost follow up. Two out of 53 patients relapsed after treatment.</p><p><bold>Conclusions</bold>: The outcome of patients in this study is favorable and comparable to international trials. Patients with advanced stages and incomplete surgical resection had a poorer outcome. Most of mortalities were caused by infection and sepsis, raising the importance of strict infection control and strong supportive care measures.</p></sec><sec id="pbc26772-sec-6980"><label>P-296</label><title>Evaluation of Prognostic Factors for Patients with Atypical Teratoid Rhabdoid Tumour (ATRT): A Meta‐Analysis</title><p><underline underline-style="single">S. Al‐Karmi</underline><sup>1</sup>, A. Fonseca<sup>1</sup>, A. Huang<sup>1</sup>, E. Bouffet<sup>1</sup></p><p><italic><sup>1</sup>The Hospital for Sick Children, Neuro‐oncology, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Atypical Teratoid Rhabdoid Tumour (ATRT) are rare, highly lethal embryonal brain tumours that occur in children predominantly younger than three years old. Recent studies have led to advancements in treatment stratification based on (epi)‐genomic and transcriptional profiling, however, prognosis despite aggressive chemotherapy remains poor for most patients.</p><p><bold>Design/Methods</bold>: We performed a systematic meta‐analysis of the literature comparing treatment strategies of ATRT patients diagnosed from 1990‐2016. Treatment information including chemotherapy, radiation and surgery, and clinical information such as age and tumour location was curated for 409 patients. We sub classified chemotherapy regimens by chemical class, and also evaluated the effect of specific delivery methods such as intrathecal (IT) and high‐dose chemotherapy (HDCT). Multivariate COX regression and survival analyses were performed to assess the efficacy of different treatment strategies.</p><p><bold>Results</bold>: Of the patients analyzed, 66% received either focal or whole brain and spine radiation. IT and HDCT was administered to only 35% and 34% of patients respectively. Most reports collected were reported post 2004 (88%). Patients were treated heterogeneously with different protocols that resulted in different clinical outcomes. Multivariate COX regression analyses reveal statistically significant differences in various treatment strategies and chemotherapeutic agents according to certain patient characteristics such as age and tumour location.</p><p><bold>Conclusions</bold>: Our results strongly indicate that patient's clinical demographics significantly influence treatment success, and that some chemical classes of drugs may not benefit all types of ATRT. A personalized approach taking into account patient age, tumour location, and molecular subtype will be required in order to tailor treatment strategies appropriately.</p></sec><sec id="pbc26772-sec-6990"><label>P-297</label><title>Treatment Efforts and Survival Benefits in Pediatric Patients with Atypical Teratoid Rhabdoid Tumors (ATRT) at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia</title><p><underline underline-style="single">A. Alkofide</underline><sup>1</sup>, E. Elshail<sup>2</sup>, M. Hassonah<sup>3</sup>, I. AlFawaz<sup>1</sup>, A. Ali<sup>1</sup>, M. Ayas<sup>1</sup>, A. Haq<sup>4</sup>, A. Mousa<sup>5</sup>, Y. Khafagh<sup>6</sup>, A. Dababo<sup>7</sup>, H.A. Hind AlHindi<sup>8</sup>, M. Foudaneel<sup>9</sup>, K. Siddiqui<sup>1</sup></p><p><italic><sup>1</sup>King Faisal Specalist Hospital & Research Center, Pediatric Hematology Oncology, Riyadh, Saudi Arabia; <sup>2</sup>King Faisal Specialist Hopsital & Research Center, Neurosciences, Riyadh, Saudi Arabia; <sup>3</sup>King Faisal Specalist Hospital & Research Center, Neurosciences, Riyadh, Saudi Arabia; <sup>4</sup>King Faisal Specalist Hospital & Research Center, Neuroscience, Riyadh, Saudi Arabia; <sup>5</sup>King Faisal Specalist Hospital & Research Center, Raidation Oncology, Riyadh, Saudi Arabia; <sup>6</sup>King Faisal Specalist Hospital & Research Center, Radiation Oncology, Riyadh, Saudi Arabia; <sup>7</sup>King Faisal Specalist Hospital & Research Center, Dept of Path Lab Medicine, Riyadh, Saudi Arabia; <sup>8</sup>King Faisal Specalist Hospital & Research Center, Dept of Path & Lab Medicine, Riyadh, Saudi Arabia; <sup>9</sup>AlFaisal Unversity, Medical College, Riyadh, Saudi Arabia</italic></p><p><bold>Background/Objectives</bold>: Atypical teratoid rhabdoid tumors (ATRT) are rare aggressive tumors with poor prognosis accounting for 1‐2% of all childhood malignancies. Primarily occur in children under the age of three though they may be seen in older age groups.</p><p><bold>Design/Methods</bold>: Medical charts of pediatric patients diagnosed with ATRT between 1993‐2013 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, were reviewed and treatment profile and outcome data were analyzed.</p><p><bold>Results</bold>: Forty three cases were evaluated. Median age at diagnosis among males (n=23, 53.5%) was 1.8 years (0.03‐20.7) compared to 2.1 years (0.17‐20.1) among females (n=20, 46.5%). All patients underwent surgery: 6 had biopsy only; 23 subtotal resection (STR), and 14 gross total resection (GTR). VP‐shunt was inserted in 9 patients prior to surgery and in 17 after surgery. All but one tumor were immunonegative for INI 1. Disease was localized in 65.1% (28) and disseminated in 34.9% (15). Rhabdomyosarcoma‐ based chemotherapy was given to 30 (68.9%) patients. Nineteen patients received radical dose of radiation therapy. Eight patients received focal irradiation while 11 had whole craniospinal axis irradiation followed by localized boost to primary lesion. Patients treated with focal radiation only, had no clinical, radiological or cytological evidence of spinal seeding. Total radiation dose for localized field ranged from 50‐50.4 Gy in 28‐32 fractions, while the craniospinal axis radiation dose ranged from 30.6 Gy to 36 Gy. At last follow‐up, 22(51.2%) patients were alive; 2(9.1%) in CR, 5(22.7%) with SD and the remaining 15(68.2%) had disease progression (PD). Median follow‐up of 25.1 months, the probability of five year overall survival was 31%, having a median survival time of 19 months (95% CI: 5.6‐32.4).</p><p><bold>Conclusions</bold>: ATRT outcome remains unsatisfactory despite multimodality treatment. Targetted strategies utilizing agents mimicking effects of INI1/ h SNF5 may hold promise in future studies for this aggressive tumor.</p></sec><sec id="pbc26772-sec-7000"><label>P-298</label><title>Excellent Neuro‐Cognitive Outcomes in Infant Patients with Medulloblastoma Treated with Post‐Operative Chemotherapy and Focal Radiation</title><p><underline underline-style="single">P. Angelini</underline><sup>1</sup>, A. Michalski<sup>1</sup>, K. Phipps<sup>2</sup>, D. Gumley<sup>3</sup></p><p><italic><sup>1</sup>Great Ormond Street Hospital, Paediatric Oncology, London, United Kingdom; <sup>2</sup>Great Ormond Street Hospital, Neurosurgery, London, United Kingdom; <sup>3</sup>Great Ormond Street Hospital, Neurosciences, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Infant medulloblastoma patients suffer severe cognitive sequelae from conventional treatment, particularly from radiotherapy. We present the results of a protocol comprising dose‐intense induction chemotherapy, focal radiotherapy and consolidation chemotherapy, and the neuro‐cognitive outcome of survivors.</p><p><bold>Design/Methods</bold>: Twenty‐six patients were treated between 11/1997 and 04/2011. All patients underwent an attempt at surgical resection, followed by induction chemotherapy (cyclophosphamide, carboplatin, vincristine). Radiotherapy was administered based on initial staging and tumour response. Post radiotherapy the patients received 4 cycles of consolidation chemotherapy (lomustine, cisplatin, vincristine).</p><p><bold>Results</bold>: Nineteen patients received radiotherapy, 14 focal, 5 craniospinal (CSI). OS was 56.8% ± 10.5%. EFS was 51.1% ±10.2%. Twelve patients relapsed, 13 died, 11 are long term survivors and two are lost to follow‐up. Gross tumour resection, desmoplastic variant and radiotherapy (either focal or CSI) correlated with better OS and EFS, while metastases, gender and age at diagnosis had no impact. Twelve of 13 evaluable patients reported one or more long term sequelae of their tumour or treatment. Fourteen patients, including all long‐term survivors, had a neuro‐psychological or developmental assessment 2 to 10 years after the diagnosis. Six had learning difficulties (42%), of whom three (female), had moderate learning difficulties, and three (boys) had severe learning disabilities. 2 children had language difficulties, one with average cognition. Six patients had normal IQ between 89 and 113 and no other problems.</p><p><bold>Conclusions</bold>: Our study confirms that 1: patients with desmoplastic medulloblastoma have a favourable prognosis and 2: delaying radiotherapy and reducing the field of radiation lead to normal neuro‐cognitive outcome in 42%, and mild deficits in 21% of survivors. However, the report of 4 second malignancies (28.6% of non‐relapsed patients) is of concern and brings into question the whole approach with chemo‐radiotherapy for these tumours.</p></sec><sec id="pbc26772-sec-7010"><label>P-299</label><title>The Promote Study: Patient Reported Outcome Measures Online to Enhance Communication and Quality of Life after Childhood Brain Tumour – Systematic Review</title><p><underline underline-style="single">K. Bull</underline><sup>1</sup>, C. Kennedy<sup>1</sup>, S. Hornsey<sup>2</sup>, J. Shepherd<sup>3</sup>, K. Welch<sup>3</sup>, C. Morris<sup>4</sup></p><p><italic><sup>1</sup>University of Southampton, Clinical and Experimental Sciences, Southampton, United Kingdom; <sup>2</sup>University of Southampton, School of Psychology, Southampton, United Kingdom; <sup>3</sup>University of Southampton, Southampton Health Technology Assessments Centre, Southampton, United Kingdom; <sup>4</sup>University of Exeter, Medical School, Exeter, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Quality of life in children treated for brain tumours is at risk of being significantly impaired into adulthood including cognitive functioning, emotional, behavioural, and social issues. However, typically there is no systematic screening for such problems. Referral to appropriate services is often reactive rather than proactive. We are testing the feasibility of individualised application of patient‐reported outcome measures (PROMs) to improve communication in outpatient consultations. We need to select appropriate PROMs based on available evidence of measurement properties.</p><p><bold>Design/Methods</bold>: We have conducted a systematic search of MEDLINE, EMBASE, and PsycINFO to identify evidence of studies evaluating measurement properties of English language versions of PROMs suitable for use with children who have been treated for brain tumours. Two reviewers have independently screened all titles and abstracts from the search to select those articles that are likely to yield relevant results. Full texts are being extracted from this list and read by 3 reviewers to confirm their relevance and ascertain their contribution to the evidence base. The review team will then consider the evidence and decide on the extent to which each PROM can be considered robust for measuring quality of life in individual children treated for brain tumours.</p><p><bold>Results</bold>: After duplicates had been removed, the systematic search identified 473 possible relevant studies in which PROMs had been psychometrically evaluated for use with children treated for brain tumours. To date 53 (21%) studies from 250 titles and abstracts screened have been included for the next stage in the review process.</p><p><bold>Conclusions</bold>: We will present evidence from this review that informs the selection of PROMs for use with children treated for brain tumours in a subsequent stage of the research for which decisions on the final selection of PROMs will be made in consultation with families and clinicians.</p></sec><sec id="pbc26772-sec-7020"><label>P-300</label><title>In Human Glioblastoma Cell Lines, Doxycycin Inhibits Tumorigenicity by Tumor Stem Cells</title><p><underline underline-style="single">C.F. Classen</underline><sup>1</sup></p><p><italic><sup>1</sup>University Childrens Hospital, Oncology Hematology, Rostock, Germany</italic></p><p><bold>Background/Objectives</bold>: Glioblastoma multiforme still is a lethal diagnosis for most patients. Operation and radiotherapy are very effective to reduce the tumor burden, however, a strong adjuvant therapy is lacking. Based on the cancer stem cell hypothesis, we expected an increased tumorigenicity in stem‐like glioblastoma cells. Our objective was then to analyse how this might be influenced by different culture conditions in vitro in cell lines established from individual patients, in order to identify therapeutic targets acting on epigenetic regulation. Since continuous exposure to temozolomide is part of standard treatment, its effect on stemness was analysed. Doxycycline is a polycyclic antibiotic, inhibiting protein biosynthesis by binding to the small subunit (30S) of bacterial ribosomes. Since it acts similarly on the 28S subunit of mitochondrial ribosomes, which could be a critical part in the metabolism of stem‐like cells it might also inhibit stem cell formation.</p><p><bold>Design/Methods</bold>: Patient derived cells were grown in classical cell culture (with 10% fetal calf serum) and cancer stem cell culture (serum free, supplemented with growth factors), both as adherent or spheroid culture. In these settings, we analysed the effect of continuous treatment with the cytostatic drug temozolomide (50μM), without and with doxycycline.</p><p><bold>Results</bold>: As we found, cells cultivated upon stem cell culture conditions displayed an increased tumorigenicity in vitro, as compared to their respective serum culture counterparts. Cells cultivated as spheroids achieved a more stem‐like phenotype than adherent cells. Interestingly, similar effects were observed after treatment with temozolomide (50μM). Furrther, doxycylin was studied it in our temozolomide‐induced tumorigenicity model. In fact, it reversed the effects of temozolomide.</p><p><bold>Conclusions</bold>: In summary, we found that by numerous modifications of growth conditions, the stem‐like phenotype and tumorigenicity of glioblastoma cells may be influenced, thus opening new options for a targeted approach in glioblastoma therapy.</p></sec><sec id="pbc26772-sec-7030"><label>P-301</label><title>Application of Visual‐Motor Exerciser in Children and Teenagers After Antitumor Therapy of Central Nervous System Cancer</title><p>V. Anisimov<sup>1</sup>, <underline underline-style="single">A. Dreneva</underline><sup>1</sup>, I. Borodina<sup>1</sup>, V. Kasatkin<sup>1</sup></p><p><italic><sup>1</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Clinical Rehabilitation Research Center for patients in remission “Russkoye pole”, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The progress of treatment in children with brain tumors has led to a significant increase in their survival. However, radiotherapy and chemotherapy produce dramatic impact on survivors’ health state. Hence, the question of effective cognitive and motor rehabilitation of survivors is in a great interest. The aim of our research was to study the applicability of a new method for motor and executive functions development and to evaluate its effectiveness in relation to rehabilitation therapy in patients with brain tumors.</p><p><bold>Design/Methods</bold>: The cohort included 46 children with posterior fossa tumors: 27 males and 19 females (median age=11). The diagnoses were: medulloblastoma (n=31), pilocytic astrocytoma (n=11), anaplastic ependymoma (n=1), diffuse brainstem glioma (n=1), neurinoma (n=1) and fibrillar meningioma (n=1). Depending on treatment protocol, 11 patients received surgery, 3 patients received surgery and radiotherapy, 1 patient received surgery and chemotherapy, and 31 patients received all three types of intervention. Remission period varied from 2 to 113 months (median=21).</p><p>All patients received occupational therapy consisted of 5‐7 sessions at Dynavision D2 ®. This training device is designed for the enhancement of visual‐motor integration and attention skills.</p><p><bold>Results</bold>: Our findings revealed significant improvement of reaction time in all patients (P<0.0126). Females showed better performance (P<0.0001) that can be explained by earlier psychomotor maturation in girls. The group of patients who received only surgical intervention demonstrated better results comparing to others (P<0.0313). Performance scores significantly correlated with ophthalmological diagnoses (P<0.00001). No significant age differences were found.</p><p>No negative feedback was received from patients during the time they were working with the device.</p><p><bold>Conclusions</bold>: The results suggest that Dynavision D2 ® can be successfully applied to training of reaction time, visual‐motor integration and hand‐eye co‐ordination in rehabilitation of pediatric cancer survivors.</p></sec><sec id="pbc26772-sec-7040"><label>P-302</label><title>Executive Functions State in Childhood Brain Tumor Survivors before and After Working Memory and Attention Training</title><p>A. Ryabova<sup>1</sup>, <underline underline-style="single">A. Dreneva</underline><sup>1</sup>, A. Aizenshtein<sup>1</sup>, V. Kasatkin<sup>1</sup></p><p><italic><sup>1</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Clinical Rehabilitation Research Center for patients in remission “Russkoye pole”, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Childhood brain tumors and their treatments are closely associated with cognitive impairment that occurs in a substantial proportion of patients. The aim of the investigation was to evaluate the impact of rehabilitation therapy, which included executive functions training, on such parameters as working memory, sustained attention and processing speed, in posterior fossa tumor survivors.</p><p><bold>Design/Methods</bold>: Thirty‐one children (20 boys, 11 girls, median age=11) were included. The diagnoses were medulloblastoma (n=24), pilocytic astrocytoma (n=4), anaplastic ependymoma (n=1), diffuse brainstem glioma (n=1), neurinoma (n=1) and fibrillar meningioma (n=1).</p><p>The executive functions training was performed in all patients during three‐week time period. The state of executive functions before and after the training was evaluated by Cambridge Neuropsychological Test Automated Battery (CANTAB ®).</p><p><bold>Results</bold>: Most of patients demonstrated significant improvement in spatial working memory capacity (P<0.0087) and delayed pattern recognition (P<0.0325). An increasing tendency was revealed for ability to manipulate visuospatial information (P<0.0743) and for immediate pattern recognition (P<0.0839).</p><p><bold>Conclusions</bold>: The results indicate the effectiveness of executive functions training in childhood brain tumor patients. They also show that CANTAB ® is a sensitive method for neuropsychological assessment in pediatric cancer survivors.</p></sec><sec id="pbc26772-sec-7050"><label>P-303</label><title>Prognostic Significance of Molecular Grouping in Russian Cohort of Medulloblastoma Patients</title><p>L. Papusha<sup>1</sup>, <underline underline-style="single">A. Druy</underline><sup>2</sup>, L. Yasko<sup>3</sup>, Y. Olshanskaya<sup>2</sup>, D. Konovalov<sup>4</sup>, S. Ozerov<sup>5</sup>, A. Samarin<sup>5</sup>, A. Nechesnyuk<sup>6</sup>, D. Kobyzeva<sup>6</sup>, I. Borodina<sup>7</sup>, A. Zaychikov<sup>8</sup>, M. Belogurova<sup>9</sup>, S. Kovalenko<sup>10</sup>, A. Shapochnik<sup>11</sup>, G. Sharapova<sup>12</sup>, A. Rumyantsev<sup>13</sup>, E. Kumirova<sup>14</sup>, A. Karachunskiy<sup>15</sup>, G. Novichkova<sup>16</sup>, A. Rumyantsev<sup>16</sup></p><p><italic><sup>1</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Pediatric department for hematology and oncology, Moscow, Russia; <sup>2</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Laboratory of Cytogenetics and Molecular Genetics, Moscow, Russia; <sup>3</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Laboratory of molecular biology, Moscow, Russia; <sup>4</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Department of pathological anatomy, Moscow, Russia; <sup>5</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Department of pediatric surgery, Moscow, Russia; <sup>6</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Department of radiation therapy, Moscow, Russia; <sup>7</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Department of medical rehabilitation, Moscow, Russia; <sup>8</sup>Regional Children's Hospital 1, Pediatric oncology ward, Yekaterinburg, Russia; <sup>9</sup>City Clinical Hospital 31, Department of pediatric oncology, St. Petersburg, Russia; <sup>10</sup>Chelyabinsk Regional Children's Hospital, Department of pediatric oncology and hematology, Chelyabinsk, Russia; <sup>11</sup>Regional Children's Hospital, Department of pediatric oncology and hematology, Orenburg, Russia; <sup>12</sup>Nizhnevartovsk Regional Chuldren's Hospital, Department of pediatric oncology and hematology, Nizhnevartovsk, Russia; <sup>13</sup>Altay Regional Children's Hospital, Department of pediatric oncology and hematology, Barnaul, Russia; <sup>14</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Department of neurooncology, Moscow, Russia; <sup>15</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Institute of pediatric oncology‐ radiology and nuclear medicine, Moscow, Russia; <sup>16</sup>National Scientific and Practical Center of Pediatric Hematology‐ Oncology and I, Medical administration, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma, the most common CNS malignancy of childhood, is known for a significant clinical heterogeneity. 4 distinct molecular subgroups (WNT, SHH, groups 3 and 4) with unequal outcome have been distinguished.</p><p><bold>Design/Methods</bold>: In the pilot study aimed to investigate clinical significance of molecular grouping of medulloblastoma in Russian cohort of patients we analyzed profile of 26 genes expression (P. Northcott et al. 2012 with slight modifications) in 33 FFPE tumor samples from patients 0‐15 years of age by Nanostring technology. All patients were treated according to HIT protocol. Median of follow‐up time achieved 23.3 months.</p><p><bold>Results</bold>: 8 patients had metastatic dissemination and 8 had incomplete resection with residual disease larger then 1.5 cm2. Molecular group distribution was as follow: WNT‐ 2, SHH‐ 9, group 3‐ 11, group 4‐ 11 patients. Classical histologic variant of medulloblastoma included all groups with the exception of SHH, anaplastic – only group 3. Correspondence of desmoplastic/nodular histology to SHH group was 7/8 in infants; however in patients >3 years desmoplastic medulloblastoma belonged to group 3 and 4 (2 and 3 patients respectively). All 8 infants with desmoplastic variant were treated only by chemotherapy (HIT SKK) and had excellent outcome, even in cases with metastatic disease. Group 3 patients had poor outcome: event‐free survival (EFS) was 0.42±0.16. 3 out of 11 patients did not respond to the first‐line therapy and 3 had a relapse.</p><p>Group 4 and WNT patients in our series had excellent outcome. In the group 4 all patients with the exception of one were above 3 years of age and received craniospinal irradiation. Differences in EFS between molecular subgroups were significant, p‐value for trend was 0.007.</p><p><bold>Conclusions</bold>: Our study confirmed the prognostic significance of molecular grouping of medulloblastoma. Nanostring is fast and reliable method for this purpose and could be offered for routine clinical practice.</p></sec><sec id="pbc26772-sec-7060"><label>P-304</label><title>Experience of the Management of Central Nervous System Tumors in Children Younger than 5 Years‐Old in the Last 15 Years</title><p><underline underline-style="single">M. Garcia‐Ariza</underline><sup>1</sup>, R. Lopez‐Almaraz<sup>1</sup>, A. Echebarria Barona<sup>1</sup>, R. Adan Pedroso<sup>1</sup>, I. Ojinaga Niño<sup>1</sup>, A. Ricondo De Diego<sup>1</sup>, N. Bilbao Salcines<sup>1</sup>, M.J. Martinez Gonzalez<sup>2</sup>, A. Garcia Rives<sup>2</sup>, I. Valduvieco<sup>3</sup>, L. Galbarriatu Gutierrez<sup>4</sup>, E. Ruiz de Gopegui Ruiz<sup>4</sup>, L. Zaldumbide Dueñas<sup>5</sup>, I. Martin Guerrero<sup>6</sup>, O. Aurtenetxe Saez<sup>6</sup>, L. Collazos Zabala<sup>7</sup>, A. Navajas Gutierrez<sup>1</sup>, I. Astigarraga Aguirre<sup>1</sup></p><p><italic><sup>1</sup>Hospital Universitario Cruces, Pediatric Hematology and Oncology Unit, Cruces‐ Bilbao, Spain; <sup>2</sup>Hospital Universitario Cruces, Pediatric Neurology Departament, Cruces‐ Bilbao, Spain; <sup>3</sup>Hospital Marques de Valdecilla, Neurosurgery Departament, Santander, Spain; <sup>4</sup>Hospital Universitario Cruces, Neurosurgery Departament, Cruces‐ Bilbao, Spain; <sup>5</sup>Hospital Universitario Cruces, Department of pathological anatomy, Cruces‐ Bilbao, Spain; <sup>6</sup>Hospital Universitario Cruces, Biocruces Health Research Institute, Cruces‐ Bilbao, Spain; <sup>7</sup>Hospital Universitario Cruces, Pediatric oncological psychology. Pediatric Hematology and Oncology Unit, Cruces‐ Bilbao, Spain</italic></p><p><bold>Background/Objectives</bold>: Treatment of young children with central nervous system (CNS) tumors remains a challenge. The objective of avoiding radiation therapy due to its long term sequelae, and the controversy about the high‐dose chemotherapy (HDCT) difficult the management of these patients. We present our experience in children with CNS tumors less than five years.</p><p><bold>Design/Methods</bold>: Review of the CNS tumors in children under five years diagnosed from 2001 to 2016. Collected and analyzed data were clinical, histological, treatment and sequelae.</p><p><bold>Results</bold>: Sixty‐three infants were identified. Males 52%. Mean age 2.7years(range 0‐5years). Tumor sites were supratentorial 62%, infratentorial 34.5% and spinal‐cord16%. Dissemination was 9.5% at diagnosis. Histologies were: low‐grade astrocytic tumor 43%, embryonal 22%, high‐grade gliomas 13%, ependymal 9.5%, neural and selar tumors 4.8% and melanocytic and choroid plexus tumor 2%. Optic‐pathway was afected in 25.4% and hypothalamus/hypophysis in 17.5%. Management included surgery 76% (complete resection 34%, partial resection 24%, biopsy 13%, and subtotal resection 5%). No biopsy in 15 cases, some optic‐pathway gliomas, DIPG and a hypophysis tumor. Chemotherapy was administered in 56%, 23% beyond the first line, and HDCT 6%. Radiotherapy, administered in 19 (30%), was focal 25% (ependymomas, medulloblastoma and PNET above 2 years‐old) and craneospinal 5% (medulloblastoma and ependymoma above 3.5 years‐old). Observation without therapy in 7 cases, predominantly low‐grade gliomas. Overall survival 63.5% with median follow‐up of 62 months (range30‐109). Most frequent sequelae were neurological (70%) and ophthalmological (52%). Three cases presented no sequelae.</p><p><bold>Conclusions</bold>: The management of children less than five‐years with CNS tumors remains challenge. We should consider carefully age, histology and localization for therapeutic decisions. Chemotherapy was administered in most cases (56%) and may contribute to the delay of RT in some patients. The role of HDCT in young children needs to be analyzed in larger studies. In survivors, the tumor and treatment sequelae were frequent and important.</p></sec><sec id="pbc26772-sec-7070"><label>P-305</label><title>Congenital Giant Cell Astrocytomas ‐ A Comprehensive Clinical, Histopathological and Molecular Evaluation</title><p><underline underline-style="single">W. Grajkowska</underline><sup>1</sup>, K. Kotulska<sup>2</sup>, J. Trubicka<sup>1</sup>, M. Roszkowski<sup>3</sup>, E. Jurkiewicz<sup>4</sup>, B. Dembowska‐Bagińska<sup>5</sup></p><p><italic><sup>1</sup>The Children's Memorial Health Institute, Pathology, Warsaw, Poland; <sup>2</sup>The Children's Memorial Health Institute, Neurology and Epileptology, Warsaw, Poland; <sup>3</sup>The Children's Memorial Health Institute, Neurosurgery, Warsaw, Poland; <sup>4</sup>The Children's Memorial Health Institute, Radiology, Warsaw, Poland; <sup>5</sup>The Children's Memorial Health Institute, Oncology, Warsaw, Poland</italic></p><p><bold>Background/Objectives</bold>: Subependymal giant cell astrocytoma (SEGA) is a brain tumor associated with tuberous sclerosis complex (TSC). It usually grows in a second decade of life, but may develop in the first months of life. The aim of this work was to establish the incidence, clinical, histopathological and molecular features, as well as outcome of congenital SEGA in TSC patients.</p><p><bold>Design/Methods</bold>: Cohort of 510 TSC patients was reviewed to identify cases with growing or hydrocephalus producing SEGAs in the first three months of life. Clinical presentation, size of the tumor, growth rate, histopahological and mutational analysis, treatment applied, as well as outcome were evaluated.</p><p><bold>Results</bold>: Twelve patients (2.4%) presented with SEGA in the first three months of life. All of them had documented SEGA growth and all developed hydrocephalus. In nine patients, mutational analysis was done, and in all of them, <italic>TSC2</italic> gene mutations were identified. Mean maximum SEGA diameter at baseline was 50 mm. Seven patients underwent SEGA surgery and surgery‐ related complications were observed in 57.1 % cases. Two patient received everolimus as a primary treatment.</p><p><bold>Conclusions</bold>: Congenital SEGA develops 2.4% of TSC patients. Patients with <italic>TSC2</italic> mutations, and especially with <italic>TSC2</italic>/<italic>PKD1</italic> mutations, are more prone to develop SEGA earlier in childhood and should be screened for SEGA from birth. In young infants with SEGA, both surgery and mTOR inhibitor should be considered as a treatment option.</p><p>This work was supported by Internal Funding from The Children's Memorial Health Institute, Warsaw, Poland (08/ZG/2016, grant titled: “Identification of molecular background of epilepsy in patients with tuberous sclerosis complex”).</p></sec><sec id="pbc26772-sec-7080"><label>P-306</label><title>Demography and Treatment of Craniopharyngioma in a Tertiary Centre in India</title><p><underline underline-style="single">S. Gupta</underline><sup>1</sup>, H. K P<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Radiotherapy, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Craniopharyngioma are rare tumors of the sellar region. Data on demographic details, symptomatology, treatment and response is limited from the Indian sub‐continent.</p><p><bold>Design/Methods</bold>: Patients included in the retrospective analysis were those who presented to the neuro‐oncology clinic under radiation oncology department after surgery between years 2003 and 2016. The treatment charts were reviewed. This is an update of data from our institution.</p><p><bold>Results</bold>: A total of 54 patients were treated. Age of presentation ranged from 2 to 45 years.The sex distribution was Male:Female of 38:16. The presenting symptom was visual symptoms in 34 patients, hormonal imbalance in 3, neurological deficit in 1 patient, seizures in 1 patient and raised intracranial tension in 15 patients. Lesion size was< 4 cm for 32 patients and > 4 cm for 22 patients. Baseline TSH levels were available for 34 patients (Raised – 1; Decreased – 3). Baseline GH levels were available for 32 patients(Raised – 0; Decreased – 3). Baseline prolactin levels were available for 29 patients (Raised – 3; Decreased – 1). Baseline ACTH levels were available for 32 patients (Raised – 1; Decreased – 6). Radiation was delivered by 3 D‐ CRT in 41 patients. IMRT in 2 patients and SRT in 1 patient. Radiation dose was 50.4 Gray in 28 fractions to 55 Gray over 5.5 to 6 weeks.36 patients had a complete response, 5 patients a partial response. 2 stable disease and 1 progressive disease. 7 patients recurred at local site. 6 patients underwent surgery. 4 of those patients had progressive disease at last follow up. No grade 3 or 4 toxicity was documented. Univariate analysis done on available data did not detect any association of age, sex, hormonal perturbations or lesion size with response to primary therapy or recurrence.</p><p><bold>Conclusions</bold>: Craniopharyngioma have good response to surgery with radiation</p></sec><sec id="pbc26772-sec-7090"><label>P-307</label><title>SFCE Metro 01 Four‐Drug Metronomic Regimen has Anti‐Tumour Activity in Pediatric Low‐Grade Glioma</title><p>M.A. Heng‐Maillard<sup>1</sup>, N. André<sup>1</sup>, P. Dory‐Lautrec<sup>2</sup>, R. Truillet<sup>3</sup>, P. Chastagner<sup>4</sup>, P. Leblond<sup>5</sup>, I. Aerts<sup>6</sup>, N. Corradini<sup>7</sup>, N. Entz‐Werle<sup>8</sup>, J.C. Gentet<sup>1</sup>, S. Honoré<sup>9</sup>, <underline underline-style="single">A. Verschuur</underline><sup>1</sup></p><p><italic><sup>1</sup>La Timone Children's Hospital, Department of Pediatric Oncology, Marseille, France; <sup>2</sup>La Timone Children's Hospital, Department of Neuroradiology, Marseille, France; <sup>3</sup>La Timone Children's Hospital, CIC‐CPCET, Marseille, France; <sup>4</sup>Children's Hospital, Department of Pediatric Oncology, Nancy, France; <sup>5</sup>Oscar Lambret Centre, Pediatric Oncology Unit, Lille, France; <sup>6</sup>Institut Curie, Pediatric Department, Paris, France; <sup>7</sup>Centre Léon Bérard, Department of Paediatric Haematology and Oncology, Lyon, France; <sup>8</sup>CHU Hautepierre, Pédiatrie Onco‐Hématologie, Strasbourg, France; <sup>9</sup>La Timone Children's Hospital, Department of Clinical Pharmacy, Marseille, France</italic></p><p><bold>Background/Objectives</bold>: To investigate the anti‐tumour activity of a 4‐drug metronomic regimen in relapsing/refractory pediatric brain tumours (BT) as defined as progression‐free survival (PFS) after 2 cycles (4 months) of therapy.</p><p><bold>Design/Methods</bold>: Patients of ≥4 to 25 years of age with progressing BT and adequate organ function. Treatment consisted of an 8‐week cycle of oral celecoxib BID daily (D1‐D56), 100/200/400 mg according to BW, weekly IV vinblastine 3 mg/m<sup>2</sup>, oral cyclophosphamide 30 mg/m<sup>2</sup>/d qd for 3 weeks alternating with oral methotrexate 10 mg/m<sup>2</sup> twice a week for 3 weeks, with a 2‐week rest period. Maximum treatment was 2 years. Kepner and Chang two‐steps model was used with 10 patients in the first stage. If primary objective was reached in 2 or more patients, 8 additional patients were recruited. This regimen was considered efficacious if PFS after 2 cycles was over 34% (alpha 10%, beta 10%).</p><p><bold>Results</bold>: 29 patients were included in 2 groups: ependymoma (N=8) and other BT:3 medulloblastoma (MB), 5 high grade glioma (HGG) (2 of which DPIG), 11 low grade glioma (LGG), 2 other. One patient with HGG stabilized for 2 years and one ependymoma stabilized 4 months. None of the other HGG, ependymoma or MB stabilized. Of the patients with LGG, median age was 9,5 years, median duration of illness 6,5 years and 10 patients received vinblastine previously. 1 PR was observed, 8 SD, 1 PD, one non evaluable after 2 cycles. Median number of cycles was 6 (range 1 to 12). Seven patients received at least 1 year of therapy. Treatment was interrupted temporarily in 5 patients for grade 3/4 toxicity.</p><p><bold>Conclusions</bold>: This metronomic regimen is active in patients with other BT, especially LGG, even if patients had received vinblastine previously. (This study was supported by “Enfants et Santé” Foundation and PHRC‐grant).</p></sec><sec id="pbc26772-sec-7100"><label>P-308</label><title>Temozolomide Effect on Mitophagy in Glioblastoma Chemoresistance Cell Lines</title><p>R. Javed<sup>1</sup>, X. Liu<sup>2</sup>, <underline underline-style="single">F. Akhter</underline><sup>3</sup>, J. Zhou<sup>2</sup>, X. Liu<sup>2</sup>, L. He<sup>1</sup></p><p><italic><sup>1</sup>Guang Zhou Women and Children's Medical Center, Guangzhou Institute of Pediatrics, Guangzhou, China; <sup>2</sup>Guangzhou Institute of Pediatrics, Pediatrics Department, Guangzhou, China; <sup>3</sup>Higuchi Bioscience Center, Department of Pharmacology and Toxicology, Kansas, USA</italic></p><p><bold>Background/Objectives</bold>: Despite aggressive therapies, including combinations of surgery, radiotherapy and chemotherapy, GBM remains a highly aggressive brain cancer with the worst prognosis of any central nervous system disease; the median post‐diagnostic survival period of GBM patient is approximately one year. Temozolomid (TMZ) first line chemotherapy drug for GBM, commonly use in the adjunctive treatment of gliomas and extends median survival from 12.1 months to 14.6 months but eventually chemotherapy becomes impaired by development of chemoresistance. Mitophagy‐The targeted degradation of unneeded and dysfunctional mitochondria, deregulation have been linked to human cancer. Mitophagy related stress tolerance can enable cell survival by maintaining energy production that can lead to tumor growth and therapeutic resistance.</p><p><bold>Objectives</bold>: To investigate whether TMZ can induce mitophagy in GBM cell lines.</p><p><bold>Design/Methods</bold>: Glioblstoma resistance cell lines T98G, U251 and U138 were treated with TMZ at different time intervals to induce mitophagy. Confocal Microscopy and Flow Cytometery were used to monitor Mitophagy.</p><p><bold>Results: Membrane potential (Δψ<sub>m</sub>)</bold> results depicted that U251 and U138 showed no loss of Δψ<sub>m</sub> at 12h but a significant loss of Δψ<sub>m</sub> were observed at 24h and 36h. T98G cell line showed no loss of Δψ<sub>m</sub> at 24h but showed comparatively higher loss of Δψ<sub>m</sub> at 36h and 48h.</p><p><bold>ROS assay results</bold> depicted that U138 cells showed slightly higher ROS positive cells in treated cells than control and similar results were observed in U251. In T98G a very significant difference were observed at 36h in treated cells than control compare to 24h and 48h.</p><p><bold>Conclusions</bold>: This study presents that TMZ could induce mitochondrial membrane potential decreased and ROS level increase in GBM cell lines so on the basis of our results we speculated that TMZ resistance may correlated to mitophagy. Further study is needed to explore the mitophagy mechanism in GBM TMZ resistance.</p></sec><sec id="pbc26772-sec-7110"><label>P-309</label><title>Childhood Medulloblastoma: Single‐Center Experience of 16 Years in Peru</title><p>L. Vasquez<sup>1</sup>, C. Alvarez<sup>2</sup>, <underline underline-style="single">E. leon</underline><sup>1</sup></p><p><italic><sup>1</sup>Hospital Nacional Edgardo Rebagliati, Pediatric Oncology, Lima, Peru; <sup>2</sup>Hospital Nacional Edgardo Rebagliati, Fellow of Pediatric Oncology, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma is an embryonal tumor with aggressive behavior and is more commonly seen in children than adults. The aim of this study was to determine epidemiological and treatment patterns and implications for survival in children with medulloblastoma.</p><p><bold>Design/Methods</bold>: A total of 67 patients younger than 18 years diagnosed with medulloblastoma from January 2002 to December 2016 were evaluated in a retrospective cohort in our institution. Prognostic Factors such as age, risk, surgery, metastates, leptomeningeal dissemination, time to delay of surgery, radiation and chemotherapy were analyzed.</p><p><bold>Results</bold>: The median follow‐up time was 18.5 months (range 1‐146 months). In patients with High‐Risk disease, 2 and 5‐year overall survival (OS) rates were 71.5% and 58.5%, and Disease Free Survival (DFS) were 53.7% and 33.5%, respectively. In patients with standard‐risk disease, 2 and 5‐year OS and DFS rates were 50.5%, 34.4% and 36.3%, 19.9%, respectively. Median duration of symptoms was 31.5 days (range, 0‐120). Seventy‐one percent of patients presented in Stage 0 and had a localized tumor. Thirty‐eight patients received radiation post‐surgery (all of them had more than 3 years) by craniospinal irradiation up to 36 gray followed by boost up to 54 gray. Median time to radiation was 39 days (range, 22‐120). In multivariate analysis, group risk was an independent prognostic factor for OS along with metastatic disease, risk and positive CSF. A delayed start of radiation therapy (>42 days) was associated to inferior OS (p=0.0186).</p><p><bold>Conclusions</bold>: In children older than 3 years, a delayed radiation start after surgery was significant factor for unfavorable prognosis. Early treatment, in addition to a quickly diagnosis, is the key to management of medulloblastoma, which still needs to be achieved.</p></sec><sec id="pbc26772-sec-7120"><label>P-310</label><title>Expression of ERCC1, TOP2A, RFC1, TUBB3 and MGMT Proteins as Markers of Drug Resistance to MTX‐OPEC and LIKE‐SJMB03 Chemotherapy in Childhood Medulloblastoma</title><p><underline underline-style="single">A. Levashov</underline><sup>1</sup>, D. Khochenkov<sup>2</sup>, A. Stroganova<sup>3</sup>, M. Ryzhova<sup>4</sup>, S. Babelyan<sup>1</sup>, S. Gorelyshev<sup>5</sup>, G. Mentkevich<sup>1</sup>, N. Subbotina<sup>1</sup>, V. Daylidite<sup>1</sup>, I. Dolgopolov<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Hematology and Oncology Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Pediatric Hematology and Oncology Institution, Moscow, Russia; <sup>2</sup>Experimental Diagnostic and Treatment of Tumor Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Experimental Diagnostic and Treatment of Tumor Institution, Moscow, Russia; <sup>3</sup>Department of pathology‐ FSBI «N.N. Blokhin Russian Cancer Research Center», Department of pathology, Moscow, Russia; <sup>4</sup>Department of Neuropathology‐ N.N. Burdenko Neurosurgical Institute, Department of Neuropathology, Moscow, Russia; <sup>5</sup>Department of Neurosurgery №1‐ N.N. Burdenko Neurosurgical Institute, Department of Neurosurgery №1, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: According to data of some international pediatric protocols there were revealed markers of unfavorable outcome (<italic>C‐MYC/N‐MYC</italic> gene amplification, iso17q (Group3)), but expression of drug resistance proteins in tumor specimens is unknown. The aim of this study was to estimate ERCC1, TOP2a, RFC1, TUBB3 and MGMT proteins expression in medulloblastoma specimens.</p><p><bold>Design/Methods</bold>: ERCC1, TOP2a, RFC1 and MGMT proteins expression was assessed by immunohistochemical method using anti‐ERCC1 (clone 8F1, Abcam), anti‐TOP2a (Ki‐S1, Dako), anti‐RFC1 (SCL19A1ab, Genetex), anti‐TUBB3 (TU‐20, SantaCruz), anti‐MGMT (MT3.1, Thermo). ERCC1, TUBB3 and MGMT positive specimen was defined as weak (+), moderate (++), strong (+++) colouring of the tumor nuclei and cytoplasm (for ERCC1 and MGMT), nuclei (for TUBB3) with number of positive tumor cells above 10% (for both ERCC1 and TUBB3), 25% (for MGMT). TOP2a and RFC1 positive specimen was defined as moderate (++), strong (+++) colouring of the tumor nuclei and cytoplasm (for TOP2a), membrane (for RFC1) with number of positive tumor cells above 25%.</p><p><bold>Results</bold>: ERCC1 positive samples were revealed in 18 out of 31 samples (58%; 66.7% for infants, 54.5% for children, p = 0.535), TOP2a in 13 out of 31 (41.9%; 33.3% for infants, 45.5% for children, p = 0.535), RFC1 in 9 out of 33 (27.2%; 0% for infants, 37.5% for children, p = 0.031), TUBB3 in 18 out of 26 (69%) and MGMT in 23 out of 37 (62%, 44.4% for infants, 67.8% for children, p = 0.208). There was also determined significant correlation between TOP2a positive specimen and molecular subgroups of medulloblastoma (33.3% for SHH, 100% for Group 3 and 20% for Group 4, p = 0.025).</p><p><bold>Conclusions</bold>: These data suggest that absence RFC1 expression in infant's medulloblastoma specimen could decrease effectiveness of methotrexate in this group. Etoposide could show more effectiveness against SHH and Group 3 medulloblastoma.</p></sec><sec id="pbc26772-sec-7130"><label>P-311</label><title>Expression of Cytokine‐Associated Proteins (VEGF, VEGFR1, VEGFR2, PDGFRA, PDGFRB, GCSFR) and Transcription Factors (C‐MYC, P‐STAT3TYR705) in Childhood Medulloblastoma</title><p><underline underline-style="single">A. Levashov</underline><sup>1</sup>, D. Khochenkov<sup>2</sup>, A. Stroganova<sup>3</sup>, M. Ryzhova<sup>4</sup>, S. Gorelyshev<sup>5</sup>, G. Mentkevich<sup>1</sup>, S. Babelyan<sup>1</sup>, N. Subbotina<sup>1</sup>, V. Daylidite<sup>1</sup>, I. Dolgopolov<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Hematology and Oncology Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Pediatric Hematology and Oncology Institution, Moscow, Russia; <sup>2</sup>Experimental Diagnostic and Treatment of Tumor Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Experimental Diagnostic and Treatment of Tumor Institution, Moscow, Russia; <sup>3</sup>Department of pathology‐ FSBI «N.N. Blokhin Russian Cancer Research Center», Department of pathology, Moscow, Russia; <sup>4</sup>Department of Neuropathology‐ N.N. Burdenko Neurosurgical Institute, Department of Neuropathology, Moscow, Russia; <sup>5</sup>Department of Neurosurgery №1‐ N.N. Burdenko Neurosurgical Institute, Department of Neurosurgery №1, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The aim of this study was to estimate expression of cytokine‐associated proteins (VEGF, VEGFR1, VEGFR2, PDGFRb, GCSFR) and transcription factors (C‐MYC, p‐STAT3<sup>tyr705</sup>) in medulloblastoma specimens.</p><p><bold>Design/Methods</bold>: These proteins expression was assessed by immunohistochemical method using anti‐VEGF (clone VG1, Daco), anti‐VEGFR1 (Polyclonal, Dako), anti‐VEGFR2 (A3, SantaCruz), anti‐PDGFRb (P‐20, SantaCruz), antu‐CMYC (EP121, CellMarque), anti‐p‐STAT3<sup>tyr705</sup> (EP2147Y, Genetex), anti‐GCSF3R (S2184, Genetex) antibodies. Positive specimen was defined as: weak (+), moderate (++), strong (+++) colouring of the tumor membrane and cytoplasm for VEGF, VEGFR, PDGFR, GCSFR, cytoplasm and nuclei for C‐MYC, p‐STAT3<sup>tyr705</sup> with number of positive tumor cells above 25%.</p><p><bold>Results</bold>: There was no estimated VEGF positive specimens within this group (0 out of 26). VEGFR1, VEGFR2 positive samples were revealed in 10 out of 26 samples (38.4%), PDGFRb in 9 out of 27 (33.3%), GCSFR in 24 out of 37 (64.5%), p‐STAT3<sup>tyr705</sup> in 9 out of 39 (23%) and C‐MYC in 2 (both with <italic>C‐MYC</italic> amplification) out of 8 (25%, only in Group 3). p‐STAT3<sup>tyr705</sup> positive specimens were presented in patients with M0 status in 8 out of 26 (30.8%), with M1 in 1 out of 13 (7.7%), predominantly with SHH medulloblastoma in 5 out of 15 (33,3%). GCSFR positive specimens were presented in patients with M0 status in 18 out of 25 (72%), with M1 in 6 out of 12 (50%), predominantly with SHH (10 out of 15 – 66.7%) and Group 4 medulloblastoma (8 out of 11 – 72.7%). There was not determined significant correlation between positive specimens and age groups (infants and children), <italic>C‐MYC/N‐MYC</italic> amplification, iso17q.</p><p><bold>Conclusions</bold>: These data suggest that childhood medulloblastoma is characterized by low activity of autocrine mechanism stimulation VEGF/VEGFR and PDGFR‐dependent signal pathway, decreased level of transcription factors (excluding variants with <italic>C‐MYC</italic> amplification) and high activity of GCSFR‐dependent signal pathway.</p></sec><sec id="pbc26772-sec-7140"><label>P-312</label><title>A 40‐Year Multi‐Institutional Review of Intracranial Germ Cell Tumours in Adolescents and Young Adults</title><p><underline underline-style="single">A. Lo</underline><sup>1,2,3,4</sup>, N. Laperriere<sup>3,4</sup>, D. Hodgson<sup>3,4</sup>, J. Dang<sup>4</sup>, S. Tyldesley<sup>1,2</sup>, E. Bouffet<sup>5,6</sup>, U. Bartels<sup>5,6</sup>, S. Cheng<sup>7,8</sup>, J. Hukin<sup>8,9</sup>, P. Bedard<sup>10,11</sup>, K. Goddard<sup>1,2</sup></p><p><italic><sup>1</sup>British Columbia Cancer Agency, Radiation Therapy, Vancouver, Canada; <sup>2</sup>University of British Columbia, Surgery, Vancouver, Canada; <sup>3</sup>University of Toronto, Radiation Oncology, Toronto, Canada; <sup>4</sup>Princess Margaret Cancer Centre, Radiation Medicine Program, Toronto, Canada; <sup>5</sup>The Hospital for Sick Children, Hematology/Oncology, Toronto, Canada; <sup>6</sup>University of Toronto, Paediatrics, Toronto, Canada; <sup>7</sup>British Columbia Children's Hospital, Hematology/Oncology, Vancouver, Canada; <sup>8</sup>University of British Columbia, Pediatrics, Vancouver, Canada; <sup>9</sup>British Columbia Children's Hospital, Neurology, Vancouver, Canada; <sup>10</sup>Princess Margaret Cancer Centre, Hematology/Oncology, Toronto, Canada; <sup>11</sup>University of Toronto, Medicine, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: The study aim was to determine the outcomes and complications of intracranial germ cell tumours (IGCT) in adolescents and young adults (AYA) according to different therapeutic approaches.</p><p><bold>Design/Methods</bold>: One‐hundred ten patients with IGCT aged 15–39 were managed at either Princess Margaret Cancer Centre or British Columbia Cancer Agency from 1975–2015. The charts of these patients were retrospectively reviewed. Kaplan‐Meier analyses were performed to calculate outcomes and complication rates at 10 years after treatment.</p><p><bold>Results</bold>: Median duration of follow‐up was 9.3 years. Ninety patients had germinomas, and 20 had non‐germinomatous germ cell tumours (NGGCT). Thirteen patients (12%) presented with spinal metastatic disease. Progression‐free survival (PFS) was 82% and overall survival (OS) was 87%. For patients with germinoma, PFS was 91% after craniospinal radiation therapy (CSRT) with chemotherapy (<italic>N</italic>=11), 100% after whole ventricular RT (WVRT) or tumour bed RT (TBRT) with chemotherapy (<italic>N</italic>=20), 91% after CSRT alone (<italic>N</italic>=43), and 37% after WVRT, whole brain RT, or TBRT alone (<italic>N</italic>=15) (<italic>P</italic><0.0005); OS was 91%, 100%, 91%, and 70%, respectively (<italic>P</italic>=0.046). For patients with NGGCT, PFS was 83% after CSRT with chemotherapy (<italic>N</italic>=6), 67% after CSRT alone (<italic>N</italic>=3), and 58% after TBRT with chemotherapy (<italic>N</italic>=8) (<italic>P</italic>=0.28); OS was 100%, 67%, and 58%, respectively (<italic>P</italic>=0.17). Irradiation‐induced complications included a 14% rate of hypopituitarism, 5% seizure disorder, 2% second neoplasms, 1% cerebrovascular events, and 1% visual deterioration. Treatment‐induced hearing loss or tinnitus was 10% after RT alone, and 28% after both chemotherapy and RT. Neurocognitive impairment from either disease or treatment was 43% after CSRT or WBRT (<italic>N</italic>=69), 48% after WVRT (<italic>N</italic>=23), and 17% after TBRT (<italic>N</italic>=18).</p><p><bold>Conclusions</bold>: We demonstrate excellent overall outcomes in the largest study of IGCT in AYA to our knowledge. High relapse rates were observed after non‐CSRT without chemotherapy in germinoma, and after TBRT with chemotherapy in NGGCT.</p><p><bold>Acknowledgements</bold>: Funded by Brain Tumour Foundation of Canada</p></sec><sec id="pbc26772-sec-7150"><label>P-313</label><title>Outcomes for Pediatric Medulloblastoma – A Single Institute Experience</title><p><underline underline-style="single">T. Mehmood</underline><sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Memorial Cancer Hospital and Research Centre, Radiation Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: We retrospectively examined the incidence, outcomes by treatment type, especially use of radiotherapy of medulloblastoma patients from 2001 to 2010.</p><p><bold>Design/Methods</bold>: The outcomes according to treatment, 5‐year groups (2001‐2005, 2006‐2010) M status, gender, age, and use of radiotherapy in first line treatment are presented.</p><p><bold>Results</bold>: 76 patients were treated over 10 years, 40 male and 36 female. 44 patients had M0 disease and 32 had metastatic disease. There were 34 patients under age 5 with a greater proportion having M+ disease: 42% vs. 30% for those older. First line therapy was chemotherapy only in 9.6% of patients, radiotherapy only in 11.4%, with a decrease from 16.4% in the first group (2001‐2005) to 6.8% in the second group (2006‐2010), and combined chemotherapy and radiotherapy in 60.8% of patients. In the 2001‐2005 period, high dose chemotherapy was used alone in 8.7% and with radiotherapy in 23.1%. Survival at 5 years was 80% for patients receiving radiotherapy and 40% for those not receiving radiotherapy (p= 0.0001). Stage M0 vs. M+, and age under 5 years were also significantly related to survival (both p=0.038) in the COX Hazard model. There was no difference in survival by gender or 5‐year periods.</p><p><bold>Conclusions</bold>: There was no improvement in survival over the study time period, and the use of radiotherapy as first line was the most important prognostic factor. Younger children, under 5 years, presented with a worse stage. There was an independent effect of young age and stage on prognosis, but to a much lower extent than the use of radiotherapy as first line therapy.</p></sec><sec id="pbc26772-sec-7160"><label>P-314</label><title>Clinical Management of Pediatric Ependymoma in Iran: A Retrospective Single Center‐Based Study</title><p><underline underline-style="single">M. Tashvighi</underline><sup>1</sup>, A. Mehrvar<sup>1</sup>, A.A. Hedayati Asl<sup>1</sup>, N. Mehrvar<sup>2</sup>, A. Naderi<sup>1</sup>, M. Alebouyeh<sup>1</sup>, I. Qaddoumi<sup>3</sup>, M. Faranoush<sup>1</sup></p><p><italic><sup>1</sup>MAHAK Pediatric Cancer Treatment and Research Center, Oncology, Tehran, Iran; <sup>2</sup>Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; <sup>3</sup>St. Jude Children's Research Hospital, Oncology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: The literature on treating pediatric ependymoma in Iran is scarce. Thus, we designed this study to review the clinical care, treatment regimens, and follow‐up of Iranian pediatric patients with ependymoma.</p><p><bold>Design/Methods</bold>: Data were gathered from medical records retrospectively based on definitive inclusion and exclusion criteria. All of the patients were younger than 15 years and had an approved histopathology report confirming the diagnosis of ependymoma. Patients were divided into two subgroups based on their age at diagnosis (i.e., ≤3 years vs >3 years) and type of initial surgical procedure (i.e., surgery vs. biopsy). Finally, parametric and nonparametric statistical analyses were done SPSS software (ver 22).</p><p><bold>Results</bold>: In total, 73 eligible patients were enrolled in the study; 20 patients were categorized into the younger group and 53 into the older group. The majority (91.8%, n=67) of patients underwent initial gross‐total or partial surgical resection, and six (8.2%) had a biopsy. Thirty patients delayed diagnosis more than 1 month after the onset of clinical signs or symptoms, and 21 patients experienced ependymoma recurrence. The median duration of follow‐up was 49 months. The 3‐year overall survival and progression‐free survival rate were 61% and 48.5%, respectively. At the time of this review, 27 patients had died of various causes.</p><p><bold>Conclusions</bold>: We conclude that accurate disease staging and histopathology reporting and standardized radiotherapy and chemotherapy regimens need to be implemented in Iran to improve the clinical care and follow‐up of pediatric patients with ependymoma.</p><p><bold>Acknowledgement</bold>: We thank colleagues in the Medical Records department at MPCTRC who provided the medical documents for this review, Mr. Tim Hammond for assistance with graphic design of the figures, and Dr. Angela McArthur for editing the manuscript.</p></sec><sec id="pbc26772-sec-7170"><label>P-315</label><title>Early Diagnosis of Optic Glioma in Children with Neurofibromatosis Type 1 (NF1)</title><p><underline underline-style="single">M. Moschovi</underline><sup>1</sup>, M. Nikolaou<sup>1</sup>, A. Athanasiadou<sup>1</sup>, I. Nikas<sup>2</sup>, G. Chrousos<sup>3</sup></p><p><italic><sup>1</sup>University of Athens Medical School, 1st Pediatric Dept‐ Hematology/Oncology Unit, Athens, Greece; <sup>2</sup>“Aghia Sofia” Children's Hospital, Department of Imaging, Athens, Greece; <sup>3</sup>University of Athens Medical School, 1st Pediatric Department, Athens, Greece</italic></p><p><bold>Background/Objectives</bold>: Children with neurofibromatosis type‐1 (NF1) develop optic pathway gliomas, which result from impaired NF1 protein regulation of Ras activity. The importance of early diagnosis of optic pathway gliomas in children with Nf1, in order to eliminate the impairment of visual activity.</p><p><bold>Design/Methods</bold>: Twenty one children with optic pathway gliomas who were diagnosed and treated in our unit were enrolled in this study. Patients were divided in three groups. Group 1: seven patients without café‐au‐lait spots who were diagnosed because of symptoms caused by the tumor. Group II: seven patients with café‐au‐lait spots who had a routine follow‐up with brain‐MRI, from early age. Group III: seven patients with café‐au‐lait spots without routine follow‐up who were diagnosed due to visual loss or heavy decrease of visual activity. All patients received chemotherapy according to the NF1 gene status. All patients remain in follow‐up except one, who died from other cause.</p><p><bold>Results</bold>: The age at diagnosis of optic pathway gliomas ranged from 3 months‐10 years. (Medium: 3 years). Group I: The age ranged from 3 months‐6 years (Median: 4 years). Total visual loss after biopsy was noted in two cases. Group II: The patients’ age ranged from 8 months‐3 years (median: 2 years). They had progressively decrease visual activity at diagnosis. They received chemotherapy. Significant improvement of the visual activity was noted. Group III: The patients’ age ranged from 3 years‐10 years (Median: 3 years). They received chemotherapy, but there was no improvement of the visual activity.</p><p><bold>Conclusions</bold>: 1) Children with Café au lait spots need a careful monitoring of the visual activity and imaging for optic glioma. 2) Early diagnosis of tumor and detection of visual impairment may help to improve the visual activity with chemotherapy. 4) Chemotherapy is not effective in delay diagnosis of the optic pathway gliomas.</p></sec><sec id="pbc26772-sec-7180"><label>P-316</label><title>Oxytocin in Childhood‐Onset Craniopharygioma ‐ First Experiences with Neuropsychological Effects of Oxytocin Administration</title><p><underline underline-style="single">H.L. Müller</underline><sup>1</sup>, A. Daubenbüchel<sup>1</sup>, A. Hoffmann<sup>1</sup>, K. Tjaden<sup>1</sup>, S. Boekhoff<sup>1</sup>, M. Warmuth‐Metz<sup>2</sup>, J. Özyurt<sup>3</sup></p><p><italic><sup>1</sup>Klinikum Oldenburg AöR‐ Medical Campus University Oldenburg, Department of Pediatrics and Pediatric Hematology / Oncology, Oldenburg, Germany; <sup>2</sup>University of Würzburg, Department of Neuroradiology, Würzburg, Germany; <sup>3</sup>Carl von Ossietzky University‐ Oldenburg, Department of Psychology, Oldenburg, Germany</italic></p><p><bold>Background/Objectives</bold>: Quality of survival after childhood craniopharyngioma (CP) is frequently impaired by hypothalamic involvement (HI) and sequelae such as obesity and neuropsychological deficits. Oxytocin (OXY) is produced in the hypothalamus, secreted by posterior pituitary gland, and plays a major role in regulation of behavior and body composition.</p><p><bold>Design/Methods</bold>: In a cross‐sectional study, OXY saliva concentrations were analyzed in 34 CP and in 73 healthy controls. OXY was measured in saliva before and after standardized breakfast and associations with gender, body mass index (BMI), HI, diabetes insipidus, and irradiation were analyzed. Furthermore, emotion recognition abilities were analyzed with regard to OXY concentrations in saliva and urine before and after nasal administration of 24 IU OXY in 10 CP with hypothalamic lesions (4 grade I: limited to anterior hypothalamus; 6 grade II: involving mammillary bodies and posterior hypothalamus). Perception and identification of emotional expressions were tested using the Geneva Multimodal Emotion Portrayals (GEMEP) corpus. Mental state was assessed by Multidimensional Mood Questionnaire.</p><p><bold>Results</bold>: CP with preoperative HI showed similar OXY levels compared to CP without HI and controls. However, CP with grade I hypothalamic lesions presented with lower OXY levels (p=0.017) under fasting condition compared to CP with grade II lesions and CP without hypothalamic lesions. CP patients’ changes in OXY levels before and after breakfast correlated (p=0.02) with BMI. In a pilot trial, nasal administration of OXY was well tolerated and resulted in increased OXY concentrations in saliva and urine. After OXY administration, CP with grade I hypothalamic lesions showed improvements in emotional identifications compared to CP with grade 2 lesions.</p><p><bold>Conclusions</bold>: CP patients continue to secrete OXY, especially when anterior hypothalamic areas are not involved, but OXY shows less variation due to nutrition. OXY might have positive effects on emotion perception in CP with specific lesions of anterior hypothalamic areas.</p></sec><sec id="pbc26772-sec-7190"><label>P-317</label><title>The Oncogenic Role of a Novel KLC1‐ROS1 Fusion Gene Identified in a Pediatric Low‐Grade Glioma</title><p><underline underline-style="single">Y. Nakano</underline><sup>1</sup>, A. Tomiyama<sup>1</sup>, K. Yamasaki<sup>1</sup>, H. Fukushima<sup>2</sup>, T. Inoue<sup>2</sup>, T. Kohno<sup>3</sup>, A. Yoshida<sup>4</sup>, K. Fukuoka<sup>1</sup>, Y. Matsusaka<sup>5</sup>, J. Hara<sup>6</sup>, H. Sakamoto<sup>5</sup>, K. Ichimura<sup>1</sup></p><p><italic><sup>1</sup>National Cancer Center Research Institute, Division of Brain Tumor Translational Research, Tokyo, Japan; <sup>2</sup>Osaka City General Hospital, Department of Pathology, Osaka, Japan; <sup>3</sup>National Cancer Center Research Institute, Division of Genome Biology, Tokyo, Japan; <sup>4</sup>National Cancer Center Hospital, Department of Pathology and Clinical Laboratories, Tokyo, Japan; <sup>5</sup>Osaka City General Hospital, Department of Pediatric Neurosurgery, Osaka, Japan; <sup>6</sup>Osaka City General Hospital, Department of Pediatric Hematology/Oncology, Osaka, Japan</italic></p><p><bold>Background/Objectives</bold>: We investigated novel oncogenic fusion genes identified in pediatric gliomas for their potential as novel therapeutic targets.</p><p><bold>Design/Methods</bold>: RNA sequencing was performed on three pediatric low grade gliomas which did not harbor any of the oncogenic driver mutations known in gliomas (BRAF, FGFR1, IDH1, IDH2 and H3F3A) to discover novel oncogenic gene fusions. The presence of candidate fusion genes in clinical samples was verified by fluorescence in‐situ hybridization and their expression by reverse transcription polymerase chain reaction and immunohistochemical staining. Several oncogenic signal transduction pathways and oncogenic phenotypes mediated by these candidates were also analyzed by immunoblotting, focus forming assay, and invasion assay using glioma cell lines overexpressing these candidates.</p><p><bold>Results</bold>: We identified a novel KLC1‐ROS1 fusion gene in a low‐grade glioma from a three‐years‐old female patient. Expression of this fusion RNA and protein in the clinical sample was confirmed. An immunoblot analysis of cell lysates of glioma cell lines expressing the KLC1‐ROS1 fusion gene demonstrated an elevated activation of growth factor‐related signaling such as ERK1/2, Akt, or mTOR. Furthermore, the glioma cell lines transfected with this fusion gene demonstrated enhanced formation of foci by focus forming assay and elevated invasiveness by transwell invasion assay, all of which were blocked by treatment with ROS1 inhibitor, Crizotinib.</p><p><bold>Conclusions</bold>: The novel KLC1‐ROS1 fusion gene which we identified from a pediatric low grade glioma has an oncogenic activity via ROS1 signaling and could potentially serve as a novel therapeutic target against gliomas which possess this fusion gene.</p></sec><sec id="pbc26772-sec-7200"><label>P-318</label><title>Molecular Characterization of NF1 Gene in a Small Turkish Population with Neurofibromatosis Type 1 and a Novel Mutation</title><p>F.G. Pinarli<sup>1</sup>, F. Alpaslan Pinarli<sup>2</sup>, H. Saat<sup>2</sup>, C. Yildirimoglu<sup>2</sup>, A. Okur<sup>1</sup>, <underline underline-style="single">C. Karadeniz</underline><sup>1</sup></p><p><italic><sup>1</sup>Gazi University Medical Faculty, Pediatric Oncology, Ankara, Turkey; <sup>2</sup>Diskapi Yildirim Beyazit Research Hospital, Medical Genetics, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: Neurofibromatosis type I (NF1) is an autosomal dominant disorder caused by heterozygous mutations in the neurofibromin gene (NF1; 613113) on chromosome 17q11. Here we describe the results of next generation sequencing (NGS) of 18 patients who presented with the clinical features of NF‐1 at Gazi University Department of Pediatric Oncology.</p><p><bold>Design/Methods</bold>: DNA was isolated from peripheral blood using MagNA Pure LC DNA Isolation Kit. Ion Ampliseq Custom NF Panel has been designed and used for massively parallel sequencing for target regions (all Exons, UTRs, Splicing sites) of NF1 gene with IonS5. Mutation surveying has been done by using Ion Reporter and Alamut Visual software and different mutation databases and tools according to the 2016 ACMG Variant Classification and Interpretation Guideline. Detected mutations which have been linked with Clinical data have been confirmed with DNA Sequencing by Capillary electrophoresis by using 3130 (Applied Biosystems).</p><p><bold>Results</bold>: The study included 10 male and 8 female patients with a median age of 10.5 years. Sixteen patients were diagnosed as NF‐1 according to clinical criteria. Two patients had only multiple café‐au‐lait spots. The family history was present in 7 patients (38.9%). Three patients had optic gliomas (16.7%) and one patient was diagnosed as atypical meningioma after surgical excision. We detected a genetic variant in 12 patients (66.6%) via NGS. The types of these mutations were as follows: likely benign (n=1), variants of uncertain significance (VUS, n=2), likely pathogenic (n=3), VUS + pathogenic (n=1), and pathogenic (n=5). One of the pathogenic variants is c.7023delC (p.Leu2342Cysfs*4) heterozygote at 47<sup>th</sup> exon, which was not previously described in the NF‐1 database, ithus ndicating a novel mutation.</p><p><bold>Conclusions</bold>: We describe a novel <italic>NF‐1</italic> gene mutation in a Turkish patient. The lack of mutation detection in 33,3% of our patients indicate that other methods than NGS must be used in <italic>NF‐1</italic> mutation screening.</p></sec><sec id="pbc26772-sec-7210"><label>P-319</label><title>Pediatric Medulloblastoma Experience in Mexico</title><p><underline underline-style="single">V.</underline><underline underline-style="single">Salceda‐rivera</underline><sup>1</sup>, F. Arreguin<sup>2</sup>, R. Gonzalez<sup>3</sup>, R. Bellido<sup>4</sup>, I. Tejocote<sup>5</sup>, S. Anaya<sup>6</sup>, R. Rivera‐luna<sup>7</sup>, E. Perez<sup>8</sup>, E. Reyes<sup>9</sup>, D. Ortiz<sup>10</sup>, R. Rivera<sup>11</sup>, C. Leal<sup>12</sup>, A. Garcia<sup>13</sup>, N. Garcia<sup>14</sup>, S. Lagarda<sup>15</sup>, T. Larios<sup>16</sup>, D. Cortes<sup>17</sup>, C. Simon<sup>18</sup>, A. Lopez<sup>19</sup>, J. Finlay<sup>20</sup></p><p><italic><sup>1</sup>Onkokid, Pediatric Oncology, Guadalajara, Mexico; <sup>2</sup>Centro Médico Nacional 20 de Noviembre, Pediatric Oncology, Ciudad de Mexico, Mexico; <sup>3</sup>Centenario Hospital Miguel Hidalgo de Aguascalientes, Pediatric Oncology, Aguascalientes, Mexico; <sup>4</sup>Hospital General Regional de León, Pediatric Oncology, Leon, Mexico; <sup>5</sup>Hospital para el Niño IMIEM, Pediatric Oncology, Toluca, Mexico; <sup>6</sup>Centro Médico Nacional La Raza, Pediatric Oncology, Ciudad de Mexico, Mexico; <sup>7</sup>Instituto Nacional de Pediatría, Pediatric Oncology, Ciudad de Mexico, Mexico; <sup>8</sup>Hospital Infantil de Morelia Eva Samano de López Mateos, Pediatric Oncology, Morelia, Mexico; <sup>9</sup>Hospital de Especialidades del Niño y la Mujer, Pediatric Oncology, Queretaro, Mexico; <sup>10</sup>Hospital General de México “Eduardo Liceaga”, Pediatric Oncology, Ciudad de Mexico, Mexico; <sup>11</sup>Hospital General de Tijuana, Pediatric Oncology, Tijuana, Mexico; <sup>12</sup>Hospital Universitario Dr. Jose E. González UNAL, Pediatric Oncology, Monterrey, Mexico; <sup>13</sup>Hospital Infantil de Especialidades, Pediatric Oncology, Chihuahua, Mexico; <sup>14</sup>Hospital del niño Dr. Federico Gómez Santos, Pediatric Oncology, Coahuila, Mexico; <sup>15</sup>Instituto Estatal de Cancerología de Colima, Pediatric Oncology, Colima, Mexico; <sup>16</sup>Hospital Infantil e Integral de la mujer del Estado de Sonora, Pediatric Oncology, Sonora, Mexico; <sup>17</sup>Hospital del Niño DIF del Estado de Hidalgo, Pediatric Oncology, Pachuca, Mexico; <sup>18</sup>Hospital del Niño Dr. Rodolfo Nieto Padrón, Pediatric Oncology, Tabasco, Mexico; <sup>19</sup>Hospital materno infantil de ISSEMYM, Pediatric Oncology, Toluca, Mexico; <sup>20</sup>Nationwide Children's Hospital, Pediatric Neuro‐Oncology, Columbus, Mexico</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma is the most common malignant brain tumor in children. Data from developing countries is limited. We describe our multi‐institutional experience in pediatric medulloblastoma in Mexico.</p><p><bold>Objectives</bold>: To describe the clinical features of Mexican children with medulloblastoma. Draw comparisons of the different chemotherapy regimens used, determine patient overall (OS) and event‐free survival (EFS). Determine clinical risk factors for death or relapse.</p><p><bold>Design/Methods</bold>: We conducted a retrospective multivariate analysis of patients with medulloblastoma from 20 hospitals around Mexico, between 1997‐2017. Statistical methods used were the Kaplan‐Meier curve, the survival log‐rank test, and Cox‐regression model. Patients were divided into two groups: 1)children >3‐5 years of age with non‐metastatic disease, and post‐surgical tumor <1.5cm<sup>2</sup>, compromised the standard‐risk group; 2)patients without the previously mentioned characteristics were classified as high‐risk.</p><p><bold>Results</bold>: A total of 255 patients were included with an average age at diagnosis of 6.8 years (0.1‐17yo), 17.6% <3yo, 23.1% were standard‐risk, and 76.9% were high‐risk. Histology: classic (53.3%), desmoplastic (14.5%), anaplastic/large cell (9.4%), not specified (22.7%). According to Chang's classification: M0(53.3%), M1(15.7%), M2(11.8), M3(11%), M4(2%). Chemotherapy regimens used were: ICE (52.2%), cisplatin‐based (22%), carboplatin‐based (10.6%), others (3.5%). The platinum‐based regimens had better OS compared to ICE (5y‐EFS 71.1% vs. 64.1%; p=0.002). The average radiation therapy dose was 29Gy (10‐55Gy) craniospinal and 52.5Gy (24‐56Gy) to the posterior fossa. The hazard ratios calculated at p<0.05 were as follows: high‐risk 3.55, residual tumor >1.5cm<sup>2</sup> 3.53, anaplastic 2.5, presence of metastasis 1.76, ICE protocol 1.73. The 5y‐OS was 61.1% and the 5y‐EFS 54.2%.</p><p><bold>Conclusions</bold>: The most commonly used chemotherapy regimen was ICE and was related to a significantly lower OS. Patients with residual tumor, anaplastic histology or metastasis were also associated with a lower OS. We need multi‐institutional prospective clinical trials to better define survival, risk factors and outcome in Mexico.</p></sec><sec id="pbc26772-sec-7220"><label>P-320</label><title>Medulloblastomas in Children Under Five Years: Current Prognostic Factors and Treatment Results</title><p><underline underline-style="single">E. Salnikova</underline><sup>1</sup>, S. Ozerov<sup>1</sup>, A. Samarin<sup>2</sup>, A. Ektova<sup>3</sup>, M. Ryzhova<sup>4</sup>, A. Korshunov<sup>5</sup>, O. Zheludkova<sup>6</sup>, L. Papusha<sup>1</sup>, I. Borodina<sup>7</sup>, A. Nechesnyuk<sup>8</sup>, D. Kobyzeva<sup>8</sup>, O. Shcherbenko<sup>9</sup>, S. Gorbatykh<sup>10</sup>, E. Erega<sup>11</sup>, A. Shapochnik<sup>12</sup>, E. Inyushkina<sup>13</sup>, A. Karelin<sup>14</sup>, A. Rumyantsev<sup>15</sup>, E. Kumirova<sup>1</sup></p><p><italic><sup>1</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Neurooncology, Moscow, Russia; <sup>2</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Surgery, Moscow, Russia; <sup>3</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Patomorfology, Moscow, Russia; <sup>4</sup>N. N. Burdenko Scientific Research Neurosurgery Institute, Neuropatomorfology, Moscow, Russia; <sup>5</sup>The German Cancer Research Center, Patomorfology, Heidelberg, Germany; <sup>6</sup>Federal State Budgetary Institution Russian Scientific Center of Roentgenoradiology, Oncology, Moscow, Russia; <sup>7</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Polyclinic, Moscow, Russia; <sup>8</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Radiotherapy, Moscow, Russia; <sup>9</sup>Federal State Budgetary Institution Russian Scientific Center of Roentgenoradiology, Radiology, Moscow, Russia; <sup>10</sup>Morozovsky Children's City Hospital, Oncology, Moscow, Russia; <sup>11</sup>Children's regional clinical hospital, Oncogematology, Khabarovsk, Russia; <sup>12</sup>Orenburg regional oncological clinic, Children's dep, Orenburg, Russia; <sup>13</sup>Moscow regional oncological clinic, Children's dep, Balashiha, Russia; <sup>14</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Medical and rehabilitation scientific center, Moscow, Russia; <sup>15</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Director General, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Current diagnostic capabilities will enable to modify risk group and individualize treatment patients with medulloblastoma. To evaluate treatment results of 48 patients under 5 years (13‐57m, median 42.5m) with primarily diagnosed medulloblastoma (MB) depending on the current risk factors.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed the data of 48 patients, who are observed in Rogachev's Center from September 2002 till February 2017. Molecular genetic testing was perfomed in all cases (DKFZ, Germany): Gr3 was diagnosed in 21 cases (44%), Gr4 ‐ 12 (25%), SHH ‐ 14 (29%), WNT in 1. MYC/MYCN amplification/17q gain/17q loss/6q loss were in 3/2/17/11/1 cases. HIT 2000/2008 treatment regimen used in 25 patients. Gr3: M0/M+ 9/12, R0/R+/Rx 6/14/1, classic/anapl/desmo 15/4/2, without regional MTX/with intraventricular/intrathecal MTX 14/6/1, with/without RT 20/1, PD in 11 cases (52.4%), are alive 14 (66.7%). Gr4: M0/M+ 5/7, R0/R+ 5/7, classic/anapl/desmo 8/3/1, without regional MTX/with intraventricular/intrathecal MTX 10/1/1, with/without RT 11/1, PD in 2 cases (16.7%), are alive 10 (83.3%). SHH: M0/M+ 7/7, R0/R+/Rx 6/6/2, classic/anapl/desmo 2/1/11, without regional MTX/with intraventricular/intrathecal MTX 7/6/1, with/without RT 10/4, PD in 3 cases (21.4%), are alive 12 (85.7%).</p><p><bold>Results</bold>: OS in Gr3/Gr4/SHH/WNT 0.63/0.77/0.86/1.00 (р=0.15). PFS in Gr3/Gr4/SHH/WNT 0.47/0.83/0.79/1.00 (р=0.06). PFS with/without MYC/MYCN‐amplification 0.4/0.69 (p=0.16). Gr3 PFS: 12‐36m/36‐60m 0.33/0.5 (p=0.56); R+/R0 0.44/0.5 (p=0.59); М0/М+ 0.56/0.42 (р=0.57); classic/anapl/desmo 0.53/0.5/0 (р=0.73); with/without regional MTX 0.5 (p=0.82); with RT 0.5±0.11. Gr4 PFS: 36‐60m 0.81±0.12, single patient 12‐36m is alive, without PD; R+/R0 0.72/1.00 (p=0.24); М0/М+ 0.8/0.86 (р=0.90); classic/anapl 0.73/1.00 (р=0.33); without/with local MTX 0.79/1.00; with/without RT 0.81/1.00. SHH PFS: 12‐36m/36‐60m 0.72/0.86 (p=0.53); R0 0.67, R+patients are alive, without PD; М0/М+ 0.72/0.86 (р=0.53); desmo 0.73±0.08; with intraventrMTX 0.5±0.15, patients without regional MTX are alive, without PD; with/without RT 0.8/0.75 (p=0.84).</p><p><bold>Conclusions</bold>: The worst prognosis in Group 3 patients under 3 years, with R+, M+. For further strategy treatment verification additional studies are needed.</p></sec><sec id="pbc26772-sec-7230"><label>P-321</label><title>The Changing Paradigm of Pediatric Medulloblastoma in Kerala; Improved Outcomes with New Challenges</title><p>S. Kotne<sup>1</sup>, A. Philip<sup>1</sup>, R. Pillai<sup>1</sup>, W. Jose<sup>1</sup>, D. Menon<sup>2</sup>, K. Pavithran<sup>1</sup>, <underline underline-style="single">H. Sankaran</underline><sup>1</sup></p><p><italic><sup>1</sup>Amrita Institute of Medical Sciences, Department of Medical Oncology, Ernakulam, India; <sup>2</sup>Amrita Institute of Medical Sciences, Department of Radiation Oncology, Ernakulam, India</italic></p><p><bold>Background/Objectives</bold>: Treatment outcomes for medulloblastoma with optimal therapy (surgery, radiation and chemotherapy) have led to 5‐year overall survival (OS) rates in developed countries of 80% and 60% for standard and high risk disease, respectively. In resource limited settings, similar outcomes are possible and new challenges include follow‐up of treatment related side effects. This study assessed the outcomes of medulloblastoma in a tertiary care setting and follow‐up of these patients.</p><p><bold>Design/Methods</bold>: A total of 36 cases of medulloblastoma below 18 years were treated on POG9031 or CCG9921 between January 2005 and January 2015. Patients were classified as standard risk or high risk disease based on modified Chang criteria. The prognostic value of age, sex, risk category, histopathological variants was assessed by univariate analysis using the log‐rank test. Nonparametric OS curves were computed using the Kaplan‐Meier estimates, and the log‐rank test was used to compare survival according to histologic subtype.</p><p><bold>Results</bold>: A total of 27 cases were eligible for analysis. The median age of diagnosis was 8 years and median follow‐up was 24 months. The 5‐year OS and 95% confidence interval was 90% (95% CI: 47‐99%) and 60% (95% CI:13‐88%) for standard risk and high‐risk disease, respectively. 17 (63%) cases had regular follow‐up with a medical provider post completion of therapy, 8 (33%) cases were documented to have mild cognitive decline, though no formal testing had been done.10 cases (40%) were regularly followed for endocrine sequelae, of which 2 cases (7%) had a diagnosed growth hormone deficiency.</p><p><bold>Conclusions</bold>: Based on our institutional data, we found that our medulloblastoma outcomes were similar to what has been reported in developed countries.</p><p>However new challenges exist in the follow‐up and management of treatment related side effects in these patients. This underlies the current need for multi‐disciplinary follow‐up and care of this ever‐growing population of cancer survivors.</p></sec><sec id="pbc26772-sec-7240"><label>P-322</label><title>Evaluation of Gaze Stability by Eye Tracking Method in Patients with Medulloblastoma</title><p>M. Shurupova<sup>1</sup>, V. Anisimov<sup>1</sup>, <underline underline-style="single">A. Drenyova</underline><sup>1</sup>, A. Latanov<sup>2</sup>, V. Kasatkin<sup>1</sup></p><p><italic><sup>1</sup>Dmitry Rogachev National Research Center, Clinical Rehabilitation Research Center for patients in remission “Russkoye pole”, Moscow, Russia; <sup>2</sup>Lomonosov State University, Faculcity of Biology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Cerebellum plays a crucial role in motor control and planning. The lesions of the cerebellum lead to oculomotor impairments. Medulloblastoma is a severe disease and is localized mostly in the area of vermis and hemispheres of cerebellum. Presence of a malignant growth and therapy's toxicity lead to stable invalidism.</p><p><bold>Design/Methods</bold>: We assessed the feasibility of a test of gaze stabilization on a target in patients with medulloblastoma. Patients underwent a standard course of rehabilitation in Rehab Centre “Russian Field” (Chekhov, Russian Federation). Five patients (three girls and two boys, aged 13.4‐17.9 years) and eight normal subjects (three girls and five boys, aged 10.6‐15.2 years) participated in the study. Eye movements were recorded by Arrington Research 60 Hz eye tracker. In experiments the participants performed the gaze stabilization test (GST) involved the focusing on the four targets (left and right, up and down at ±19° and ±11° of eccentricities, respectively). Two GST sessions were carried out during first and second rehabilitation courses separated by 3.2‐9.2 months interval.</p><p><bold>Results</bold>: The gaze dispersion in patients were higher compared with that in normal subjects (p<0.0001). Such instability relates foremost to oculomotor control disorders in patients which manifest in macrosaccadic oscillations, nystagmus, intrusive saccades, and square wave jerks. A decrease of gaze dispersion in four patients (p<0.0001 for each) occurred in the second GST session, presumably caused by reduction of intrusive saccades frequency and context inappropriate saccades both representing higher efficacy of voluntary attention control.</p><p><bold>Conclusions</bold>: Patients with medulloblastoma demonstrated poor gaze stability compared to normal subjects. The positive dynamics of gaze stability in patients has been achieved by rehabilitation courses. Eye movement patterns could be considered as objective indicators of specific oculomotor disorders. Eye tracking method represents additional diagnostic tool in rehabilitation practice.</p></sec><sec id="pbc26772-sec-7250"><label>P-323</label><title>Focal Radiotherapy and Temozolomide Following Complete Resection are Superior to Intensive Chemotherapy in Children with Embryonal Tumors with Multilayered Rosettes (ETMR)</title><p><underline underline-style="single">I. Slavc</underline><sup>1</sup>, A. Peyrl<sup>1</sup>, A.A. Azizi<sup>1</sup>, J. Gojo<sup>1</sup>, D. Reisinger<sup>1</sup>, L. Mayr<sup>1</sup>, T. Czech<sup>2</sup>, K. Dieckmann<sup>3</sup>, C. Haberler<sup>4</sup></p><p><italic><sup>1</sup>Medical University of Vienna, Pediatrics, Vienna, Austria; <sup>2</sup>Medical University of Vienna, Neurosurgery, Vienna, Austria; <sup>3</sup>Medical University of Vienna, Radiotherapy, Vienna, Austria; <sup>4</sup>Medical University of Vienna, Institute of Neurology, Vienna, Austria</italic></p><p><bold>Background/Objectives</bold>: Embryonal tumor with multilayered rosettes (ETMR) is a rare new entity characterized by LIN28A expression and alterations in the C19MC locus at 19q13.42. ETMR occurs in young children and has a dismal prognosis. We report on our single institution experience in seven consecutive patients.</p><p><bold>Design/Methods</bold>: Between 2006 and 2016, seven patients were diagnosed with an ETMR. Diagnosis was established prospectively by characteristic histopathologic features, LIN28 immunostaining and amplification of the locus 19q13.42 in five patients and retrospectively confirmed in 2 additional patients originally diagnosed as CNS PNET (central nervous system primitive neuroectodermal tumor).Tumor location was supratentorial in all patients. Median age at diagnosis was 25 months (range 6‐38). Male to female ratio was 1:6.</p><p><bold>Results</bold>: All patients had a GTR or near total resection and the first five patients were treated according to high risk PNET or ATRT (atypical teratoid rhabdoid tumor) protocols including high‐dose chemotherapy in three patients. All five patients recurred after a median of 6 months (range 2‐11) and all except one patient who died after high dose chemotherapy succumbed to their disease after a median of 13 months (range 7‐28). Following a case report by Mozes et. al., (1) the last two patients were treated with primary focal radiotherapy, intrathecal therapy and concomitant temozolomide followed by 12 courses of temozolomide 150‐200mg/m2. Both patients are in CR 18 and 12 months after diagnosis.</p><p><bold>Conclusions</bold>: Complete surgical removal followed by early focal radiotherapy and temozolomide seems to be superior to intensive conventional therapy including high‐dose chemotherapy.</p><p>(1) Mozes P., Hauser P., Hortobagyl T. et al., Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR). J Neurooncol (2016) 126:99‐105</p></sec><sec id="pbc26772-sec-7260"><label>P-324</label><title>Application of VMAT Technology in the Treatment of Anaplastic Ependymoma</title><p><underline underline-style="single">E. Slobina</underline><sup>1</sup>, F. Antonenko<sup>1</sup>, O. Zheludkova<sup>1</sup>, N. Zelinskaya<sup>1</sup></p><p><italic><sup>1</sup>Russian Scientific Center of RoentgenoRadiology, Radiotherapy of Children Diseases, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Demonstrate the possibility of clinical application of modern methods of radiation therapy of anaplastic ependymoma.</p><p><bold>Design/Methods</bold>: From January 2016 to February 2017, five patients (median age 3 years) for anaplastic ependymoma received complex treatment according to the protocol HIT2014, consisting of courses of weekly vincristine‐containing chemotherapy and external beam irradiation in the volume of craniospinal irradiation (CSR) (dose per fraction 1,6Gr, total dose 24Gr (35.2 Gy), followed by local irradiation of the postoperative bed of the removed tumor, dose per fraction 1.8Gr up to total dose 55Gr was carried out. Preliminary radiotherapy planning was performed using the 3D conformal radiotherapy with optimization (IMRT) for all patients. After analyzing the received dose‐volume histograms (DVH), VMAT was used in the CSR in 2 patients, and in 3 patients in the local irradiation. In 4 patients, treatment was performed using 1‐2 coplanar treatment arches, in 1 patient ‐ using 2 non‐planar therapeutic arches. Radiotherapy using VMAT technology was performed using the Eclipse planning system on the Truebeam linear accelerator.</p><p><bold>Results</bold>: When comparing the results of the preliminary planning of IMRT and VMAT, the total treatment time was reduced from 10‐15 minutes with IMRT up to 2‐4 minutes at VMAT. The number of monitoring units (MU) decreased 2.3 times on average with VMAT, while the coverage of the planned treatment volume with 95% treatment isodose did not significantly differ: 97.6% (IMRT) and 94.8% (VMAT) with a significant reduction in the radiation load on the dose‐limiting organs. The early and late side effects of radiation therapy (RTOG scale) were minimal.</p><p><bold>Conclusions</bold>: The use of VMAT opens new possibilities in the treatment of oncological diseases in children, because due to the above described properties, the risk of developing induced secondary tumors will decrease, and the time of finding the child on the treatment unit will be significantly reduced.</p></sec><sec id="pbc26772-sec-7270"><label>P-325</label><title>Targeted Therapy in Patients with Progressive Low Grade Gliomas</title><p><underline underline-style="single">D. Sumerauer</underline><sup>1</sup>, S. Cyprova<sup>1</sup>, M. Kyncl<sup>2</sup>, J. Zamecnik<sup>3</sup>, L. Krskova<sup>3</sup>, E. Kabickova<sup>1</sup></p><p><italic><sup>1</sup>Faculty Hospital Motol, Department of Pediatric Hematology and Oncology, Prague 5, Czech Republic; <sup>2</sup>Faculty Hospital Motol, Department of Imaging Methods, Prague 5, Czech Republic; <sup>3</sup>Charles University, Department of Pathology and Molecular Medicine, Prague 5, Czech Republic</italic></p><p><bold>Background/Objectives</bold>: Pediatric low‐grade gliomas are the most common brain tumors in children. They are characterized by alterations of the Ras/MAPK pathway. Although frequently cured with complete resection, patients with unresectable lesions experience multiple progressions and are at increased risk for long‐term neurological sequelae.</p><p><bold>Design/Methods</bold>: We present our experience with targeted therapy in 4 patients with recurrent low grade glioma, treated at the time of progression with either BRAF inhibitor (dabrafenib) or MEK‐inhibitor (trametinib) according to the molecular alteration detected in the tumor tissue.</p><p><bold>Results</bold>: Two patients, 8.5 year old boy with recurrent thalamic PXA and 6‐month old boy with rapidly progressing optic pathway glioma started dabrafenib treatment at a dose 5.25 mg/kg/day upon BRAF V600E activating mutation was detected in the recurrent tumor. Both boys experienced profound radiological response and rapid clinical improvement. No toxicities were seen except self‐limiting itchy macular rash in older boy lasting for two weeks only, immediately at the beginning of the treatment. Two other patients (4.5 year old boy with OPG, 17 year old girl with NF‐1 and posterior fossa/brainstem glioma) with BRAF fusion, were treated with trametinib at a dose 0.025 mg/kg/day. Both patient obtained disease stabilization while on treatment, but the girl repeatedly experienced grade 2 papulopustular rash.</p><p><bold>Conclusions</bold>: Dabrafenib is active and well tolerated among patients with BRAF V600 mutation‐positive pediatric recurrent low‐grade glioma, trametinib at least stabilizes tumors with BRAF fusion, again with minimal toxicity</p></sec><sec id="pbc26772-sec-7280"><label>P-326</label><title>Clinicopathological Review of Paediatric Meningioma from A Single Centre</title><p><underline underline-style="single">E. Tan</underline><sup>1</sup>, K. Phipps<sup>2</sup>, S. Yasin<sup>3</sup>, J. Pickles<sup>3</sup>, M. Jorgensen<sup>4</sup>, K. Aquilina<sup>2</sup>, T.S. Jacques<sup>3</sup>, D. Hargrave<sup>4</sup></p><p><italic><sup>1</sup>KK Women's and Children's Hospital, Paediatric Haematology & Oncology, Singapore, Singapore; <sup>2</sup>Great Ormond Street Hospital, Department of Neurosurgery, London, United Kingdom; <sup>3</sup>UCL Great Ormond Street Institute of Child Health, Developmental Biology & Cancer Programme, London, United Kingdom; <sup>4</sup>Great Ormond Street Hospital, Department of Haematology & Oncology, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Paediatric meningiomas constitute ∼2% of paediatric CNS tumours, and differ from adult meningiomas in certain aspects. Current management recommendations include complete resection, careful pathological review and multidisciplinary discussions regarding postoperative treatment.</p><p><bold>Design/Methods</bold>: Retrospective analysis of 37 children with meningioma diagnosed between 1990 to 2016 was conducted. Data on patient demographics, tumour characteristics, treatment and outcomes was obtained from hospital records. Histopathological specimens were reviewed to align the subtype and grade with the WHO 2016 classification.</p><p><bold>Results</bold>: Median age of diagnosis was 10.01 years (range: 1.03 – 16.03). Male: female ratio was 1.4:1. Nine patients had neurofibromatosis type‐2 (NF‐2) (24.3%), one had neurofibromatosis type‐1 (NF‐1) and two had previous cranial radiotherapy. Histopathology review confirmed the majority of meningiomas to be low grade (WHO Grade I or II). Two had rhabdoid meningioma (WHO Grade III) – one died within 5 months despite complete resection (CR) and radiotherapy, whereas the other patient is still alive 6 years after CR. Three had multiple meningiomas in both intracranial and spinal compartments. About one third of patients had meningiomas at skull base (n=12). Other tumour locations were intraventricular (n=6), convexity (n=6), spinal (n=5), extracranial (two involving optic nerve sheath, one occurring in maxillary sinus antrum) and sylvian fissure (n=2).2 patients had biopsies, 13 had incomplete resection and 22 achieved complete resection (5 achieved with more than 1 operative procedures). 7 patients had adjuvant radiotherapy as part of primary treatment.Median follow‐up was 5.18 years (range: 0.15 – 21.75). Relapse occurred in 2/22 (9.1%) with complete resection and in 6/10 (60%) with incomplete resection and no adjuvant radiotherapy.</p><p><bold>Conclusions</bold>: The strong association with NF2 reinforces recommendations for genetics referral to look for associated syndromes. Age, extent of resection and histological grade are factors for consideration in postoperative treatment. Relapse was higher without complete resection.</p></sec><sec id="pbc26772-sec-7290"><label>P-327</label><title>Investigation of RBM24 as a Potential Regulator of Cellular Proliferation, Apoptosis and Chemoresistance in Medulloblastoma</title><p>G. Alencastro Veiga Cruzeiro<sup>1</sup>, M. Baroni<sup>2</sup>, K. Bezerra Salomão<sup>2</sup>, R.C. Peixoto Lira<sup>2</sup>, L. Geron<sup>2</sup>, A.F. Andrade<sup>3</sup>, C. Alves Corrêa<sup>2</sup>, D. Antunes Moreno<sup>2</sup>, V. Silva Silveira<sup>4</sup>, C.A. Scrideli<sup>2</sup>, <underline underline-style="single">L. Gonzaga Tone</underline><sup>2</sup></p><p><italic><sup>1</sup>Ribeirao Preto Medical School ‐ University of Sao Paulo, Pediatrics, Ribeirao Preto, Brazil; <sup>2</sup>FMRP USP, Pediatrics, Ribeirão Preto, Brazil; <sup>3</sup>Institut de Recherche en Cancérologie de Montpellier IRCM‐ France, Cancérologie, Montpellier, France; <sup>4</sup>FMRP USP, Genetics, Ribeirão Preto, Brazil</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma (MB) is the most common malignant brain tumor in children and is classified in subgroup Wnt, Shh, Group 3 and Group 4. Despite the current therapy displayed good outcomes, patients with MB SHH TP53 mutant have poor prognosis due to primary resistance to chemotherapy and progressive metastasis. Our study identified a RNA Binding protein named RBM24 overexpressed in MB SHH TP53 mutant cell lines and in TP53 allele Loss in patients. We performed Knockout in RBM24 gene on mutant <italic>TP53</italic> cell lines in prior to investigate its roles in Apoptosis and proliferation.</p><p><bold>Design/Methods</bold>: To assess mRNA levels of <italic>RBM24</italic> in MB cell lines and patients with MB. It was performed Real Time PCR using TaqMan probes for RBM24 (Hs00290607_m). The platform Methylation array Illumina 450k was used to asses copy number profile of TP53 in patients with MB. Trough lentiviral transduction and flow sorting of GFP‐expressing cells, it was generated UW473 CRISPR RBM24‐KO (KO) Mutant TP53 MB cell line. It was performed <italic>in vitro</italic> Proliferation assay using CKK8 cell counting and Annexin‐V (FITC) kit for apoptosis assay. All experiments were performed thrice. One‐way ANOVA was performed for Statistical analysis.</p><p><bold>Results</bold>: Our study identified reduction of cellular proliferation and increase of apoptosis levels in KO cell lines. Moreover, when treated with Doxorubicin for 48h, we identified a decrease in proliferation of 95% when compared to untreated control and 45% compared to treated control. For apoptosis, 80% of KO cells went for early apoptosis and 20% for late apoptosis. We also detected an increase in protein levels of P53 phosphorylation, P63‐alpha, P73 and P21 in KO cell lines.</p><p><bold>Conclusions</bold>: This data suggests a new role of RBM24 as a negative regulator of P53 family members and a potential oncogene suppressor of apoptosis, driver of proliferation and promoter of chemoresistance.</p><p>Finantial Support by FAPESP Process Num.2013/12006‐3</p></sec><sec id="pbc26772-sec-7300"><label>P-328</label><title>Differential Expression of MST2 and MST4 Among the Molecular Subgroups of Medulloblastoma</title><p>M. Baroni<sup>1</sup>, A.F. Andrade<sup>1</sup>, G.A.V. Cruzeiro<sup>1</sup>, C.A.P. Correa<sup>1</sup>, C.G. Carlotti<sup>2</sup>, S. Aguiar<sup>3</sup>, J.A. Nunes<sup>3</sup>, S.R. Brandalise<sup>3</sup>, C.A. Scrideli<sup>4</sup>, <underline underline-style="single">L.G. Tone</underline><sup>1</sup></p><p><italic><sup>1</sup>Ribeirão Preto Medical School ‐ USP, Genetics, Ribeirão Preto, Brazil; <sup>2</sup>Ribeirão Preto Medical School ‐ USP, Surgery, Ribeirão Preto, Brazil; <sup>3</sup>Centro Infantil Boldrini, Pediatrics, Campinas ‐ SP, Brazil; <sup>4</sup>Ribeirão Preto Medical School ‐ USP, Pediatrics, Ribeirão Preto, Brazil</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma (MB) is the most common tumor of central nervous system in childhood. The MB molecular classification was based on several studies dividing in four molecular subgroups: WNT, SHH, Group 3 and Group 4, facilitating diagnosis and treatment. In the search for potential targets, we found MST2 and MST4, members of MST kinases family (Mammalian Sterile Twenty Like). Several studies have shown the involvement of MSTs in carcinogenesis of different tumor types, and some studies show the relationship with developmental pathways associated with MB. Therefore, the aim of this study was to analyze the expression of MST kinases in MB samples, and investigated the difference of MST expression among molecular subgroups.</p><p><bold>Design/Methods</bold>: We analyzed the expression of <italic>MST2</italic> and <italic>MST4</italic> in 48 samples of MB, 4 cell lines of MB and 5 non‐neoplastic human cerebellum controls by qRT‐PCR. For this analysis, it was used Taqman gene probes and the endogenous controls were <italic>GUS</italic> and <italic>HPRT</italic>. Comparisons of MST expression in tumor samples versus cerebellum non‐neoplastic and molecular subgroups was performed using Mann‐Whitney test.</p><p><bold>Results</bold>: MST2 is upregulated in tumors (p=0,015) and cell lines (p=0,032) when compared to non‐neoplastic cerebellum, and the expression of <italic>MST4</italic> have no difference comparing tumor and cell lines with controls. Analysis of gene expression among molecular subgroups showed difference of <italic>MST2</italic> expression comparing Group Shh/Wnt and Group 3/4, <italic>MST2</italic> is upregulated in the Group Shh/Wnt (p=0,033).<italic>MST4</italic> expression is also different between the molecular subgroups. Group Wnt has <italic>MST4</italic> downregulated compared with others groups: Wnt x Shh (p=0,001), Wnt x Group 3 (p=0,027) and Wnt x Group 4 (p=0,006).</p><p><bold>Conclusions</bold>: The <italic>MST2</italic> and<italic>MST4</italic> expression shows relationship to molecular subgroups of MB and may be related with molecular pathways like Wnt and Shh. Studies and novel assays are being conducted to understand better these findings.</p></sec><sec id="pbc26772-sec-7310"><label>P-329</label><title>The Germline Variants in DNA Repair Genes and Life‐Threatening Toxicity During Chemotherapy in Children with Medulloblastoma</title><p><underline underline-style="single">J. Trubicka</underline><sup>1</sup>, T. Żemojtel<sup>2</sup>, J. Hecht<sup>3</sup>, R. Płoski<sup>4</sup>, D. Piekutowska‐ Abramczuk<sup>5</sup>, M. Perek‐Polnik<sup>6</sup>, M. Drogosiewicz<sup>6</sup>, W. Grajkowska<sup>1</sup>, K. Chrzanowska<sup>5</sup>, B. Dembowska‐Bagińska<sup>6</sup>, M. Łastowska<sup>1</sup></p><p><italic><sup>1</sup>The Children's Memorial Health Institute, Pathology, Warsaw, Poland; <sup>2</sup>Charité Universitätsmedizin Berlin, Institute for Medical Genetics and Human Genetics, Berlin, Germany; <sup>3</sup>Charité Universitätsmedizin Berlin, Berlin‐Brandenburg Center for Regenerative Therapies, Berlin, Germany; <sup>4</sup>Warsaw Medical University, Department of Medical Genetics, Warsaw, Poland; <sup>5</sup>The Children's Memorial Health Institute, Department of Medical Genetics, Warsaw, Poland; <sup>6</sup>The Children's Memorial Health Institute, Department of Oncology, Warsaw, Poland</italic></p><p><bold>Background/Objectives</bold>: Agents which interfere with DNA repair mechanisms are employed as therapeutic compounds in pediatric oncology. Furthermore, alterations in DNA repair genes in patients may affect repair efficiency and response to therapy. The purpose of this study was to establish relationship between presence of abnormalities in selected DNA repair genes and life‐threatening toxicity during chemotherapy in children with <italic>medulloblastoma</italic>.</p><p><bold>Design/Methods</bold>: The coding sequences of <italic>MSH2</italic> and <italic>RAD50</italic> genes were investigated using targeted gene sequencing, and <italic>NBN</italic> pathogenic variants (p.I171V and p.K219fs*19) by Sanger sequencing in altogether >100 patients. In three patients with presence of rare life‐threatening adverse events (AE) and no detected variants in the analyzed genes, whole exome sequencing was performed. Presence of identified variants was correlated with the occurrence of rare life‐threatening AE, other clinical features and molecular group of tumour.</p><p><bold>Results</bold>: Potentially pathogenic variants in DNA repair genes were identified in eight out of fifteen patients who suffered from life‐threatening toxicity during chemotherapy. The altered genes included: <italic>MSH2</italic> (variants: p.A733T and p.V606I), <italic>RAD50</italic> (variant p.R1093*), <italic>FANCM</italic> (variant p.L694*), <italic>ERCC2</italic> (variant p.R695C) and <italic>EXO1</italic> (variant p.V738L), in addition to two known <italic>NBN</italic> gene variants. Patients with defects in either of <italic>MSH2</italic>, <italic>RAD50</italic> or <italic>NBN</italic> genes suffered from rare life‐threatening AE more frequently than in control group (p=0.0005).</p><p><bold>Conclusions</bold>: Our results, based on the largest systematic study of <italic>medulloblastoma</italic>, provide preliminary evidence for a link between defects in DNA repair genes and treatment related toxicity. We suggest, that for patients with presence of DNA repair genes variants, the special vigilance during and after currently applied therapeutic regiments is required. Also, the potential revision of the mode of treatment should be considered for those patients in the future.</p><p>This work was supported by National Science Centre (6917/B/P01/2011/40,N N407 691740; 2016/21/B/NZ2/01785) and by Funding from the CMHI (S124/2012 and 233/15).</p></sec><sec id="pbc26772-sec-7320"><label>P-330</label><title>Primary Intracranial Tumors Diagnosed in the First Year of Life: A Retrospective Study of Belgian Cases Between 2001 and 2014</title><p>J. Derême<sup>1</sup>, S. Jacobs<sup>2</sup>, E. Sariban<sup>3</sup>, S. Schifflers<sup>4</sup>, L. Willems<sup>5</sup>, J. Verlooy<sup>6</sup>, N. Van Damme<sup>7</sup>, B. Depreitere<sup>8</sup>, M.C. Nassogne<sup>9</sup>, B. Brichard<sup>1</sup>, <underline underline-style="single">A. Van Damme</underline><sup>1</sup></p><p><italic><sup>1</sup>Cliniques Universitaires Saint Luc, Pediatric Hematology and Oncology, Woluwe Saint Lambert, Belgium; <sup>2</sup>Universitaire Ziekenhuizen Leuven, Pediatric Hematology and Oncology, Leuven, Belgium; <sup>3</sup>Hôpital des Enfants Reine Fabiola, Pediatric Hematology/Oncology, Brussels, Belgium; <sup>4</sup>CHC Liège, Pediatric Hematology/Oncology, Liège, Belgium; <sup>5</sup>University Hospital Ghent, Pediatric Hematology/Oncology, Ghent, Belgium; <sup>6</sup>University Hospital Antwerpen, Pediatric Hematology/Oncology, Antwerp, Belgium; <sup>7</sup>Belgian Cancer Registry, Belgian Cancer Registry, Brussels, Belgium; <sup>8</sup>University Hospital Leuven, Neurosurgery, Leuven, Belgium; <sup>9</sup>Cliniques Universitaires Saint Luc, Pediatric Neurology, Woluwe Saint Lambert, Belgium</italic></p><p><bold>Background/Objectives</bold>: Brain tumours represent 15% of cancers in children younger than one year. Studies describing brain tumours in this age group are limited and some revealed differences compared to the older paediatric population. We aimed to describe brain tumours in children under one year of age in Belgium and to define how they differ from older children.</p><p><bold>Design/Methods</bold>: Retrospective analysis of records of patients diagnosed with primary intracranial neoplasms in the first year of life in Belgium between 2001 and 2014. Eligible patients were retrieved from hospital databases of Belgian Paediatric Oncology Departments and the Belgian Cancer Registry. Brain metastases, vascular malformations, spinal tumours and hamartomas were excluded. Various parameters such as clinical presentation, intracranial localisation, histologic subtype, late morbidity and outcome, were recorded.</p><p><bold>Results</bold>: Sixty patients met the inclusion criteria. Median age at diagnosis was 7 months. Fifteen percent of tumors were metastatic at diagnosis. The median follow‐up time was 86.19 months. The median pre‐diagnosis interval was 28 days. The most frequent tumour type was pilocytic astrocytoma (25%), atypical teratoid/rhabdoid tumour (11.6%) and glioblastoma (8.3%). Signs of intracranial hypertension were present in 64.3% of cases. The most common signs were vomiting (43.3%) and bulging fontanelles (26.7%). Hydrocephalus was present in 41.7%. Clinical presentation correlated with anatomical localisation. Five‐year overall survival was 66.6%. Survival varied significantly with histologic type, grade and completeness of surgical resection. However, age, localisation, age at diagnosis, prediagnosis symptom interval and primary dissemination did not correlate with overall survival.</p><p><bold>Conclusions</bold>: Most infants with brain tumours present with signs of intracranial hypertension. Outcome is determined by histology and completeness of resection. Outcomes compare favourably with series from the literature, possibly due to a higher proportion of low grade lesions. This series describes clinical characteristics, treatment and outcome of infant brain tumours in infants before the era of molecular diagnostics and therapeutics.</p></sec><sec id="pbc26772-sec-7330"><label>P-331</label><title>The Link Between Neurocognitive Functioning and Health‐Related Quality of Life in Pediatric Brain Tumors</title><p><underline underline-style="single">L. Van den Wyngaert</underline><sup>1</sup>, G. Vercruysse<sup>1</sup>, K. Vandenabeele<sup>1</sup>, M. Haers<sup>1</sup>, C. Sleurs<sup>1</sup>, A. Uyttebroeck<sup>1</sup>, S. Jacobs<sup>1</sup>, J. Lemiere<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Leuven, Pediatric Hematology‐Oncology, Leuven, Belgium</italic></p><p><bold>Background/Objectives</bold>: Thanks to medical advances during the last decades, children with a brain tumor reach adulthood more often. Measurements of health‐related quality of life (HRQOL) and neuropsychological functioning have therefore become increasingly important. Our study aimed to examine the impact of neurocognitive functioning on HRQOL in patients, both immediately after diagnosis and in follow‐up.</p><p><bold>Design/Methods</bold>: Children diagnosed with a brain tumor at the University Hospitals Leuven, were followed with neuropsychological assessments. In total, 49 patients (mean age at diagnosis 8.91 ± 4.18 years) were included, diagnosed with pilocytic astrocytoma (<italic>n</italic>=25), medulloblastoma (<italic>n</italic>=9), ependymoma (<italic>n</italic>=3), craniopharyngioma (<italic>n</italic>=3) and atypical brain tumors (<italic>n</italic>=9). Neuropsychological assessments were acquired within maximum six months after diagnosis, as well as after two years. Assessments included objective measurements of cognition (intelligence, memory, visual‐motor functioning, attention and executive functioning) and subjective measurements of HRQOL (PedsQL<sup>TM</sup> Brain Tumor Module). Paired T‐tests and pearson correlations were used to assess relationships between the neurocognitive variables and HRQOL in this population.</p><p><bold>Results</bold>: Based on paired T‐tests, attention (<italic>t</italic>(48)=‐3.39, p=0.001) and executive functioning (<italic>t</italic>(48)=‐2.27, p=0.03) declined over time. Consistent with literature, we found few significant correlations between the neurocognitive variables and the general measure of HRQOL. At diagnosis, a significant association between memory and patient‐reported HRQOL was found (<italic>r</italic>=0.453, p<0.05). Interestingly, the follow‐up measurement showed different correlations. More specifically, parent‐reported HRQOL was correlated with both performance intelligence and executive functioning (<italic>r</italic>=0.410, p<0.01;<italic>r</italic> =‐0.323, p<0.05). Correlations between subscales of HRQOL showed at diagnosis an association between verbal intelligence and parent‐reported cognition (<italic>r</italic>=0.427, p<0.05) and at follow‐up between attention and parent‐reported cognition (<italic>r</italic>=‐0.356, p<0.05).</p><p><bold>Conclusions</bold>: Newly arising correlations after two years suggest a stronger link between attention and executive functioning, most strongly declining neurocognitive functions in our population, and subjective measurements of HRQOL. Possibly, parents’ expectations of daily life functioning also change throughout time.</p></sec><sec id="pbc26772-sec-7340"><label>P-332</label><title>Central Nervous System Tumors</title><p><underline underline-style="single">B. Yilmaz</underline><sup>1</sup>, N. Eker<sup>1</sup>, G. Tokuc<sup>1</sup>, O. Dogru<sup>1</sup>, E. Senay<sup>1</sup>, B. Berk<sup>1</sup></p><p><italic><sup>1</sup>Marmara University Pendik Training and Research Hospital, Pediatric Hematology and Oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Central nervous system (CNS) tumors are the most common solid tumors in childhood. Our instution is the one of the major referral center for pediatric brain tumors in Turkey. We aimed to analyzed children with brain tumors who were diagnosed and treated at our center in this study.</p><p><bold>Design/Methods</bold>: This is a retrospective study of 96 pediatric patients with brain tumors treated in between 2009 to 2017. Sixteen patients were lost to follow‐up and 80 patients were included in the analysis. Demographic informations, histologic subtypes, stage at diagnosis, treatment modalities and outcomes were evaluated, retrospectively.</p><p><bold>Results</bold>: Of the 80 patients, 42 (52.5%) were males, 38.5 (47.5%) were females. The mean age was 6.8 ± 4.6 years (ranging from 0.17 years to 15.5 years). The mean duration of follow up was 30 months. Mean survival time was 71.4 months (95% CI: 61.8 ‐ 80.9). The most common localization was the infratentorial area (38.8%). Among all of the patients, gliomas are the most common histologic form (54 %) and 51,3% had grade IV stage for WHO. Five‐year overall survival (OS) is 68 %. The most important factor for OS was tumor total resectabity. Total resectable patients OS was 81% vs gross total resection (GTR) was 49.5% vs partial resection was only 28% within 5 years. The children with diffuse infiltrative pontine glioma (DIPG) and atypical teratoid/rhabdoid tumor (AT/RT) had the worst prognosis and these patients died in the first year of their treatment.</p><p><bold>Conclusions</bold>: In developing countries, as the use of molecular studies could not be routinely performed in clinical practice. Brain tumors are relatively common cancers among children.usually the first and the most important step in therapy. Patients with the most complete resection have significantly longer survival despite all of the technological advances.</p></sec><sec id="pbc26772-sec-7350"><label>P-333</label><title>Comparative Analysis of miRNA Expression in Pediatric Neuronal and Mixed Neuronal‐Glial Tumors</title><p><underline underline-style="single">M. Zakrzewska</underline><sup>1</sup>, W. Fendler<sup>2</sup>, K. Stawiski<sup>2</sup>, R. Gruszka<sup>1</sup>, K. Zakrzewski<sup>3</sup>, P.P. Liberski<sup>1</sup></p><p><italic><sup>1</sup>Medical University of Lodz, Department of Molecular Pathology and Neuropathology, Lodz, Poland; <sup>2</sup>Medical University of Lodz, Department of Biostatistics and Translational Medicine, Lodz, Poland; <sup>3</sup>Polish Mother Memorial Hospital Research Institute, Department of Neurosurgery, Lodz, Poland</italic></p><p><bold>Background/Objectives</bold>: The current knowledge concerning the molecular biology of pediatric low‐grade brain tumors is still unsatisfactory. Moreover the data concerning the biology of CNS neuronal and mixed neuronal‐glial tumors continue to be enigmatic due to their rare occurrence.Those tumors show considerable genomic heterogeneity even in case of the same histological features. The aim of the study was to evaluate the microRNA profiles of pilocytic astrocytoma (PA), ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNT).</p><p><bold>Design/Methods</bold>: A total group of 60 cases in equal proportion of histological types was incorporated into this study. The material for molecular analyses was obtained during standard neurosurgical procedures. Total RNA was extracted according to the standard procedures. Microarray testing was performed with the using of the miRCURY LNA™ microRNA Array technology. After filtration 782 miRNAs were eligible for analysis. Obtained data was compared using the analysis of variance (ANOVA) with the Benjamini‐Hochberg procedure used to estimate false discovery rates (FDR). MicroRNAs that were significant in ANOVA were considered eligible for further post‐hoc pairwise comparisons using the t‐test.</p><p><bold>Results</bold>: The pattern of expression changes differed considerably among the miRNAs between analysed subgroups of tumors with: miR‐4754, miR‐4350, miR‐4777 and miR‐628 having the highest expression in DNTs, miR‐155 being elevated in GGs and miR‐3660 showing elevated expression levels in the PAs. Conversely, miR‐PlusA‐1086, let‐7b, miR‐891a and miR‐4758 were downregulated in DNTs tumors in comparison to the other groups.</p><p><bold>Conclusions</bold>: Current study provides information regarding the miRNA alterations related to the pediatric low grade brain tumors especially to the relatively rare neuronal and mixed neuronal‐glial tumors. Each tumor type showed characteristic miRNA expression profile. It could be interesting particularly in case of PA which could be the component of the most DNT as well as the main manifestation of its plausible recurrence.</p><p>Work supported by the Polish NCN Grant No. 2014/15/B/NZ4/00744</p></sec><sec id="pbc26772-sec-7360"><label>P-334</label><title>Use of Bevacisumab as a Single or in Adjunct with Single Agent Carboplatin or Vinblastin or Vincristine/Carboplatin Regimens in Children with Unresectable or Progressive PLGG</title><p><underline underline-style="single">N. Zhukova</underline><sup>1</sup>, R. Rajagopal<sup>2</sup>, A. Lam<sup>4</sup>, L. Coleman<sup>4</sup>, P. Shipman<sup>3</sup>, T. Walwyn<sup>2</sup>, M. Campbell<sup>1</sup>, M. Sullivan<sup>1</sup>, K. Bhatia<sup>1</sup>, N. Gottardo<sup>2</sup>, J.R. Hansford<sup>1</sup></p><p><italic><sup>1</sup>Children's Cancer Centre, The royal Children's Hospital, Melbourne, VIC; <sup>2</sup>Department of Paediatric and Adolescent Clinical Haematology and Oncology, Princess Margaret Hospital for Children, Perth, WA; <sup>3</sup>Department of Radiology, Princess Margaret Hospital for Children, Perth, WA; <sup>4</sup>Department of Radiology, The royal Children's Hospital, Melbourne, VIC</italic></p><p><bold>Background/Objectives</bold>: Low grade gliomas (LGG) are difficult to treat due to variable degree of chemosensitivity and common proximity to vital brain structures which makes them not amenable to surgical resection, as a result many children experience multiple progressions of their disease and require several lines of therapy during their life. Historically being a mainstream therapy, radiation is now deferred as a last resort due to numerous significant side effects especially in young children and multiple chemotherapy regiments are employed with encouraging outcomes. Single agents Vinblastine and Carboplatin, Vincristine/Carboplatin combination have demonstrated progression free survival (PFS) of 39‐53% at 5 years with variable toxicity profile, which remains suboptimal to irradiated tumours with PFS of 60‐80%. Vascular Endothelial Growth Factor (VEGF) is important for tumour neovascularisation and is increased in gliomas. Bevacizumab, a humanized monoclonal antibody to VEGF has shown antineoplastic effects in multiple malignancies in adult and paediatric population.</p><p><bold>Design/Methods</bold>: Addition of Bevacizumab to the treatment regimens of progressive LGG will result in durable stabilisation of disease, clinical and radiological improvement, and decrease tumour‐related morbidity. Bevacizumab was added to the 2<sup>nd</sup> to 4<sup>th</sup> line of therapy for progressive PLGG between 06/2014‐02/2016. Combinations of single agent Carboplatin or Vinblastine and Vincristine/Carboplatin with Bevacizumab. Bevacizumab was administered as a single IV dose of 10mg/kg once biweekly or once monthly as per discretion of treating physician. Clinical and radiological responses were assessed.</p><p><bold>Results</bold>: We present the treatment outcomes of 15 patients with progressive PLGG with optic pathway/midline/thalamic/spinal location and disseminated disease treated with the above approach. Patients were given between 3 and 18 doses of Bevacizumab. Responses were variable with the majority of patients having a partial response. Toxicity was acceptable, the tumour related morbidity was prevented in all cases.</p><p><bold>Conclusions</bold>: Avastin can be used in treatment of PLGG.</p></sec><sec id="pbc26772-sec-7370"><label>P-335</label><title>Subgroup‐Specific Quantitative Proteomic Profiling in Medulloblastoma</title><p>L. Hernychova<sup>1</sup>, M. Nekulova<sup>1</sup>, M. Kyr<sup>2</sup>, P. Dvorakova<sup>1</sup>, L. Capkova<sup>1</sup>, O. Slaby<sup>3</sup>, Z. Pavelka<sup>2</sup>, M. Jezova<sup>4</sup>, B. Vojtesek<sup>1</sup>, J. Sterba<sup>2</sup>, <underline underline-style="single">K. Zitterbart</underline><sup>2</sup></p><p><italic><sup>1</sup>Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Brno, Czech Republic; <sup>2</sup>University Hospital Brno and Faculty of Medicine‐ Masaryk University, Department of Pediatric Oncology, Brno, Czech Republic; <sup>3</sup>Central European Institute of Technology, Molecular Oncology II, Brno, Czech Republic; <sup>4</sup>University Hospital Brno and Faculty of Medicine‐ Masaryk University, Department of Pathology, Brno, Czech Republic</italic></p><p><bold>Background/Objectives</bold>: Medulloblastoma, an embryonal neuroectodermal tumor of the cerebellum, is the most common malignant brain tumor in children. Molecular genetic studies led to the consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) based on transcriptional profiling. Recently, quantitative proteomics developed as a robust approach additional to genomics to identify prognostic markers and drugable targets in human cancer. Here, we employed a shotgun proteomic method to identify main pro‐oncogenic signaling components in different molecular and clinical subgroups of medulloblastoma.</p><p><bold>Design/Methods</bold>: Briefly, medulloblastoma tissues (n=28) were lysed using urea buffer, stored at ‐80°C overnight and centrifuged for 30 minutes and the protein concentration was determined using BCA protein assay kit. One hundred micrograms of protein was digested using filter aided sample preparation. Peptides were labeled using 10plex isobaric mass tags and mixed together. Finally, the samples were analyzed using Orbitrap Elite coupled with UltiMate 3000 RSLCnano chromatograph and the acquired data processed with Proteome Discoverer 1.4.</p><p><bold>Results</bold>: A list of quantified proteins from tumor proteome was obtained and subjected to bioinformatical and statistical evaluation. The clustering revealed that proteomic analyses recapitulate transcription‐based subgroup assignment in medulloblastoma and identified subgroup‐specific proteins, which were further classified by gene‐annotation enrichment analysis and pathway mapping.</p><p><bold>Conclusions</bold>: To sum, we demonstrate that a mass spectrometry‐based proteomic approach allows to distinguish molecular signatures linked to medulloblastoma subgroups.</p><p>The study was supported by Ministry of Health of the Czech Republic grant AZV 15‐30657A and the project MEYS‐NPS I – LO1413.</p></sec></sec><sec id="pbc26772-sec-7380"><title>Treatment and Care ‐ Surgery (IPSO)</title><sec id="pbc26772-sec-7390"><label>P-336</label><title>Use of 3D Printing and Augmented Reality for Preoperative Planning of Complex Central Abdominal Tumors</title><p><underline underline-style="single">S. Abdessalam</underline><sup>1</sup>, L. Wong<sup>2</sup>, G. Linke<sup>1</sup>, T. vonAhlefeld<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital and Medical Center, Pediatric Surgery, Omaha, USA; <sup>2</sup>Children's Hospital and Medical Center, Pediatric Radiology, Omaha, USA</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is the most common solid extracranial tumor in the pediatric population. One of the most difficult locations to remove these tumors is within the central abdomen where encasement/abutment of major vascular structures makes removal very challenging and is accompanied by high morbidity and potential mortality. CT scans and MRI are used as the primary modalities in preoperative planning. At the forefront of technological growth in the world of medicine are 3D printing and Augmented Reality (AR). We are the first to use these technologies to help with the preoperative planning and intraoperative management of patients with central neuroblastomas.</p><p><bold>Design/Methods</bold>: CT scanning is done with 1 mm cuts of a prospective patient with a central neuroblastoma. The scans are reviewed between the surgeon and the radiologist to determine which structures are to be modeled. A 3D technologist works closely with the radiologist to accurately render a digital 3D model in medical segmentation software suite. The computer generated model is then reviewed with the surgeon for final approval using Augmented Reality glasses. Finally the model is printed in a piecemeal fashion for ease of manipulating the structures.</p><p><bold>Results</bold>: For our last three patients with a central neuroblastoma, we implemented the above technologies with excellent results. All three patients had successful removal of the entire tumor and associated lymphadenopathy with no major or minor intraoperative complications.</p><p><bold>Conclusions</bold>: 3D printing and Augmented Reality are very useful technological tools that go beyond the two dimensional world of CT. The ability to physically look at and touch the 3D print gives the surgeon insight into the precise anatomic detail of the complex vascular structures providing for safer operations. Also worth noting, patient/family satisfaction and understanding were heightened as a result of the physical model in comparison to showing images from the CT's.</p></sec><sec id="pbc26772-sec-7400"><label>P-337</label><title>CTNNB1 Gene‐Encoding Β ‐Catenin Deletions or Mutations in Hepatoblastoma in India</title><p><underline underline-style="single">S. Agarwala</underline><sup>1</sup>, A. Varshney<sup>1</sup>, A. Chopra<sup>2</sup>, R. Kumar<sup>2</sup>, S. Bakhshi<sup>3</sup>, V.K. Iyer<sup>4</sup>, V. Bhatnagar<sup>1</sup></p><p><italic><sup>1</sup>All India Institute of Medical Sciences, Pediatric Surgery, Delhi, India; <sup>2</sup>BRAIRCH‐ All India Institute of Medical Sciences, Laboratory Oncology, Delhi, India; <sup>3</sup>BRAIRCH‐ All India Institute of Medical Sciences, Medical Oncology, Delhi, India; <sup>4</sup>All India Institute of Medical Sciences, Pathology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: The incidence of Hepatoblastoma(HB) is significantly elevated in patients with familial adenomatous polyposis who carry germ‐line mutations in the APC tumor suppressor gene suggesting a role of over activation of the Wnt signaling pathway in tumor pathogenesis. Mutation or deletion of exon 3 in CTNNB1 gene‐encoding β‐catenin has been frequently detected in hepatoblastoma cases worldwide. Mutation presence has been correlated with better response to neoadjuvant chemotherapy and better overall survival.</p><p><bold>Design/Methods</bold>: Analyses of oncogenic mutations(missense mutations and interstitial deletions in exon 3) were performed by focusing on exon 3 of CTNNB1 in 26 HBL tumor samples, using standard PCR followed by subsequent DNA sequencing. Mutation identification was confirmed with at least 2 amplification reactions from the original DNA.</p><p><bold>Results</bold>: Samples from 23 patients in and age range 6‐132 months were included. There were 9 standard risk(SR) and 14 High risk(HR) patients. All patients received neo‐adjuvant chemotherapy (Cisplatin monotherapy for SRHB or PLADO for HRHB). Poor response to neoadjuvant chemotherapy was seen in 5/23(22%). Two older patients (108 and 132 months) could not be resected while the remaining 21 underwent resection. Five of the 23 (22%) patients died while 2 who could not be resected discontinued therapy. Of the 21 resected patients there were 7 (33.3%) recurrences, of whom 3 are alive after salvage therapy, 1 died and 3 discontinued therapy with progressive disease. Exon 3 β‐catenin gene deletion was detected only in a single patient who was a 11‐month old PRETEXT‐3 SRHB patient with good response to neoadjuvant chemotherapy and is in CR after resection. No missense mutations in CTNNB1 gene were detected. No correlation was found between presence of mutation and response to neoadjuvant chemotherapy or ultimate outcome.</p><p><bold>Conclusions</bold>: Beta catenin gene deletion or mutation seems to be rare in hepatoblastoma in India and may not be important in pathogenesis of hepatoblastoma.</p></sec><sec id="pbc26772-sec-7410"><label>P-338</label><title>Is Antibiotic Prophylaxis Beneficial: A Comparative Study in Totally Implantable Venous Access Devices</title><p><underline underline-style="single">S.A. Akbar</underline><sup>1</sup>, Z.F. Qudsia<sup>2</sup>, N. Ashraf<sup>3</sup>, M.A. Tarar<sup>1</sup>, A.Q. Qazi<sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Cancer Hospital and Research Center, Surgical Oncology, Lahore, Pakistan; <sup>2</sup>Prince Philips hospital, Breast Surgery, Llanelli Carmarthenshire, United Kingdom; <sup>3</sup>Aga Khan University, Medical College, Karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Totally implantable venous access devices (TIVADs) play an important role in administering chemotherapeutic agents in children with oncological disorders. This study aimed to analyze the efficacy of prophylactic antibiotic at the time of insertion of TIVADs in preventing early central line associated blood stream infection (CLABSI).</p><p><bold>Design/Methods</bold>: Consecutive patients with TIVAD insertion between January 2005 and June 2016 were reviewed retrospectively. There was a natural division of the patients into two groups due to change of surgeons in 2013 with a different surgical practice: Group A (n = 351) who received a single dose co‐amoxiclav before September 2013 and Group B (n = 279) did not receive it. CLABSI was defined as per CDC guidelines.</p><p><bold>Results</bold>: Both groups were comparable in terms of gender ratio, type of malignancy and neutrophil count with no major confounding factors. Mean age was significantly higher in the group that received antibiotic (68.7 versus 51.1 months, p‐value 0.038). The rate of CLABSI was slightly lower in the group that received antibiotic (11.6 versus 12.9%) but the difference was statistically insignificant (p‐value 0.365). The device was removed in first month in 17 cases (10/41 in group A and 7/36 in group B). Tip culture was positive in 10% in the group that received antibiotic as compared to 57% in the other group but the p‐value was insignificant (0.06), although the numbers were very small to assess.</p><p><bold>Conclusions</bold>: In our study there is no advantage of using prophylactic antibiotic at the time of TI‐VAD insertion in preventing early postoperative CLABSI. To establish this a prospective RCT is recommended.</p></sec><sec id="pbc26772-sec-7420"><label>P-339</label><title>Advanced Hepatoblastoma with Tumoral Thrombi in Right Atrium and Inferior Vena Cava: Which is the Best Management?</title><p><underline underline-style="single">R. Angelico</underline><sup>1</sup>, A. Passariello<sup>2</sup>, M. Pilato<sup>3</sup>, T. Cozzolino<sup>2</sup>, M. Piazza<sup>3</sup>, R. Miraglia<sup>4</sup>, D. Paolo<sup>5</sup>, C. Grimaldi<sup>1</sup>, M.C. Saffioti<sup>1</sup>, D. Alberti<sup>6</sup>, M. Spada<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Hospital Bambino Gesu', Abdominal Transplant and hepatopancreaticbiliary surgery, Roma, Italy; <sup>2</sup>University of Naples “Federico II”‐ Naples‐ Italy, Department of Translational Medical Science, Naples, Italy; <sup>3</sup>IRCCS ‐ ISMETT Mediterranean Institute for Transplantation and Advanced Specialized Therapies, 4Cardiac Surgery and Heart Transplantation Unit‐ Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, Palermo, Italy; <sup>4</sup>IRCCS ‐ ISMETT Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Radiology service, Palermo, Italy; <sup>5</sup>“Giovanni Di Cristina” Children's Hospital, Palermo, Italy; <sup>6</sup>Spedali Civili” Children's Hospital, Pediatric surgery, Brescia, Italy</italic></p><p><bold>Background/Objectives</bold>: Advanced hepatoblastoma (HBL) with tumour thrombi extending into major vessels needs multimodal treatment approaches combining chemotherapy and surgery. Surgical recommendations for pretreatment extent disease (PRETEXT) staging III‐IV strongly advocate primary liver transplantation (LT). However, when tumour thrombi infiltrate the inferior vena cava (IVC) and the right atrium, LT might be technically challenging and it is associated with unfavourable survival rates for local recurrence HBL. Therefore, the best surgical approach is not clear and transplant surgeons are exploring technical alternatives.</p><p><bold>Design/Methods</bold>: A 11‐months‐old boy with serum alpha‐fetoprotein(AFP) of 50.795.200IU/mL and computed tomography showing a right hepatic lobe mass(90x78mm) suspicious of HBL, with tumour thrombi extending from the right hepatic vein into the IVC up to the right atrium, and bilateral lung lesions (PRETEXT III) was referred. After 8 months of chemotherapy (SIOPEL 2004‐high risk Protocol), HBL decreased to 61x64mm and lung lesions disappeared, but the tumour thrombi was still present. The child underwent ante situm liver resection: en bloc resection of the extended‐right hepatic lobe, retro/suprahepatic IVC, tumoral trombi extended into the right atrium. The IVC was replaced with fresh aortic graft from blood‐group compatible cadaveric donor. During the resection, the remnant liver (SII‐III) was perfused through the portal vein with Celsior at 4°C, cooled with ice, and reimplanted by end‐to‐side anastomosis of the left hepatic vein to the neo‐IVC.</p><p><bold>Results</bold>: The post‐operative course was uneventful and after 10 months of follow‐up the child is in good clinical condition with normal liver function test, AFP of 1.1UI/mL, free of disease recurrence and with patent aortic graft.</p><p><bold>Conclusions</bold>: This is the first case of ante situm liver resection combined with hypothermic CPB and IVC replacement for HBL, which is a realistic option to avoid LT for skilled transplant surgeons thanks to the improvement of LT technique.</p></sec><sec id="pbc26772-sec-7430"><label>P-340</label><title>Comparative Cost Analysis of Treatment of Pediatric Solid Tumors in Semi‐Governmental Hospital in India</title><p><underline underline-style="single">S. Bhatnagar</underline><sup>1</sup></p><p><italic><sup>1</sup>B.J.Wadia Hospital for Children‐ Bombay Hospital, Pediatric Surgery, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: The rate structuring in hospitals in India show a huge fluctuation ranging from completely free of cost public hospitals (Government), charitable institutes with subsidized rates, semi‐government to autonomous, corporate/private hospitals/nursing homes with varying rate structures. The cost of treatment of pediatric solid tumors varies widely from one facility to another even within the same city. The parents concerns regarding the cost of therapy when child is diagnosed with tumor becomes very difficult to satisfy for multiple reasons, the foremost of which is lack of hospital based cost analysis data. Hence, study of comparative cost analysis with different modalities of treatment of solid tumors in children has been undertaken.</p><p><bold>Design/Methods</bold>: From the time the child is clinically detected to have solid tumor, the cost study has been performed by including cost of hospitalization (bed charges), cost of diagnostic studies, cost of chemotherapy stage wise, cost of surgery and related costs, cost of intensive care monitoring, cost of consumables, cost of radiotherapy, cost of supportive therapy, cost of immunization during treatment. The ancillary costs like accommodation, food and travel, loss of wages for parents, etc. have not been studied. The study has been undertaken taking into account most recent expenses at tertiary care semi‐government/charitable institute in Mumbai, India.</p><p><bold>Results</bold>: Of the overall expenditure for treatment, cost analysis for a stage 3 tumor showed the various costs as: Diagnosis ‐ 7%, Chemotherapy ‐ 43%, Consumables ‐ 14%, Surgery ‐ 7%, Intensive care ‐ 3%, Radiotherapy ‐8.5%, Supportive treatment ‐ 14%. Cost analysis tumor wise and stage wise revealed that with advanced disease, the cost of chemotherapy, intensive care and supportive care increased drastically.</p><p><bold>Conclusions</bold>: Costing is a crucial tool in counseling and stratifying the financial status of the parents, thus creating pathways to achieve completion of therapy even with the poor socio‐economic section of society.</p></sec><sec id="pbc26772-sec-7440"><label>P-341</label><title>Outcomes of Pediatric Chest Wall Reconstruction Using a Bio‐Prosthetic Absorbable Material</title><p><underline underline-style="single">M. Collin</underline><sup>1</sup>, M. Mutch<sup>1</sup>, J. Karpelowsky<sup>2,3</sup></p><p><italic><sup>1</sup>The Children's Hospital at Westmead, Paediatric Surgery, Westmead, Australia; <sup>2</sup>The Children's Hospital at Westmead, Paediatric Oncology and Thoracic Surgery, Westmead, Australia; <sup>3</sup>University of Sydney, Children's Cancer Research Unit, Sydney, Australia</italic></p><p><bold>Background/Objectives</bold>: Reconstruction in large chest wall tumours aims to create an airtight cavity, rigidity to protect thoracic contents, stability to permit respiration and long‐term aesthetically acceptable results. Described techniques (using non‐absorbable prosthetics) have limitations, especially in pre‐pubertal children in which growth deformity may result. We aim to review medium‐term outcomes when using bio‐prosthetic absorbable materials.</p><p><bold>Design/Methods</bold>: This retrospective series includes pre‐pubertal children that have undergone chest wall reconstruction at our centre. Poly‐L‐lactide struts (to replace cartilage/bone structures) and a porcine dermal collagen patch with muscle flaps where available (to provide soft‐tissue replacement) were used as a matrix for native‐tissue ingrowth and allow complete implant resorption. Complications, functional and cosmetic results were obtained with review of photography and axial imaging.</p><p><bold>Results</bold>: Five patients were included; 4 males and 1 female, median age 4 years (range 0‐10), median follow‐up 3 years (range 1‐4). Pathology included 2 Ewing sarcomas, 1 osteochondroma, 1 chondromesenchymal hamartoma and 1 high‐grade spindle‐cell sarcoma. A median of 3 ribs were resected (range 1‐4). The single‐rib reconstruction (for osteochondroma) was required for significant adjacent rib displacement with a subsequent large thoracic defect. Four patients remain disease free while 1 patient suffered metastatic Ewing relapse (with local control persisting). Complications included a seroma at 2 months in one patient and a sterile collection at 8 months in another (both drained and resolved). The reconstruction provided good initial thoracic integrity enabling early extubation. Long‐term cosmetic and functional results are satisfactory, with good chest wall shape and function. There were no post‐operative restrictions on daily activities, including sport in patients old enough (4/5). Pitfalls include the low‐level PET avidity of the prosthesis (when considering relapse surveillance) and the presence of mild scoliosis noted on imaging.</p><p><bold>Conclusions</bold>: The technique of a bio‐prosthetic absorbable chest wall reconstruction in the pediatric population has had good functional and cosmetic results.</p></sec><sec id="pbc26772-sec-7450"><label>P-342</label><title>Outcomes of Brachytherapy in Pediatric Non‐Rhabdomyosarcoma Pelvic Sarcomas</title><p><underline underline-style="single">M. Collin</underline><sup>1</sup>, J. Chard<sup>2</sup>, V. Ahern<sup>2</sup>, E. Flower<sup>3</sup>, J. Karpelowsky<sup>4,5</sup></p><p><italic><sup>1</sup>The Children's Hospital at Westmead, Paediatric Surgery, Westmead, Australia; <sup>2</sup>The Children's Hospital at Westmead, Radiation Oncology, Westmead, Australia; <sup>3</sup>University of Sydney, Institute of Medical Physics, Camperdown, Australia; <sup>4</sup>The Children's Hospital at Westmead, Paediatric Oncology and Thoracic Surgery, Westmead, Australia; <sup>5</sup>University of Sydney, Children's Cancer Research Unit, Sydney, Australia</italic></p><p><bold>Background/Objectives</bold>: Pelvic brachytherapy is well described in association with surgery for obtaining local control for rhabdomyosarcoma of the pelvis. Its primary benefits are as an organ sparing technique, whilst delivering high doses to the target volume. We describe our use of brachytherapy in the setting of non‐rhabdomyosarcoma of the pelvis in the paediatric population.</p><p><bold>Design/Methods</bold>: Selected patients with non‐rhabdomyosarcoma of the pelvis were treated at our institute with brachytherapy. Cases were identified from theatre databases and the data was collated as a retrospective audit to report the technique of brachytherapy, associated surgical procedure and outcomes including overall mortality, and morbidity including bladder and bowel function</p><p><bold>Results</bold>: Three female patients (age range 11‐18 months) have been treated with pelvic brachytherapy for non‐rhabdomyosarcomas at our institute. Two cases involved pre‐operative brachytherapy to the tumour volume with transperineal catheters placed under image guidance. The third case involved post‐surgical resection placement of a modified Frieburg flap applicator into the pelvis and sciatic notch. All 3 patients received high dose rate brachytherapy with excellent dose coverage of the target volume and organ at risk doses within set constraints. Two of the 3 patients have survived to 2 and 4 years post intervention with no evidence of relapse. The oldest child has maintained good bladder and bowel function despite some initial concerns of urinary incontinence, with ultrasound demonstrating good bladder capacity and voiding (managed well with timed and double voiding and subsequently continent). The second case remains too young to assess continence. There was one mortality in the remaining case who unexpectedly developed brainstem metastases six weeks post treatment.</p><p><bold>Conclusions</bold>: Our initial short to medium term follow ups indicate that the use of pelvic brachytherapy may be extended to non‐rhabdomyosarcoma sarcomas of the pelvis in highly selected young children as an organ sparing technique.</p></sec><sec id="pbc26772-sec-7460"><label>P-343</label><title>Biopsy and Excision of Pulmonary Metastasis in Children with Extra‐Cranial Solid Tumors: Current Practice at Stand‐Alone Children's Hospitals</title><p><underline underline-style="single">K. Corkum</underline><sup>1</sup>, G. Ares<sup>1</sup>, E. Rowell<sup>1</sup>, J. Reichek<sup>2</sup>, T. Lautz<sup>1</sup></p><p><italic><sup>1</sup>Ann and Robert H. Lurie Children's Hospital of Chicago, Surgery, Chicago, USA; <sup>2</sup>Ann and Robert H. Lurie Children's Hospital of Chicago, Oncology, Chicago, USA</italic></p><p><bold>Background/Objectives</bold>: Pulmonary metastases occur frequently in children with extra‐cranial solid tumors, yet the optimal approach for evaluating and treating suspicious nodules remains unresolved. Lung biopsy and nodule excision may be indicated to stage disease, guide therapy, or achieve cure. The objective was to evaluate current national practices for addressing pulmonary nodules in patients with extra‐cranial solid tumors.</p><p><bold>Design/Methods</bold>: The Pediatric Health Information System (PHIS) database was queried from 2010‐2015 for patients with extra‐cranial solid tumors and associated pulmonary procedures. The approach and maximal extent of surgery were stratified by primary tumor location.</p><p><bold>Results</bold>: During the 6‐year period, 15,640 patients were hospitalized, of which 19.6% had pulmonary metastatic disease, and 8.1% underwent a pulmonary procedure. Most common primary tumors were bone (20.3%), soft tissue (14.6%), kidney (14.5%), adrenal (13.0%) and liver (7.5%). Biopsy occurred in 6.4% of patients and only 12.2% required further intervention with thoracoscopy/thoracotomy. Thoracoscopy was the first‐line approach in 51.0% of patients, with only 12.2% of those patients requiring subsequent thoracotomy. Thoracotomy was the initial approach in 42.6% of patients, for which bone tumors accounted for half of the cases. Patients with bone tumors were also more likely to undergo multiple procedures than other solid tumors. Bone as a primary tumor site (OR 2.22), documented pulmonary metastasis (OR 2.80), high‐volume center (OR 1.95), and anticipated lobectomy (OR 11.34) were predictive of thoracotomy. ICU utilization, mechanical ventilation, and post‐procedural complications were more common in open cases compared to thoracoscopic or percutaneous approaches (p<0.001).</p><p><bold>Conclusions</bold>: At least eight percent of children with extra‐cranial solid tumors currently undergo lung biopsy or resection. The approach and extent of resection varies by patient and hospital factors, including primary tumor site. Further effort is required to define the optimal workup and treatment algorithm for these patients to maximize diagnostic and therapeutic yield while minimizing complications.</p></sec><sec id="pbc26772-sec-7470"><label>P-344</label><title>The Clinical Characters of Non‐Rhabdmyosarcoma Soft Tissue Sarcomas—A Retrospective Study in a Single Institution in 11 Years</title><p><underline underline-style="single">K. Dong</underline><sup>1</sup>, W. Tang<sup>1</sup>, X. Xiao<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital of Fudan University, surgery, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: Non‐rhabdmyosarcoma soft tissue sarcomas (NRSTS) is a heterogenous group of tumors and encompass many histology types, but they are less frequently encountered and account for 3‐5% of all childhood malignancies.The purpose of the study is to summarize our experience in diagnosis and treatment on the non‐rhabdomyosarcoma soft tissue sarcomas.</p><p><bold>Design/Methods</bold>: We performed a retrospective analysis of all the data of non‐rhabdomyosarcoma soft tissue sarcomas in our hospital in 2003‐2014.</p><p><bold>Results</bold>: 56 cases were found in this period. Pathology study shows there were 8 types: synovical sarcoma, fibrosarcoma, PNET, hyalocyte sarcoma, acinous soft tissue sarcoma, embryonal sarcoma, malignant small cell sarcoma and extraosseous Ewing's sarcoma. The case load of these 8 types were 15(26.8%), 15(26.8%), 10(17.9%), 5(8.9%), 4(7.1%), 3(5.4%), 3(5.4%) and 1(1.8%), respectively. There was a difference about tumor location among sarcomas (P<0.01). There was no difference about the therapeutic protocols. (P>0.05) But radical operation and radical operation plus chemotherapy were the popular therapeutic protocols. There was a difference about the use of chemotherapy(P<0.01).The utilization of chemotherapy in PNET, malignant small cell sarcoma, acinous soft tissue sarcoma and embryonal sarcoma were 100%, while the utilization of chemotherapy were 42.7% in other four sarcomas. The 2‐year survival rate and 5‐year survival rate was 35.7%(20/56) and 8.9%(5/56), respectively. The case fatality rate within 2 years was 26.8%(15/56).</p><p><bold>Conclusions</bold>: Pediatric NRSTS had many histological subtypes. Although prognosis was not very good, radical operation plus chemotherapy have the effect of improving the survival rate in non‐rhabdomyosarcoma soft tissue sarcomas.</p></sec><sec id="pbc26772-sec-7480"><label>P-345</label><title>Curative Surgical Treatment for Hepatoblastomas by Live Donor Liver Transplantation Combined with ICG Navigation</title><p><underline underline-style="single">Y. Fuchimoto</underline><sup>1</sup>, Y. Yamada<sup>1</sup>, K. Hoshino<sup>1</sup>, N. Takahashi<sup>1</sup>, K. Matsubara<sup>2</sup>, T. Hibi<sup>2</sup>, Y. Abe<sup>2</sup>, H. Yagi<sup>2</sup>, N. Shimojima<sup>1</sup>, M. Shinoda<sup>2</sup>, M. Kitago<sup>2</sup>, H. Obara<sup>2</sup>, Y. Kitagawa<sup>2</sup>, T. Kuroda<sup>1</sup></p><p><italic><sup>1</sup>Keio University School of Medicine, Pediatric Surgery, tokyo, Japan; <sup>2</sup>Keio University School of Medicine, Surgery, tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: The prognosis of hepatoblastomas depends greatly on curative treatment by surgical resection. We performed the world's first re‐liver transplantation using ICG navigation technology in a case of recurrent hepatoblastomas after liver transplantation.</p><p><bold>Design/Methods</bold>: The patient was a 15‐year‐old boy, had undergone 2 hepatectomies after an explosion of hepatoblastomas when aged 8 years. At age 11 years he had a rescue living body liver transplantation for recurrence of the tumors, with his mother acting as the donor. His AFP level increased gradually in the 4 years after transplantation and a partial hepatectomy was performed because of tumor recurrence in the transplanted liver. We found a peritoneal dissemination at this operation and simultaneously resected the dissemination lesion, diagnosed pathologically as stump‐positive. Because the AFP level increased post‐operatively and a metastatic lesion was detected in the liver we resected the dissemination and intrahepatic metastatic lesion using ICG navigation technology. ICG was administered 3 days before the abdominal operation using Photodynamic Eye (PDER, Hamamatsu Photonics). The nodules of liver and peritoneum revealed pathologically well‐differentiated fetal type hepatoblastoma.</p><p><bold>Results</bold>: Transplant intrahepatic multiple recurrences had occurred, thereafter we performed an exploratory laparotomy using ICG navigation for the purpose of considering the need for re‐transplantation. This showed that the dissemination lesion was controlled and confirmed that recurrence was localized to the liver. After the approval of the Ethical Review Board, we performed a re‐liver transplantation using ICG navigation, with the donor being the father. Pathology showed the tumor was localized in the liver with normal changes in AFP level.</p><p><bold>Conclusions</bold>: ICG navigation was useful in the detection of micro lesions not detected by imaging or the naked eye such as peritoneal dissemination and intrahepatic metastases. Liver transplantation combined with ICG navigation provided curative treatment for hepatoblastomas, indicating this was a potential new surgical treatment for these tumors.</p></sec><sec id="pbc26772-sec-7490"><label>P-346</label><title>Diagnostic Utility of Frozen Section in Paediatric Testicular and Paratesticular Lesions</title><p><underline underline-style="single">H. Gabra</underline><sup>1</sup></p><p><italic><sup>1</sup>Great North Children Hospital, Paedaitric Surgery, Newcastle Upon Tyne, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Frozen sections are used routinely to assess suspected tumours in adults and aid surgical decision making. Similar application in paediatric tumours remains limited, especially in the evaluation of paediatric paratesticular lesions where diagnosis is reliant on clinical and imaging findings. Many benign paratesticular lesions in infancy and childhood may be difficult to distinguish from malignant lesions and result in unnecessary orchidectomy.</p><p><bold>Design/Methods</bold>: Retrospective of a series of 3 patients who underwent frozen section at the time of surgery for suspected testicular/ paratesticular lesions were reviewed. Clinical information including age, histological diagnosis were recorded.</p><p><bold>Results</bold>: Case 1: 11‐month old infant with a firm para‐testicular mass not involving the testis. Rhabdomyosarcoma was suspected clinically and on imaging which was atypical. Intra‐operative frozen section diagnosis confirmed a benign lesion (fibrous hamartoma of infancy). The mass was excised and the testis left in situ.</p><p>Case 2: 14 year old boy who presented with a large complex paratesticular mass closely abutting the entire testis. Even though radiologically it was suspected to be benign, the clinical features were suspicious and orchidectomy was thought to be the most pragmatic option. Frozen sections showed dysplasia of the rete testis and epididymis, confirmed by standard histology with no malignant changes.</p><p>Case 3: 9 year old with presented with chronic testicular pain, USS was suspicious of polar testicular lesion. Frozen sections showed normal histology and testis was spared.</p><p><bold>Conclusions</bold>: Frozen sections may accurately diagnose testicular and paratesticular masses. Though orchidectomy could be avoided only in case 1 and 3, frozen sections may aid surgical decision making with regards to sparing the testis in selected paediatric cases. Pathologists must endeavour to make themselves familiar with the potential advantages and limitations of frozen sections and the role of intraoperative frozen sections warrants further multidisciplinary evaluation.</p></sec><sec id="pbc26772-sec-7500"><label>P-347</label><title>Laparoscopic Adrenalectomy in Children with Adrenal Tumors</title><p><underline underline-style="single">P. Kerimov</underline><sup>1</sup>, A. Kazancev<sup>1</sup>, D. Rybakova<sup>1</sup></p><p><italic><sup>1</sup>Russian Cancer Research Center. NN Blokhina, Surgical separation of tumors of thoracoabdominal localization, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: laparoscopic adrenalectomy was introduced relatively recently and took the leading position in choosing the volume of surgery for adrenal neoplasm in children.</p><p><bold>Design/Methods</bold>: We present the results of treatment of 91 patients with various adrenal tumors in children aged 1 to 18 years who underwent 91 laparoscopic operations in the volume from 2007 to 2017: laparoscopic adrenalectomy (LA) on the right ‐ 50, LA on the left ‐ 41. Male were 50 patients, 41 female. The most common neuroblastoma was diagnosed in 71 cases, the ganglioneuroma was diagnosed in 9 cases, the following diseases were observed in single observations: adrenocortical adenoma 2, adrenal cortex cancer 2, pheochromocytoma 2, gangloneuroblastoma 2, adrenocortical cancer 1, neurinoma ‐ 1, fibroma ‐ 1.</p><p><bold>Results</bold>: The duration of operations ranged from 40 to 90 min. The average blood loss was 20 ml. The drainage tube was installed to the entire patient and was removed on the first day after the operation. The stay in the intensive care ward was 1 day. There were no lethal outcomes, cases of access conversion, serious intraoperative complications. We have not been diagnosed with any cases of recurrence of the disease or implantation metastases in malignant tumors of the adrenal gland. The median follow‐up was 82 months.</p><p><bold>Conclusions</bold>: Laparoscopic adrenalectomy in children with adrenal tumor pathology is an effective and safe method that is accompanied by minimal surgical trauma and excellent cosmetic results, shortens the duration of the postoperative period and does not worsen the oncological prognosis. Laparoscopic adrenalectomy in children can be considered as the preferred surgery regardless of the age and body weight of the patient with both benign and malignant organ tumors.</p></sec><sec id="pbc26772-sec-7510"><label>P-348</label><title>Epidemiology of Paediatric Solid Tumors and Treatment Challenges at a Tertiary Care Hospital in a Developing Country</title><p><underline underline-style="single">V. Khanna</underline><sup>1</sup>, R. Muffazzal<sup>1</sup>, S. Roy Choudhury<sup>1</sup>, P. Singh Yadav<sup>1</sup>, A. Puri<sup>1</sup>, R. Chadha<sup>1</sup></p><p><italic><sup>1</sup>Lady Hardinge Medical College & Associated Kalawati Saran Children's Hospital, Paediatric Surgery, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: A study on epidemiology, treatment challenges and logistic difficulties in managing paediatric solid tumors.</p><p><bold>Design/Methods</bold>: Prospective observational study from February/2014 till January/2017 including all paediatric solid tumors.</p><p><bold>Results</bold>: A total of 101 patients (58males,43females) were included. Primary diagnosis was Wilms tumor(WT) 22(21.7%); Neuroblastoma(NB) 21(20.8%); Germ cell tumors(GCT) 15(14.8%); Sacrococcygeal teratoma(SCT) 14(13.8%); Hepatoblastoma(HB) 5(4.9%), PNET 6(5.9%), Rhabdomyosarcoma(RMS) 4(3.9%) and miscellaneous 14(13.8%). Out of 14 patients with WT requiring DD4A chemotherapy+Radiotherapy (COG protocol), 11(78.5%) could not receive radiotherapy due to lack of necessary infrastructure at our hospital, financial constraints and already overburdening of centres giving radiotherapy. Two patients, 1 with Clear cell sarcoma of kidney(CCSK) and other with Rhabdoid tumor of kidney(RTK) were given WT chemotherapy as they were reported as Wilms in initial histopathology reports. CCSK patient is alive with disease while RTK patient expired 2 months post‐surgery. Out of 21 NB patients, 13(62%) were high risk. Low awareness and diagnostic delays rendered presentation to our hospital at a very advanced stage. Eleven(52.3%) NB patients died and 8(38%) are alive with disease. The salvage rate remains low due to limited access to myeloablative treatments with bone marrow rescue and biologic therapy. Two (14.2%) patients with SCT had recurrence which were detected late due to logistic difficulty in getting alphafetoprotein levels(AFP) done. Both these patients died due to febrile neutropenia in addition to their poor nutritional status on initiation of salvage chemotherapy. All five patients with HB, 3 standard risk(SR) and 2 high risk(HR) received PLADO. Three underwent surgery and are alive and disease free.</p><p><bold>Conclusions</bold>: Lack of education, poor government support system and referral facilities decrease survival in cancer patients in developing nations. The cancer treatment protocols are institutionalized depending on the availability of resources, technology and research at disposal. Multidisciplinary tumor treatment facilities with public‐private partnership are the need of hour.</p></sec><sec id="pbc26772-sec-7520"><label>P-349</label><title>Preoperative Blood Count Parameters and Prophylactic Antibiotics and their Effects on Early Catheter‐Related Bloodstream Infections in Pediatric Cancer Patients Undergoing Port‐A‐Cath Insertion</title><p>R. Wang<sup>1</sup>, V. Lee<sup>1</sup>, <underline underline-style="single">S.M. Cheah</underline><sup>2</sup>, Y.T. Lee<sup>3</sup>, C.B. Tan<sup>4</sup>, S.E. Saffari<sup>7</sup>, J.C.M. Lam<sup>5</sup>, C.Y. Chong<sup>6</sup>, A.H.P. Loh<sup>3</sup></p><p><italic><sup>1</sup>National University of Singapore, Yong Loo Lin School of Medicine, Singapore, Singapore; <sup>2</sup>KK Women's and Children's Hospital, Department of Paediatric Medicine, Singapore, Singapore; <sup>3</sup>KK Women's and Children's Hospital, Department of Paediatric Surgery, Singapore, Singapore; <sup>4</sup>KK Women's and Children's Hospital, Division of Nursing, Singapore, Singapore; <sup>5</sup>KK Women's and Children's Hospital, Department of Paediatric Subspecialties Haematology Oncology Service, Singapore, Singapore; <sup>6</sup>KK Women's and Children's Hospital, Department of Paediatric Subspecialties Infectious Diseases Service, Singapore, Singapore; <sup>7</sup>Centre for Quantitative Medicine, Duke‐NUS Medical School, Singapore</italic></p><p><bold>Background/Objectives</bold>: Prior to port‐a‐cath insertions in pediatric cancer patients, preoperative antibiotic prophylaxis has been employed either routinely or based on blood count parameters, but the basis of this practice is not well studied. We aimed to analyse preoperative risk factors associated with early catheter‐related bloodstream infections (CRBSIs) in port‐a‐cath insertions.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed the clinical charts of pediatric cancer patients who had port‐a‐caths placed between January 2009 and December 2015. Standardized skin preparation, implants, and technique were used on all patients, though preoperative antibiotic use varied. Demographics, disease factors, intra‐operative factors, and preoperative blood count parameters were correlated with occurrence of early CRBSI within the first 30 postoperative days.</p><p><bold>Results</bold>: In total 279 central venous catheters were placed during the study period, of which 250 were port‐a‐caths. Among these, 159 (64%) had acute lymphoblastic leukemia (ALL) and 15 (6%) had acute myleogenous leukemia (AML); 160 (65%) patients had preoperative antibiotics administered. Median preoperative absolute neutrophil count (ANC) was 1.18 (range: 0.27–15.5) x 10<sup>9</sup>/L. Fifteen CRBSIs occurred at median 14 (range: 8–28) postoperative days. Only cancer type was significantly associated with early CRBSIs (P=0.004); these were encountered in 8, 3, 2, and 2 patients with ALL, AML, other leukemias, and solid tumours, respectively. Notably, preoperative ANC <1 x 10<sup>9</sup>/L and use of prophylactic preoperative antibiotics were not associated with occurrence of early CRBSIs (P=0.816 and P=0.996, respectively). Surgeon and operative factors were also not associated with early CRBSI. However, early CRBSI was significantly associated with early port removal within 30 days of insertion (P=0.009).</p><p><bold>Conclusions</bold>: Preoperative ANCs of 1 x 10<sup>9</sup>/L, and use of preoperative antibiotic prophylaxis were not found to be associated with a lower incidence of early CRBSIs within the first 30 postoperative days.</p></sec><sec id="pbc26772-sec-7530"><label>P-350</label><title>Testicular Transposition in Children Undergoing Brachytherapy for Bladder‐Prostate Rhadomyosarcoma</title><p><underline underline-style="single">G. De Lambert</underline><sup>1</sup>, F. Guérin<sup>1</sup>, C. Chargari<sup>2</sup>, C. Haie‐Meder<sup>2</sup>, V. Minard‐Colin<sup>3</sup>, H. Martelli<sup>1</sup></p><p><italic><sup>1</sup>Bicetre hospital APHP, Paediatric Surgery, Le Kremlin Bicetre, France; <sup>2</sup>Gustave Roussy Cancer Campus, Brachytherapy, Villejuif, France; <sup>3</sup>Gustave Roussy Cancer Campus, Paediatric Oncology, Villejuif, France</italic></p><p><bold>Background/Objectives</bold>: Fertility preservation is a major goal in children 's cancer. Spermatogonias are affected by a dose of 0.15 Gy and dose more than 4 Gy may lead to definitive sterility. Leydig cells are more resistant and endocrine function can be maintained after exposure to dose up to 20 Gy in prepubescent males.</p><p>To describe a new technique of testicular transposition in patients treated with pulse‐dose‐rate brachytherapy for bladder neck and/or prostate rhabdomyosarcoma (BP RMS).</p><p><bold>Design/Methods</bold>: Medical records of consecutive patients treated between september 2016 and february 2017 were studied. These patients underwent a testicular transposition performed during BP surgery by the same suprapubic incision. The external oblique aponeurosis was not incised. The spermatic cord was mobilized up to the external inguinal ring and the gubernaculum attachments were delivered from the scrotum. The testis was then flipped over with care taken to avoid injury of the vessels or the vas, wrapped in a silicone material and sutured under the abdominal skin with a transfixing stitch facing the anterior superior iliac spine. At the end of brachytherapy, the testis was relocated in the scrotum during general anesthesia for removal of tubes and stents.</p><p>Surgical outcome and dosimetric parameters were examined.</p><p><bold>Results</bold>: Five patients were identified.</p><p>Median age was 25 months (range 22 – 80 months). All had embryonal BP RMS and received chemotherapy according to RMS 2005 protocol prior to local treatment. All patients underwent conservative surgery followed by brachytherapy (60 Gy) and could have testicular transposition of one testis.</p><p>None of the patients had intraoperative or postoperative complication.</p><p>Median radiation dose to the transposed testis was 3 Gy (range: 2 ‐ 4.8) and 9 Gy (range: 6.6 ‐ 11) to the testis left in place.</p><p><bold>Conclusions</bold>: Testicular transposition is feasible in order to potentially preserve fertility and future quality of life in children undergoing brachytherapy for BP RMS.</p></sec><sec id="pbc26772-sec-7540"><label>P-351</label><title>Recurrent Inflammatory Myofibroblastic Tumor of the abdomen treated with Surgery and ALK Inhibitors in a Child</title><p><underline underline-style="single">S. Mishra</underline><sup>1</sup>, S. Jain<sup>2</sup>, S. Singh<sup>3</sup>, G. Kapoor<sup>2</sup></p><p><italic><sup>1</sup>Rajiv Gandhi Cancer Institute and Research Hospital‐ Sector 5‐ Rohini‐, Pediatric Surgical Oncology, Delhi, India; <sup>2</sup>Rajiv Gandhi Cancer Institute and Research Hospital‐ Sector 5‐ Rohini‐, Pediatric Hematology Oncology, Delhi, India; <sup>3</sup>Rajiv Gandhi Cancer Institute and Research Hospital‐ Sector 5‐ Rohini‐, Surgical Oncology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Extrapulmonary Inflammatory myofibroblastic tumor (IMT), also known as inflammatory pseudotumor is a rare in children. IMT is known for its fibroinflammatory and pseusosarcomatous appearance on histopathology (HPE). Immunohistochemistry (IHC) is a useful tool in confirming the diagnosis. Surgery is the mainstay of treatment and local recurrences are common. We wish to share our experience with one case of recurrent IMT of the abdomen successfully treated with surgery and Anaplastic Lymphoma Kinase (ALK) inhibitors.</p><p><bold>Design/Methods</bold>: Retrospective review of hospital records.</p><p><bold>Results</bold>: Eleven years old boy presented with loss of appetite and vomiting for 3 months. He had a palpable left lower abdominal mass of size 8 x8 cms. Imaging confirmed a non‐metastatic mesenteric mass suggestive of a low‐grade spindle cell tumor on FNAC. He underwent en bloc excision of mass with segmental colectomy. HPE was suggestive of IMT. He was kept on close follow‐up during which he developed a local relapse in the right abdomen after 7 months. Review of previous HPE revealed the IMT to be ALK positive on IHC in addition to SMA (diffuse +) and Desmin (weak +). He was started on Crizotinib and was closely followed‐up. There was partial response with 50% reduction in size which became static. After 9 months of Crizotinib he underwent laparotomy and resection of residual calcified mass in ileocolic mesentery without bowel resection. HPE confirmed residual viable IMT. Postoperatively he was continued on Crizotinib for 6 months and is disease free at 6 months follow‐up after last surgery.</p><p><bold>Conclusions</bold>: ALK positivity in abdomino‐pelvic IMT is considered a favorable prognostic marker. In the absence of definitive adjuvant therapy for locally recurrent IMT, ALK inhibitors are a feasible option for targeted therapy of these rare tumors as evidenced by this case report. However there are no guidelines available for the duration of recommended treatment.</p></sec><sec id="pbc26772-sec-7550"><label>P-352</label><title>Anterior Mediastinal Mass in Children‐ Pathway for Safe Diagnosis</title><p><underline underline-style="single">R. Malik</underline><sup>1</sup>, D. Mullassery<sup>2</sup>, A. Atra<sup>1</sup>, B. Okoye<sup>2</sup></p><p><italic><sup>1</sup>St George's Hospital NHS TRust, Department of paediatric oncology, London, United Kingdom; <sup>2</sup>St George's Hospital NHS Trust, Department of Paediatric Surgery, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Anterior mediastinal masses pose a diagnostic challenge due to the cardiorespiratory risks associated with the mass which are exaggerated during a general anaesthetic for biopsy. We reviewed our institutional practice to assess the safety of our approach.</p><p><bold>Design/Methods</bold>: Retrospective case record review of all patients with an anterior mediastinal mass for diagnosis at our tertiary paediatric oncology and surgery centre. All patients admitted between January 2013 and December 2016 were assessed for co‐morbidities, clinical presentation, method of tissue diagnosis and complications.</p><p><bold>Results</bold>: There were 34 patients (median age 11.5 years, range 1 to 17 years, 21 male) admitted for diagnosis of AMM during the study period. Fifteen patients presented with respiratory symptoms. Eleven children had evidence of tracheobronchial compression on imaging. Histological diagnoses included Hodgkin's lymphoma (11), Non Hodgkin's lymphoma (10), leukaemia (8), lipoblastoma (1), teratoma (1), PNET (1), rhabdomyosarcoma (1) and mediastinal metastasis from nasopharyngeal carcinoma (1). Sixteen patients had a lymph node biopsy. Alternative tissues (pleural fluid‐ 4, peripheral blood film‐ 3) were used for diagnosis in 7 patients. Eight patients had image guided core biopsy of the mediastinal mass and one patient had mediastinoscopic biopsy of paratracheal node. Ketamine sedation was used in 15 patients and 10 patients had a general anaesthetic.</p><p>There were no anaesthetic complications. Four patients needed admission to PICU for tumour lysis syndrome. Two patients needed a repeat node biopsy ( 1 post steroid and one inadequate sample).</p><p><bold>Conclusions</bold>: Safe tissue diagnosis of anterior mediastinal masses can be obtained by a personalised multidisciplinary approach. Alternative tissue and local anaesthetic must be used when appropriate. Ketamine sedation is a good alternative for some high risk cases as it obviates the need for a full general anaesthetic.</p></sec><sec id="pbc26772-sec-7560"><label>P-353</label><title>Ultrasound‐Guided Brachiocephalic Vein Catheterization Compared to Internal Jugular in Infants with Cancer at a Developing Country Setting</title><p><underline underline-style="single">R.C. Ribeiro</underline><sup>1</sup>, W.E. Oliveira Júnior<sup>1</sup>, V. Kremer<sup>1</sup></p><p><italic><sup>1</sup>Barretos Childrens Cancer Hospital, Pediatric Surgery Department, Barretos, Brazil</italic></p><p><bold>Background/Objectives</bold>: Central vein catheterization is a challenge in infants even in experienced hands. US guidance has become the gold standard for central vein catheterization in the last two decades. US‐guided internal jugular vein (IJV) catheterization is generally the route recommended for children. Most of the studies concerning infants are on internal jugular vein or subclavian vein (SCV) catheterization in which technical success rates are lower than in adults and complications are frequent. Recent studies shows the use of the technique of ultrasound‐guided supraclavicular brachiocephalic vein (BCV) catheterization in infants as a favorable approach providing high technical success and less complications. This study proposes to assess the degree of difficulty of vein catheterization by comparing the facility of guidewire progression in the ultrasound‐guided brachiocephalic vein and internal jugular vein puncture.</p><p><bold>Design/Methods</bold>: Children who underwent BCV or IJV catheterization by the Pediatric Surgery Department at our Pediatric Oncology Hospital from December 2014 to March 2017 were retrospectively analyzed. Demographic features, disease, chooses vein, vein side, guidewire progression and complications were obtained. Guidewire progression were classified as easy or difficult.</p><p><bold>Results</bold>: A hundred‐fifty ‐five procedures were performed, 68 on IVJ and 87 on BCV. Were evaluated eighty‐seven male patients (68 female), 108 with solid tumors (47 hematologic malignancies) with a median of 66 months of age and 21 kilograms. From IVJ patients, 21 had guidewire progression classified as difficult compared to 10 difficult progressions in the other group, showing statistic significance of BCV vein catheterization (p‐value: 0,0027). No major complications occurred in the BCV group.</p><p><bold>Conclusions</bold>: Ultrasound‐guided brachiocephalic vein catheterization by supraclavicular is a easier way when compared to internal jugular approach in children. A possible explanation is because this technique enables visualization of the needle and the BCV in the longitudinal axis while preventing the vein from compression by the US.</p></sec><sec id="pbc26772-sec-7570"><label>P-354</label><title>Association of Large Vessel Compression and Contralateral Extension with Operational Risks in the Resection of Wilms Tumors</title><p><underline underline-style="single">T. Oue</underline><sup>1</sup>, A. Yoneda<sup>2</sup>, M. Zenitani<sup>1</sup>, N. Tanaka<sup>1</sup>, T. Sasaki<sup>1</sup>, N. Usui<sup>3</sup>, H. Okuyama<sup>4</sup></p><p><italic><sup>1</sup>Hyogo College Of Medicine, Pediatric Surgery, Nishinomiya‐shi‐ Hyogo, Japan; <sup>2</sup>Osaka City General Hospital, Pediatric Surgery, Osaka, Japan; <sup>3</sup>Osaka Medical Center and Research Institute for Maternal and Child Health, Pediatric Surgery, Izumi, Japan; <sup>4</sup>Osaka Univerity Graduate School of medicine, Pediatric Surgery, Suita, Japan</italic></p><p><bold>Background/Objectives</bold>: In the USA and Japan, the standard treatment for Wilms tumor (WT) is primary resection followed by chemotherapy. However, in cases with large tumors, hemorrhage and tumor spillage due to rupture or its extension beyond the tumor capsule increase the surgical risk to patients. In such cases, chemotherapy should be administered prior to tumor resection. In the present study, we performed preoperative image analyses to identify factors associated with these surgical risks.</p><p><bold>Design/Methods</bold>: Twenty‐nine patients with WT treated between 2000 and 2015 were enrolled in this study. Patient clinical records and image results, including computed tomography (CT) scans, were collected and retrospectively analyzed. Image factors, such as tumor size, tumor volume, relationship among large vessels, and contralateral extension of the tumor, were evaluated, and their relationship with surgical factors including operating time, hemorrhage, tumor spillage, and unresectability were analyzed.</p><p><bold>Results</bold>: Operating time and hemorrhage per body weight were significantly related with tumor size, area, and volume. Operating time was significantly longer and hemorrhages were significantly more in cases with compression of abdominal aorta and/or vena cava by the tumor (p = 0.0156, p = 0.0161, respectively) and extension of the tumor beyond the center of the vertebral body (p = 0.0124, p = 0.0323, respectively). Three patients had unresectable tumors and four had tumor spillage; tumors of these patients were more frequently associated with large vessel compression and contralateral extension.</p><p><bold>Conclusions</bold>: Besides the tumor size, large vessel compression and contralateral extension were significantly correlated with surgical risks. These factors are easily determined using CT images and are therefore useful in predicting the surgical risks and unresectability of tumors and deciding whether to use preoperative chemotherapy as a primary treatment strategy for large localized WT.</p></sec><sec id="pbc26772-sec-7580"><label>P-355</label><title>Bowel Obstruction After Abdominal Surgery for Cancer in Children</title><p>N. Piché<sup>1</sup>, <underline underline-style="single">J. Côté</underline><sup>2</sup>, L. Krauel Gimenez Salinas<sup>3</sup>, J. Trebichavsky<sup>1</sup></p><p><italic><sup>1</sup>CHU Sainte‐Justine, Surgery, Montreal, Canada; <sup>2</sup>Université de Montréal, Faculty of medicine, Montreal, Canada; <sup>3</sup>Hospital Sant Joan de Déu, Pediatric surgery, Barcelone, Spain</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer frequently affects intra‐abdominal organs and surgery is indicated for most cases. Few publications have addressed the complication of post operative bowel obstruction in that context. We analysed our data over a 10 year period to determine the frequency, etiology and treatment options of this complication.</p><p><bold>Design/Methods</bold>: Retrospective data analysis of all patients undergoing an abdominal surgery for malignancy between 2005 and 2015 in a tertiary pediatric hospital. Data collection included demographics, tumor characteristics, details of operative procedure, details of adjunct treatments (chemotherapy and radiotherapy), incidence of bowel obstruction and details regarding its management. Patients with obstruction were statistically compared to those without obstruction using chi –square and students’ t‐test with significance reported for p<0,05.</p><p><bold>Results</bold>: The analysis included 130 patients with a median follow‐up of 3,5 years (mean 4y). A majority of patients were female (58%) with a median age at time of surgery for the entire cohort of 3,8 years. The most frequent diagnosis was Wilm's tumor (37%) followed by neuroblastoma (28%), hepatoblastoma (10%) and germ cells tumor (6%). The surgical approach was an open procedure in 95% of cases. Fifteen patients had a postoperative occlusion (11,5%): 13 cases of adhesions, 1 internal hernia and 1 SB volvulus. The mean operative time (396 min Vs. 311min, p=0,05) and mean blood loss (875ml Vs. 262 ml, p<0,01) was significantly higher for patients with bowel obstruction. Conservative management was attempted for all cases of obstruction with a success rate of 47% after a mean of 3 days. For 8 patients requiring surgical intervention, minimally invasive approach was successful for two patients.</p><p><bold>Conclusions</bold>: Bowel obstruction is a significant complication after abdominal surgery for cancer in children. Conservative management is frequently successful. For patients requiring surgical treatment, laparoscopy can be a valuable option.</p></sec><sec id="pbc26772-sec-7590"><label>P-356</label><title>Solid Pseudopapillary Neoplasm of the Pancreas in Children: An Experience in Developing Country</title><p><underline underline-style="single">R. Ribeiro</underline><sup>1</sup>, V. kremer<sup>1</sup>, R. Balceiro<sup>2</sup>, W. Oliveira Jr<sup>1</sup>, L. Lopes<sup>2</sup></p><p><italic><sup>1</sup>Barretos Children Cancer Hospital, Pediatric Surgery, Barretos, Brazil; <sup>2</sup>Barretos Children Cancer Hospital, Pediatric Oncology, Barretos, Brazil</italic></p><p><bold>Background/Objectives</bold>: Pancreatic tumors are very rare entity in children. We reviewed the clinical and pathologic features of pediatric patients with pancreatic solid pseudopapillary neoplasm (PSPPN), also called as Frantz tumor, at a single institution.</p><p><bold>Design/Methods</bold>: We conducted a retrospective analysis of the demographic data, clinical features, surgical approach, and long‐term outcomes of all patients diagnosed with PSPPN between 2010 and 2016.</p><p><bold>Results</bold>: There were six patients during the study period with solid pseudopapillary neoplasm. All patients were female. The median age at presentation was 15 years (range: 11 to 18 years). Abdominal pain was the most presenting symptom shown in 4 girls. Preoperative imaging studies included computed tomography (all cases) and magnetic resonance imaging (3 cases). The median maximum diameter of the tumor was 56 mm with a range of 36 to 120 mm. None of the patients had evidence of metastasis at presentation. Regarding the pancreatic location, three patients had a pancreatic head tumor, two underwent pancreaticoduodenectomy and one nodulectomy; two girls the tumor was in tail and underwent distal pancreatectomy with splenectomy, one of those laparoscopic; and one patient had a pancreatic body tumor and underwent a distal pancreatectomy. We had only one late complication, related to a pancreatic pseudocysts treated with drainage and octreotide. On immunohistochemistry, chromogranin was negative in 4 cases of 5 analyzed, whereas vimentin were positive in all analyzed cases. Enolase was positive in three cases analyzed.No adjuvant therapy was done. All patients are alive and without evidence of disease on a median follow up of 28 months (3 to 71 months).</p><p><bold>Conclusions</bold>: We present our experience and long‐term follow up data on children with PSPPN. In agreement with multiple clinical series, we believe that despite PSPPN generally has a benign behavior; complete resection with clear margins is mandatory to achieve the best long‐term outcomes</p></sec><sec id="pbc26772-sec-7600"><label>P-357</label><title>Surgery Options and Results of Treatment of Children with Solid Pseudopapillary Tumors of the Pancreas</title><p><underline underline-style="single">D. Rybakova</underline><sup>1</sup>, P. Kerimov<sup>1</sup>, A. Kazancev<sup>1</sup></p><p><italic><sup>1</sup>Federal State Budgetary Institution “Russian Cancer Research Center. NN Blokhin ”of the Ministry of Health of Russia, children oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Development rational surgery for solid pseudopapillary tumor (SPT) of the pancreas and implementation of Endosurgery.</p><p><bold>Design/Methods</bold>: 15 children with SPT were operated since 2004 to November 2016. We analyzed clinical data, operation options and results of treatment.</p><p><bold>Results</bold>: All patients were girls age from 9 to 15 years (median 13y.o.). Localization tumors in pancreas: in the tail – 5, in the body ‐ 6 and in the head ‐ 4. The size: 8.7 – 1.5 sm (M 4.6 sm). 5 children underwent laparoscopic distal pancreatectomy with splenic preservation, 1 ‐ laparoscopic central resection; 3 ‐ gastropancreatoduodenal resection, 3 – central resection of pancreas; 1 ‐ distal subtotal resection with resection of the superior mesenteric vein and 1 ‐ Uncinate process of pancreas resection with resection of duodenal wall. Time of operations: 95 – 290 min. Bleeding: Complications occurred in 5 patients: in 3 cases – pancreatitis with pancreatic fistula, 1 ‐ bleeding from the pancreatic branch of the splenic artery after Whipple operation and 1 ‐ pneumonia. There were 2 reoperation for complications. The observation period of the patients was from 1 month to 8 years. All patients are alive without evidence of disease recurrence</p><p><bold>Conclusions</bold>: The main method of treatment is surgery, however there is a moderate risk of complications because of tumor localization. Great attention should be paid to the prevention of postoperative pancreatitis. A promising method is endosurgery providing early rehabilitation and cosmetic effects.</p></sec><sec id="pbc26772-sec-7610"><label>P-358</label><title>Water Jet Dissection Technique for Liver Resections in Pediatric Oncology Surgery</title><p><underline underline-style="single">T. Sharoev</underline><sup>1</sup>, A. Prityko<sup>2</sup>, M. Rokhoev<sup>1</sup>, A. Kotlovsky<sup>3</sup></p><p><italic><sup>1</sup>St Luka's Clinical Research Centre for Children‐ Moscow‐ Russia, Oncology, Moscow, Russia; <sup>2</sup>St Luka's Clinical Research Centre for Children‐ Moscow‐ Russia, Administration, Moscow, Russia; <sup>3</sup>St Luka's Clinical Research Centre for Children‐ Moscow‐ Russia, paediatric surgery, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The water jet dissection technology (WJDT) is particularly advantageous in liver surgery for isolating major blood vessels adjacent to the tumor and also for sparing the surrounding hepatic parenchyma. In Russia we have pioneered the WJDT in pediatric oncology surgery. The objective of this review is to estimate the effectiveness of the WJDT for liver resections in children with hepatic tumors in our single‐centre practice.</p><p><bold>Design/Methods</bold>: From 2010 to 2017, liver resections of various anatomical types using the WJDT were performed in 25 children with hepatic tumors. Technologically, the ERBEJET in the ERBE VIO system was utilized. The patient data was prospectively collected and then analyzed, in particular considering tumor characterization and details of the surgical procedures.</p><p><bold>Results</bold>: The mean patient age was 4.3 years (from 2 weeks to 17 years). Malignant tumors were diagnosed in 22 cases. The following types of liver resections were carried out: hemihepatectomy (n=11), trisegmentectomy (n=5), bisegmentectomy (n=8), segmentectomy (n=1). All procedures were completed successfully. Blood transfusions were required in 15 cases (60%). Postoperatively bile leak occurred in one patient (4%). No other complications related to the technique used were noted. The complete tumor clearance with negative surgical margins was histologically evident in all cases while the mean volume of the tumors removed was 413 cm<sup>3</sup> and the maximum size ‐ 24 cm (in the largest dimension).</p><p><bold>Conclusions</bold>: In our experience the WJDT is a technically straightforward, safe and effective technique for liver resections of various anatomical types in children with hepatic tumors, in particular, in infants aged under 1 year. This technique allows provision of the reliable hemostasis while maximally sparing the hepatic parenchyma. We therefore believe that application of the WJDT should be widespread for liver resections in pediatric oncology practice.</p></sec><sec id="pbc26772-sec-7620"><label>P-359</label><title>The Navigation Surgery Using Indocyanine Green Fluorescent Imaging for a Hepatoblastoma Patient</title><p><underline underline-style="single">R. Souzaki</underline><sup>1</sup>, Y. Kinoshita<sup>1</sup>, N. Kawakubo<sup>1</sup>, Y. Koga<sup>2</sup>, J. Takemoto<sup>3</sup>, K. Kohashi<sup>3</sup>, Y. Oda<sup>3</sup>, S. Ohga<sup>2</sup>, T. Taguchi<sup>1</sup></p><p><italic><sup>1</sup>Kyushu university, Department of Pediatric Surgery, FUKUOKA, Japan; <sup>2</sup>Kyushu university, Department of Pediatrics, FUKUOKA, Japan; <sup>3</sup>Kyushu university, Department of Anatomic Pathology, FUKUOKA, Japan</italic></p><p><bold>Background/Objectives</bold>: Navigation surgery using indocyanine green (ICG) fluorescent imaging for metastasectomy of lung and hepatectomy in hepatoblastoma (HB) patients has been reported. However, the usefulness of this surgery for HB has not been fully clarified. Furthermore, no cases using this surgical navigation during video‐assisted thoracoscopic surgery (VATS) for metastasectomy of the lung have been reported. We herein report experiences with surgical navigation for metastasectomy of the bilateral lung including a VATS procedure and hepatectomy in an HB patient.</p><p><bold>Design/Methods</bold>: In a PRETEXT III HB patient with bilateral lung metastasis following chemotherapy, a primary tumor and lung metastatic lesions were intraoperatively examined using a 10‐mm infrared fluorescence imaging scope after the administration of ICG preoperatively.</p><p><bold>Results</bold>: Navigation surgery using ICG fluorescent imaging was performed for an HB patient. The metastatic lesions were recognized by computed tomography (CT) in both lungs. The lesion in the left lung was 1.5 cm in diameter, so thoracotomy was performed for the left lung. For the right lung, VATS was performed. No lesions expect for those detected by CT were palpable in the left lung. Although only one lesion not detected by CT exhibited intense fluorescence in the right lung, all lesions detected by CT exhibited intense fluorescence. All of these fluorescence‐positive lesions except for the one lesion of the right lung not detected by CT were pathologically proven to be made up of HB cells. None of the resection stumps for the metastectomies showed fluorescence, and all of the tumors were found to have been completely resected on a pathological examination. Although the liver tumor was strongly attached to the diaphragm, no fluorescence‐positive lesions were seen at the diaphragm after resection.</p><p><bold>Conclusions</bold>: Navigation surgery using ICG for a patient with HB was useful for identifying metastatic lesions and confirming complete resection, even with VATS.</p></sec><sec id="pbc26772-sec-7630"><label>P-360</label><title>Retroperitoneal Tumors and Congenital Vascular Anomalies of Abdominal Great Vessels</title><p><underline underline-style="single">S.W.M. TIP</underline><sup>1</sup>, Y.T. LEE<sup>1</sup>, P.H. TANG<sup>2</sup>, A.H.P. LOH<sup>1</sup></p><p><italic><sup>1</sup>KK Women's and Children's Hospital, Department of Paediatric Surgery, singapore, Singapore; <sup>2</sup>KK Women's and Children's Hospital, Department of Diagnostic and interventional Imaging, singapore, Singapore</italic></p><p><bold>Background/Objectives</bold>: Congenital vascular anomalies of the abdominal great vessels are uncommon but can potentially impact surgical procedures and affect outcomes negatively, yet their incidence and clinical impact is poorly studied. We sought to assess the incidence of vascular anomalies of the abdominal great vessels in patients with retroperitoneal embryonal tumors, and study their impact on surgical and oncologic outcomes.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed imaging, surgical, treatment and survival data of all pediatric patients with retroperitoneal tumors who underwent resection in KK Women's and Children's Hospital between January 2007 and October 2016. Preoperative scans were compared with corresponding intraoperative observations. Disease and treatment parameters, and survival outcomes, were compared using Chi‐square test and Kaplan‐Meier method, respectively.</p><p><bold>Results</bold>: Among 66 children studied, primary tumors arose from the kidney in 26 (39%), adrenal gland in 22 (33.3%) and paravertebral in 18 (27.3%) patients. Mean age at diagnosis was 3.7 years (S.D., 2.9). Vascular anomalies were found in 6 (9%) cases, namely renal (n=5) and adrenal (n=1) vessels. Interestingly, vascular anomalies were only associated with right‐sided tumors (22.2%) and not left‐sided tumors (P=0.023). Intraoperative complications were more common in patients with vascular anomalies (67%) than those without (15%, P=0.013). Complete tumor resection was achieved in 5 of 6 (83.3%) cases with vascular anomalies and 46 of 60 (76.7%) cases without. Relapse was more frequent in patients with vascular anomalies (n=2 (33%)) than those without (n=11 (18.3%)), but was not statistically significant (P=0.317). The presence of vascular anomalies, extent of resection, and intraoperative complications were not associated with overall and event‐free survival, but relapse was associated with overall and event‐free survival (P<0.001).</p><p><bold>Conclusions</bold>: Vascular anomalies of abdominal great vessels occurred in 9% of our patients with retroperitoneal tumors. Vascular anomalies were associated with higher rates of intraoperative complications and disease relapse but did not impact survival outcomes.</p></sec></sec><sec id="pbc26772-sec-7640"><title>Treatment and Care ‐ Radiation Oncology (PROS)</title><sec id="pbc26772-sec-7650"><label>P-361</label><title>Radiation Necrosis in Pediatric Patients with Brain Tumors Treated with Pencil Beam Scanning Proton Therapy</title><p><underline underline-style="single">B. Bojaxhiu</underline><sup>1</sup>, F. Ahlhelm<sup>2</sup>, M. Walser<sup>3</sup>, L. Placidi<sup>3</sup>, U. Kliebsch<sup>3</sup>, L. Mikroutsikos<sup>3</sup>, P. Morach<sup>3</sup>, A. Bolsi<sup>3</sup>, L. Tony<sup>3</sup>, R. Schneider<sup>3</sup>, D.C. Weber<sup>3</sup></p><p><italic><sup>1</sup>Inselspital, Radiation Oncology, Bern, Switzerland; <sup>2</sup>Kantonsspital Baden, Radiology, Baden, Switzerland; <sup>3</sup>Paul Scherrer Institute, Center for Proton Therapy, Villigen PSI West, Switzerland</italic></p><p><bold>Background/Objectives</bold>: To assess the rate of radiation‐induced radiation necrosis (RN) and white matter lesions (WML) and related neurologic symptoms in pediatric patients with primary brain tumors treated with Pencil Beam Scanning (PBS) proton therapy (PT) with or without concomitant chemotherapy at the Paul Scherrer Institute, Switzerland.</p><p><bold>Design/Methods</bold>: One hundred and seventy‐one pediatric patients (<18 years) with brain tumors were treated with PBS PT between 1999 and 2015. Median age at diagnosis was 3.3 years (range, 0.3‐17.0). Post PT brain parenchymal alterations (WML and RN) were defined as a new area of abnormal signal intensity on T2‐weighted images or increased signal intensity on T2‐weighted images, and contrast enhancement on T1 occurring in the brain parenchyma included in the radiation treatment field, which did not demonstrate any abnormality before PT. The median follow‐up period for the surviving patients was 49.8 months (range, 5.9‐194.7).</p><p><bold>Results</bold>: One hundred and twenty‐four patients (72%) did not develop any parenchymal brain alteration after PT. Twenty‐nine (17%) patients developed RN at a median time of 5 months (range, 1‐26), most of them (n=17; 59%) being asymptomatic (grade 1). Grade 2, 4 and 5 toxicities occurred in 8, 2 and 2 patients, respectively. Eighteen (11%) patients developed WML at a median time of 14.5 months (range, 2‐62), most of them (n=13; 72%) being asymptomatic (grade 1). Grade 2 and 3 toxicities occurred in 4 and 1 patients, respectively. The 5‐year RN‐free survival was 83% and the WML‐free survival was 87%. In univariate analysis, neo‐adjuvant chemotherapy (P=0.025), hydrocephalus before PT (P=0.035), and ependymoma (P=0.026) were significant predictors of RN.</p><p><bold>Conclusions</bold>: Children treated with PT demonstrated a low prevalence of symptomatic radiation necrosis (7%) or white matter lesion (3%). Chemotherapy administration before proton therapy, ependymoma, and hydrocephalus as an initial symptom were significant risk factors associated with radiation necrosis in these children with brain tumors.</p></sec><sec id="pbc26772-sec-7660"><label>P-362</label><title>Role of Radiotherapy to Primary/Metastatic Sites in Pediatric Patients with Metastatic Rhabdomyosarcoma in the Bernie Study</title><p>A. Cameron<sup>1</sup>, J. Chisholm<sup>2</sup>, M. Elze<sup>3</sup>, M. Casanova<sup>4</sup>, B. Geoerger<sup>5</sup>, M. Gaze<sup>6</sup>, O. Oberlin<sup>5</sup>, <underline underline-style="single">J. Bachir</underline><sup>7</sup>, S. Fürst‐Recktenwald<sup>7</sup>, J.H.M. Merks<sup>8</sup></p><p><italic><sup>1</sup>University Hospitals Bristol NHS Foundation Trust, Bristol Haematology and Oncology Centre, Bristol, United Kingdom; <sup>2</sup>The Royal Marsden NHS Foundation Trust, Children and Young People's Unit, Sutton, United Kingdom; <sup>3</sup>F. Hoffmann‐La Roche Ltd, Innovative Pediatric Oncology Drug Development, Basel, Switzerland; <sup>4</sup>Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology Unit, Milan, Italy; <sup>5</sup>Gustave Roussy, Department of Pediatric and Adolescent Oncology, Villejuif, France; <sup>6</sup>University College London Hospitals NHS Foundation Trust, Department of Oncology, London, United Kingdom; <sup>7</sup>F. Hoffmann‐La Roche Ltd, Pediatric Oncology, Basel, Switzerland; <sup>8</sup>Emma Children's Hospital‐Academic Medical Center EKZ‐AMC, Department of Pediatric Oncology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Local control is a key part of treatment of local/locoregional rhabdomyosarcoma (RMS) and often involves radiotherapy with/without surgery. The role of radiotherapy in metastatic RMS is uncertain, with little published evidence to guide clinicians. We analyzed data from the BERNIE trial to assess the benefit of radiotherapy for patients with metastatic RMS.</p><p><bold>Design/Methods</bold>: In BERNIE (NCT00643565), patients aged ≥6 months to <18 years with metastatic RMS were randomized to receive chemotherapy with/without bevacizumab, surgery and/or radiotherapy (at cycle 6–9) then maintenance chemotherapy. Radiotherapy was recommended for all sites of metastases if feasible (investigator discretion allowed, resulting in variability in actual radiotherapy given). Patients were categorized into those receiving radiotherapy for all sites of disease, partial radiotherapy, and no radiotherapy. Event‐free survival (EFS) and overall survival (OS) were calculated using Cox proportional hazards models and a landmark approach: only patients who were event free at day 221 (i.e. end of cycle 9 +1 month) were included (EFS, n=85; OS, n=97). Variables adjusted for treatment (as randomized), disease type (alveolar/embryonal/other), risk group, age >10yrs, and metastatic lesion count (1, 2–3, 4+). The analysis was non‐randomized, exploratory, and post hoc.</p><p><bold>Results</bold>: Of 102 patients with RMS, 22 received no radiotherapy, 49 partial radiotherapy, and 31 radiotherapy to all sites. Baseline characteristics were mostly balanced; comparable proportions of patients received bevacizumab. Significantly longer OS (hazard ratio [HR]=0.249; 95% confidence interval [CI]: 0.119–0.524; p=0.00025) and a non‐significant EFS improvement (HR=0.520; 95% CI: 0.267–1.011; p=0.05405) were observed in the radiotherapy‐treated group versus no radiotherapy. The 3‐year EFS and OS, respectively, were 9% and 23% (no radiotherapy), 42% and 53% (partial radiotherapy), and 58% and 84% (radiotherapy to all sites).</p><p><bold>Conclusions</bold>: Radiotherapy in metastatic RMS was associated with significant OS benefits, albeit in small patient numbers. This should be confirmed in a prospective randomized trial.</p></sec><sec id="pbc26772-sec-7670"><label>P-363</label><title>Paediatric Radiation Therapy Across Europe – A European Questionnaire Survey Supported by the SIOPE, ESTRO, PROS and Several National Paediatric Hematology‐Oncology Societies (NAPHOS)</title><p><underline underline-style="single">C. Demoor‐Goldschmidt</underline><sup>1</sup>, C. carrie<sup>2</sup>, G. whitfield<sup>3</sup>, P. meijinders<sup>4</sup>, K. dieckmann<sup>5</sup>, P. banovic<sup>6</sup>, M. solak mekic<sup>7</sup>, Y. lassen<sup>8</sup>, K. alexopoulou<sup>9</sup>, J. giralt<sup>10</sup>, J. vizkeleti<sup>11</sup>, L. jarusevicius<sup>12</sup>, B. ondrova<sup>13</sup>, P. daly<sup>14</sup>, P. brandal<sup>15</sup>, G. Janssens<sup>16</sup>, U. ricardi<sup>17</sup>, R. dieter‐kortmann<sup>18</sup></p><p><italic><sup>1</sup>Inserm, U1018, Villejuif, France; <sup>2</sup>centre léon berard, Radiotherapy, Lyon, France; <sup>3</sup>The Christie, Radiotherapy, Manchester, United Kingdom; <sup>4</sup>Iridium Cancer Network Antwerp‐GZA‐ University of Antwerp, Radiation oncology, Antwerp, Belgium; <sup>5</sup>university of vienna, radiotherapy, Vienna, Austria; <sup>6</sup>IMC Banja Luka ‐ Member of the Affidea Group, Radiotherapy, Banja Luka, Bosnia ‐ Herzegovina; <sup>7</sup>Clinical Hospital Center “Sestre milosrdnice”‐University Hospital for Tumors, radiotherapy, zagreb, Croatia; <sup>8</sup>Aarhus University Hospital, radiotherapy, Aarhus, Denmark; <sup>9</sup>Athens General Hospital for Children & Adolescents, radiotherapy, athen, Greece; <sup>10</sup>Hospital Universitari Valld'Hebron, radiotherapy, barcelone, Spain; <sup>11</sup>national institute of oncology, radiotherapy, budapest, Hungary; <sup>12</sup>The Hospital of Lithuanian University of Health Sciences LSMU Kauno klinikos, radiotherapy, kaunas, Lithuania; <sup>13</sup>Proton therapy center Czech, radiotherapy, prague, Czech Republic; <sup>14</sup>St Lukes Radiation Oncology centre, radiation oncology, dublin, Ireland; <sup>15</sup>Norwegian Radium Hospital, oncology, oslo, Norway; <sup>16</sup>University Medical Center Utrecht – Princess Maxima Center for Pediatric Oncology, radiotherapy, utrecht, The Netherlands; <sup>17</sup>univeristy or turin, radiotherapy, turin, Italy; <sup>18</sup>univeristy of Leipzig, radiotherapy, leipzig, Germany</italic></p><p><bold>Background/Objectives</bold>: Increased focus has been made to improve the quality of care and access to European trials in paediatric oncology. Information about paediatric radiotherapy (Ped‐RT) through Europe is not widely available. The aim of this study was to provide an overview of resources and organization for Ped‐RT.</p><p><bold>Design/Methods</bold>: Experts in Ped‐RT oncology were invited by email to complete a 21‐points questionnaire.</p><p><bold>Results</bold>: Sixty‐eight answers from 24 countries (7 centres with proton) were collected and 16 centres were visited. A minority of radiation oncologists (11.74%) treat only children, which is in contrast with paediatric oncologists (93.44%) or surgeons (71.67%) who are more often dedicated. In 5 countries, ped‐RT is centralized in one centre. Access to ped‐RT formations in unequal through Europe even if everyone agree with the fact that specific knowledges are needed.</p><p>Regarding the techniques, 12% use sometimes, meaning for some patients, 2D‐ conventional radiotherapy, 4% still use Cobalt and 15% never or rarely use IMRT (Intensity Modulated Radiotherapy), 64% use hypofractionated treatments, defined as at least 3Gy per fraction and 32% when considering 5 Gy or more. Eighty‐four percent have access to paediatric devices for personalized immobilization. Radiation treatments can be easily delivered under anaesthesia in 75% of the centres if necessary, or under hypnosis in 9% of centres (2 countries).</p><p>The environment is mostly adapted to children, with dedicated dedicated waiting area (47%), patient information (83%), gifts (98%), the possibility to listen to music or songs (93%) or watch cartoons (12%).</p><p><bold>Conclusions</bold>: This survey provides quantitative data demonstrating the current healthcare inequalities for children and adolescents who need radiotherapy in Europe. Nevertheless, an effort to guarantee a treatment of quality with the local environment has been pointed out.</p><p><bold>Acknowledgments</bold>: We thank European NaPHOS and paediatricians who contributed to disseminate the survey in their countries as well as every respondent.</p></sec><sec id="pbc26772-sec-7680"><label>P-364</label><title>A French Multicenter Treatment Planning in Silico Inter‐Comparison: A Skull Base Rhabdomyosarcoma Radiotherapy Case</title><p><underline underline-style="single">A. Ducassou</underline><sup>1</sup>, G. Hangard<sup>2</sup>, C. Lanaspeze<sup>2</sup>, V. Bernier<sup>3</sup>, S. Bolle<sup>4</sup>, F. Goudjil<sup>5</sup>, S. Helfre<sup>6</sup>, C. Kerr<sup>7</sup>, J. Leseur<sup>8</sup>, X. Muracciole<sup>9</sup>, L. Padovani<sup>9</sup>, H. Potet<sup>10</sup>, S. Supiot<sup>11</sup>, G. Truc<sup>12</sup>, C. Vigneron<sup>13</sup>, A. Laprie<sup>1</sup></p><p><italic><sup>1</sup>Institut Claudius regaud ‐Institut Universitaire du Cancer ‐ Toulouse Oncopole, Radiation oncology, Toulouse, France; <sup>2</sup>Institut Claudius regaud ‐Institut Universitaire du Cancer ‐ Toulouse Oncopole, Departement of physics, Toulouse, France; <sup>3</sup>Centre Alexis Vautrin, Radiation oncology, Nancy, France; <sup>4</sup>Institut Gustave Roussy, Radiation Oncology, Villejuif, France; <sup>5</sup>Institut Curie, Department of physics, Paris, France; <sup>6</sup>Institut Curie, Radiation oncology, Paris, France; <sup>7</sup>Institut du Cancer de Montpellier, Radiation Oncology, Montpellier, France; <sup>8</sup>Centre Eugène Marquis, Radiation Oncology, Rennes, France; <sup>9</sup>CHU La Timone, Radiation Oncology, Marseille, France; <sup>10</sup>Institut Jean Godinot‐, Radiation Oncology, Reims, France; <sup>11</sup>Centre René Gauducheau, Radiation Oncology, Nantes, France; <sup>12</sup>Centre Georges‐François Leclerc, Radiation Oncology, Dijon, France; <sup>13</sup>Centre Paul Strauss, Radiation Oncology, Strasbourg, France</italic></p><p><bold>Background/Objectives</bold>: To compare 13 radiotherapy plans of a parameningeal alveolar rhabdomyosarcoma of the skull base in a 5‐year‐girl, optimized in ten centers with IMRT, VMAT, Tomotherapy or Proton therapy, and identify possible dose distribution differences.</p><p><bold>Design/Methods</bold>: Dose prescription was 50.4 Gy in 28 fractions on PTV<sub>1</sub> (involved volume before chemotherapy) with a sequential boost of 5.4 Gy in 3 fractions in a reducted volume (PTV<sub>2</sub>).</p><p>Six Tomotherapy, 4 VMAT, 1 IMRT step and shoot and 1 passive scattering Proton therapy plans were completed and compared. We also evaluated a commercially available treatment planning system (TPS) for a PT plan in Pencil Beam Scattering (RayStation provided by RaySearch Laboratories®).</p><p>Comparisons were performed on the artiview system (Aquilab ®).</p><p><bold>Results</bold>: All institutions achieved the planning objectives, with CTV and PTV<sub>1 and 2</sub> V95 of 95% whatever the modality chosen. Mean conformity index (CI) for PTV<sub>1</sub> and PTV<sub>2</sub> were respectively 1.11 and 2.45 with VMAT, 1.24 and 2.78 with Tomotherapy and 1.31 and 2.95 with Proton therapy.</p><p>Mean standard deviations (STD) for CTV and PTV low risk were respectively 1.57 and 0.71 with VMAT, 1.43 and 0.59 with Tomotherapy and 1.8 and 0.4 with Proton therapy.</p><p>No significant correlations between chosen modality and DVH for targets and organs at risk (OARs) were observed. The optimization strategies selected by the planners played a key role in the delivered dose to the OARs. The cohort was too small to enhance a significant sparing of critical structures.</p><p><bold>Conclusions</bold>: In this complex pediatric tumor, the human factor and the constraints imposed to the target volumes and OARs have a greater dosimetric impact than treatment planning and radiation delivery technology.</p></sec><sec id="pbc26772-sec-7690"><label>P-365</label><title>The Impact of Particle Therapy in Pediatric Tumors with Emphasis on Clinical Toxicity</title><p><underline underline-style="single">J.L. Habrand</underline><sup>1</sup>, D. Stefan<sup>1</sup>, S. Bolle<sup>2</sup>, D. Lecomte<sup>1</sup>, J. Datchary<sup>1</sup>, S. Helfre<sup>3</sup>, C. Alapetite<sup>3</sup></p><p><italic><sup>1</sup>Centre François Baclesse, Radiation oncology, Caen, France; <sup>2</sup>Gustave Roussy Cancer Campus, Radiation oncology, Villejuif, France; <sup>3</sup>Institut Curie, Radiation oncology, Paris, France</italic></p><p><bold>Background/Objectives</bold>: Assessing the impact of particle radiation therapy (PT) on toxicity and sequelae in pediatric and adolescent patients (pts) populations, through literature in the context of modern technologies, with emphasis on comparative clinical studies.</p><p><bold>Design/Methods</bold>: We performed an extensive review of published articles (pub), from 01/2005 through 12/2015 through MEDLINE, according to following key‐words: Radiotherapy, English, Toxicity (acute & late sequelae), Novel technologies, excluding case reports, editorials, letters, inexploitable data. Our review concentrated on comparative studies between PT and photon therapy (XRT), with emphasis on clinical evaluations.</p><p><bold>Results</bold>: 128 pub were selected. Clinical studies represented 71/128 (55%), ranging from small (<20pts:19), to medium (<50pts:22), large (<100pts:13), very large (<500pts:15), and extra‐large (≥500pts:2) cohorts, totalizing >7,000 pts. 18% addressed inter‐comparisons between XRT and XRT technologies (1276 pts, one pub), or PT vs XRT (1,151 pts, 13 pub). 12/13 pub concerned protons (P), and 1/13 carbon ions (C). Main types of toxicity per #pts/#pub investigated: Lung: 303/1, CNS/Quality of life (QOL): 244/4, Second cancers (K2): 161/2, Endocrine: 160/3, acute toxicity: 150/3, Salivary/Head‐Neck (HN): 133/1, respectively. According to impact on technique: IM>3D‐XRT:1 pub (pS), PT>XRT:8 pub (pS:6), XRT>PT:3 pub (pS:2), PT=XRT:2 pub. According to impact on toxicity: Lung: XRT>PT (pS); CNS/QOL: PT>XRT: 2 pub (pS:1); XRT>PT: 1 pub (pS); K2: PT>XRT: 2 (pS:1); Endocrine: PT>XRT: 3 pub (pS:2); Acute: PT>XRT: 2 pub (pS). HN: XRT>PT:1 (pS); C=PT+XRT: 1 pub</p><p><bold>Conclusions</bold>: Few clinical comparative studies between PT and XRT were performed, and none randomized. Most PT were related with P, and only one with C. Impact on toxicity is still controversial although acute, endocrine and CNS/QOL tend to benefit most from PT. This early evaluation needs to be strengthened by further literature.</p></sec><sec id="pbc26772-sec-7700"><label>P-366</label><title>Data Completeness is Directly Correlated with Funding Support in the Pediatric Proton Consortium Registry (PPCR)</title><p><underline underline-style="single">C. Hess</underline><sup>1</sup>, D. Indelicato<sup>2</sup>, A. Paulino<sup>3</sup>, W. Hartsell<sup>4</sup>, C. Hill‐Kayser<sup>5</sup>, S. Perkins<sup>6</sup>, N. Laack<sup>7</sup>, R. Ermoian<sup>8</sup>, A. Chang<sup>9</sup>, O. Cahlon<sup>10</sup>, V. Mangona<sup>11</sup>, A. Mahajan<sup>7</sup>, S. Gallotto<sup>1</sup>, E. Weyman<sup>1</sup>, D. Gaudet<sup>1</sup>, N. Bedos<sup>12</sup>, L. Raeke<sup>12</sup>, S. Baedorf‐Kassis<sup>1</sup>, B. Yeap<sup>1</sup>, T. Yock<sup>1</sup></p><p><italic><sup>1</sup>Massachusetts General Hospital, Radiation Oncology, Boston‐ MA, USA; <sup>2</sup>University of Florida, Radiation Oncology, Jacksonville‐ FL, USA; <sup>3</sup>MD Anderson Cancer Center, Radiation Oncology, Houston‐ TX, USA; <sup>4</sup>Northwestern Medicine and Radiation Oncology Specialists, Radiation Oncology, Chicago‐ IL, USA; <sup>5</sup>University of Pennsylvania, Radiation Oncology, Philadelphia‐ PA, USA; <sup>6</sup>Washington University, Radiation Oncology, St. Louis‐ MO, USA; <sup>7</sup>Mayo Clinic, Radiation Oncology, Rochester‐ MN, USA; <sup>8</sup>University of Washington, Radiation Oncology, Seattle‐ WA, USA; <sup>9</sup>ProCure‐ Oklahoma City, Radiation Oncology, Oklahoma City‐ OK, USA; <sup>10</sup>ProCure New Jersey and Memorial Sloan Kettering Cancer Center, Radiation Oncology, Somerset‐ NJ, USA; <sup>11</sup>Texas Center for Proton Therapy, Radiation Oncology, Irving‐ TX, USA; <sup>12</sup>Massachusetts General Hospital, Program for the Coordination and Oversight of Research Protocols PCORP, Boston‐ MA, USA</italic></p><p><bold>Background/Objectives</bold>: The Pediatric Proton Consortium Registry (PPCR) was established to expedite research on PRT and to better define its role in pediatric cancers by collecting important late effects outcomes.</p><p><bold>Design/Methods</bold>: The PPCR is a consented registry residing on the NIH‐supported REDCap platform that comprehensively integrates baseline demographics, insurance status, disease/health information, treatment details, proton radiation plan, follow‐up vital status, late toxicity, and surveillance imaging. All participating sites offer enrollment to pediatric patients <22 years old. Sites were paid on a per capita basis until 6‐30‐2015 when per capita funding ceased. We report patient numbers by diagnoses and how data field completeness varied by budget era.</p><p><bold>Results</bold>: By 3‐20‐17, 1,634 patients were enrolled across 12 sites. The most common CNS (63%) and non‐CNS (37%) diagnoses are: medulloblastoma/PNET (242), ependymoma (205), gliomas (177), craniopharyngiomas (146), GCT (94); and rhabdomyosarcoma (172), bone sarcomas(114), Hodgkin lymphoma(60), chordoma/chondrosarcoma (51) and neuroblastoma (45). Eleven key registry fields including consent date, DOB, gender, race, referring MD, surgery, chemotherapy, RT‐related start date, site, field description, and total dose were examined. Missing data ranged from 0‐1.4% per field before per capita funding ceased and 0‐53% thereafter. Notably, demographic and diagnosis field completeness were unaffected by budget cuts, but treatment details were missing 30‐53% of the time. Follow‐up data and vital status were missing 23% and 34% of the time before and after budget cuts. The relatively high rate (23%) of missing follow‐up data prior to funding cuts, highlights the challenges of obtaining follow‐up when patients are not locally followed at the proton center.</p><p><bold>Conclusions</bold>: The PPCR has now accrued significant disease specific patient cohorts that can answer important research questions. PPCR Site PIs remain engaged despite lack of resources prompting innovation of new data collection techniques. Innovative solutions for data collection efficiency include selective review of shared electronic medical records by centralized researchers aided by patient reported outcomes (PROs).</p></sec><sec id="pbc26772-sec-7710"><label>P-367</label><title>Facial Growth Deformation Following Pediatric Head and Neck Sarcoma: Should Dose Constraints Regarding Specific Bony Structures Be Considered?</title><p><underline underline-style="single">M.L. Hol</underline><sup>1,2</sup>, B. Pieters<sup>3</sup>, J. Wiersma<sup>3</sup>, A. Bel<sup>3</sup>, N. Freling<sup>4</sup>, B. Balgobind<sup>3</sup>, R. Davilla Fajardo<sup>5</sup>, T. Maal<sup>6</sup>, P. Saeed<sup>7</sup>, J. Chisholm<sup>8</sup>, O. Slater<sup>9</sup>, T. Alderliesten<sup>3</sup>, A. Becking<sup>10</sup>, H. Mandeville<sup>11</sup>, M. Gaze<sup>12</sup>, J. Merks<sup>1</sup>, L. Smeele<sup>2</sup></p><p><italic><sup>1</sup>Academic Medical Center, Department of Pediatric Oncology, Amsterdam, The Netherlands; <sup>2</sup>Academic Medical Center, Department of Maxillofacial Surgery and Head and Neck Surgery, Amsterdam, The Netherlands; <sup>3</sup>Academic Medical Center, Department of Radiation Oncology, Amsterdam, The Netherlands; <sup>4</sup>Academic Medical Center, Department of Radiology, Amsterdam, The Netherlands; <sup>5</sup>Princess Máxima Center for Pediatric Oncology / University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands; <sup>6</sup>RadboudUMC, Department of Maxillofacial Surgery‐ 3D lab, Nijmegen, The Netherlands; <sup>7</sup>Academic Medical Center, Department of Orbital Surgery, Amsterdam, The Netherlands; <sup>8</sup>Royal Marsden Hospital, Department of Pediatric Oncology, Sutton, United Kingdom; <sup>9</sup>Great Ormond Street Hospital, Department of Pediatric Oncology, London, United Kingdom; <sup>10</sup>Academic Medical Center, Department of Maxillofacial Surgery, Amsterdam, The Netherlands; <sup>11</sup>Royal Marsden Hospital, Department of Radiation Oncology, Sutton, United Kingdom; <sup>12</sup>University College London, Department of Radiation Oncology, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: During radiotherapy planning in patients with pediatric head and neck cancer, multiple organs at risk are taken into account and corresponding dose constraints are considered. However, dose constrains related to facial bony growth have never been verified for specific facial bones. The purpose of this study was to investigate the relation between dose to facial bony structures and facial growth deformations.</p><p><bold>Design/Methods</bold>: This cross‐sectional multicenter study included 35 children treated for head and rhabdomyosarcoma (average treatment age:6years, range:1‐14years) with EBRT or brachytherapy for whom the original radiotherapy planning and facial growth deformity data (mean follow‐up of 10 years) based on 3D stereophotograph analysis were available. All bony structures within the field of view of the (reconstructed) planning CT scans were delineated, resulting in 712 delineated facial structures. For each delineated bony structure, the planned mean and maximum dose were analysed with regard to the growth deformity quantified for the corresponding facial part on the 3D stereophotograph.</p><p><bold>Results</bold>: Growth deformities were more severe in patients treated at a younger age than in patients treated when they were older. A correlation between growth deformities and dose indices was not found. However, overall more severe growth deformities were observed when the dose exceeded 24Gy. Some bony structures were more susceptible to growth disruption than others, for example the mandibular condyle and lacrimal bone exhibited more growth deformities after receiving the same mean and maximum dose than the frontal‐temporal bone complex (<italic>both p<0.05</italic>).</p><p><bold>Conclusions</bold>: We found significant differences for the susceptibility to growth deformity between different facial bony structures. In the future, dose constraints for specific bony structures of the face might therefore be beneficial in pediatric radiotherapy to limit facial deformities. Further research based on a larger data set is needed to derive appropriate dose constraints for each facial bone.</p></sec><sec id="pbc26772-sec-7720"><label>P-368</label><title>High Dose Rate (HDR) Brachytherapy in Childhood Rhabdomyosarcomas: Experience of a Single Center</title><p><underline underline-style="single">S. Kamer</underline><sup>1</sup>, A. Celik<sup>2</sup>, A. Avanoglu<sup>2</sup>, O. Ergun<sup>2</sup>, M. Palamar<sup>3</sup>, A. Yagci<sup>3</sup>, B. Kadioglu<sup>4</sup>, N. Cetingul<sup>5</sup>, M. Kantar<sup>5</sup>, T. Turhan<sup>6</sup>, Y. Anacak<sup>7</sup></p><p><italic><sup>1</sup>Ege University Faculty of Medicine, Radiation Oncology, IZMIR, Turkey; <sup>2</sup>Ege University Faculty of Medicine, Department of Pediatric Surgery, izmir, Turkey; <sup>3</sup>Ege University Faculty of Medicine, Department of Ophthalmology, IZMIR, Turkey; <sup>4</sup>Behcet Uz Children's Hospital, Department of Pediatric Oncology, IZMIR, Turkey; <sup>5</sup>Ege University Faculty of Medicine, Department of Pediatric Oncology, IZMIR, Turkey; <sup>6</sup>Ege University Faculty of Medicine, Department of Neurosurgery, IZMIR, Turkey; <sup>7</sup>Ege University Faculty of Medicine, Department of Radiation Oncology, IZMIR, Turkey</italic></p><p><bold>Background/Objectives</bold>: Radiotherapy (RT) is an important component of the treatment in childhood rhabdomyosarcomas (RMS). Brachytherapy is a special irradiation technique which gives a possibility to protect surrounding healthy tissues and organs from unnecessary irradiation. The use of brachytherapy is favorable over external RT in particular sites of childhood RMS. In this study we present the results of the Ege University Hospital.</p><p><bold>Design/Methods</bold>: From January 2008 to October 2016, HDR brachytherapy was used as part of the treatment in 18 cases with RMS in Ege University Hospital. Median age was 6 (range: 3‐17) and Male/Female ratio was 1.5/1. Localization of the tumors were vagina in 1 case, bladder in 8 cases, non‐paramenengial head and neck in 3 cases, orbita in 4 cases, pelvic wall in 1 case and biliary tractus in 1 case. IRS III or IV chemotherapy regimens were used before RT. RT dose was 24‐36 Gy and a combined external and brachytherapy was used in 2 cases.</p><p><bold>Results</bold>: From January 2008 to October 2016, HDR brachytherapy was used as part of the treatment in 18 cases with RMS in Ege University Hospital. Median age was 6 (range: 3‐17) and Male/Female ratio was 1.5/1. Localization of the tumors were vagina in 1 case, bladder in 8 cases, non‐paramenengial head and neck in 3 cases, orbita in 4 cases, pelvic wall in 1 case and biliary tractus in 1 case. IRS III or IV chemotherapy regimens were used before RT. RT dose was 24‐36 Gy and a combined external and brachytherapy was used in 2 cases.</p><p><bold>Conclusions</bold>: Brachytherapy is effective in the local–regional control of childhood RMS. Careful planning of RT is extremely important for maximum benefit. Late effects need to be monitored for long term.</p></sec><sec id="pbc26772-sec-7730"><label>P-369</label><title>Nasopharyngeal Carcinoma in Children: A Ten Year Experience with IMRT</title><p><underline underline-style="single">S. Laskar</underline><sup>1</sup>, A. Bindal<sup>1</sup>, N. Khanna<sup>1</sup>, S. Chaudhari<sup>2</sup>, G. Chinnaswami<sup>3</sup>, T. Vora<sup>3</sup>, S. Kembhavi<sup>4</sup>, S. Shah<sup>5</sup>, M. Ramadwar<sup>6</sup>, S. Qureshi<sup>7</sup>, M.A. Muckaden<sup>8</sup>, P. Kurkure<sup>3</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Radiation Oncology, Mumbai, India; <sup>2</sup>Tata Memorial Hospital, Medical Physics, Mumbai, India; <sup>3</sup>Tata Memorial Hospital, Paediatric Oncology, Mumbai, India; <sup>4</sup>Tata Memorial Hospital, Radiodiagnosis, Mumbai, India; <sup>5</sup>Tata Memorial Hospital, Bio Imaging, Mumbai, India; <sup>6</sup>Tata Memorial Hospital, Pathology, Mumbai, India; <sup>7</sup>Tata Memorial Hospital, Surgical Oncology, Mumbai, India; <sup>8</sup>Tata Memorial Hospital, Palliative Medicine, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: To evaluate the disease outcome in children with Nasopharyngeal Carcinoma (NPC) treated with Intensity Modulated Radiotherapy (IMRT) at the Tata Memorial Hospital.</p><p><bold>Design/Methods</bold>: Between 2005 and 2015, 95 children with NPC were treated at our Institute. The median age was 14 years [8‐18 years]. Majority (92%) of patients had either T3‐T4 or N2‐N3 disease at presentation. They received neoadjuvant Chemotherapy (CTh) followed by IMRT and adjuvant CTh. Three clinical target volumes (CTV) were defined for IMRT. High Risk CTV (70.2 Gy/33 fr) included nasopharyngeal region and involved nodes, intermediate risk CTV (59.4 Gy/33 fr) included nodal regions adjacent to the involved nodes and low risk CTV (54.8 Gy/33 fr) included uninvolved nodal levels beyond intermediate risk CTV. CTh consisted of Bleomycin, Methotrexate and Cisplatin.</p><p><bold>Results</bold>: The loco‐regional control, disease‐free survival and overall survival for the cohort were 85%, 60% and 65%, respectively. At a median follow up of 33 mths (4‐148 mths), 53 (56%) patients remained alive & disease free. Three patients (3.2%) with regional recurrence alone were salvaged with reirradiation, surgery and CTh, and remain disease free. All patients with regional recurrence and distant metastases (11.6%) died of progressive disease. Twenty four (25.3%) developed distant metastasis only. Of them 4/24 (16.6%) with oligometastases were salvaged with RT and CTh and are disease free, while 2/24 (8.3%) remain alive with metastatic disease and 18/24 (75%) died of metastases. Four (4.2%) patients died of CTh related complications. Xerostomia (16% Gr II),clinical hypothyroidism (23%), autotoxicity (20% Gr III), visual field defects (6.3%), and dental carries (20%) were the major toxicities.</p><p><bold>Conclusions</bold>: Combined treatment with IMRT and CTh resulted in acceptable disease control & toxicities. Distant metastasis remains a major cause of death in these children.</p></sec><sec id="pbc26772-sec-7740"><label>P-370</label><title>Impact of Postoperative Abdominal Irradiation on Local Recurrence in Unilateral Intermediate and High‐Risk Wilms Tumour (SIOP‐2001/GPOH)</title><p><underline underline-style="single">P. Melchior</underline><sup>1</sup>, Y. Dzierma<sup>1</sup>, G. Mogeniene<sup>1</sup>, R. Furtwängler<sup>2</sup>, N. Graf<sup>2</sup>, C. Rübe<sup>1</sup></p><p><italic><sup>1</sup>Saarland University Hospital, Radiation Oncology, Homburg‐Saar, Germany; <sup>2</sup>Saarland University Hospital, Pediatric Hematology and Oncology, Homburg‐Saar, Germany</italic></p><p><bold>Background/Objectives</bold>: To report the clinical outcome of children with Wilms tumour (WT) after multimodality treatment following the SIOP‐2001/GPOH protocol with special regard to radiotherapy.</p><p><bold>Design/Methods</bold>: Analysis of 175 patients with unilateral WT eligible for abdominal irradiation according to histological subtype and postoperative SIOP‐stage, treated between 2001 and 2015.</p><p><bold>Results</bold>: According to the SIOP‐2001 protocol 175 of 967 children (18.1%) were eligible for postoperative abdominal radiotherapy (PORT). The median follow up was 4.8 years. Median age at diagnosis was 3.4 years. There were 132 children with intermediate risk histology (IR) (stage III) and 43 children with high risk histology (HR) (diffuse anaplastic (stage II and III) and blastemal type (stage III)). 40 of 175 eligible patients were not irradiated.</p><p>There were 18 abdominal relapses (10.3%) in the whole cohort. There were 6 local failures in 40 non‐irradiated (15%) vs. 12 in 135 irradiated children (8.9%). In 4 patients, local relapse was the only site of failure. Most local recurrences (14 of 18) were combined with distant metastasis. Mean time to the first event was 0.98 years. Local recurrence occurred in IR in 3 of 30 (10%) nonirradiated vs. 5 of 102 (4.9%) irradiated patients, in HR in 3 of 10 (30%) nonirradiated vs. 7 of 33 (21.2%) irradiated patients. Twelve of 18 local relapses were localised in the flank, 8 infield failures and only 4 relapses outside the radiation field.</p><p>The 5‐year local control was 91.6% in the irradiated vs. 84.3% in the nonirradiated group (p=0.29); 75.3% in HR vs. 94.5% in IR patients with PORT.</p><p><bold>Conclusions</bold>: Children with WT treated with a PORT have an excellent local control, especially for IR. Most local relapses occurred inside the radiation field and were combined with distant metastases. Further prospective analyses are necessary to evaluate new highly conformal radiation techniques.</p></sec><sec id="pbc26772-sec-7750"><label>P-371</label><title>Radiation Dose and Let Distributions in Pediatric Craniopharyngioma Patients with and Without Radiation‐Induced Cerebral Vasculopathies</title><p>A. Pica<sup>1</sup>, D.G. Correia<sup>1</sup>, L. Placidi<sup>1</sup>, A. Bolsi<sup>1</sup>, <underline underline-style="single">D.C. Weber</underline><sup>1</sup></p><p><italic><sup>1</sup>Paul Scherrer Institut, ProtonTherapy Center CPT, Villigen, Switzerland</italic></p><p><bold>Background/Objectives</bold>: The study aims are: a) to report two cases of radiation‐induced vasculopathies (RIV) after pencil beam scanning (PBS) proton therapy (PT) for pediatric craniopharyngioma patients and b) to evaluate local dose and linear energy transfer (LET) distributions for these RIVs.</p><p><bold>Design/Methods</bold>: We reviewed a series of 16 patients treated at Paul Scherrer Institute (median dose 54 GyRBE). Two (13%) out of 16 patient showed RIVs (one stenosis of right ICA and one progressive multifocal RIV in the region of the circle of Willis, 14 and 24 months after irradiation, respectively). A control group (no RIV) was selected based on the same fields’ arrangement and the tumour size. CTs and MRIs pre and post PT were used to contour organs at risks (OARs; bilateral ICAs and circle of Willis). DVH parameters and dose distributions were analysed. Dose weighted LET distributions (Gy * keV/mm) and LET distributions were analysed.</p><p><bold>Results</bold>: Dose distributions for patient in the control group and presenting with RIV did not show any significant difference in terms of target coverage and OARs sparing, while RIV structures have a lower Dmean,without significant difference in the Dmax and in the D2%. Both patients presenting with RIV toxicities were treated with ipsilateral fields, thus resulting in marked asymmetric LET distributions. Despite high LET areas at the distal edge of the PTV, no significant differences were found in the maximum and mean LET values for the RIV between patients with toxicities and control patients.</p><p><bold>Conclusions</bold>: Quantitative analysis was not able to show significant correlations between delivered dose, LET and RIV. Ipsilateral planning approach seems to have an impact in the presence VT toxicity. This approach is generally less dosimetrically robust than the other one and it results in asymmetric LET distributions, with high LET values at the contralateral distal edge of the PTV.</p></sec><sec id="pbc26772-sec-7760"><label>P-372</label><title>Optimizing Technique and Technology and Cost of Radiotherapy for Management of Childhood Cancer: Experience from Regional Cancer Centre in India (A Low‐ and Middle‐Income Country)</title><p><underline underline-style="single">V.K. Ramaiah</underline><sup>1</sup></p><p><italic><sup>1</sup>Kidwai Cancer Institute, Radiation Oncology, Bangalore, India</italic></p><p><bold>Background/Objectives</bold>: Cobalt‐based conventional technique (CCT) to linear accelerator based conformal radiotherapy (3‐D CRT) / particle therapy with or without incorporating adoptive technology for regular position verification are the different modalities that may be available with unpredictable variability for radio‐therapeutic management of childhood cancers in developing countries. Radiation portals or tumor targets can be delineated by conventional un‐calibrated x‐ray, x‐ray / fluoroscope with simulator scale or any of 3‐D imaging. In‐expensive soldering lead wire placed on the border of radiation portal and over the every centimeter mark on adhesive tape can be utilized to customized radiation field. Need for sedation / anesthesia is mostly patient‐dependent rather than the technology itself. Advanced radiotherapy techniques and technology have reduced long‐term side‐effects due to dosimetric improvement without alteration the tumor control. We do not have large long‐term outcome results of resource‐intensive novel radiotherapy technology and techniques. In such scenario, affordability and waiting time are the two main factors determining the type of radiation technology utilization in particular patients in low‐resource setting.</p><p><bold>Design/Methods</bold>: Retrospective analysis of radiation registers of pediatric patients with cancer treated between 2012 and 2016 at Kidwai Cancer Institute, Bangalore</p><p><bold>Results</bold>: 8% (85) of all patients undergoing radiotherapy was pediatric patients in our center. >1/2 (45) of all pediatric patients were diagnosed with acute lymphoblastic leukemia (ALL) and had undergone prophylactic cranial irradiation. 59 (69%) and 22 (25%) were treated by CCT and 3‐D CRT.Cost of radiotherapy of children with cancer for the same period was Indian National Rupee 962500 i.e. 5.3% of total money spent on radiotherapy for all patients.</p><p><bold>Conclusions</bold>: CCT still appears to be provide in‐expensive treatment for large number of pediatric patients with cancer. 3‐D CRT has benefit of sparing normal tissue in intra‐cranial, intra‐thoracic and intra‐abdominal tumors and for dose‐escalation to boost local tumors.</p></sec><sec id="pbc26772-sec-7770"><label>P-373</label><title>Customized Technique for Radiotherapy Simulation of Children with Cancer to Improvise Radiation Delivery in Severely Resource‐Constrained Setting</title><p><underline underline-style="single">V.K. Ramaiah</underline><sup>1</sup>, L. Vishwanath<sup>1</sup></p><p><italic><sup>1</sup>Kidwai Cancer Institute, Radiation Oncology, Bangalore, India</italic></p><p><bold>Background/Objectives</bold>: Radiotherapy simulation is a process where treatment is simulated but not really given. Radiation portals are defined during simulation after patient positioning and defining target area / region for subsequent irradiation. Simulation can be achieved by done by conventional simulator or 3‐dimensional computed imaging. However, in severely resource‐constrained setting, Co‐60 tele‐therapy equipment may be the only available radiation equipment for management of patients. Surface anatomical marking are the only landmark utilized for radiation portal placement. Conventional X‐ray without scale may be of little help without optical distance indicator and cross hair scale to account for magnification. There is a need to improvise radiation simulation with the available technology in resource‐constrained developing countries. To this effect, we simulated children with cancer by utilizing customized soldering lead wire scale, portal lead marker and conventional x‐ray.</p><p><bold>Design/Methods</bold>: Hemi‐length of adhesive porous plastic surgical tape was stuck on to scale and small bits of soldering lead wire was placed at a distance of 1 centimeter. Radiation portal was marked manually by utilizing anatomic surface landmark and lead markers placed on all the borders of this portal with the help of same adhesive tape. The customized scale was stuck on to the body within field of view of X‐ray. Patients were subjected to x‐ray and radiation portal was redefined based on the images of scale on x‐ray film.</p><p><bold>Results</bold>: In the absence of any kind of simulator, we were able to plan almost all children with cancer presenting to our centre. Positional and rotational movements and other errors of maginification may be taken care of by corresponding the x‐ray defined portal with surface anatomic landmarks.</p><p><bold>Conclusions</bold>: Our is one of the first study to report successful radiotherapy simulation of children with cancer by customized simulation technique in acutely resource‐constrained developing countries</p></sec><sec id="pbc26772-sec-7780"><label>P-374</label><title>Radiotherapy Under Anaesthesia of Children with Cancer in Developing Countries: Simulation and Treatment Under Dissimilar Conditions is the Source of Geometric Tumor Miss</title><p>V.K. Ramaiah<sup>1</sup>, <underline underline-style="single">S. Bhasker</underline><sup>2</sup></p><p><italic><sup>1</sup>Kidwai Cancer Institute, Radiation Oncology, Bangalore, India; <sup>2</sup>All India Institute of Medical Scieces, Radiotherapy, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Children with cancer needing radiotherapy as part of multi‐modality therapy are sometimes not cooperative for radiotherapy immobilization, simulation and / or treatment. Counselling, sedation, general anesthesia or combination of these are generally prescribed to prevent movement of children during radiotherapy immobilization, simulation and treatment. Sometimes, patients are cooperative / non‐cooperative to one or more steps of radiotherapy process. Such situation creates dissimilar condition between steps of radiotherapy planning and treatment that in turn manifest as non‐overlap between the simulation position and treatment position. Muscle relaxation after anaesthesia is the main reason for such positional mismatch between two different steps of radiotherapy process. Our paper discuss of this mismatch between various steps of radiotherapy and devised methods to minimize such mismatch for radiotherapy planning and delivery using thermoplastic immobilization device.</p><p><bold>Design/Methods</bold>: Patients are immobilized in hospital area without anaesthesia after appropriate counselling of patients that is different from the area of simulation and treatment in resource‐constrained. Patients were immobilized by immobilization device during the whole process of radiotherapy and assessed for snugness of fit of immobilization device.</p><p><bold>Results</bold>: Anaesthesia induced muscle relaxation is responsible for loosening of immobilization and subsequent geographical tumor miss.</p><p><bold>Conclusions</bold>: Whole radiotherapy process of children with cancer has to be carried‐out under similar circumstances .i.e. all process to be done under anaesthesia or all process to be carried‐out without anaesthesia to avoid geometric miss of tumor during radiotherapy</p></sec><sec id="pbc26772-sec-7790"><label>P-375</label><title>Ripetitive Pediatric Anesthesia in a Hospital Based Proton Center</title><p><underline underline-style="single">B. Rombi</underline><sup>1</sup>, S. Vennarini<sup>1</sup>, D. Pedrotti<sup>2</sup>, M. Detassis<sup>2</sup>, P. Betonte<sup>2</sup>, L. Meneghello<sup>3</sup>, C. Bonazza<sup>3</sup>, L. Gazzola<sup>3</sup>, A. Petrone<sup>3</sup>, L. Valle<sup>2</sup>, A. Di Palma<sup>3</sup>, M. Geat<sup>2</sup>, M. Amichetti<sup>1</sup></p><p><italic><sup>1</sup>Trento Hospital, Oncology Department ‐ Proton Therapy Center, Trento, Italy; <sup>2</sup>S. Chiara Hospital, Anaesthesiology Department, Trento, Italy; <sup>3</sup>S. Chiara Hospital, Paediatric Department, Trento, Italy</italic></p><p><bold>Background/Objectives</bold>: Repetitive sedation/anesthesia (S/A) for children receiving fractionated proton beam radiotherapy (PBT) requires well‐organized daily setting of a multidisciplinary team with high degree of competence during the induction and recovery phases for several weeks. Typical cases for PBT due to setup and treatment complexity usually require longer S/A comparing photon based ‐ sessions. Our preliminary experience with A/S by age and gender in children receiving daily PBT is reported.</p><p><bold>Design/Methods</bold>: Records of 42 pediatric patients (≤18 years) were reviewed between June 2015 and March 2017 at Proton Therapy Center ‐ APSS, Trento (Italy) of whom 17 received PBT under A/S. All patients were treated for CNS tumors.</p><p><bold>Results</bold>: Fourteen (83%) children aged ≤ 6 years and three (17%) patients aged 7–9 years received daily A/S for a median number of 30 fractions. Seven (41%) patients with median age 7 years received cranio‐spinal irradiation (CSI) under sedation while the following local primary boost was performed without anesthesia after a week of dedicated training. Total time under anesthesia ranged from 30 to 90 minutes for more complex cases (i.e. CSI) with the use of Propofol. There were no deaths. No cardiopulmonary resuscitation or aspiration was required. Less serious events were more common with O(2) desaturation below 90% for more than 30 s and central apnea or airway obstruction occurred in 0.5% of the 568 sedation/anesthesia administrations. No stridor, laryngospasm or vomiting was reported and excessive secretions occurred in 0.2% of cases. No unexpected admissions were required</p><p><bold>Conclusions</bold>: The occurrence of undesired effects of A/S in our experience was very low. A strong emphasis on teamwork may have contributed to this favorable event rate. A/S can be safely implemented in a technically and clinically complex PBT context.</p></sec><sec id="pbc26772-sec-7800"><label>P-376</label><title>Potential Reduction of Acute Hematological Toxicity in Dual‐Phase Craniospinal Proton Therapy for Pediatric Medulloblastoma</title><p><underline underline-style="single">S. Vennarini</underline><sup>1</sup>, B. Rombi<sup>1</sup>, P. Farace<sup>1</sup>, S. Lorentini<sup>1</sup>, G.S. Colafati<sup>2</sup>, A. Carai<sup>3</sup>, A. Cacchione<sup>4</sup>, A. Mastronuzzi<sup>4</sup>, M. Amichetti<sup>1</sup></p><p><italic><sup>1</sup>Trento Hospital, Oncology Departement‐Proton Therapy Center, Trento, Italy; <sup>2</sup>IRCCS Bambino Gesù Children's Hospital, Neuroradiology Unit‐ Imaging Department, Rome, Italy; <sup>3</sup>IRCCS Bambino Gesù Children's Hospital, Neurosurgery Unit‐Department of Neuroscience and Neurorehabilitation, Rome, Italy; <sup>4</sup>IRCCS Bambino Gesù Children's Hospital, Department of Pediatric Hematology and Oncology, Rome, Italy</italic></p><p><bold>Background/Objectives</bold>: To evaluate acute hematological toxicity during craniospinal irradiation (CSI) with proton therapy (PT) for children with high‐risk (HR) medulloblastoma after intensive myeloablative chemotherapy (CHT).</p><p><bold>Design/Methods</bold>: We evaluated haematological toxicity in ten pediatric patients (average age 7, range 4‐9), who underwent CSI from February to December 2016. All patients received the last CHT cycle with carboplatin at 550 mg/m2 one month before irradiation. All patients completed PT at a total dose of 36GyRBE in two phases without interruption: a first phase (20GyRBE) including the whole vertebral body and a second phase (16GyRBE) to spinal cord excluding the vertebral body. Two patients were administered oral temozolomide at 75 mg/m2/day during the treatment. White blood cells (WBC), hemoglobin, platelets and absolute neutrophil (ANC) were counted pre‐CSI, at the end of the first phase (middle‐CSI) and at the end of the second phase (end‐CSI). Paired T‐test was applied to statistically compare (p<0.05) values at the different phases.</p><p><bold>Results</bold>: WBC significantly decreased from pre‐CSI (median 2.81×10^<sup>9</sup>/L, range 1.4‐7.4) to middle‐CSI (1.39, 1.1‐2.1) and then significantly increased at end‐CSI (2.34, 1.4‐4.4) to values not significantly different form pre‐CSI. Hemoglobin did not significantly change from pre‐CSI (median 10.59mg/dL, range 9.1‐10.4), to middle‐CSI (10.39, 9.2‐11.1) and end‐CSI (10.41, 9.3‐11.8). Platelets significantly decreased from pre‐CSI (median 266.9×10^<sup>9</sup>/L, range 128‐409) to middle‐CSI (144, 99‐185), and then significantly increased at end‐CSI (183.2, 137‐214) but to values still significantly lower than pre‐CSI. ANC decreased from pre‐CSI (median 1.37×10^<sup>9</sup>/L, range 0.3‐3.9) to middle‐CSI (0.85, 0.5‐1.3), and then significantly increased at end‐CSI (1.49, 0.6‐3.2,) to values not significantly different form pre‐CSI.</p><p><bold>Conclusions</bold>: Due to the distal fall‐off, PT can effectively deliver dual‐phase CSI, with only limited dose to the vertebral body (around 20GyRBE) that can reduce acute hematological toxicity during treatment. It could be useful in reducing also long‐term growth impairment.</p></sec><sec id="pbc26772-sec-7810"><label>P-377</label><title>Pre‐Operative Intensity‐Modulated Radiotherapy Compared to Three‐Dimensional Conformal Radiotherapy for High Grade Extremity Sarcomas in Children: Analysis of Childrens Oncology Group (COG) Study ARST0332</title><p><underline underline-style="single">A. Rao</underline><sup>1</sup>, Q. Chen<sup>1</sup>, L. Million<sup>2</sup>, S. Spunt<sup>3</sup>, T. FitzGerald<sup>4</sup>, F. Laurie<sup>5</sup>, S. Kessel<sup>5</sup>, K. Morano<sup>5</sup>, S. Terezakis<sup>1</sup></p><p><italic><sup>1</sup>Johns Hopkins University School of Medicine, Radiation Oncology and Molecular Radiation Sciences, Baltimore, USA; <sup>2</sup>Stanford University School of Medicine, Radiation Oncology, Palo Alto, USA; <sup>3</sup>Stanford University School of Medicine, Department of Pediatrics, Palo Alto, USA; <sup>4</sup>University of Massachusetts Medical School, Radiation Oncology, Worcester, USA; <sup>5</sup>IROC Rhode Island, UMASS ‐ QARC, Lincoln, USA</italic></p><p><bold>Background/Objectives</bold>: We assessed tumor coverage and dose to bone and skin in pediatric patients treated with IMRT vs. 3D‐CRT on ARST0332.</p><p><bold>Design/Methods</bold>: Of the 551 eligible patients, 200 were enrolled in Arm D of ARST0332 in which patients age<30 years received neoadjuvant ifosfamide/doxorubicin and 45 Gy, surgery, and an RT boost based on margins. 121 RT plans were available for remote review through the Imaging and Radiation Oncology Core (IROC) Rhode Island database. Of these, 56 patients had extremity STS and 54 were in proximity to a long bone (humerus/femur/tibia). The dose delivered to the clinical target volume (CTV), skin (contoured from the surface to depth of 5 mm), and in‐field bone was analyzed.</p><p><bold>Results</bold>: Thirty‐eight patients (65%) received 3D‐CRT and 18 (32%) received IMRT. There was no difference in distribution of site treated with IMRT vs. 3D‐CRT with the exception of 0% vs. 11% of patients treated with IMRT vs. 3D‐CRT to upper arm STS. There was no difference in CTV volume between patients treated with IMRT or 3D‐CRT (p=0.920); however, IMRT resulted in significantly improved CTV coverage with 100% of the prescription dose compared 3D‐CRT (median CTV coverage, 95% vs. 87%, p=0.011). In patients without skin bolus, skin V45Gy was significantly lower in patients treated with IMRT compared to 3D‐CRT (mean percentage, 3% vs. 8% respectively, p=0.039). IMRT resulted in higher in‐field bone V10Gy (mean 89.8% vs. 68.7%, p=0.001) and V20Gy (mean 85.4% vs. 63.8%, p=0.014) compared to 3D‐CRT. There was no difference in higher doses to bone (V30/V40/V45) between radiation techniques.</p><p><bold>Conclusions</bold>: Pre‐operative IMRT compared to 3D‐CRT may result in improved RT target coverage with reduced dose to the skin, but with increased low dose exposure to in‐field bone. Future studies should assess if these dosimetric findings translate into differences in clinical and toxicity outcomes.</p></sec><sec id="pbc26772-sec-7820"><label>P-378</label><title>Feasibility and Toxicity of Simultaneously Administrated Chemotherapy and Proton Therapy in Children and Adolescents</title><p><underline underline-style="single">E. Schürmann</underline><sup>1</sup>, S. Tippelt<sup>1</sup>, N. Siegler<sup>1</sup>, R. Mikasch<sup>1</sup>, S. Borkens<sup>1</sup>, C. Plass<sup>2</sup>, S. Peters<sup>2</sup>, B. Timmermann<sup>2</sup>, D. Reinhardt<sup>1</sup>, G. Fleischhack<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Essen, Pediatric Oncology and Hematology, Essen, Germany; <sup>2</sup>University Hospital Essen, West German Proton Therapy Centre in Essen WPE, Essen, Germany</italic></p><p><bold>Background/Objectives</bold>: Proton therapy (PT) is a promising alternative in radiotherapy of solid tumors in eloquent regions. While most recent studies deal with the outcome or long term side effects of PT, the aim of this study is the investigation of feasibility and acute toxicity of the simultaneous chemotherapy (CT) and PT.</p><p><bold>Design/Methods</bold>: This retrospective study enrolled all consecutive patients at age <18 years treated at the West German Proton Therapy Center in Essen, Germany, between September 2013 and December 2016. Based on the PT Registry and the patients’ records data about patient's characteristics, pretreatment, recent treatment and acute adverse events (AE) were collected and analyzed.</p><p><bold>Results</bold>: Two‐hundred‐ninety‐three children (169 male, 124 female, median age 6.3 years) suffering from CNS tumors (n=166, 56.6%), sarcomas (n=92, 31.4%) or other tumor entities (n=35, 11.9%) received in total 294 PT cycles. PT was performed in 202 patients (68.7%) at primary treatment and in 92 (31.3%) at recurrence. 131 (44.6%) patients received a simultaneous CT. Severe AE (SAE, CTCAE°3/°4) were observed in 130 (44.2%) PT cycles, and were mostly hematotoxicity (n=105; 80.8%) and infections (n=28; 21.5%). Seventy‐three hospitalizations due to an unexpected event (mostly infections, mucositis, electrolyte imbalance) were necessary in 54 out of 294 PT cycles. In the group with simultaneous CT 53 patients (40.5%) could not receive the recommended CT dose or time schedule. The frequency of SAE was significant higher in the group with simultaneous CT than in the group without (71.8% vs. 22.1%, χ² test, p<0.001).</p><p><bold>Conclusions</bold>: With regard to the increasing number of children in the PT centers in Western Europe, our data demonstrate the requirement of a well experienced interdisciplinary team and an adequate infrastructure for management of complex patients regarding infectious, neurological, endocrinological problems and especially the individual adjustment of a simultaneous chemotherapy.</p><p><italic>Supported by German Children's Cancer Foundation</italic></p></sec><sec id="pbc26772-sec-7830"><label>P-379</label><title>Proton Beam Therapy for Childhood Cancers: A Case Series of Shizuoka Cancer Center and Children's Hospital Collaboration</title><p><underline underline-style="single">K. Watanabe</underline><sup>1</sup>, Y. Ishida<sup>2</sup>, S. Yurikusa<sup>1</sup>, H. Kitazawa<sup>1</sup>, H. Kato<sup>2</sup>, K. Kawaguchi<sup>1</sup>, I. Takahashi<sup>1</sup>, T. Ogura<sup>1</sup>, Y. Horikoshi<sup>1</sup>, T. Wataya<sup>3</sup>, N. Urushihara<sup>4</sup>, S. Murayama<sup>5</sup></p><p><italic><sup>1</sup>Shizuoka Children's Hospital, Department of Hematology and Oncology, Shizuoka, Japan; <sup>2</sup>Shizuoka Cancer Center Hospital, Division of Pediatrics, Nagaizumi, Japan; <sup>3</sup>Shizuoka Children's Hospital, Department of Neurosurgery, Shizuoka, Japan; <sup>4</sup>Shizuoka, Japan; <sup>5</sup>Shizuoka Cancer Center Hospital, Division of Proton Therapy, Nagaizumi, Japan</italic></p><p><bold>Background/Objectives</bold>: Proton beam therapy (PBT) offers more precise targeting than conventional photon radiation therapy and may limit radiation exposure to normal tissue. Therefore, PBT has been increasingly applied for treatment of childhood cancers in an attempt to reduce treatment‐related long‐term toxicities such as second malignancy. Cooperation of a pediatric oncology team with a PBT facility is crucial to include PBT in a context of multimodal management of children with cancer. We have applied proton therapy for childhood cancers in close collaboration between a cancer center and children's hospital in Shizuoka prefecture in Japan for more than 10 years.</p><p><bold>Design/Methods</bold>: From April 2005 to February 2016, 35 children with cancer in Shizuoka Children's Hospital referred to Shizuoka Cancer Center to receive PBT. We reviewed their medical records and retrospectively analyzed clinical data and outcome.</p><p><bold>Results</bold>: The median age at the time of receiving PBT is 5 years old (range:1‐16). Ten patients were female. Twenty‐seven patients (77%) had central nervous system tumor (medulloblastoma, 6; atypical teratoid/rhabdoid tumor, 3; choroid plexus carcinoma, 1; brainstem glioma, 6; intracranial germ cell tumor, 4; ependymoma, 5; malignant meningioma, 1; undifferentiated sarcoma, 1), and the other patients (n=8, 23%) had non‐CNS solid tumors (neuroblastoma, 4; Ewing sarcoma, 1; PNET, 1; undifferentiated sarcoma, 1; hemangioma, 1). All patients with medulloblastoma and one with choroid plexus carcinoma received proton beam CSI. The irradiation dose ranged from 19.6 to 67.2 GyE (mostly in 1.8GyE/fr). Twenty‐seven patients (77%) were alive at the median follow up of 63 months (range: 4‐134). There were no severe acute toxicities.</p><p><bold>Conclusions</bold>: PBT may be applied effectively and safely to treatment of various childhood cancers under close collaboration between a regional cancer center and children's hospital. Further study is needed to elucidate long‐term complications of PBT in patients with childhood cancer.</p></sec></sec><sec id="pbc26772-sec-7840"><title>Treatment and Care ‐ New Drugs/Experimental Therapeutics</title><sec id="pbc26772-sec-7850"><label>P-380</label><title>Caffeine Citrate is a Novel Candidate Enhancing Platinum‐Based Chemotherapy for Sarcoma</title><p><underline underline-style="single">K. Abe</underline><sup>1</sup>, N. Yamamoto<sup>1</sup>, K. Hayashi<sup>1</sup>, A. Takeuchi<sup>1</sup>, T. Higuchi<sup>1</sup>, Y. Taniguchi<sup>1</sup>, H. Aiba<sup>1</sup>, Y. Araki<sup>1</sup>, H. Tsuchiya<sup>1</sup></p><p><italic><sup>1</sup>Kanazawa University, Orthopaedic Surgery, Kanazawa, Japan</italic></p><p><bold>Background/Objectives</bold>: The prognosis in patients with sarcoma has been dramatically improved by multi‐agent chemotherapy. However, the chemotherapeutics have hardly changed for 30 years. We developed caffeine‐potentiated chemotherapy for musculoskeletal sarcoma in 1989 and have reported the excellent response and oncological outcome. Even with this excellent result, it was difficult to conduct an initiated clinical trial without patent. Citric acid was also reported that it could enhance the cytocidal effect of cisplatin in gastric cancer. So, the purpose of this study was to evaluate the cytocidal effect of cisplatin combined with caffeine citrate compared to cisplatin combined with or without caffeine and citric acid. Caffeine citrate is a newly emerged candidate enhancing anticancer agents.</p><p><bold>Design/Methods</bold>: We used human osteosarcoma and fibrosarcoma cell lines (HOS and HT1080). These cells were treated with cisplatin combined with or without anhydrous caffeine, citric acid, and caffeine citrate. Cell survival ability, cell proliferation, and mitochondrial membrane potential were assessed by WST‐8 cell proliferation assay, thymidine analog thymidine analog 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, and tetramethylrhodamine ethyl ester (TMRE) assay, respectively. Moreover, combination index (CI) of caffeine citrate was calculated as a combination of anhydrous caffeine and citric acid, and the synergy was evaluated (CI<1.0).</p><p><bold>Results</bold>: In all assays, cisplatin combined with caffeine citrate significantly reinforced the anticancer effect compared with cisplatin alone, combination of cisplatin and anhydrous caffeine, and combination of cisplatin and citric acid (P<0.01). Moreover, CI was <0.1 in all conditions. The anticancer agent reinforcement effect of caffeine citrate was synergy of anhydrous caffeine and citric acid. These results were observed in both cell lines. Based on these results, we have filed a patent application.</p><p><bold>Conclusions</bold>: This is the first report that cisplatin combined with caffeine citrate showed a significant greater effect. Although further analysis is mandatory, this novel treatment expects to ameliorate the prognosis of the patients with sarcoma.</p></sec><sec id="pbc26772-sec-7860"><label>P-381</label><title>FDA Written Requests: Identified Trends in Timelines and Drug Types</title><p><underline underline-style="single">A. Barone</underline><sup>1</sup>, D. Casey<sup>1</sup>, G. Reaman<sup>1</sup></p><p><italic><sup>1</sup>FDA, Office of Oncology and Hematology Products, Silver Spring, USA</italic></p><p><bold>Background/Objectives</bold>: The Best Pharmaceuticals for Children Act authorizes the Food and Drug Administration (FDA) to request pediatric studies of a drug in approved or unapproved indications via a Written Request (WR). Fulfillment of the WR provides a company with a six‐month marketing exclusivity for the entire drug moiety. Historically, WRs were issued following approval for an adult indication. Our objective was to identify trends associated with WRs issued by FDA for oncology products with regard to time of issue within the drug development program, time to completion, and drug class types.</p><p><bold>Design/Methods</bold>: A review of FDA's Document Archiving, Reporting &Regulatory Tracking System was performed to identify WRs issued for oncology drugs. WRs were reviewed for milestone dates, amendments, and status with regard to exclusivity determination.</p><p><bold>Results</bold>: Between 2000 and 2016, 58 WRs were issued for oncology products and 45 were accepted. Overall, the proportion of WRs issued prior to the marketing approval of a drug was 24% compared to 43% in 2016. Seventeen oncology products were granted exclusivity upon completion of the studies outlined in the WR. The average time from issuance of a WR to exclusivity determination was 4.5 years. WRs were issued for cytotoxic (N=22), immune‐oncology (N=7), and targeted (N=16) therapies. Between 2011 and 2016, the proportion of WRs issued for targeted and immune‐oncology therapies combined (84.4%) was greater than that for cytotoxic drugs (15.5%)</p><p><bold>Conclusions</bold>: The WR is a powerful tool that can expedite early evaluation of the safety and effectiveness of relevant drugs for pediatric cancers. A modest increase was observed in the proportion of WRs issued prior to marketing approval of a drug in recent years. The increased investigation of targeted and immune‐oncology therapies reflects the changing landscape of cancer treatment in pediatric patients. FDA encourages parallel drug development programs when appropriate for adult and pediatric cancer indications.</p></sec><sec id="pbc26772-sec-7870"><label>P-382</label><title>The Efficacy and Safety of Allium Porrum in Reducing Neutrophil Recovery Time in Childhood Cancer with Febrile Neutropenia</title><p><underline underline-style="single">M. Bordbar</underline><sup>1</sup>, M. Vahidifar<sup>2</sup>, M. Shahryari<sup>1</sup>, S. Zareifar<sup>1</sup>, O. Zekavat<sup>1</sup>, M. Karimi<sup>1</sup></p><p><italic><sup>1</sup>Shiraz University of Medical Sciences ‐ School of Medicine, Pediatric Hematolgy‐Oncology, shiraz, Iran; <sup>2</sup>Shiraz University of Medical Sciences ‐ School of Medicine, Pediatrics, shiraz, Iran</italic></p><p><bold>Background/Objectives</bold>: Febrile neutropenia is frequently observed in cancer patients following chemotherapy. Experimental animal studies have shown the potential benefits of the herbal agent “Allium Porrum” in boosting the immune system. However, such findings have not been confirmed in human subjects. The aim of this study was to evaluate the efficacy of allium extract on bone marrow recovery time in children with cancer suffering from febrile neutropenia.</p><p><bold>Design/Methods</bold>: In this randomized double‐blind clinical trial, 107 children with different kinds of cancers in the age range of 2‐18 years who were admitted due to fever and neutropenia were enrolled. All the patients were given supportive care including broad‐spectrum antibiotics, and granulocyte‐colony‐stimulating‐factor (GCSF). Those in the treatment group were treated with 500 mg Allium extract in the form of capsule twice daily for 7 days. The patients in the control group were treated similarly with placebo capsules. Total white blood cell (WBC) and absolute neutrophil counts (ANC) were checked on a daily basis and bone marrow recovery time in both groups were compared.</p><p><bold>Results</bold>: WBC and ANC were not significantly different in the 2 groups. Patients in the treatment group experienced shorter neutrophil recovery compared to the control group (4.02 ± 2.32 days vs 6.38 ± 2.80 days respectively, P˂0.001). Patients in the treatment group were discharged from the hospital 2 mean days earlier than the control group (7.54±5.66 days vs 9.66±8.58 days), but it did not reach statistical significance (P=0.133). The drug was well tolerated and no adverse effect was reported.</p><p><bold>Conclusions</bold>: Allium may effectively reduce ANC recovery time leading to earlier discharge from hospital. The drug is safe with no serious adverse effect reported. Larger multi‐center studies are required to confirm its efficacy and safety.</p></sec><sec id="pbc26772-sec-7880"><label>P-383</label><title>Implementation of a Precision Medicine Program in Pediatric Oncology: Prospective Feasibility Study at Relapse/Progression in Spain</title><p>P. Berlanga<sup>1</sup>, L. Pedrola<sup>2</sup>, I. Calabria<sup>2</sup>, M.J. Aparisi<sup>2</sup>, M. Llavador<sup>3</sup>, Á. Zuñiga<sup>4</sup>, S. Dolz<sup>5</sup>, A. Marco<sup>6</sup>, P. Gargallo<sup>1</sup>, C. Esquembre<sup>7</sup>, P. Escobar<sup>8</sup>, J. Cervera<sup>4</sup>, J. Font de Mora<sup>5</sup>, V. Castel<sup>1</sup>, <underline underline-style="single">A. Cañete</underline><sup>1</sup></p><p><italic><sup>1</sup>Hospital La Fe, Pediatric Oncology Unit, Valencia, Spain; <sup>2</sup>La Fe Hospital Research Institute, Genomic Unit, Valencia, Spain; <sup>3</sup>Hospital La Fe, Department of Pathology, Valencia, Spain; <sup>4</sup>Hospital La Fe, Genetics Unit, Valencia, Spain; <sup>5</sup>La Fe Hospital Research Institute, Laboratory of Cellular and Molecular Biology‐ Center of Translational Medicine, Valencia, Spain; <sup>6</sup>Hospital La Fe, Pediatric Surgery Department, Valencia, Spain; <sup>7</sup>Hospital General Alicante, Pediatric Oncology Unit, Alicante, Spain; <sup>8</sup>Hospital La Fe, Department of Pharmacy, Valencia, Spain</italic></p><p><bold>Background/Objectives</bold>: To evaluate the integration of advanced genomic sequencing technologies in the clinical management of pediatric/adolescent patients with progressive/relapsed cancer in Spain.</p><p><bold>Design/Methods</bold>: Consecutive case series of all patients ≤ 18 years with recurrent solid tumors included in a precision medicine research project were analyzed. This project was developed in our institution and open for recruitment of patients from other centers. New tumor sampling at progression/relapse was recommended. Tumor profiling was perfomed using two commercial Next Generation Sequencing (NGS) cancer panels: <italic>Ion Ampliseq<sup>TM</sup> Cancer Hotspot Panel v2</italic> (before December 2015; only for tumor samples) and <italic>Human Comprehensive Cancer GeneRead DNAseq Targeted Panel</italic> (since January 2016; for paired blood and tumor samples). Tumor material was mainly fresh frozen (57%). Tumor samples were mainly obtained at the time of last relapse (55%) or previous relapses (12%). For sixteen (33%) patients with no available tumor sample at recurrence, the profiling was performed on the tumor sample at diagnosis. Genomic profiling results were reviewed following a target prioritization algorithm by a multi‐disciplinary tumor board with basic and translational researchers, molecular biologists, pathologists, geneticists and pediatric oncologists.</p><p><bold>Results</bold>: From December 2014 to February 2017, 49 patients from nine different hospitals were included. Main diagnosis was neuroblastoma (37%), followed by CNS tumors (22%). All patients, except three, had suffered at least one relapse/progression. In twenty patients (41%), at least one somatic pathogenic mutation was detected, and eleven patients (22%) had at least one actionable target alteration. In three patients (6%), we identified germline pathogenic mutations, two of them without family history of cancer.</p><p><bold>Conclusions</bold>: These results show that precision medicine applied to pediatric and adolescent tumors using NGS technology is feasible in our country. Commercial cancer panels could identify actionable target alterations in 20% of the patients. Target prioritization algorithm and interdisciplinary tumor board discussion is of foremost importance.</p></sec><sec id="pbc26772-sec-7890"><label>P-384</label><title>SFCE Metro‐01 Four‐Drug Metronomic Regimen Phase II Trial for Pediatric Extra‐Cranial Tumour</title><p>M.A. Heng‐Maillard<sup>1</sup>, <underline underline-style="single">A. Verschuur</underline><sup>1</sup>, A. Aschero<sup>2</sup>, P. Petit<sup>2</sup>, E. Jouve<sup>3</sup>, P. Chastagner<sup>4</sup>, P. Leblond<sup>5</sup>, I. Aerts<sup>6</sup>, N. Corradini<sup>7</sup>, N. Entz‐werle<sup>8</sup>, J.C. Gentet<sup>1</sup>, B. Deluca<sup>9</sup>, N. André<sup>1</sup></p><p><italic><sup>1</sup>La Timone Children's Hospital, Department of Pediatric Oncology, Marseille, France; <sup>2</sup>La Timone Children's Hospital, Department of Radiology, Marseille, France; <sup>3</sup>La Timone Children's Hospital, CIC‐CPCET, Marseille, France; <sup>4</sup>Children's Hospital, Department of Pediatric Oncology, Nancy, France; <sup>5</sup>Oscar Lambret Centre, Pediatric Oncology Unit, Lille, France; <sup>6</sup>Institut Curie, Pediatric Department, Paris, France; <sup>7</sup>Centre Léon Berard, Department of Paediatric Haematology and Oncology, Lyon, France; <sup>8</sup>CHU Hautepierre, Pédiatrie Onco‐Hématologie, Strasbourg, France; <sup>9</sup>La Timone Children's Hospital, Department of Clinical Pharmacy, Marseille, France</italic></p><p><bold>Background/Objectives</bold>: To investigate the anti‐tumour activity of a 4‐drug metronomic therapy (MT) in relapsing/progressing pediatric extracranial solid tumours (EST). Primary objective was no progression after 2 cycles of therapy.</p><p><bold>Design/Methods</bold>: Patients of ≥4 to 25 years of age with progressing EST and adequate organ function. Treatment consisted of an 8‐week cycle of oral celecoxib BID, weekly vinblastine 3 mg/m2, oral cyclophosphamide 30 mg/m2/d qd for 3 weeks alternating with oral methotrexate 10 mg/m2 twice a week for 3 weeks, with a 2‐week rest. Maximum treatment was 2 years. Kepner‐ Chang two steps model was used with 10 patients in first stage. If primary objective was reached in 2 or more patients, 8 additional patients were included according to 4 groups: Neuroblastoma (NBL), Soft‐tissue sarcoma (STS), Bone sarcoma (BS), Miscellaneous (Misc). IRB approval was obtained.</p><p><bold>Results</bold>: 47 patients were evaluable: 8 STS with 1 SD after 2 cycles: 1 patient with metastatic hemangioendothelioma stabilized and was treated during 24 months; 11 Misc with one patient stabilized for one year; 10 BS (8 osteosarcoma and 2 Ewing) all progressed; 18 NBL with 3 patient stabilized. Of the patients with SD, 1 stopped MT after 4 cycles being stable (physician's choice) and 2 patients remained stable for 1 year. 16 patients progressed before cycle 3. Median number of cycles was 2 (range 0.5‐6). Grade 3/4 toxicity occured in 13 patients.</p><p><bold>Conclusions</bold>: This MT has no activity in BS and Misc and limited though interesting activity in NBL and STS with some patients being stable for > 1 year. (This study was supported by “Enfants et Santé” Foundation and PHRC‐grant).</p></sec><sec id="pbc26772-sec-7900"><label>P-385</label><title>Ex Vivo Expanded Multi‐Antigen Specific Lymphocytes for the Treatment of Refractory/Relapsed Solid Tumors</title><p><underline underline-style="single">A. Houghtelin</underline><sup>1</sup>, C.R. Cruz<sup>1</sup>, L. McLaughlin<sup>1</sup>, J. Hoover<sup>1</sup>, F. Hoq<sup>1</sup>, C. Barese<sup>1</sup>, P. Hanley<sup>1</sup>, C. Bollard<sup>1</sup>, H. Meany<sup>1</sup></p><p><italic><sup>1</sup>Children's National Health System, Hematology/Oncology, Washington‐ DC, USA</italic></p><p><bold>Background/Objectives</bold>: Patients with solid tumors refractory to standard therapies have poor prognoses, and most salvage therapies are toxic and ineffective. T cell therapies, which have been successful in hematologic malignancies, offer a promising alternative for targeted therapy. We hypothesize that patient‐derived tumor‐associated antigen‐specific T cells (TAA‐T) targeting WT1, PRAME, and survivin expressed by many pediatric solid tumors can be safely administered to treat relapsed/refractory disease. The objective of this phase I clinical trial is to determine the safety of administering TAA‐T to patients with refractory/relapsed solid tumors. Secondary objectives include determination of disease response and immune reconstitution post‐infusion.</p><p><bold>Design/Methods</bold>: T cells expanded from patient peripheral blood are stimulated weekly with antigen presenting cells expressing an overlapping peptide library spanning the tumor antigens WT1, PRAME, and survivin in the presence of cytokines. Following release testing (cytotoxicity assay, culture, flow cytometry), patients are infused with TAA‐T every 4 weeks on a dose escalation study ranging from a dose of 1 × 10<sup>7</sup>/m<sup>2</sup> (level 1) to a maximum dose of 4 × 10<sup>7</sup>/m<sup>2</sup> (level 3). Clinical and immune reconstitution studies are performed post‐infusion to monitor for adverse effects and assess disease and immune responses.</p><p><bold>Results</bold>: We have generated TAA‐T products from 5 patients enrolled with relapsed/refractory solid tumors (neuroblastoma, osteosarcoma, Wilms tumor, Ewing sarcoma), all passing release criteria. We have safely infused 2 patients with no product‐related adverse events post‐infusion. To date Patient 1 had partial response initially but later progressed; Patient 2 had progressive disease 6 weeks post‐infusion and came off study. We are currently enrolling additional patients and characterizing the persistence and anti‐tumor effects of TAA‐T in vivo.</p><p><bold>Conclusions</bold>: To date, the infusion of TAA‐T products has been shown to be safe. Response has been mixed thus far. We continue to evaluate, as outlined above, product and patient samples for functionality, specificity, and persistence.</p></sec><sec id="pbc26772-sec-7910"><label>P-386</label><title>Omegachild ‐ An Early Clinical Study Aiming at a Novel Approach to Treat Neural Tumors and Prevent Long‐Term Side Effects</title><p><underline underline-style="single">L. Ljungblad</underline><sup>1</sup>, M. Wickström<sup>1</sup>, N. Eissler<sup>1</sup>, J. Pickova<sup>2</sup>, J.I. Johnsen<sup>1</sup>, K. Tedroff<sup>1</sup>, B. Strandvik<sup>1</sup>, H. Gleissman<sup>1</sup>, P. Kogner<sup>1</sup></p><p><italic><sup>1</sup>Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden; <sup>2</sup>Swedish University of Agricultural Sciences, Department of Food Science, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: The long chain polyunsaturated omega‐3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have anticancer properties that have been implicated in cancer prevention. Additionally, tumor growth has been inhibited <italic>in vitro</italic> and <italic>in vivo</italic> and the effect of cytostatic drugs enhanced. DHA is abundant in the brain and has been implicated in neuroprotection. In addition, omega‐3 supplementation has positive effects on children with neurodevelopmental disorders.</p><p>Altogether, these results suggest that omega‐3 exhibits beneficial properties both as an adjuvant in the treatment of childhood cancer and as a dietary supplement for prevention of relapses and reducing long term side effects in childhood cancer survivors.</p><p><bold>Design/Methods</bold>: This dose escalating, dose‐finding study was designed to find the phase‐2 omega‐3 dose that increases the omega‐3 index to an optimum level >8% without side‐effects.</p><p>Secondary objectives were to evaluate omega‐3 supplementation effects on platelet clotting ability, body weight and composition, immuneprofile, inflammatory parameters, lipid peroxidation, and perception/cognition/neuropsychiatric symptoms. We included forty children aged 2‐18 (median 9.5) in remission after completed cancer treatment; eight in each dose‐level: 400, 800, 1200, 2400 and 3000 mg/m<sup>2</sup> omega‐3 fatty acids in 200 mL fruit juice daily for 90 days. Food frequency questionnaire was performed at start. Blood and urine sampling, body measurements and behavior questionnaires were performed before, during and after the study.</p><p><bold>Results</bold>: Thirty‐three out of forty completed the study with compliance 83%‐100%, seven withdrew voluntarily. No severe adverse events were registered. Daily intake of omega‐3 enriched fruit juice significantly increased omega‐3 index >8% already at 800 mg/m<sup>2.</sup></p><p><bold>Conclusions</bold>: Daily intake of omega‐3 increases omega‐3 index significantly without severe adverse events and is feasible with high compliance. The dose‐escalation strategy provides robust evidence to calculate appropriate dosages for future trials with the goal of promoting improved relapse‐free survival with less long‐term side effects.</p></sec><sec id="pbc26772-sec-7920"><label>P-387</label><title>Long‐Term Growth and Development in Bevacizumab‐Treated Pediatric and Adolescent Patients: An Integrated Analysis</title><p><underline underline-style="single">H.L. Müller</underline><sup>1</sup>, J.H.M. Merks<sup>2</sup>, B. Geoerger<sup>3</sup>, J. Grill<sup>3</sup>, D. Hargrave<sup>4</sup>, J. Glade Bender<sup>5</sup>, S. Gururangan<sup>6</sup>, F. Navid<sup>7</sup>, M. Johnston<sup>8</sup>, J. Bachir<sup>9</sup>, M. Hilton<sup>9</sup>, S. Fürst‐Recktenwald<sup>9</sup></p><p><italic><sup>1</sup>Klinikum Oldenburg AöR‐ Medical Campus University Oldenburg, Department of Pediatrics and Pediatric Hematology / Oncology, Oldenburg, Germany; <sup>2</sup>Emma Children's Hospital‐Academic Medical Center EKZ‐AMC, Department of Pediatric Oncology, Amsterdam, The Netherlands; <sup>3</sup>Gustave Roussy, Department of Pediatric and Adolescent Oncology, Villejuif, France; <sup>4</sup>Great Ormond Street Hospital, Department of Haematology and Oncology, London, United Kingdom; <sup>5</sup>Columbia University Medical Centre, Department of Pediatrics, New York, USA; <sup>6</sup>McKnight Brain Institute‐ University of Florida, Preston Wells Center for Brain Tumor Therapy, Gainesville, USA; <sup>7</sup>Children's Hospital Los Angeles‐ Keck School of Medicine‐ University of Southern California, Children's Center for Cancer and Blood Diseases, Los Angeles, USA; <sup>8</sup>Genentech, Safety Science, San Francisco, USA; <sup>9</sup>F. Hoffmann‐La Roche Ltd, Pediatric Oncology, Basel, Switzerland</italic></p><p><bold>Background/Objectives</bold>: Bevacizumab has an established safety profile in adults, but long‐term data in children are limited. This analysis examined the effects of BEV on growth and development in pediatric and adolescent patients.</p><p><bold>Design/Methods</bold>: Data (height, weight, body mass index [BMI], bone age data) were pooled from five trials: NCT00643565 (Phase II, soft tissue sarcoma); NCT01390948 (Phase II, high‐grade glioma); NCT00085111 (Phase I, refractory solid tumors); NCT00667342 (Phase II, osteosarcoma); and NCT00381797 (Phase II, glioma, medulloblastoma, ependymoma). Patients were aged <18 years and received ≥1 dose of bevacizumab and chemotherapy (n=268) or chemotherapy alone (n=135). Analyses were exploratory and descriptive. Reference growth data were taken from WHO (<2 years) and Centres for Disease Control (≥2 years).</p><p><bold>Results</bold>: Across the trials, the mean number of bevacizumab administrations per patient ranged from 5.6 to 19.9 (dose 5–15mg/kg, every 2 or 3 weeks). Median follow‐up time for bevacizumab plus chemotherapy was 37.9 months (range 2.4–64.2); for chemotherapy only, this was 22.9 months (range 2.8–69.2). At baseline, median height, weight, and BMI were close to that of the reference population (mean standard deviation scores [SDS] close to 0). Over 60 months, a slight decline was observed in the mean SDS for height and weight in both arms in this cohort of patients with different tumors and treatments, but remained within the normal range of healthy children. Trends were similar for BMI. No delay in growth velocity or bone age in bevacizumab‐treated patients versus chemotherapy only was observed over a 3‐year follow‐up, regardless of age or gender. A subgroup analysis of patients in the growth hormone‐dependent development phase was consistent with the overall results.</p><p><bold>Conclusions</bold>: In this analysis, bevacizumab inclusion in the treatment regimen did not have a negative impact on pediatric growth and development beyond that of chemotherapy alone.</p></sec><sec id="pbc26772-sec-7930"><label>P-388</label><title>A Pediatric Phase 1 Study of Larotrectinib, A Highly Selective Inhibitor of the Tropomyosin Receptor Kinase (TRK) Family</title><p><underline underline-style="single">R. Nagasubramanian</underline><sup>1</sup>, K. Albert<sup>2</sup>, N. Federman<sup>3</sup>, B. Turpin<sup>4</sup>, L. Mascarenhas<sup>5</sup>, A.S. Pappo<sup>6</sup>, D.S. Hawkins<sup>2</sup>, B. Tupper<sup>7</sup>, S. Smith<sup>8</sup>, S. Cruickshank<sup>8</sup>, M.C. Cox<sup>8</sup>, S.G. DuBois<sup>9</sup>, T.W. Laetsch<sup>10</sup></p><p><italic><sup>1</sup>Nemours Children's Hospital, Oncology, Orlando, USA; <sup>2</sup>Seattle Children's Hospital‐ University of Washington‐ Fred Hutchinson Cancer Research Center, Oncology, Seattle, USA; <sup>3</sup>University of California‐ Los Angeles, Pediatric Oncology, Los Angeles, USA; <sup>4</sup>Cincinnati Children's Hospital Medical Center‐, Oncology, Cincinnati, USA; <sup>5</sup>Children's Hospital Los Angeles‐ Keck School of Medicine‐ University of Southern California, Oncology, Los Angeles, USA; <sup>6</sup>St Jude Children's Research Hospital, Oncology, Memphis, USA; <sup>7</sup>Loxo Oncology, Clinical Development, Stamford, USA; <sup>8</sup>Loxo Oncology, Clinical Development, South San Francisco, USA; <sup>9</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Oncology, Boston, USA; <sup>10</sup>University of Texas Southwestern Medical Center/Children's Health, Oncology, Dallas, USA</italic></p><p><bold>Background/Objectives</bold>: Larotrectinib is the first selective small‐molecule inhibitor of TRKA/B/C in clinical development. The adult phase 1 trial demonstrated prolonged responses in patients (pts) with TRK fusions and a favorable tolerability profile.</p><p><bold>Design/Methods</bold>: This multicenter phase 1 study enrolled pts with refractory solid tumors aged ≥ 1 month – 21 years. Pts were dosed orally BID on a continuous 28‐day schedule either by capsule or solution. Pharmacokinetic (PK)‐directed intra‐subject dose escalation was permitted, with exposures targeting the adult recommended Phase 2 dose (RP2D) of 100mg BID. The primary objective was to define the MTD / RP2D; secondary objectives included PK and efficacy using RECIST v1.1.</p><p><bold>Results</bold>: As of December 31, 2016, 17 pts (12 with TRK fusions, 5 without TRK fusions) with a median age of 5.2 years (0.4 – 18.3) were enrolled to 3 dose levels. Pts were enrolled with fusions of all 3 NTRK genes in heterogeneous tumor diagnoses: infantile fibrosarcoma (IFS) (n=6), other sarcoma (n=4), and papillary thyroid cancer (n=2). Most common AEs regardless of attribution were vomiting, diarrhea, and fatigue. While 8 (47%) pts experienced grade 3‐4 AEs, none were attributed to larotrectinib. No DLTs were observed and an MTD was not established. 12 pts (10 with TRK fusions, 2 without TRK fusions) remain on treatment with median follow‐up of 2.8 months (0.7 – 8.4). Among TRK fusion pts, the vast majority have achieved confirmed RECIST responses regardless of tumor diagnoses. No responses were seen in pts without TRK fusions (n=4). 5 pts discontinued therapy, including 2 with TRK fusions: 1 pt with IFS had sufficient response to allow tumor resection, and 1 pt with IFS progressed with a documented acquired resistance mutation.</p><p><bold>Conclusions</bold>: Larotrectinib has demonstrated a favorable tolerability profile and histology‐ independent efficacy in pediatric pts harboring TRK fusions. Updated safety and efficacy data will be presented.</p></sec><sec id="pbc26772-sec-7940"><label>P-389</label><title>Drug Development and Market Challenge: Charity Stakeholder Perspective</title><p><underline underline-style="single">S. Richards</underline><sup>1</sup>, L. Knox<sup>1</sup>, N. Bird<sup>1</sup>, J. Rogers<sup>1</sup>, D. Ludwinski<sup>2</sup></p><p><italic><sup>1</sup>Solving Kids' Cancer Europe, Research Advocacy, London, United Kingdom; <sup>2</sup>Solving Kids' Cancer, Research Advocacy, New York, USA</italic></p><p><bold>Background/Objectives</bold>: Drug development and marketing explicitly for paediatric cancers presents formidable challenges. A case study of dinutuximab, an anti‐GD2 antibody proven to be effective against high‐risk neuroblastoma in a pivotal US trial, gained US Food and Drug Administration approval, but was rejected by National Institute for Health and Care Excellence (NICE) for reimbursement in the UK National Health Service (NHS) because of cost.</p><p><bold>Design/Methods</bold>: A charity based in the US and UK has proven to play a vital role challenging the NICE appraisal process, which is not suitable for evaluating the cost effectiveness of paediatric rare disease drugs. Relying on patient representative input, media engagement, parent community awareness, pro bono legal assistance, and emotive but expert arguments were submitted as a challenge to the NICE decision to reject the drug in the UK.</p><p><bold>Results</bold>: In the first appeal of a NICE decision by a charity, the challenge was successfully upheld despite lack of input or engagement from the pharmaceutical company. The drug company subsequently withdrew submission for NICE reappraisal when demand exceeded available drug supply, and drug will no longer be provided for marketing outside of North America in the foreseeable future.</p><p><bold>Conclusions</bold>: Charities have been proven to play a vital role in advocating for policies and regulatory issues affecting children with cancer.</p></sec><sec id="pbc26772-sec-7950"><label>P-390</label><title>Indisulam Inhibits Carbonic Anhydrases Expression and Modulates Apoptotic Factors in Pediatric Glioblastoma Cell Line</title><p>C.C.D. Monção<sup>1</sup>, S.A. Teixeira<sup>1</sup>, A.F. Andrade<sup>2</sup>, P.V. De Andrade<sup>3</sup>, R.G.P. Queiroz<sup>1</sup>, C.G. Carlotti<sup>4</sup>, L.G. Tone<sup>1</sup>, <underline underline-style="single">C.A. Scrideli</underline><sup>1</sup></p><p><italic><sup>1</sup>Faculdade de Medicina De Ribeirão Preto‐USP, Pediatrics, Ribierão Preto, Brazil; <sup>2</sup>Université de Montpellier, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France; <sup>3</sup>Faculdade de Medicina De Ribeirão Preto‐USP, Genetics, Ribierão Preto, Brazil; <sup>4</sup>Faculdade de Medicina De Ribeirão Preto‐USP, Surgery and Anatomy, Ribierão Preto, Brazil</italic></p><p><bold>Background/Objectives</bold>: The treatment of glioblastoma (GB) remains a major challenge since this tumor is highly resistant to radio‐ and chemotherapy, and recurrence is extremely common. The poor prognosis of patients with GB is due to the intratumoral heterogeneity, invasive behavior, resistance to apoptosis and the hypoxic tumoral microenvironment. The hypoxic condition of GB cells upregulates the expression of membrane‐bound carbonic anhydrases (CAs) 9 and 12 that have been shown to act on acidification of the tumor microenvironment. In our previously study, it was found antitumor effects when CA9 and CA12 was downregulated in pediatric glioblastoma cell lines, hence the aim of this study was to validate and evaluate the effects of Indisulam (IS) on the CAs 9 and 12, and the apoptotic factors BAX and BCL‐2 expression in pediatric GB cell line.</p><p><bold>Design/Methods</bold>: The pediatric GB cell line SF188 was pretreated with Cobalt Chloride (50μM) to mimic hypoxia for 24 hours. After, cells were treated with IS (IC50) and incubated for 48 hours. Gene and protein expression of CA9, CA12, BAX and BCL‐2 were assessed using qRT‐PCR and western blotting, respectively.</p><p><bold>Results</bold>: Indisulam significantly decreased gene expression of CA9 (<italic>P</italic><0.05) and upregulated CA12 (<italic>P</italic>>0.05). A similar pattern to the CA9 and CA12 gene expression was observed in the protein expression. A downregulation in protein expression were also found in BAX (<italic>P</italic><0.05) and BCL‐2 (<italic>P</italic><0.001), with a greater reduction of BCL‐2 factor.</p><p><bold>Conclusions</bold>: This study suggest that IS may have an antitumoral effect, evidenced by inhibition of CA9 gene and protein expression and modulation of apoptotic factors. Thus, CAs could be particularly relevant to understand the mechanisms of glioma cell propagation and resistance to treatment and Indisulam may be an interesting candidate for the development of antitumor therapies based on the inhibition of tumor‐associated carbonic anhydrase.</p></sec><sec id="pbc26772-sec-7960"><label>P-391</label><title>Combination Therapy of Primary Tumor Resection and Immune Checkpoint Inhibitors for Metastases of Osteosarcoma: A Promising Therapeutic Strategy</title><p><underline underline-style="single">T. Shimizu</underline><sup>1</sup>, Y. Fuchimoto<sup>1</sup>, K. Fukuda<sup>2</sup>, H. Okita<sup>3</sup>, Y. Kitagawa<sup>2</sup>, T. Kuroda<sup>1</sup></p><p><italic><sup>1</sup>Keio University School of Medicine, Pediatric Surgery, Shinjuku‐ku, Japan; <sup>2</sup>Keio University School of Medicine, General and Gastrointestinal Surgery, Shinjuku‐ku, Japan; <sup>3</sup>Keio University School of Medicine, Pathology, Shinjuku‐ku, Japan</italic></p><p><bold>Background/Objectives</bold>: Immune checkpoint inhibitors have been used as innovative immunotherapies for cancer. Metastases are thought to be the most important prognostic factor in pediatric solid tumors. The efficacy of immune checkpoint inhibitors for lung metastases of osteosarcoma has been reported in several murine models. In this study, combination therapy with immune checkpoint inhibitors and primary tumor resection was evaluated by using a murine model of spontaneous lung metastasis.</p><p><bold>Design/Methods</bold>: In C3H mice, 5 × 10<sup>6</sup> LM8 (osteosarcoma originating from C3H mouse) cells were transplanted subcutaneously (primary tumor lesion). Thereafter, the mice were divided into 4 groups as follows: the control group received no intervention (CG, n = 5); the primary tumor resection group, primary tumor resection 11 days after transplantation (PTRG, n = 10); the triple antibody therapy group, 200 μg of three antibodies (anti‐Tim‐3, anti‐PD‐L1, and anti‐OX‐86) intraperitoneally on post‐transplantation days 11, 14, 18, and 21 (ATG, n = 10); and the combination therapy group, primary tumor resection on day 11 and 200 μg of the three antibodies on days 11, 14, 18, and 21 (CMBG, n = 10). Survival curves were plotted by using the Kaplan‐Meier method and compared with that plotted with the log‐rank test. Then, the lungs of the mice in the 4 groups were pathologically evaluated.</p><p><bold>Results</bold>: The CMBG showed significantly longer survival than the other three groups (p = 0.001–0.03). Six mice in the CMBG survived more than 10 weeks after tumor transplantation. Pathological study revealed multiple lung metastases 4 weeks after tumor transplantation in all the groups but no lung metastasis 16 weeks after tumor transplantation in the CMBG.</p><p><bold>Conclusions</bold>: The results of this study suggest that the combination therapy of primary tumor resection and immune checkpoint inhibitors could be a curative treatment for metastasis of pediatric solid tumors.</p></sec><sec id="pbc26772-sec-7970"><label>P-392</label><title>Indisulam Affects Pediatric and Adult Glioblastoma by Reducing Cell Proliferation and Migration, Promoting Radio‐Sensitization and Prolonging Survival in Mouse Models</title><p><underline underline-style="single">S. Teixeira</underline><sup>1,2</sup>, M. Sebastian Viapiano<sup>2</sup>, A. Faria Andrade<sup>3</sup>, N. Mohan Sobhanna<sup>2</sup>, C. Monção Damasceno<sup>1</sup>, V. Kill Suazo<sup>1</sup>, C. Gilberto Carlotti<sup>4</sup>, L. Gonzaga Tone<sup>1,3</sup>, C. Alberto Scrideli<sup>1</sup></p><p><italic><sup>1</sup>Ribeirão Preto Medical School‐ University of São Paulo, Department of Pediatrics, Ribeirão Preto, Brazil; <sup>2</sup>Brigham and Women's Hospital & Harvard Medical School, Neurosurgery, Boston, USA; <sup>3</sup>Ribeirão Preto Medical School‐ University of São Paulo, Department of Genetics, Ribeirão Preto, Brazil; <sup>4</sup>Ribeirão Preto Medical School‐ University of São Paulo, Department of Surgery and Anatomy, Ribeirão Preto, Brazil</italic></p><p><bold>Background/Objectives</bold>: Carbonic anhydrases (CA), tumor‐associated enzymes highly expressed under hypoxic conditions, have been considered as potential biomarkers of tumor cells and a promising target for specific therapies. In hypoxia, there are genetic alterations that lead to the expression of membrane‐bound extracellular facing CA9 and CA12. In glioblastoma (GBM), the most aggressive form of brain cancer with a dismal prognosis in children and adults, CAs has been linked to aggressive and invasive behavior of cells and resistance to therapy. Indisulam (IS) is a potent sulfonamide inhibitor of CAs that has been used as an anti‐cancer drug. Then, the aim of this study was to evaluate the effects of inhibition of the CA9 and CA12 by IS <italic>in vitro</italic> and <italic>in vivo</italic> models.</p><p><bold>Design/Methods</bold>: The pediatric (KNS42 and SF188) and adult (U87 and U251) GBM cells lines were cultured in hypoxia 1% and treated with IS (8‐256μM). The effect of IS on cell proliferation, migration, clonogenic capacity, apoptosis and radio‐sensitizing was measured <italic>in vitro</italic>. The <italic>in vivo</italic> antitumor and chemo‐sensitizing effects of IS were assessed in athymic nude mice (n=6) inoculated with the U87‐GFP. The mice were and treated (IP) with IS (25 or 50mg/kg). Tumor growth and potential treatment toxicity were monitored until survival endpoint.</p><p><bold>Results</bold>: IS significantly reduced cell proliferation (dose‐time‐dependent), inhibited clonogenic capacity (<italic>P<0.05</italic>) and increased apoptosis (<italic>P<0.05</italic>) of pediatric and adult GBM cells. IS also reduces cell migration and potentiated the effect of radiotherapy (<italic>P<0.01</italic>) <italic>in vitro</italic>. The pediatric cell line KNS42 was the most sensible to IS treatment. Our results, in intracranial mouse xenograft models, indicated that IS crossed BBB and significantly increased animal survival (<italic>P=0.001</italic>).</p><p><bold>Conclusions</bold>: This study provides evidence of the therapeutic potential of IS as a radio‐chemo‐sensitizing agent in drug‐resistant tumor cells and represent an attractive strategy to improve adjuvant therapy for GBM.</p><p>Financial Support: FAPESP 2011/05957‐6, 2011/07488‐1, 2014/08899‐5</p></sec><sec id="pbc26772-sec-7980"><label>P-393</label><title>A Phase I/II Study of Atezolizumab in Pediatric and Young Adult Patients with Refractory/Relapsed Solid Tumors (Imatrix‐Atezolizumab)</title><p><underline underline-style="single">T. Trippett</underline><sup>1</sup>, G. Rossato<sup>2</sup>, A.M. Langevin<sup>3</sup>, J. Michon<sup>4</sup>, D. Frappaz<sup>5</sup>, F. Locatelli<sup>6</sup>, M. Kowgier<sup>7</sup>, M. Tagen<sup>8</sup>, A. Kwan<sup>9</sup>, M. Das Thakur<sup>10</sup>, B. Geoerger<sup>11</sup></p><p><italic><sup>1</sup>Memorial Sloan Kettering Cancer Center, Pediatric Developmental Therapeutics, New York, USA; <sup>2</sup>F. Hoffmann‐La Roche Ltd, Pediatric Oncology, Basel, Switzerland; <sup>3</sup>University of Texas Health Science Center, Pediatric Hematology/Oncology, San Antonio, USA; <sup>4</sup>Insitut Curie, Department of Pediatrics, Paris, France; <sup>5</sup>Institut d'Hématologie et d'Oncologie Pédiatrique, Pediatric and Adult Neuro‐oncology, Lyon, France; <sup>6</sup>Ospedale Pediatrico Bambino Gesù‐ University of Pavia, Department of Pediatric Hematology and Oncology, Rome, Italy; <sup>7</sup>F. Hoffmann‐La Roche Ltd, Pediatric Oncology, Mississauga, Canada; <sup>8</sup>Genentech, Pediatric Oncology, San Francisco, USA; <sup>9</sup>Genentech, Safety Science, San Francisco, USA; <sup>10</sup>Genentech, Oncology Biomarker Development, San Francisco, USA; <sup>11</sup>Gustave Roussy, Department of Pediatric and Adolescent Oncology, Villejuif, France</italic></p><p><bold>Background/Objectives</bold>: Atezolizumab targets programmed death‐ligand 1 (PD‐L1), leading to enhanced anti‐cancer T‐cell response. The iMATRIX‐Atezolizumab study (phase I/II, multi‐center, open‐label; NCT02541604) assessed safety, pharmacokinetics, and preliminary efficacy of atezolizumab in pediatric/young adult patients with refractory/relapsed solid tumors.</p><p><bold>Design/Methods</bold>: Patients aged <30 years with refractory/relapsed non‐central nervous system solid tumors received atezolizumab every 3 weeks until loss of clinical benefit (<18 years old, 15mg/kg [maximum dose 1200mg]; ≥18 years old, 1200mg). Safety/pharmacokinetics were assessed across tumor types, and initial response was assessed by tumor‐type cohorts after approximately ten patients in each cohort had been treated.</p><p><bold>Results</bold>: As of February 1, 2017, 85 patients (median age 14 years; range 2–29) were enrolled: osteosarcoma, n=12; Ewing sarcoma, n=11; neuroblastoma, n=11; rhabdomyosarcoma, n=10; non‐rhabdomyosarcoma soft tissue sarcoma, n=10; Wilms tumor, n=10; Hodgkin lymphoma (HL), n=9; non‐HL, n=3; and other tumor types, n=9. Pharmacokinetic data (n=62) were similar to that reported in adults. Most tumors had score 0 (<1%) tumor cell (TC) or tumor‐infiltrating immune cell (IC) PD‐L1 expression. TC‐ and IC‐positive expression rates (score 1–3) were seen in 7% and 10% of patients, respectively. HL had higher TC and IC PD‐L1 expression (≥5% [score 2–3]) compared with other tumors. 81/82 of the safety evaluable population who received atezolizumab (median cycles 2.5; range 1–16) had ≥1 adverse event (AE); 21 patients (26%) had treatment‐related grade 3–4 AEs. Two patients had AEs that led to study drug discontinuation. Common AEs were pyrexia (45%), constipation (34%), and fatigue (33%). 2/9 patients with HL and one patient with a rhabdoid tumor (RT) had a partial response.</p><p><bold>Conclusions</bold>: The pharmacokinetic/safety profile of atezolizumab in pediatric/young adult patients is similar to that in adults. Preliminary anti‐tumor activity was seen in HL and RT. Atypical teratoid RT and RT cohorts have been opened to explore this signal.</p></sec><sec id="pbc26772-sec-7990"><label>P-394</label><title>Supra‐Regional Study Sites to Improve the Pediatric Oncologic Patient Care and Recruitment into Early‐Phase Clinical Trials: A German Model</title><p><underline underline-style="single">K. Waack</underline><sup>1</sup>, B. Wulff<sup>2</sup>, K. Roellecke<sup>1</sup>, D. Schneider<sup>3</sup>, M. Paulussen<sup>4</sup>, T. Zuzak<sup>5</sup>, A. Laengler<sup>5</sup>, T. Niehues<sup>6</sup>, N. Brauer<sup>6</sup>, I. Feddersen<sup>7</sup>, U. Kontny<sup>8</sup>, G. Calaminus<sup>9</sup>, D. Dilloo<sup>9</sup>, M. Irnich<sup>10</sup>, A. Prokop<sup>11</sup>, N. Graf<sup>12</sup>, B. Hero<sup>13</sup>, M. Fischer<sup>13</sup>, T. Simon<sup>13</sup>, D. Reinhardt<sup>2</sup></p><p><italic><sup>1</sup>Center for Research Acceleration in Pediatrics, AML‐BFM Trial Center, Essen, Germany; <sup>2</sup>University Hospital of Essen, Pediatric Oncology and Hematology‐ Pediatrics III, Essen, Germany; <sup>3</sup>Municipal Hospital Dortmund, Clinic of Pediatrics, Dortmund, Germany; <sup>4</sup>Witten/Herdecke University, Vestische Kinder‐ und Jugendklinik, Datteln, Germany; <sup>5</sup>Gemeinschaftskrankenhaus Herdecke, Department of Integrative Pediatric and Adolescent Medicine, Herdecke, Germany; <sup>6</sup>HELIOS Klinikum Krefeld, Childrens Hospital, Krefeld, Germany; <sup>7</sup>Klinikum Mutterhaus der Borromäerinnen, Pediatric Oncology and Hematology, Trier, Germany; <sup>8</sup>University Medical Center, Division of Pediatric Hematology‐ Oncology and Stem Cell Transplantation, Aachen, Germany; <sup>9</sup>University of Bonn Medical Center, Department of Pediatric Hematology and Oncology‐ Center for Pediatrics, Bonn, Germany; <sup>10</sup>Asklepios Hospital, Department of Pediatrics‐ Division of Haematology and Oncology, St. Augustin, Germany; <sup>11</sup>Municipal Clinics of Cologne, Department of Pediatrics‐ Division of Pediatric Oncology and Hematology, Cologne, Germany; <sup>12</sup>University of Saarland, Department of Pediatric Hematology and Oncology, Homburg, Germany; <sup>13</sup>University of Cologne, Department of Pediatric Hematology and Oncology, Cologne, Germany</italic></p><p><bold>Background/Objectives</bold>: Early‐phase clinical trials could be a potential therapeutic possibility to patients without any other treatment options in regular patient care. Trial recruitment is hampered by the unevenly geographic distribution of only three to five study sites for whole Germany, that limited the recruitment radius just to a few kilometers otherwise patients must be willing to travel to the center for each visit or must be transferred to trial centers even in a pre‐terminal situation. A defined supra‐regional virtual study site could solve this challenging situation and simultaneously meet patients´ and stakeholders’ requirements.</p><p><bold>Design/Methods</bold>: Therefore, pediatric oncology centers (n=12) committed to form a network covering one geographic area (Northrhine‐Westphalia). It is organized by one supra‐regional study site/central working study office (University of Essen) that acts as a coordinating site for merging the associated sites. A periodically updated (every 6 to 12 months) resource data and training plan for equipment and staff will be analyzed and strengths and weaknesses can be balanced between all participating centers. Whatever cannot be done decentral the coordinating study office will cover the task centrally. All activities will be performed according to Good Clinical Practice. The structure and its activities are supervised by a scientific leading group.</p><p><bold>Results</bold>: Patients can enter early‐phase clinical trials near the patient's home. It improves the patient access and compliance to experimental treatment options as well as the recruitment‐rate early‐phase clinical trials. The supra‐regional site acts as one single site to sponsors, ethic committees (EC) and competent authorities (CA). In spring 2017, one industry‐sponsored and one academic study apply that model to EC and CA.</p><p><bold>Conclusions</bold>: The supra‐regional study site presents an attractive structure model addressing the specific requirements in recruiting pediatric oncology patients to early clinical trials in unevenly populated area states like Germany.</p></sec></sec><sec id="pbc26772-sec-8000"><title>Treatment and Care ‐ Supportive Care</title><sec id="pbc26772-sec-8010"><label>P-395</label><title>Cancer‐Related Fatigue in Egyptian Children</title><p><underline underline-style="single">E.R. Abdel Khalek</underline><sup>1</sup>, L.M. Sherif<sup>2</sup>, M. Almalky<sup>3</sup>, N. Fawzy<sup>3</sup></p><p><italic><sup>1</sup>Faculty of medicine‐ Zagazig University, Pediatrics, Cairo, Egypt; <sup>2</sup>Faculty of Medicine‐ Zagazig University, Peditarics, Zagazig, Egypt; <sup>3</sup>Faculty of Medicine‐ Zagazig University, Pediatrics, Zagazig, Egypt</italic></p><p><bold>Background/Objectives</bold>: Cancer‐Related Fatigue (CRF) is one of the most frequent and stressful symptoms in children with cancer that has a profound effect on Quality of Life (QOL).</p><p><bold>Aim</bold>: The purpose of this study is to find out the prevalence and patterns of (CRF) in children during cancer treatment</p><p><bold>Design/Methods</bold>: A prospective longitudinal descriptive study was conducted on 60 children with cancer, aged 5–15 years, who were receiving inpatient chemotherapy in the pediatric oncology department of Zagazig University. The “PedQL Multidimensional Fatigue scale” and a sociodemographic data form were given to the patients and their parents as well as 60 healthy control children. Participants were enrolled in this study just before the start of a new round of chemotherapy (CTX) and then following them for 10 days and before the next cycle. Hemoglobin level and blood indices were recorded with each fatigue measures.</p><p><bold>Results</bold>: There is a statistically significant increase in fatigue scores and all domains during treatment. There is the tendency of overestimating the fatigue by the parents for sleep and cognitive domains. A peak in fatigue occurs on the day 6 after starting CTX and then become better towards the beginning of the next cycle. No significant variation in total fatigue score and all its domains according to the gender and age at presentation, However, exist regarding the diagnosis; solid tumors are associated with better fatigue scores than lymphoma and leukemia. Low hemoglobin level was associated with high fatigue score and all its domains. (p<0.05)</p><p><bold>Conclusions</bold>: Patients have more problems with fatigue in the first few days after the start of a cycle of CTX. An assessment of fatigue should be done for every patient undergoing CTX and repeated at different times to apply a timely and tailored intervention to prevent fatigue.</p></sec><sec id="pbc26772-sec-8020"><label>P-396</label><title>Challenges in Managing Chemotherapy Induced Febrile Neutropenia in Paediatric Oncology in Developing Countries: The Children's Hospital Lahore Pakistan Experience</title><p><underline underline-style="single">A. Ahmad</underline><sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital and the Institute of Child Health Lahore, Paediatric Haematology/Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: The Oncology Department Of The Children's Hospital Lahore is a 60 bedded unit providing free treatment to over 1000 new childhood cancer cases each year.The aim of this prospective study was to analyze the burden of chemotherapy induced FN and to assess the leading risk factors.</p><p><bold>Design/Methods</bold>: Prospective review of 100 patients with FN admitted in July to August 2016 was done. Data regarding their clinical features, baseline CBC, course of therapy, hospital stay and understanding of caregivers regarding FN analyzed.</p><p><bold>Results</bold>: Total 100 patients with age ranging from< 1 to 15 years (67% <5 yrs) were included. 72% of cases had ALL and 28% with solid tumors. 28% had last chemotherapy received in 72 hours, 30% in last week and rest in more than a week time 36% had <bold>respiratory tract infections</bold>, 18% gastrointestinal infections, 20% mucositis, 10% no focus found and rest 16% had other manifestations Only 2 % presented in 5 days duration of symptoms. 45% had <bold>Hb</bold> <8 gm%, 33% had <bold>platelets</bold> <50000, and 54% had <bold>WBC</bold> <1000 and 63% had <bold>ANC <</bold>100.(<bold>p‐Value=0.003‐</bold>Hospital Stay). 29% presented with first episode while 51 % had 3 or more FN episodes.28% cases stayed 1 hour distance from CHL while <bold>72% had to travel >1‐5 hrs</bold>. 17% had no treatment before reached PTC. Only19% caregivers had <bold>adequate awareness</bold> regarding FN, 72% had some understanding while 9% had no knowledge about FN (<bold>p‐value=0.000</bold>). 40% had social issues, 41% were unaware while 13% showed negligence in seeking treatment (<bold>p‐Value=0.005</bold>)</p> <p><bold>Conclusions: Health education</bold> of caregivers and health professionals is of utmost importance to prevent and manage FN effectively. Need of capacity building in pediatric oncology in low income countries is essential for provision of standard childhood cancer care.</p></sec><sec id="pbc26772-sec-8030"><label>P-397</label><title>Yield of Surveillance Imaging for Invasive Fungal Infection: Solid Tumors VS. Hematologic Malignancies</title><p><underline underline-style="single">A. Al‐ Nassan</underline><sup>1</sup>, M. Sabha<sup>2</sup>, M. Mustafa Ali<sup>3</sup>, I. Sultan<sup>1</sup></p><p><italic><sup>1</sup>King Hussien Cancer Center, Pediatric, Amman, Jordan; <sup>2</sup>University of Tolido, Internal medicine, Tolido, USA; <sup>3</sup>Cleveland Clinic, Internal Medicine, Cleveland, USA</italic></p><p><bold>Background/Objectives</bold>: According to most recent guidelines for the management of febrile neutropenia in children with cancer, CT imaging to rule out fungal infection remains an essential tool that is commonly utilized despite risk of radiation exposure and uncertain yield in different disease categories.</p><p><bold>Design/Methods</bold>: After obtaining an Institutional Review Board (IRB) approval, we used our departmental database, the Pediatric Oncology Network Database (POND) to identify patients who were registered between June 2010 and July 2013. We combined data from the POND registry and data collected by chart review in one excel database.</p><p><bold>Results</bold>: We identified 843 patients who were registered in POND over the 3‐year studied period. Median follow up was 9months(range, 0 to 37). Patients were diagnosed with leukemia(N=191, 23%), lymphoma(N=103,12%), solid tumors(N=371,44%), central nervous system (CNS) tumors(N=143,17%) and others(N=35,4.2%). There were 3561 CT scans ordered in our center for 560 patients(out of 843 registered patients,66%). Median number of scans per patient were 5(range, 1‐43). A total of 557 surveillance scans were ordered for 131 patients (median=4). Surveillance scans were ordered after a median of 6 days following the onset of neutropenia (range 0‐47 days). The majority of surveillance scans were done for patients with leukemia/lymphoma(N=480) vs. solid/CNS tumors(N=77). The most commonly scanned sites were chest(N=272), sinus(N=211) and abdomen(N=44). Positive predictive value (PPV) for possible fungal infection was 26% for all scans. PPV per site were 25% for sinus scans, 21% for chest and 10% for abdomen. There was no difference in PPV of patients with leukemia/lymphoma vs. Solid/CNS tumors (P=0.62).</p><p><bold>Conclusions</bold>: Surveillance for fungal infections were commonly ordered for our patients according to our clinical practice guidelines with leukemia/lymphoma patients most commonly scanned. When patients with solid/CNS tumors were scanned, the chance of having fungal infection was similar to those with leukemia/lymphoma.</p></sec><sec id="pbc26772-sec-8040"><label>P-398</label><title>Timely Administration of Antibiotics in Pediatric Hematology/Oncology Patients with Febrile Neutropenia: A Retrospective Study in a Tertiary Care Center</title><p><underline underline-style="single">T. Bauters</underline><sup>1</sup>, P. Schelstraete<sup>2</sup>, G. Laureys<sup>1</sup>, A. Mannaerts<sup>1</sup>, N. Herman<sup>1</sup>, C. Dhooge<sup>1</sup></p><p><italic><sup>1</sup>Ghent University Hospital, Pediatric Hematology‐ Oncology and Stem Cell Transplantation, Ghent, Belgium; <sup>2</sup>Ghent University Hospital, Pediatric Pulmonology and Infectious Diseases, Ghent, Belgium</italic></p><p><bold>Background/Objectives</bold>: Febrile neutropenia (FN) is a common complication in pediatric hematology/oncology (PHO). Current guidelines advocate timely administration of empirical broad‐spectrum antibiotics. Antibiotic delivery to patients with FN in < 60 min is an increasingly important quality measure associated with improved outcomes. The aim of this study was to measure the time to antibiotic administration (TAA) for inpatients and outpatients in our department, targeting a TAA of < 60 minutes.</p><p><bold>Design/Methods</bold>: A retrospective study was performed, in which TAA was defined as time between prescription and administration of antibiotics (inpatients) and time between admission to hospital and antibiotic administration (outpatients).</p><p><bold>Results</bold>: The study population involved 42 patients (59.5% males), mean age 6.7 years (range 2 months‐16 years), representing 61 FN‐episodes from which 25/61 inpatient (41.0%) and 36/61 outpatient (59.0%) episodes. For inpatients, mean TAA was 82 minutes (range 0‐269); for outpatients 114 minutes (range 0‐420). A total of 44.3% FN‐episodes (27/61) were within the targeted TAA of < 60 minutes, from which 13 (13/61; 21.3%) even within 30 minutes. In 18 FN‐episodes (18/61; 29.5%) TAA was between 1 and 2 hours. TAA for outpatients with FN was more than 2 hours in 16/61 (26.2%) of episodes (range 121‐420 minutes).</p><p><bold>Conclusions</bold>: Results indicate a TAA of < 60 minutes for 44.3% of FN‐episodes, which is a higher percentage than in literature data, indicating 16‐20% of FN episodes with TAA of < 60 minutes. The TAA for outpatients is higher than for inpatients. A possible explanation lies in time involvement of anamnesis, clinical examinations upon arrival in hospital and waiting time for laboratory results. This study confirms that all efforts are performed to keep the TAA, proposed as a quality‐of‐care indicator in our department, as low as possible both for inpatients and outpatients.</p></sec><sec id="pbc26772-sec-8050"><label>P-399</label><title>Spectrum of Respiratory Viral Infections in Children with Cancers: Experience from a Tertiary Cancer Centre in Eastern India</title><p><underline underline-style="single">A. Bhattacharyya</underline><sup>1</sup>, A. Das<sup>1</sup>, G. Goel<sup>2</sup>, S. Bhattacharya<sup>2</sup></p><p><italic><sup>1</sup>Tata Medical Center, Paediatric Oncology, Kolkata, India; <sup>2</sup>Tata Medical Center, Microbiology, Kolkata, India</italic></p><p><bold>Background/Objectives</bold>: Pattern of respiratory viral infections (RVI) in children with cancers is not well characterized in India. We conducted this study to determine the spectrum, incidence of fever‐neutropenia, need for hospital admission, economic burden, and outcome (concomitant bacterial/fungal infections, need for ICU care, and death) of RVI in our pediatric‐oncology unit.</p><p><bold>Design/Methods</bold>: Data was prospectively collected over 19 months (July 2015‐February 2017). All children under treatment for cancer presenting with cough and coryza underwent multiplex PCR for respiratory viruses from nose and throat swab.</p><p><bold>Results</bold>: Positive results were obtained in 222/421 (52.73%) cases, of which data was incomplete in 8 cases. Final analysis was done on 214 cases. Fever was present in 81%. Median age was 5.35 years (range 0.5‐17.8 years). Sixty percent were receiving intensive chemotherapy and 85% had a haematolymphoid malignancy. Commonest viruses isolated were Influenza A and B (46%), Respiratory Syncytial Virus (RSV 25%) and Human Metapneumovirus (14%). Peak months of incidence were July to September which is the rainy season. Fifty percent (106) patients needed admission, while 73/106 had ANC<500 during the episode. Concomitant bacterial/fungal infection was seen in 11.2% cases. Median duration of admission was 5 days (range 1‐35 days), and median cost was USD 258 (range: 33‐1939). Fifteen patients needed ICU admission of which 11 had concomitant bacterial/fungal infection (p=0.0001). Ventilation (invasive or non‐invasive) was required in 8/15 patients of which 4 had RSV. Two deaths were recorded, both in patients with RSV and concomitant bacteremia.</p><p><bold>Conclusions</bold>: RVI adds significantly to the burden of admissions and expenses. Influenza vaccination given universally may prevent a significant number of such illnesses and admissions. Such a programme has been initiated at our center, and data is being prospectively collected to measure its impact. Concomitant bacterial/fungal infections add to morbidity/mortality.</p><p><bold>Acknowledgements</bold>: Manashpratim Gogoi (data collection)</p><p>R Bhalachandra (sample collection)</p><p>Anusha Harishankar (PCR processing)</p></sec><sec id="pbc26772-sec-8060"><label>P-400</label><title>Profile, Reason and Disclosure of Pediatric Oncohematologic Patients Admitted in a Pediatric Intensive Care Unit in a General Brazilian Hospital</title><p>G. Bomfim<sup>1</sup>, <underline underline-style="single">C. Cintra</underline><sup>1</sup>, S. Brandi<sup>1</sup>, E. Santos<sup>1</sup></p><p><italic><sup>1</sup>hospital Israelita Albert Einstein, Pediatria, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Our intensive care unit is a general unit with 15 beds and a media of 1000 admissions/year; it attends clinical and surgical patients whose reason of admission may be elective, urgency or emergency. OBJECTIVE: to know the profile, causes of admission and disclosures of pediatric oncohematologic patients in the pediatric intensive care (PICU) of a general hospital.</p><p><bold>Design/Methods</bold>: METHOD: retrospective analyze of oncohematologic patients admitted in the PICU in 2016.</p><p><bold>Results</bold>: RESULTS in 1073 admissions, 1.8% were oncohematologic patients. The indications were: elective (25%), urgency (65%) and emergency (10%); 60% percent was female and 40% male; 25% was under 1 year old, 35% between 1 and 5 years, 10% between 5 and 10 years and 30% older than 10 years old. The rapid response team attended 20% of these patients, 80% were evaluated by the local staff and sent to the PICU. The origin was emergency room (20%), oncology and bone transplantation unit (35%), pediatric unit (15%) and surgery rooms (30%); and the causes for admissions were post‐operatory care (25%), hemodynamic monitoring/sepsis (45%), respiratory failure (25%). Many of these patients were submitted to invasive procedures: 30% had a central venous catheter, 25% invasive arterial pressure, 20% enteral feeding, and 30% bladder catheter. None of the patients had complications as infection or pressure ulcer. Eighty percent was discharged for the origin unit, 15% to home and just one patient died.</p><p><bold>Conclusions</bold>: The oncohematologic pediatric patients admitted in the PICU require specialized intensive care and most of them were admitted in emergency and urgency situations. They are discharged back to the origin unit and then to home. Other information can be added to the already collected in the PICU, and a historical series allow this data to be accompanied and compared to other institutions.</p></sec><sec id="pbc26772-sec-8070"><label>P-401</label><title>The Aetiology of Fever in Children with Cancer in the North of Scotland</title><p>T. Lawes<sup>1</sup>, <underline underline-style="single">J. Calley</underline><sup>1</sup>, L. Adam<sup>1</sup>, N. Abdelrazig<sup>1</sup>, H. Bishop<sup>1</sup>, N. Ahmad<sup>1</sup></p><p><italic><sup>1</sup>Royal Aberdeen Children's Hospital, Department of Paediatric Oncology, Aberdeen, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Outcomes in children with cancer continue to improve but febrile neutropenia (FN) remains a major cause of mortality. Mortality from FN episodes is 2‐3% and 5 year mortality in acute lymphoblastic leukaemia due to infection is 2.4%. Rapid antibiotic delivery (< 60 minutes) is associated with improved outcomes. Guidance is available from the National Institute for Health and Care Excellence (NICE) and the Managed Service Network (MSN) for Children & Young People with Cancer in Scotland regarding empiric antibiotic prescribing. Our centre is currently unique in Scotland in practicing single agent first line empirical antibiotic therapy with piperacillin/tazobactam. Our aims were to assess the aetiology of febrile episodes in children with cancer in the North of Scotland and evaluate the adequacy of our empiric antibiotic policy in light of our local antibacterial resistance patterns.</p><p><bold>Design/Methods</bold>: Positive microbiological data for all paediatric oncology patients treated in the years 2013‐2015 was provided by our local laboratory for analysis. Isolates and resistance patterns were compared with data from 2006‐2012.</p><p><bold>Results</bold>: Microbiological isolates demonstrate secular trends of increased non‐fermenting and environmental gram negatives and a reduction in <italic>Staph. aureus</italic>. There were non‐significant increases in resistance to key antimicrobials in both gram positive and gram negative organisms. Between 2013‐2015 there were 10 of an estimated total of 166 febrile episodes where initial dual therapy with piperacillin/tazobactam and gentamicin would have provided superior cover compared to piperacillin/tazobactam monotherapy.</p><p><bold>Conclusions</bold>: The number needed to treat to improve our coverage based on this data would be 17. This needs to be balanced against the known adverse effects of empirical aminoglycoside when deciding appropriate local antimicrobial policies.</p></sec><sec id="pbc26772-sec-8080"><label>P-402</label><title>Can We Identify Chemotherapy‐Related Toxicity in Children with Cancer Through Automatized Integration of Healthcare Information Systems?</title><p>P. Berlanga<sup>1</sup>, M.J. Herrero<sup>2</sup>, A. Tórtola<sup>3</sup>, M. Correcher<sup>3</sup>, P. Gargallo<sup>4</sup>, A. Marco<sup>4</sup>, V. Castel<sup>4</sup>, B. Valdivieso<sup>5</sup>, <underline underline-style="single">A. Cañete</underline><sup>4</sup></p><p><italic><sup>1</sup>Hospital Universitario la Fe, Pediatric Oncology Unit, Valencia, Spain; <sup>2</sup>La Fe Hospital Research Institute, Pharmacogenetics Unit, Valencia, Spain; <sup>3</sup>Hospital La Fe, Systems Department, Valencia, Spain; <sup>4</sup>Hospital La Fe, Pediatric Oncology Unit, Valencia, Spain; <sup>5</sup>Hospital La Fe, Planning Department, Valencia, Spain</italic></p><p><bold>Background/Objectives</bold>: Integration of seamless healthcare data from multiple hospital data sources to identify chemotherapy‐related toxicity in pediatric patients.</p><p><bold>Design/Methods</bold>: Integration into a DASHBOARD, using Excel 2013 dynamic tables and Powerpivot, of all healthcare data from the following hospital sources: Farmis_Oncofarm® (chemotherapy), GestLab (clinical laboratory analysis), Delphin (blood bank), Philips ICCA(Intensive Care Unit), IRIS (HIS Hospital LaFe) y Orion Clinic (electronic medical record). Extract, Transform, Load (ETL) data integration process to acquire a data store (DATAMART) with the automatic integration of all prior information, as well as laboratory toxicity grading according to CTCAE 4.0 criteria and identification of chemotherapy delays/dose reductions and unplanned hospitalizations. Manual data extraction from patients’ medical records (solid tumors) treated in our pediatric oncology unit and comparison of automatized data extraction reliability.</p><p><bold>Results</bold>: The fine tunning of the information tool was carried out following the next steps: A) Information tool design, B) Information tool testing 1 (manual data extraction of toxicity related to 65 chemotherapy courses and comparison), C) Information tool testing 2 (manual data extraction of toxicity related to 145 chemotherapy courses and comparison). Automatized data extraction was superior to manual data extraction with regards to identification of laboratory toxicity and chemotherapy dose reductions. A final test with more than 800 chemotherapy courses is currently ongoing.</p><p><bold>Conclusions</bold>: Automatized data extraction and integration of healthcare data from different hospital data sources is superior to manual data extraction. This information tool can simplify data extraction, allow early identification of chemotherapy‐related toxicities and improve quality of care. Acknowledgments: this work has been funded by “Ayudas Investigación Fundación Mutua Madrileña 2016”</p></sec><sec id="pbc26772-sec-8090"><label>P-403</label><title>Impact of Removing Mucosal Barrier Injury Laboratory‐Confirmed Bloodstream Infections on Central Line‐Associated Bloodstream Infection Rates in Pediatrics Cancer Centers in Latin America</title><p>M. Gonzalez<sup>1</sup>, H. Forrest<sup>1</sup>, M. Homsi<sup>1</sup>, J. Kirby<sup>1</sup>, <underline underline-style="single">M. Caniza</underline><sup>1</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Global Pediatric Medicine, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Bloodstream infections may result from translocation of gut microorganism into the bloodstream of immunocompromised patients. In January 2013, the National Healthcare Safety Network (NHSN) released the mucosal barrier injury laboratory‐confirmed bloodstream infection (MBI‐LCBI) to identify the subset of central line‐associated bloodstream infections (CLABSIs) most likely associated with mucosal barrier injury. Infectious Diseases (ID) – Global Pediatric Medicine initiative mentored Infection Care and Prevention (ICP) teams in pediatric cancer centers (PCCs) in Latin America to separately track MBI and non‐MBI events using the NHSN/MBI‐LCBI protocol. Here, we describe MBI‐LCBIs reported and determine impact of removing MBI‐LCBIs from CLABSI rates.</p><p><bold>Design/Methods</bold>: Data were collected prospectively by our ICP teams in Honduras, Ecuador, México, and Argentina. For this report, we reviewed the collected ID‐IO standardized HAI surveillance monthly report data between January 2014 and December 2016. CLABSI rates per 1000 central‐line days were calculated with and without the inclusion of MBI‐LCBIs to determine rate differences.</p><p><bold>Results</bold>: From four PCCs with an average device utilization ratio of 0.32 (range 0.12‐0.94), 129 CLABSIs were reported; 41(32%) met the MBI‐LCBI 1 criteria. The overall CLABSI rate was 6 (range 3‐14) per 1000 CL‐days. When removing MBI‐LCBIs, the CLABSI rate decreased to 4 (range 2‐10) per 1000 CL‐days. In general, the percent change in the CLABSI rate was 32% (ranges 16‐43%). Among these PCCs, removing MBI‐LCBI from the CLABSI rate determination produced the greatest CLABSI rate decrease (43%) in Mexico (3 vs. 2 per 1000 CL‐days). The most common pathogens were <italic>Klebsiella pneumonia</italic> (34%), <italic>Escherichia coli</italic> (22%), and <italic>Serratia marcescens</italic> (10%).</p><p><bold>Conclusions</bold>: Our results support separate monitoring and reporting of MBI and non‐MBI–‐LCBIs in low‐ to middle‐income countries to allow accurate detection and tracking of preventable (non‐MBI) bloodstream infections.</p></sec><sec id="pbc26772-sec-8100"><label>P-404</label><title>Implementation of a Program Based on Adapted Physical Activity and Recommendations for Second Cancers Prevention for Adolescents and Young Adults with Cancer</title><p><underline underline-style="single">J. Carretier</underline><sup>1</sup>, A. Lion<sup>1</sup>, B. Fervers<sup>1</sup>, H. Boyle<sup>2</sup>, P. Marec‐Bérard<sup>2</sup></p><p><italic><sup>1</sup>Centre Léon Bérard, Cancer Environment, Lyon, France; <sup>2</sup>Centre Léon Bérard, Adolescents and Young Adults with cancer Department, Lyon, France</italic></p><p><bold>Background/Objectives</bold>: Around 700 adolescents and young adults (AYAs; 15 to 25 years) are diagnosed each year with cancer in the French Auvergne‐Rhône‐Alpes region. While long term survival is about 80%, they are six times more likely to develop a second primary cancer (SPC) compared to their peers. This risk is multifactorial and depends on the type of first cancer, the treatment received and the prevalence of risk factors (smoking, overweight, sedentary lifestyle, environmental exposures...).</p><p>This project aims to implement a clinical program based on adapted physical activity and cancer prevention recommendations for AYAs with cancer.</p><p><bold>Design/Methods</bold>: Patients attended adapted physical activity sessions during the active treatment period (4‐6 months). They were given questionnaires about physical activity (IPAQ) and quality of life (EORTC QLQ‐C30) at baseline (T1) and at the end of treatment (T2). They participated to individual information meetings on SPC risk prevention (T3), and responded to a final QoL questionnaire by phone 1 year after T1 (T4).</p><p><bold>Results</bold>: So far, 57 AYAs (63% boys, 37% girls; median age=18 [15‐25]) have been included and completed T1. On average, they participated in 4 sessions [2‐12] at the hospital and 15 [4‐42] at home. Currently, 41 AYAs (72%) have completed the T2 assessment. Preliminary results indicate an increase in the level of physical activity between T1 (680 MET‐min/week [0‐3666]) and T2 (1377 MET‐min/week [0‐2259]). Sedentary time seems to decrease on average from 51 h/week [10‐70] at T1 to 42 h/week [7‐90] at T2. At T3, 36 AYAs (63%) were highly satisfied with the program.</p><p><bold>Conclusions</bold>: This study responds to AYAs’ needs for support and information regarding physical activity and SPC prevention. To improve the quality of the program and its implementation, a gym room will be built at the hospital, and a therapeutic education program dedicated to AYAs will be developed.</p></sec><sec id="pbc26772-sec-8110"><label>P-405</label><title>Neck Circumference: An Indicator for Assessment of Nutritional Status in Children and Adolescents with Malignant Neoplasms at the Time of Diagnosis?</title><p>R.L. Ferretti<sup>1</sup>, <underline underline-style="single">P.S. Maia‐Lemos</underline><sup>1</sup>, K.J.T. Guedes<sup>1</sup>, E.M.M. Caran<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Oncology Institute ‐ IOP/GRAACC/UNIFESP, Pediatric, Sao Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Malignant neoplasms in children and adolescents will trigger malnutrition, which may be underestimated in the diagnosis of the disease, when considering General Adiposity Indexes, such as the Body Mass Index (BMI). Anthropometric indicators may be able to detect early malnutrition, especially at the time of diagnosis of the disease. However, it is necessary that these indicators present good correlation with those that are consecrated to predict the muscular mass of the patient, such as the Arm Muscular Area (AMA). Neck circumference (NC) is a simple, low cost and easy to apply in clinical practice. The main objective of this study was to verify if there is a correlation between NC measurement and AMA of children and adolescents with malignant neoplasms in the diagnosis of the disease.</p><p><bold>Design/Methods</bold>: A cross‐sectional study that evaluated children and adolescents aged 0 to 20 years with malignant neoplasms at a Pediatric Oncology Specialized Institute from December 2015 to June 2016. Measurements of NC were evaluated and, for AMA calculation, arm circumference and skinfolds triceps were evaluated, all performed by trained evaluators, following standardized anthropometric techniques. The correlation between NC and AMA was performed through the Pearson correlation.</p><p><bold>Results</bold>: Among 40 new cases patients, 50% (20) were male. The median age was 12.03 (± 4.75) for the female sex and 13.43 (± 6.99) for the male sex.The correlation between NC and AMA was linear positive and very strong for both sexes, female (r=0.94) and male (r=0.93).</p><p><bold>Conclusions</bold>: It is concluded that there is a strong correlation between NC and AMA for boys and girls, and it can be a promising indicator in clinical practice, because of its practicality in the measurement, low cost, early detection of changes in the nutritional status of these individuals, allowing rapid Intervention and implementation of nutritional therapy.</p></sec><sec id="pbc26772-sec-8120"><label>P-406</label><title>Calf Circumference: A Good Indicator of Muscle Mass Depletion in Children and Adolescents with Malignant Neoplasms?</title><p>R.L. Ferretti<sup>1</sup>, <underline underline-style="single">P.S. Maia‐Lemos</underline><sup>1</sup>, K.J.T. Guedes<sup>1</sup>, E.M.M. Caran<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Oncology Institute ‐ IOP/GRAACC/UNIFESP, Pediatric, Sao Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Children and adolescents with malignant neoplasms may present early malnutrition, but this finding may be underestimated when only the Body Mass Index is considered due to the various metabolic changes, hydration status, and the side effects caused by the therapy antineoplastic. Anthropometric measures are able of early detection of malnutrition, specifically muscle mass depletion, such as calf circumference (CC). The main objective of this study is to verify if there is a correlation between the measurement CC and Arm Muscle Area (AMA), Triceps skinfold (TSF), and Body Mass Index (BMI).</p><p><bold>Design/Methods</bold>: A cross‐sectional study evaluated children and adolescents from 0 to 20 years of age with malignant neoplasms at a Pediatric Oncology Specialized Institute between October 2015 and June 2016. Measurements of CC were evaluated and, for AMA calculation, arm circumference (AC) and TSF were evaluated. The values of weight and length / height were obtained for the calculation of BMI. All measurements were performed by trained evaluators. Correlation between CC and other variables (AMA, BMI and TSF) was performed through the Pearson correlation.</p><p><bold>Results</bold>: Among 1232 patients, 43,59% (537) were female. The mean age for males was 10.0 (± 7.19) and for females, 9.84 (± 7.16). When analyzing the correlation between CC and the other independent variables, there were linear and positive correlations between CC and AMA (r=0.87), CC and BMI (r=0.79) and CC and TSF (r=0.64).</p><p><bold>Conclusions</bold>: It is concluded that there is a strong correlation between Calf Circumference and the independent variables analyzed (AMA, BMI and TSF). This result is greater between CC and AMA, strengthening CC, besides being an easy and low cost measure to be used in clinical practice, has a strong correlation with AMA, which also reflects muscle mass stores, being a good indicator for monitoring the nutritional status of children and adolescents with malignant neoplasms.</p></sec><sec id="pbc26772-sec-8130"><label>P-407</label><title>Outcomes of Paediatric Oncology Admissions to the Paediatric Intensive Care Unit ‐ A Single Tertiary Centre Experience</title><p><underline underline-style="single">S. Dillon</underline><sup>1</sup>, J. Weitz<sup>1</sup></p><p><italic><sup>1</sup>Oxford University Hospitals NHS Foundation Trust, Paediatric Critical Care, Oxford, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Paediatric cancer remains a leading cause of death in children, but continued advances in treatment and supportive care have helped to improve survival. Paediatric oncology patients make up a significant proportion of admissions to paediatric intensive care units (PICU). The aim of this study was to assess the outcomes of children with cancer that were admitted to PICU within a tertiary hospital.</p><p><bold>Design/Methods</bold>: A retrospective analysis of the PICU database system (Carevue, Phillips) in a tertiary paediatric hospital was performed. All patients aged between 0 to 18 years with an Oncological diagnosis, that were admitted between June 2014 and March 2017 were included.</p><p><bold>Results</bold>: A total of 111 patients were admitted to PICU on 139 occasions. Sixty‐eight admissions (48.9%) had a diagnosis of CNS malignancy, 50 (35.9%) were haematological and 20 (14.4%) were solid tumour. The median length of stay was 2.2 days, with the longest stay being 40.9 days. Ninety‐one of these admissions were for post‐operative care and 47 for medical care. Forty‐three of the admissions required ventilator support (26 post‐operative and 17 medical patients). Three of the ventilated admissions also required inotropic support (2 post‐operative and 1 medical patient). Two admissions required continuous venonegativenous haemofiltration (CVVH). One hundred and seven (96.4%) of the patients survived to discharge home. Three patients died on PICU (2 post‐operative and 1 medical patient). One patient was discharged from PICU but did not survive to discharge from the hospital.</p><p><bold>Conclusions</bold>: A large proportion of oncology patients admitted to PICU requiring intervention survived to discharge to continue their treatment regimes. Several factors affected the duration of stay for these patients, including the reason for admission, underlying diagnosis, and the number of interventions required. Compared with data from previous studies our results suggest that PICU outcomes for oncology patients have greatly improved in terms of survival.</p></sec><sec id="pbc26772-sec-8140"><label>P-408</label><title>Aromatherapy with Citrus Oils for Chemotherapy‐Related Nausea and Vomiting</title><p><underline underline-style="single">W. Dirksen</underline><sup>1</sup>, M. Torbecke<sup>1</sup></p><p><italic><sup>1</sup>University Hospital Münster, Pediatric hematology and oncology, Münster, Germany</italic></p><p><bold>Background/Objectives</bold>: At the pediatric cancer center of University Children´s Hospital Muenster, 120 to 140 children and adolescents with newly diagnosed cancer are admitted per year and receive treatment with intensive chemotherapies. Nausea and vomiting are among the most frequent and at the same time most distressing side effects of chemotherapy. In support of antiemetic drug therapy, complementary nursing procedures can be applied. In this observational study, we evaluated the use of aromatherapy with citrus oils in our patient population.</p><p><bold>Design/Methods</bold>: Aromatherapy is based on the local application of 100% natural etheric oils on intact skin. The oils act against nausea via the olfactory system and by penetrating the skin surface. In the professional nursing care of patients with nausea and vomiting, especially citrus oils have shown efficacy. These include lemon, orange, tangerine, and grapefruit essential oils. Two to three drops of the etheric citrus oil are added to a clean cotton pad and locally applied at least twice daily on intact skin of the chest or close to the head.</p><p><bold>Results</bold>: Most patients with chemotherapy‐related nausea and vomiting report to benefit from the smell of citrus oils which overlay nausa‐enhancing smells. The symptoms are often mitigated and in some instances, occurrence of symptoms can be avoided.</p><p><bold>Conclusions</bold>: Aromatherapy with citrus oils can suppport drug‐based antiemetic therapy. Individual preferences for smells, often shaped by personal memories and emotions, are highly relevant for therapeutic success and therefore should be considered for the choice of the smell. In combination with the medical standard of care, this and other complementary nursing procedures have an added value in the control of the agonizing side effects of chemotherapy and can thereby enhance the patients compliance with the subsequent therapy.</p></sec><sec id="pbc26772-sec-8150"><label>P-409</label><title>Relationship Between State and Nutritional Risk Assessed by Instrument for Screening Children and Adolescents with Cancer</title><p><underline underline-style="single">K.N. DA SILVA</underline><sup>1</sup>, R.V. PATIN<sup>1</sup>, C.F. MARÇON<sup>2</sup>, P.D.S. MAIA‐LEMOS<sup>2</sup></p><p><italic><sup>1</sup>UNIP, Nutrition, São Paulo, Brazil; <sup>2</sup>IOP/GRAACC/UNIFESP, Pediatric, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Malnutrition is highlighted as a common condition in cancer patients. Adequate nutritional conducts are taken from the effective nutritional evaluation, being necessary to the presence of a screening tool, which analyzes and evaluates the nutritional risks Murphy et al. (2015) proposed a specific screening tool for children on cancer treatment, the Screening Tool for Childhood Cancer (SCAN).</p><p>To rate the relationship between state and nutritional risk verified through an instrument for screening children and teenagers with cancer.</p><p><bold>Design/Methods</bold>: A cross‐sectional, retrospective study with secondary data of 673 patients seen from August 2015 to August 2016.The results analyzed were based on the screening performed by the nutrition team in that period and compared with the concomitant anthropometric evaluations. Parametric analyzes were performed by the STATA v.10 program.</p><p><bold>Results</bold>: The degree of nutritional risk of cancer patients changes according to their location and cause of hospitalization It was identified in the study that the diagnosis of nutritional risk was related to the values of BMI (Body Mass Index) altered, being observed a significant relation between nutritional risk and body composition only in teenagers.</p><p><bold>Conclusions</bold>: It was found that SCAN may assist clinical practice in screening patients at nutritional risk, but further studies should be performed to confirm their effectiveness, especially with preschool and school children.</p></sec><sec id="pbc26772-sec-8160"><label>P-410</label><title>Outcome of a Three‐Week Supplementation Program in Children and Adolescents with Cancer and ITS Association with Acceptance in a Clinical Trial</title><p><underline underline-style="single">A. GAROFOLO</underline><sup>1</sup>, P.S. MAIA‐LEMOS<sup>1</sup>, F. ANCONA‐LOPEZ<sup>2</sup>, A.S. PETRILLI<sup>1</sup></p><p><italic><sup>1</sup>IOP/GRAACC/UNIFESP, Pediatric, São Paulo, Brazil; <sup>2</sup>UNIFESP, Pediatric, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Malnutrition in cancer patients impairs prognosis, increases the costs of treatment and decreases quality of life. To study protocol compliance and nutritional outcome in malnourished patients with cancer after a 3‐week oral supplementation program and the association of that outcome with type of supplement and severity of malnutrition at admission.</p><p><bold>Design/Methods</bold>: This clinical trial included patients with 1 year old or above, followed during anticancer therapy. They were divided in two groups: mild and severe malnutrition. The severely malnourished received only the industrialized oral supplements (IOS) for three weeks, whereas the mildly malnourished were randomized to receive IOS or non‐industrialized oral supplementation (NIS) for three weeks. The supplement supplied 45% of the daily energy requirements. A new approach to intervention (NAI) was indicated in the severely malnourished group, if no adequate nutritional response was achieved and in the mildly malnourished under IOS if the subjects developed severe malnutrition.</p><p><bold>Results</bold>: One hundred and seventeen patients completed the follow up: 58 severely and 59, mildly malnourished. Adequate nutritional outcome was observed in 38% of those with a severe condition; therefore 62% had a NAI. The same analyses showed that 2.8% of the mild malnutrition IOS group and 22.7% of the NIS group required NAI (p<0.05). IOS and severity of malnutrition were significantly associated with nutritional outcome; IOS demonstrated better outcome and the severity of malnutrition worse outcome.</p><p><bold>Conclusions</bold>: These results suggest that IOS could minimize nutritional deficit, mainly in patients with mild malnutrition and the severity of malnutrition was associated with worse nutritional outcomes.</p></sec><sec id="pbc26772-sec-8170"><label>P-411</label><title>Beyond Supportive Care: A Collaboration to Improve the Intensive Care Management of Critically ILL Pediatric Oncology Patients in Resource‐Limited Settings</title><p><underline underline-style="single">E. Dray</underline><sup>1</sup>, R. Mack<sup>2</sup>, D. Soberanis<sup>3</sup>, C. Rodriguez‐Galindo<sup>4</sup>, A. Agulnik<sup>5</sup></p><p><italic><sup>1</sup>Dartmouth Hitchcock Medical Center, Pediatric Intensive Care Unit, West Lebanon, USA; <sup>2</sup>Unidad Nacional de Oncologia Pediatrica, Intensive Care, Guatemala City, Guatemala; <sup>3</sup>Unidad Nacional de Oncologia Pediatrica, Nursing Education, Guatemala City, Guatemala; <sup>4</sup>St. Jude Children's Research Hospital, St. Jude Global, Memphis, USA; <sup>5</sup>St. Jude Children's Research Hospital, St. Jude Global/Intensive Care, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Hospitalized children with cancer are a high‐risk population who frequently require critical care and intensive interventions. Survival for children with cancer in low and high‐resource settings is dependent on early recognition of cancer diagnoses, timely implementation of treatment protocols, management of side effects, and prevention of deterioration. In recent years, survival for pediatric oncology patients with critical illness in high‐resource centers has improved drastically. Resource‐limited hospitals, however, continue to be challenged by this population, resulting in poor inpatient outcomes and high mortality.</p><p><bold>Design/Methods</bold>: Since 1998, the Asociación de Hemato‐Oncología Pediátrica Centroamericana (AHOPCA) has demonstrated that multi‐center collaboration can improve outcomes for children with cancer in low‐ and middle‐income countries. Using the AHOPCA infrastructure, St. Jude Children's Research Hospital sponsored a multidisciplinary conference on February 25<sup>th</sup> 2017 to identify challenges to the care of pediatric oncology patients with critical illness in resource‐limited settings and identify opportunities for multidisciplinary collaboration.</p><p><bold>Results</bold>: Over 47 nurses, oncologists, and intensivists attended the conference from all ten AHOPCA member countries. The sessions focused on quality improvement methods and the intensive care experience at each hospital to elucidate challenges and goals. The group identified several major challenges to the provision of critical care to pediatric oncology patients in resource‐limited settings: lack of adequate physical, personnel, and educational resources, inadequate institutional support, and provider resistance to allowing access to intensive care resources for these patients. The group identified over 27 multidisciplinary projects to address these challenges, fitting into the framework of topics addressing Quality Improvement, Research, Education, and Activism.</p><p><bold>Conclusions</bold>: This meeting represents the first multidisciplinary conference focused on the intensive care of pediatric oncology patients in Central America. This experience demonstrated that resource‐limited hospitals face similar challenges in caring for this population. The challenges identified can be addressed by innovative solutions formed as a result of multidisciplinary and multi‐institutional collaborations.</p></sec><sec id="pbc26772-sec-8180"><label>P-412</label><title>Evaluation of a Nutritional Supplementation Program for Pediatric Oncology Patients with Malnutrition in Lilongwe, Malawi</title><p><underline underline-style="single">I. Mtete‐Kumwenda</underline><sup>1</sup>, M. Butia‐Mutai<sup>1</sup>, P. Wasswa<sup>1</sup>, M. Chasela<sup>1</sup>, M. Mtunda<sup>1</sup>, A. Mpasa<sup>1</sup>, S. Wachepa<sup>1</sup>, P. Mehta<sup>2</sup>, P. Kazembe<sup>3</sup>, N. El‐Mallawany<sup>2</sup></p><p><italic><sup>1</sup>Kamuzu Central Hospital, Pediatrics, Lilongwe, Malawi; <sup>2</sup>Texas Children's Hospital, Pediatrics, Houston, USA; <sup>3</sup>Baylor College of Medicine Children's Foundation Malawi, Pediatrics, Lilongwe, Malawi</italic></p><p><bold>Background/Objectives</bold>: Malnutrition is a critical co‐morbidity for pediatric oncology patients and increases risk for life‐threatening complications. Supportive care for patients with malnutrition is essential. However, we encountered challenges treating pediatric oncology patients according to nutritional rehabilitation unit (NRU) clinical guidelines in Lilongwe, Malawi, for two reasons: (1) World Health Organization malnutrition guidelines generally focus on patients under 5 years of age, and (2) protocols often struggle to identify cancer patients with bulky tumors because the tumor mass misleadingly contributes to the child's weight, thereby masking malnutrition, especially in older children, for whom weight‐independent measurement of mid‐upper arm circumference (MUAC) is not commonly applied.</p><p><bold>Design/Methods</bold>: A nutritional supplementation program was implemented at Kamuzu Central Hospital (KCH) in July 2016. All pediatric oncology patients received supplemental feeds with porridge, regardless of nutritional status. Patients with mild/moderate malnutrition received ready‐to‐use therapeutic food (RUTF) derived from peanuts, while patients with severe malnutrition received therapeutic milk initially, followed by RUTF. All patients underwent anthropometric measurements including weight, height, MUAC, body mass index (BMI) and were scheduled to have follow‐up evaluations. We evaluated and describe the results of our intervention.</p><p><bold>Results</bold>: There were 25 patients; median age was 8 years (interquartile range 5.1‐11.3). Diagnoses included solid tumor of abdomen (36%), lymphoma (24%), other solid tumors (24%), leukemia (16%). One patient died. Severe malnutrition was found in 48%, moderate 24%, mild 28%. Severity was defined by BMI (52%), MUAC (20%), BMI/MUAC both (16%), and presence of pitting edema (12%). Re‐evaluation of weight at 1‐month/and 2‐3 month intervals found: weight gain (36%/24% at 1 month/2‐3 months respectively), no change (12%/16%), weight loss (24%/32%), and no data (28%/28%).</p><p><bold>Conclusions</bold>: Nutritional supplementation improved weight gain for some pediatric oncology patients with malnutrition. However more consistent and comprehensive re‐evaluation is required, in addition to investigating causes for failure to improve.</p></sec><sec id="pbc26772-sec-8190"><label>P-413</label><title>National Exercise Counseling Practices of Pediatric Oncologists for Pediatric Cancer Patients</title><p><underline underline-style="single">L.L. Yelton</underline><sup>1</sup>, C.L. Gupta<sup>2</sup>, A. Stolfi<sup>3</sup>, A. El‐Sheikh<sup>4</sup></p><p><italic><sup>1</sup>Boonshoft School of Medicine Wright State university, Medical Student 3rd year, Dayton, USA; <sup>2</sup>Boonshoft School of Medicine Wright State university, Wright State University Student, Dayton, USA; <sup>3</sup>Boonshoft School of Medicine Wright State University, Public Health/Statistician, Dayton, USA; <sup>4</sup>Dayton Children's Hospital, Pediatric Hematology Oncology, Dayton, USA</italic></p><p><bold>Background/Objectives</bold>: Currently, there are over 380,000 child cancer survivors in America. Studies show this population has reduced physical activity when compared to their peers, which has led to many comorbidities. The Children's Oncology Group (COG) Long‐Term Follow‐Up Guidelines include exercise recommendations for pediatric cancer patients post treatment. The objective of this study was to determine 1) if pediatric oncologists are aware of these recommendations, 2) their exercise counseling practices, and 3) barriers to exercise counseling.</p><p><bold>Design/Methods</bold>: An online survey modified from Abramson et al. in “Personal Exercise Habits and Counseling Practices of Primary Care Physicians: A National Survey” was sent to attending physicians and fellows in the COG member list.</p><p><bold>Results</bold>: Two‐hundred ninety‐five attending physicians and 59 fellows returned completed surveys. Almost all (99%) believe exercise is important, but only 29% were familiar with COG post treatment exercise recommendations. Fifty‐eight percent of attending physicians reported counseling at least half of their patients post treatment, compared to 20% of fellows (P<0.001, chi‐square test). For patients on active treatment, 40% of attendings and 9% of fellows counseled at least half of their patients (P<0.001). Over 44% of fellows reported not having enough time for exercise counseling, compared to 22% of attendings (P<0.001). Of physicians who counsel patients on active treatment, 97% counsel verbally, and 76% recommend at least 3 days/week for 30 minutes. The more time physicians spent counseling seemed to improve patient compliance, especially when at least 3‐5 minutes was spent.</p><p><bold>Conclusions</bold>: Although most physicians believe exercise is important for pediatric oncology patients, there is a gap in knowledge of current COG recommendations. Additionally, there are no published guidelines for exercise in this population. Further research should investigate methods to increase physicians’ knowledge regarding exercise counseling for pediatric cancer patients and ways to improve counseling practices.</p></sec><sec id="pbc26772-sec-8200"><label>P-414</label><title>Supporting Transport Needs of Cancer Patients to Reduce Treatment Abandonment</title><p>L. Burns<sup>1</sup>, F. Pinho<sup>2</sup>, A.A. Khaing<sup>3</sup>, P. Freccero<sup>1</sup></p><p><italic><sup>1</sup>World Child Cancer, Operations, London, United Kingdom; <sup>2</sup>Please Take Me There, Operations, Cambridge, United Kingdom; <sup>3</sup>Yangon Children's Hospital, Paediatric Haematology‐Oncology, Yangon, Myanmar Burma</italic></p><p><bold>Background/Objectives</bold>: The cost of transport has been identified as one of the key reasons for patients to abandon treatment at Yangon Children's Hospital (YCH) in Myanmar. An assessment in 2013 found abandonment to be as high as 50%. NGO Please Take Me There is working in partnership with World Child Cancer to address this issue. A pilot project was developed to understand the transport needs of paediatric oncology patients at YCH.</p><p><bold>Design/Methods</bold>: A 2 week survey was conducted to understand barriers to accessing care. 107 interviews were conducted and criteria were established for offering transport support. A 4 week pilot project was then run using this criteria. During the pilot 125 patients were supported through 172 grants. A computer programme was designed to capture accurate data and the results were used to design a support package with the aim of reducing abandonment.</p><p><bold>Results</bold>: The average monthly household income of families at YCH is $78, while total treatment‐related costs amount to >$2,200. In 40% of Burmese States, the return cost of travel to the hospital amounted to more than monthly household income. More than 70% of caregivers had to stop work regularly, or entirely, after diagnosis. 30 of the families had up to 5 follow‐up appointments scheduled within the period of the project and the project team identified only one case of a family that did not return. Families became very close to the project team, contacting them frequently to provide updates on their travel arrangements. Caregivers felt more connected with the project team/social workers and often asked for support.</p><p><bold>Conclusions</bold>: The total of providing transport costs to all patients and families at YCH would be $88,000 per year. Providing the amount required for a round trip means that children will return for outpatient appointments and treatment, resulting in a lower rate of abandonment.</p></sec><sec id="pbc26772-sec-8210"><label>P-415</label><title>The Feasibility of Physical Activity Interventions during the Intense Treatment Phase for Children and Adolescents with Cancer</title><p><underline underline-style="single">S. Grimshaw</underline><sup>1</sup></p><p><italic><sup>1</sup>Royal Children's Hospital, Allied Health, Melbourne, Australia</italic></p><p><bold>Background/Objectives</bold>: Physical activity may have benefits for children undergoing intense treatment for cancer, but such programmes are challenging to implement. This systematic review aimed to investigate the feasibly of physical activity interventions during intense cancer treatment for children and adolescents.</p><p><bold>Design/Methods</bold>: A systematic search of seven electronic databases (Cumulative Index to Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, Public/Publisher MEDLINE, Psychological Information Database, Sportsdiscuss, Excerpta Medica Database, Allied and Complementary Medicine Database) from 2005 to August 2015 was completed. The risk of bias was assessed using the Downs and Black Checklist and The Critical Review Form– Qualitative Studies. Results were summarised descriptively across eight domains of feasibility: acceptability, demand, implementation, adaptation, practicality, integration, expansion and limited efficiency testing (including effectiveness).</p><p><bold>Results</bold>: Eleven quantitative studies and one qualitative study were identified for inclusion. Physical activity interventions were typically supervised, individualised programmes that prescribed a variety of activity types for hospital inpatients. There was evidence that physical activity interventions during the intense phase of cancer treatment were acceptable to parents and children, safe and successfully implemented. A trend of positive effects across all aspects of functioning was noted. Data were unavailable documenting feasibility for the domains of integration, adaptation and expansion.</p><p><bold>Conclusions</bold>: There is preliminary evidence that physical activity interventions are feasible, in that they are acceptable, safe and potentially beneficial for children with cancer but more work needs to be done to understand the most effective ways to implement these types of programmes.</p></sec><sec id="pbc26772-sec-8220"><label>P-416</label><title>Investigating Vincristine Neurotoxicity in Paediatric Haematology/Oncology Patients: A Role for Genotyping</title><p><underline underline-style="single">S. Guram</underline><sup>1</sup>, E. Richards<sup>1</sup>, B. Messahel<sup>1</sup></p><p><italic><sup>1</sup>Addenbrookes Hospital‐ Cambridge, Paediatric Haematology and Oncology Department, Cambridge, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Vincristine is a vinca alkaloid which is used as a chemotherapeutic agent for multiple paediatric haematological and solid tumours. This is frequently complicated by dose‐dependent neurological toxicity. Studies suggest that polymorphisms of the CYP3A and ABCB1 genes contribute to vincristine‐related neurotoxicity, which may explain variation in the prevalence of this side effect and overall prognosis. An established link between mercaptopurine toxicities and polymorphisms led to the incorporation of targeted genetic screening into therapy, suggesting a potential for tailored vincristine treatment. We aim to identify cases of vincristine‐related neurotoxicity within our patient population, characterise trends in these toxicities and investigate any demographic influence on these side effects.</p><p><bold>Design/Methods</bold>: This five year retrospective study from December 2008 to February 2014 focused on paediatric patients presenting to our oncology unit who were undergoing first line chemotherapy for Acute Lymphoblastic Leukaemia, Low Grade Glioma and Wilms Tumour. These malignancies were chosen as they had a heavy burden of vincristine in their treatment protocols. Neurotoxicity was assessed using the Common Terminology Criteria of Adverse Events (CTCAE). Patient records were studied for details of neurotoxicity using this tool and any subsequent changes that were made to their dosage of vincristine.</p><p><bold>Results</bold>: <italic>Frequency</italic>: There were 66 “neurotoxic events”. A high incidence of neurotoxic events of grade 1‐3 severity was found with 71% of patients experiencing one or more events. Motor neurotoxicity was the modal group. <italic>Demographic</italic>: Toxicity was higher amongst females and the older age categories. There was an ethnic variation of trend toward increased toxicity. There was no clear relationship between tumour type and neurotoxicity. <italic>Timing</italic>: Two thirds of all neuropathies occurred within the first three months.</p><p><bold>Conclusions</bold>: This pilot study demonstrates a high rate of vincristine‐related neurotoxicity within a subset of the paediatric haematology and oncology population, warranting a larger study and potential pharmacogenetic analysis.</p></sec><sec id="pbc26772-sec-8230"><label>P-417</label><title>Experience of Using Galactomannan Testing for Diagnosis of Invasive Aspergillosis in Immunocompromised Patients from a Tertiary Care Centre in North India</title><p><underline underline-style="single">R. H N</underline><sup>1</sup>, V. Dinand<sup>2</sup>, N. Radhakrishnan<sup>1</sup>, J. Oberoi<sup>3</sup>, A. Sachdeva<sup>1</sup></p><p><italic><sup>1</sup>Sir Ganga Ram Hospital, Pediatric hematology oncology, Delhi, India; <sup>2</sup>Sir Ganga Ram Hospital, Department of Research, Delhi, India; <sup>3</sup>Sir Ganga Ram Hospital, Department of Microbiology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Invasive aspergillosis (IA) is the most frequent and one of the most lethal invasive fungal infections in high‐risk oncology patients. The diagnosis of IA is difficult and relies in part on the detection of galactomannan (GM).</p><p>Aims and objectives: To study the utility of GM assay in diagnosing IA in paediatric oncology, paediatric critical care and stem cell recipients. A focus was placed on evaluating the assay sensitivity, specificity, and negative predictive value in paediatric patients.</p><p><bold>Design/Methods</bold>: Retrospective analysis of febrile neutropenia or prolonged febrile episodes in non‐neutropenic immunocompromised patients between 1 July 2007 to 31 October 2016 was done. Standard EORTC criteria were used for defining fungal infections. Clinical profile, GM assay, radiological imaging and need for mould active antifungal therapy was assessed.</p><p><bold>Results</bold>: 507 patients with 825 episodes of suspected IA were enrolled in the study. This included 288 haematological malignancies, 78 stem cell transplant recipient and 58 non‐oncological patients from paediatric ICU. 9 proven and 25 probable were observed during this period. GM assay was considered as positive for values >1. The sensitivity, specificity and negative predictive value of the assay in diagnosing IA was 76.5%, 86.5% and 98.8% respectively.</p><p><bold>Conclusions</bold>: Data suggests that GM assay has a very good negative predictive value in diagnosing IA. GM EIA testing may be useful in diagnosing and/or excluding IA in at‐risk paediatric patients, but the low incidence rate of probable or proven IA in this study precludes the ability to make any definitive conclusions.</p></sec><sec id="pbc26772-sec-8240"><label>P-418</label><title>Correlation Between Galactomannan Antigen and Absolute Neutrophil Counts in Immunosuppressed Patients with Invasive Aspergillosis</title><p><underline underline-style="single">R. H N</underline><sup>1</sup>, N. radhakrishnan<sup>1</sup>, V. Dinand<sup>1</sup>, A. Sachdeva<sup>1</sup>, J. Oberoi<sup>2</sup></p><p><italic><sup>1</sup>Sir Ganga Ram Hospital, Pediatric hematology oncology, Delhi, India; <sup>2</sup>Sir Ganga Ram Hospital, Department of microbiology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Galactomannan (GM) assay is being used widely as a diagnostic marker for invasive aspergillosis (IA) in immunocompromised patients. Most of the studies of GM have involved severely neutropenic patients, screened two or three times weekly during a neutropenic risk period. Time to positivity of Galactomannan depends on the neutrophil count and which is often ignored while interpreting the results.</p><p>Aims and objectives: The aim of the study was to determine whether the diagnostic yield of GM was comparable in neutropenic and in non‐neutropenic patients with and without microbiologically documented IA.</p><p><bold>Design/Methods</bold>: Retrospective observational analysis. The episodes of IA occurring in the haematology department were retrospectively classified according to the EORTC criteria as proven, probable or possible IA. From 1 July 2007 to 31 October 2016, patients data were analysed including the neutrophil count and galactomannan assays.</p><p><bold>Results</bold>: 507 patients were enrolled with 825 episodes of suspected IA. This included 288 patients of hematological malignancy and 78 stem cell transplant recipients. Thirty four episodes of proven (n=9) and probable (n=25) IA were observed. GM was considered positive if value >1 (n=131/824). 255 patients received anti‐mould therapy for IA. When ANC was compared to positivity of Galactomannan in patients who received treatment for IA, a trend towards higher GM positivity in lower ANC was observed, although not statistically significant. (45.8% in ANC <50/mm<sup>3</sup>, 38.9% in 50‐100/mm<sup>3</sup>, 20% in 101‐200/mm<sup>3</sup>etc.) In patients who received mould active antifungals, median ANC in those with GM positive was 273/mm<sup>3</sup> and those in GM negative was 330/mm<sup>3</sup> (p=0.18). In those who were CT positive for IA, median ANC in those with GM positive was 309/mm<sup>3</sup> and those in GM negative was 572/mm<sup>3</sup>(p=0.38).</p><p><bold>Conclusions</bold>: Galactomannan may be falsely negative in patients with ANC>500/mm3 and this should be kept in mind while interpreting the Results:</p></sec><sec id="pbc26772-sec-8250"><label>P-419</label><title>Validation of a Classification System for Treatment‐Related Mortality in Children with Cancer</title><p><underline underline-style="single">H. Hassan</underline><sup>1,2</sup>, M. Rompola<sup>1,2</sup>, A. Glaser<sup>1,2</sup>, S. Kinsey<sup>1,2</sup>, B. Phillips<sup>2,3</sup></p><p><italic><sup>1</sup>University of Leeds, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom; <sup>2</sup>Leeds Teaching Hospital NHS Trust, Depeartment of Paediatric Haematology and Oncology, Leeds, United Kingdom; <sup>3</sup>University of York, Centre for Reviews and Dissemination, York, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Death not directly due to cancer has been termed “treatment‐related mortality” (TRM). Appreciating the differences between TRM and disease‐related death is critical in directing strategies to improve supportive care, interventions delivered or disease progression. However, it is poorly defined and reported in clinical trials. Recently, a global collaboration developed and validated a consensus‐based classification tool and attribution system. This study aimed to evaluate the newly developed consensus‐based definition of TRM and cause‐of‐death attribution system in a single institution, at a regional paediatric oncology centre in the North of England.</p><p><bold>Design/Methods</bold>: Thirty medical records of the most recent deaths in children with cancer, two and four weeks prior to death were anonymised and presented to the participants. Two senior physicians and two clinical research associates independently classified deaths as “treatment related mortality” or “not treatment related” according to the algorithm developed. When TRM occurred, reviewers applied the cause‐of‐death attribution system. Inter‐relater reliability was assessed using the Kappa statistic (k).</p><p><bold>Results</bold>: Reliability of the classification was deemed almost perfect between CRA and consultants (k=0.86, 95% confidence interval 0.72‐0.97). Ten deaths were classified as TRM; of which infection was the most frequent cause identified. Reviewers disagreed on the primary cause of death (e.g. respiratory vs infection) when applying the cause‐of‐death attribution system in 6 cases. The study identified how the algorithm may not identify TRM deaths in patients receiving non‐curative therapy.</p><p><bold>Conclusions</bold>: The classification and cause of death attribution system could be implemented in different health care settings. Adaptation of the classification tool in patients receiving non‐curative interventions and the cause of death attribution system should be considered.</p></sec><sec id="pbc26772-sec-8260"><label>P-420</label><title>The Efficacy and Safety of Probiotics in People with Cancer: An Updated Systematic Review and Meta‐Analysis</title><p><underline underline-style="single">H. Hassan</underline><sup>1,2</sup>, M. Rompola<sup>1,2</sup>, A. Glaser<sup>1,2</sup>, S. Kinsey<sup>1,2</sup>, B. Phillips<sup>2,3</sup></p><p><italic><sup>1</sup>University of Leeds, Leeds Institute of Cancer and Pathology, Leeds, United Kingdom; <sup>2</sup>Leeds Teaching Hospital NHS Trust, Department of Paediatric Haematology and Oncology, Leeds, United Kingdom; <sup>3</sup>University of York, Centre for Reviews and Dissemination, York, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Probiotics are living microorganisms that confer a health benefit on the host when administered in adequate amounts. This study updates a systematic review and meta‐analysis investigating the efficacy and safety of probiotics in adult and paediatric patients diagnosed with cancer.</p><p><bold>Design/Methods</bold>: An updated systematic review and meta‐analysis was undertaken (PROSPERO registration: CRD42016050252). Randomised controlled trials (RCT), identified through screening multiple databases were included for analyses of efficacy. Non‐randomised controlled‐trials and case reports were included for safety analysis. Outcomes included the reduction in the incidence and severity of diarrhoea, and adverse events. Where possible, data were combined for meta‐analysis using a random‐effects model and sub‐group analysis (including children) undertaken to investigate strains and dosage of probiotic, and patient characteristics.</p><p><bold>Results</bold>: Twenty one studies (N = 2,982 participants) were included for assessment of efficacy. Results show that probiotics may reduce the incidence of diarrhoea in patients with cancer [odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.34‐0.78, I‐sq 36.9%, 5 studies], duration of pyrexia [standardized mean difference 0.64 days, 95% CI 053‐0.77, I‐sq 0.01%, 5 studies] and possibly the severity of diarrhoea for example Common Toxicity Criteria grade 3 and 4 diarrhoea [OR=0.51, 95% CI 0.12‐2.2, I‐sq 92.5%, 4 studies]. However, more studies are required to assess the true effect. There were insufficient data to perform subgroup analysis on children, strains, and dosage due to marked heterogeneity. Twenty five studies (N = 2,242) were included in the safety analysis. Five case reports and a participant from 1 RCT showed probiotic‐related bacteraemia/fungaemia/positive blood cultures.</p><p><bold>Conclusions</bold>: There remain insufficient studies to assess the true effect of probiotics in people with cancer. Evidence suggests probiotics may be beneficial but further study is still required, particularly in children.</p></sec><sec id="pbc26772-sec-8270"><label>P-421</label><title>Predictive Value of Serum Angiopoietin 1/2, SFLT‐1 and VEGF Levels in the Diagnosis of Sepsis in Febrile Neutropenic Children</title><p><underline underline-style="single">I. Ilhan</underline><sup>1</sup>, S. Cakmakci<sup>1</sup>, C. Sonmez<sup>2</sup>, N. Sari<sup>1</sup></p><p><italic><sup>1</sup>Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Pediatric Hematology and Oncology, Ankara, Turkey; <sup>2</sup>Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Clinical Biochemistry, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: Febrile neutropenia (FN) is one of the major causes of morbidity and mortality in patients with cancer. Endothelial damage and dysfunction is one of the important features of sepsis. This study sought to investigate the role of serum levels of Angiopoietin‐1 (Ang‐1), Angiopoietin‐2 (Ang‐2), Vascular endothelial growth factor (VEGF) and Soluble fms‐like tyrosine kinase‐1 (sFlt1) in predicting the risk of sepsis in febrile neutropenic children</p><p><bold>Design/Methods</bold>: From January 2014 to December 2016, we prospectively measured concentrations of ang‐1, ang‐2, VEGF and sFlt1 at onset and after 48 hour of fever in FN episodes, and evaluated the diagnostic accuracy of these mediators as predictors of sepsis and bacteriemia.</p><p><bold>Results</bold>: Eighty‐six episodes of FN in 52 patients (F:23, M:29, median age:7.7 years (0.7‐18)) were evaluated. The most common diagnosis were acute lymphoblastic leukemia and osteosarcoma (%22), followed by Ewing's sarcoma (%19). Twenty‐nine FN episodes (%34) were complicated with sepsis and in 12 FN episode (%14) an microbiological agent was isolated. At baseline, Ang‐2 levels (160.57 pg/ml, range 15.64‐1,111 pg/ml, p=0.02) and sFlt1 levels (1,622 pg/ml, range 750‐3,980 pg/ml, p<0.001) were higher and Ang‐1(696 pg/ml, range 11.57‐14,452 pg/ml, p<0.001) and VEGF levels (128.77 pg/ml, range 0‐1,001 pg/ml, p<0.001) were lower in patient group compared to healthy individuals. Serum concentrations of Ang‐2 were significantly higher at onset of fever in patients with sepsis (med:145.82 pg/ml) than in patients without sepsis (med:75.13 pg/ml, Mann‐Whitney test, P = 0.017). There were no statistically significant differences of Ang‐1, VEGF and sFlt‐1 levels in patients with noncomplicated FN compared to patients that developed sepsis and/or bacteriemia.</p><p><bold>Conclusions</bold>: We conclude that a high Ang‐2 level at onset of fever could be an indicative of sepsis in febrile neutropenic patients in pediatric cancer population.</p></sec><sec id="pbc26772-sec-8280"><label>P-422</label><title>Caregiver Decision Making: A Comprehensive Approach to “Care and Connect”</title><p><underline underline-style="single">V. Inglis</underline><sup>1</sup>, S. Richards<sup>1</sup>, L. Knox<sup>1</sup>, C. Hislop<sup>1</sup>, D. Ludwinski<sup>2</sup></p><p><italic><sup>1</sup>Solving Kids' Cancer Europe, Care and Connect, London, United Kingdom; <sup>2</sup>Solving Kids' Cancer, Research Advocacy, New York, USA</italic></p><p><bold>Background/Objectives</bold>: Families with children affected by paediatric cancer benefit from emotional support and information to empower decision making from diagnosis and throughout disease treatment. Informed decisions are augmented by recognition of emotional needs, social well‐being, and knowledge of disease and clinical research landscape. Increasingly, more families are seeking access to clinical trials across borders when options become limited locally. A flexible multi‐model approach termed “Care and Connect” for family support is a forward‐thinking and unique paradigm developed to offer comprehensive support to children and their families.</p><p><bold>Design/Methods</bold>: The “Care and Connect” program employs a team led by a Family Coordinator to meet the needs of individual cancer patients and families. This crucial role provides a trusted and experienced parent‐professional who listens, identifies key needs, and provides tailored support and guidance throughout a cancer journey. The support provided in remit of access to novel therapies at home and abroad includes assessing and navigating the clinical trial landscape with the guidance of a researcher/clinician network, treatment cost negotiations, travel logistics, and annual parent education conferences to provide insight to current research.</p><p><bold>Results</bold>: To date more than 190 families worldwide have been positively impacted by this model, and case studies of three families presented demonstrate the necessity for flexibility and illustrate the range of resources required for supportive cancer care. This multi‐model approach directly helped families in making informed decisions with regard to palliative care, access clinical trial overseas, and improve quality of life in survivorship.</p><p><bold>Conclusions</bold>: Families are empowered to make informed decisions regarding their child's cancer care when this multi‐modal approach of caring and connecting is applied.</p></sec><sec id="pbc26772-sec-8290"><label>P-423</label><title>Hope for Cancer Kids Insurance Program for Childhood and Adolescent Cancer Treatment in Kenya</title><p><underline underline-style="single">I. Jaboma</underline><sup>1</sup></p><p><italic><sup>1</sup>Kenya Hospices and Palliative Care Association KEHPCA, HOPE FOR CANCER KIDS, NAIROBI, Kenya</italic></p><p><bold>Background/Objectives</bold>: Hope for Cancer Kids (H4CK) is a charitable organization in Kenya. One of the most successful programs H4CK has is Health Insurance program that covers all costs related to treating any childhood cancer in a Kenyan public hospital.</p><p><bold>Design/Methods</bold>: It has been made possible through National Hospital Insurance Fund(NHIF), a government State Corporation which has provided all Kenyans citizens who have attained the age of 18 years, with an opportunity to have access to an, affordable, sustainable and quality health insurance. H4CK has established a special partnership with the NHIF to ensure the registration of all children and adolescents suffering from cancer and their families at 5 USD monthly or 60 USD yearly for the whole family, as well as orphans at a subsidized rate of 5 USD monthly or 60 USD yearly per 5 orphans. It has provided a special reduced one month activation period for all parents registered under H4CK as opposed to the normal three month activation period for any other Kenyan.</p><p><bold>Results</bold>: As of February 28<sup>th</sup> 2017, 294 children have benefited from this program, 2 have completed treatment successfully, 270 are still going on with treatment and 22 have died. H4CK gets about 15‐20 new patients monthly in dire need of this support and most of the children affected in Kenya come from poor backgrounds. Cancer treatment is very costly; however it has ensured that all children suffering from Cancer can access treatment</p><p><bold>Conclusions</bold>: It has resulted in giving hope and motivation to many parents to take their children to the hospital for cancer treatment since they are relieved of the financial burden. As a result more children and adolescents suffering from cancer in Kenya have been able to access treatment.</p></sec><sec id="pbc26772-sec-8300"><label>P-424</label><title>Clinical Severity of Dengue Fever Relates to Treatment Intensity in Children with Malignancy</title><p><underline underline-style="single">P. Jain</underline><sup>1</sup>, N. Radhakrishnan<sup>1</sup>, V. Dinand<sup>1</sup>, A. Sachdeva<sup>1</sup></p><p><italic><sup>1</sup>Sir Ganga Ram Hospital‐ Delhi, Pediatric Hematology Oncology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Clinical spectrum of dengue fever ranges from mild febrile illness to catastrophic haemorrhagic fever. Managing dengue fever in children with malignancy is often challenging. The clinical presentation, course and risk for mortality is discussed here.</p><p><bold>Design/Methods</bold>: We retrospectively analysed the data of children who developed dengue fever while on treatment for a malignancy (2009‐2015). Dengue fever was diagnosed based on NS1antigen±IgM positivity.</p><p><bold>Results</bold>: We evaluated 21 patients (Male:female13:8; median age 8years, range 8months‐17years). Underlying diagnoses included ALL(n=12), AML(n=2), post‐HSCT(n=2) and solid tumours(n=5). Nine were on intensive phase of treatment (4‐ALL, 1 day+17 post HSCT for relapsed ALL, 1‐relapsed AML, and 3‐solid tumours). Fever was the presenting complaint in 19/21 patients, followed by vomiting, abdominal distension, unexplained oliguria and unexpected fall in platelet counts. Median minimum platelet count was 6,000/mm<sup>3</sup> (interquartile range 3,000‐9,000) with a mean time to platelet recovery of 7 days (range 3‐13) in children on intensive treatment. Patients not on intensive treatment had significantly higher median minimum platelet count of 15,000/mm<sup>3</sup> (IQR 13,000‐93,750; P=0.003) and shorter mean time to platelet recovery (3 days, P=0.013). Significant bleeding manifestations and severe illness with plasma leakage were found in 6/9 children on intensive treatment and 1/12 on non‐intensive regimen (P=0.02). Two children died of dengue haemorrhagic fever during ALL induction and consolidation chemotherapy respectively, in 2010, probably due to a delay in diagnosing dengue fever. Investigations for dengue were sent on day 3 or 4 of fever during the 2010 epidemic while the same was done on day 1 of fever during the 2015 epidemic, contributing to early diagnosis and prompt management of dengue fever and no mortality in 2015.</p><p><bold>Conclusions</bold>: A high index of suspicion should be kept for dengue infection in immunocompromised children suffering from malignancy during the annual epidemics. Aggressive support is mandatory especially for those under intensive treatment phase.</p></sec><sec id="pbc26772-sec-8310"><label>P-425</label><title>Oral Cryotherapy to Reduce the Incidence of Severe Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation: Results of a Randomized Clinical Trial</title><p><underline underline-style="single">T. Kamsvåg Magnusson</underline><sup>1</sup>, L. von Essen<sup>2</sup>, J. Arvidson<sup>1</sup>, A. Svanberg<sup>3</sup>, K. Mellgren<sup>4</sup>, K. Garming‐Legert<sup>5</sup>, J. Toporski<sup>6</sup>, J. Winiarski<sup>7</sup>, G. Ljungman<sup>1</sup></p><p><italic><sup>1</sup>Uppsala University, Departmend of Women's and Children's Health, Uppsala, Sweden; <sup>2</sup>Uppsala University, Departmend of Women's and Children's Health‐ Clinical psychology in healthcare, Uppsala, Sweden; <sup>3</sup>Uppsala University, Department of Medical Sciences‐ Hematology, Uppsala, Sweden; <sup>4</sup>Sahlgrenska Academy, Department of Clinical Sciences‐ Pediatrics, Gothenburg, Sweden; <sup>5</sup>Karolinska Institute, Department of Dental Medicine, Stockholm, Sweden; <sup>6</sup>Skåne University Hospital, Department of Clinical Sciences‐ Section of Pediatric Oncology/Hematology, Lund, Sweden; <sup>7</sup>Karolinska Institute, Department of Clinical Science‐ Intervention and Technology, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Oral mucositis (OM) is a common adverse effect in hematopoietic stem cell transplantations (HSCT). Oral cryotherapy (OC), cooling of the mouth during chemotherapy infusion, has been shown to reduce OM in adults but the effect in children has not been evaluated. The study aimed to examine if OC reduces the incidence of severe OM (WHO oral toxicity score 3‐4) and use of opioids in children undergoing HSCT.</p><p><bold>Design/Methods</bold>: The study was a multicenter randomized clinical trial. Children 4‐17 years old were randomized to either OC or standard treatment. The OC‐group was instructed to cool their mouth with ice as long as they could during chemotherapy infusions with an intended time of at least 30 minutes. Time was recorded by a nurse after each infusion and the child evaluated the treatment with a purpose‐designed questionnaire. Grade of mucositis was recorded using the WHO‐scale from the day of transplant to engraftment. Use of opioids was collected from the child's medical chart. Opioid doses were converted to equivalent intravenous doses of morphine.</p><p><bold>Results</bold>: Forty‐nine children (mean age of 10.7 + 4.2 years) were included in the study. Twenty‐six children were randomized to OC and 23 to standard care. Compliance to OC varied considerably with only15 children being able to use OC according to protocol. Severe mucositis was reported in 20 children (41 %) with no difference between the two groups. Children used opioids for a mean of 8.7 + 7.2 days with a mean total dose of 184 + 262 mg IV morphine. There was no difference in the use of opioids between the two groups.</p><p><bold>Conclusions</bold>: OC did not reduce the incidence of severe OM or use of opioids in children undergoing HSCT. However, compliance to OC was poor, especially among the youngest children, which may have influenced the results.</p></sec><sec id="pbc26772-sec-8320"><label>P-426</label><title>Establihsing the Dental Needs at Diagnosis in Pediatric Oncology Patients from Maritimes, Canada: Results of the E‐POD Study</title><p><underline underline-style="single">J. Kearns</underline><sup>1</sup>, T. Doyle<sup>1</sup>, K. Kulkarni<sup>2</sup></p><p><italic><sup>1</sup>IWK Health Centre, Pediatric Dentistry, Halifax, Canada; <sup>2</sup>IWK Health Centre, Pediatric Hematology Oncology‐ Department of Pediatrics, Halifax, Canada</italic></p><p><bold>Background/Objectives</bold>: The recommendation for dental evaluation and treatment prior to commencement of oncology therapy is well recognized; however, data on dental needs at diagnosis of pediatric oncology patients is very scant. This population based study was designed to assess and report the oral health status and dental needs of pediatric oncology patients at the time of diagnosis, as well as the treatment provided.</p><p><bold>Design/Methods</bold>: After ethics approval, all pediatric oncology patients from the 3 Maritime Provinces managed at the Izaac Walton Killam (IWK) Health Centre from January 2013 to December 2015 were identified for inclusion in the study. Part of the routine oncology care plan for patients undergoing chemotherapy is a referral to dentistry for pre‐therapy evaluation.</p><p>Data was extracted from (i) Pediatric oncology hospital database, (ii) Dental Clinic records, and (iii) Electronic medical records. The total number of patients with and without dental needs at time of diagnosis, treatment rendered, method of treatment, and caries risk status (CRS) were computed. SPSS version 24 was used for statistical analysis.</p><p><bold>Results</bold>: Of the 172 patients, 112 (65.11%) (male:female::1.4:1, median age: 75 months)were reviewed by Dentistry and included in the study. Among patients aged 0‐5, 6‐11 and 12‐19 years, 16.3%, 60.7% and 62.9% experienced caries respectively. Other dental pathologies observed were: abscess (n=8), retained primary teeth (n=3), soft tissue pathology (n=2), and previous trauma (n=2). High CRS was observed in 56.3% (n=63) while excellent oral hygiene only in 1.8% (n=2). Treatment was required by 42.9% (n=48) of the patients and was coordinated with other procedures in 76%. Twenty eight patients required 1 or more extractions while 22 received sealants. Type of cancer was not associated with incidence of caries.</p><p><bold>Conclusions</bold>: A substantial burden of dental disease requiring therapy was identified in our study population. Care can be successfully delivered in a coordinated and multidisciplinary model.</p></sec><sec id="pbc26772-sec-8330"><label>P-427</label><title>Hepatosplenic Fungal Infections in Children with Leukemia, Risk Factors and Outcome:A Multicentric Study</title><p>H. Kızılocak<sup>1</sup>, <underline underline-style="single">R. Kebudi</underline><sup>1,2</sup>, G. Dikme<sup>1</sup>, A. Kalyoncu Uçar<sup>3</sup>, N.Y. Özbek<sup>4</sup>, E. Unal<sup>5</sup>, N. Sarper<sup>6</sup>, T. Patıroğlu<sup>5</sup>, N. Yaralı<sup>4</sup>, E. Zengin<sup>6</sup>, Ü. Koçak<sup>7</sup>, E. Kürekçi<sup>8</sup>, D. Tuğcu<sup>9</sup>, E. Uysalol<sup>10</sup>, S. Kuruoglu<sup>3</sup>, I. Adaletli<sup>3</sup>, T. Celkan<sup>1</sup></p><p><italic><sup>1</sup>Istanbul University Cerrahpasa Medical Faculty, Pediatric Hematology‐Oncology, İstanbul, Turkey; <sup>2</sup>Istanbul University Oncology Institute, Pediatric Hematology‐Oncology, İstanbul, Turkey; <sup>3</sup>Istanbul University Cerrahpasa Medical Faculty, Radiology, İstanbul, Turkey; <sup>4</sup>Ankara Pediatric Hospital, Pediatric Hematology and Oncology, Ankara, Turkey; <sup>5</sup>Erciyes University Medical Faculty, Pediatric Hematology and Oncology, Kayseri, Turkey; <sup>6</sup>Kocaeli University Medical Faculty, Pediatric Hematology and Oncology, Kocaeli, Turkey; <sup>7</sup>Gazi University Medical Faculty, Pediatric Hematology and Oncology, Ankara, Turkey; <sup>8</sup>Lösante Hospital, Pediatric Hematology Department, Ankara, Turkey; <sup>9</sup>Istanbul University İstanbul Medical Faculty, Pediatric Hematology‐Oncology, Istanbul, Turkey; <sup>10</sup>Kanuni Sultan Süleyman Research and Training Hospital, Pediatric Hematology and Oncology, İstanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Children with leukemia are at increased risk for invasive fungal infections, including hepatosplenic fungal infections (HSFI). We aimed to assess the risk factors, treatment and outcome of HSFI in children with leukemia.</p><p><bold>Design/Methods</bold>: We retrospectively evaluated the risk factors, diagnostic approach, treatment and outcome of HSFI in children with leukemia in nine centers in Turkey.</p><p><bold>Results</bold>: HSFI were seen in 26 children with leukemia (15 female, 11 male); 21 ALL (15 precursor B‐ALL, 3 T‐ALL, 1 biphenotypic, 1 B‐ALL, 1 relapsed), four AML (1 relapse) and one CML. All cases were diagnosed radiologically with abdominal ultrasound, that was performed at a median of 9 (1‐21) days after febril neutropenia, some also had computerized tomography and magnetic resonance imaging. Twelve patients had hepatosplenic, five splenic and nine hepatic involvement. Most episodes occurred at the end of induction in ALL cases. Twenty‐two patients had received steroids prior to HSFI. All cases were diagnosed during evaluation for persistent febrile neutropenia; three cases had abdominal pain, thirteen cases had back pain extending to the shoulder. In one patient the liver nodule was excised and mucor was diagnosed by pathology, in five trucut biopsy was done. All patients received broad spectrum antibiotics due to febril neutropenia and various antifungals (liposomal amphotericin B, caspofungin, voriconasole, micafungin, posaconasole). Fifteen patients had radiologic/microbiology evidence of fungal infection in other sites (11 lungs, 2 lungs‐kidney, 1 brain, 1 esophagus). Eight patients were transferred to ICU. Hemophagocytosis was observed in two patients. Two patients received granulocyte suspensions. Twenty patients recovered, six died (three due to HSFI, three due to progressive leukemia).</p><p><bold>Conclusions</bold>: We suggest that an abdominal ultrasound should be added to the standard recommendation of CT of lungs, for the evaluation of persistent febrile neutropenia; to diagnose hepatosplenic fungal infections. Mucor should be considered in the antifungal treatment spectrum.</p></sec><sec id="pbc26772-sec-8340"><label>P-428</label><title>Folate and Vitamin B12 Deficiency in Children with Acute Lymphoblastic Leukemia in LMIC'S: Better Nutrition or Supplementation</title><p><underline underline-style="single">S. Khera</underline><sup>1</sup>, A. Trehan<sup>1</sup>, S. Attri<sup>1</sup>, R. Jain<sup>1</sup>, D. Bansal<sup>1</sup></p><p><italic><sup>1</sup>PGIMER, Pediatrics, Chandigarh, India</italic></p><p><bold>Background/Objectives</bold>: Vitamin B12 & Folic acid (FA) help in making the cell stroma conducive to the proliferation of the malignant clone. Lower middle income countries (LMIC's) are fraught with malnutrition and vitamin deficiencies. Refraining from folate supplementation to patients with malignancies in LMIC's has been questioned. We evaluated the incidence of vitamin B12/FA deficiency in children on therapy for Acute Lymphoblastic Leukemia (ALL).</p><p><bold>Design/Methods</bold>: Children on therapy for ALL were randomly evaluated for serum B12 and folate levels. Serum B12 < 211pg/ml and Folate< 2 ng/ml were taken as deficient. Deficiency status was correlated to undernutrition.[Weight for age < ‐2zscore (WHO)].</p><p><bold>Results</bold>: Hundred children, age 6.5 years (5.8‐7.1), 50 each on maintenance and induction chemotherapy with 50 age/sex matched controls were evaluated.</p><p>Induction Therapy: Eleven of 50 children (22%) were undernourished. Mean B12 levels were 331.3 pg/ml (269.3 to 393.2), with 15 (30%) being deficient, 2 being undernourished. Mean Folate levels were 9.06 ng/ml (7.67 to 10.44) with 1 child being deficient.</p><p>Maintenance Therapy: Fourteen children (28%) were undernourished. Mean B12 levels were 500.56pg/ml (419.75 ‐ to 581.37). Deficiency: 5(10%), 3 being undernourished. Mean Folate levels were 6.61ng/ml (5.56‐7.66). Deficiency: 4 (8%), 3 being undernourished. The mean levels of Folate and B12 were lower in children who were undernourished during maintenance.</p><p>There was no difference of B12 & Folate levels between gender and risk groups of ALL. The control group was not deficient.</p><p><bold>Conclusions</bold>: Childhood under‐nutrition in India is 45.9% with prevalence of B12 & FA deficiency in the general population being 7‐33% and 20‐33%; with a higher prevalence in the undernourished. In our cohort 25% had undernutrition. We had 5% & 20% children with Folate & B12 deficiency. Patients with undernutrition had greater B12/FA deficiency. Under‐nutrition remains the monster to be tackled in LMIC's. Countering undernutrition and not supplementation is the key in LMIC's.</p></sec><sec id="pbc26772-sec-8350"><label>P-429</label><title>Central Venous Catheter (CVC) Dysfuction Requiring One or More Doses of Tissue Plasminogen Activator is Associated with Significantly Increased Need of Subsequent CVC Placement</title><p>J. MacLean<sup>1</sup>, T. MacDonald<sup>1</sup>, C. Digout<sup>1</sup>, K. Rigby<sup>1</sup>, <underline underline-style="single">K. Kulkarni</underline><sup>1</sup></p><p><italic><sup>1</sup>IWK Health Center, Pediatric Hematology Oncology‐ Department of Pediatrics, Halifax, Canada</italic></p><p><bold>Background/Objectives</bold>: Dysfunction (defined as inability to flush and/or draw blood) is common complications of central venous catheters (CVCs). Tissue plasminogen activator (tPA) is well demonstrated to reverse CVC dysfunction. However, the association between number of doses of tPA and requirement of CVCs is not clear. We hypothesized that requirement of an increasing number of doses of tPA are incrementally associated with requirement of CVCs in pediatric oncology patients.</p><p><bold>Design/Methods</bold>: Data was abstracted for all pediatric oncology patients from the 3 Maritime Provinces managed by the Izaac Walton Killam (IWK) Health Centre from January 2,000 to December 2,015 after institutional ethics approval. Patients who required ≥1 CVC were included. Data were combined from: (i) Pediatric oncology hospital database, (iii) Electronic medical records, (iv) Pharmacy database and (v) IWK central line database.</p><p><bold>Results</bold>: Of the study population (n=741) 26% (n=195) received ≥1 doses of tPA. Fiftyseven patients received ≥2 doses of tPA. The mean number of CVCs (2.05±1.29 per individual patient, 55% of the patients needed >1 CVCs) required by patients who received ≥1 dose of tPA was significantly higher than the mean number of CVCs (1.52±0.95 per individual patient, 32% needed more than 1 CVC) required by patients who did not receive tPA (p=0.0001). The mean number of CVCs (2.3±1.5 per individual patient, 60% needed more than 1 CVC) required by patients who received ≥2 dose of tPA was significantly higher compared to the remainder (1.6±1 per individual patient) (p=0.001).</p><p><bold>Conclusions</bold>: The present study demonstrates that patients requiring tPA for CVC dysfunction are at an incremental risk of requiring more CVCs based on the number of tPA doses. Our observations may indicate that requirement of tPA may identify patients at higher risk of CVC loss. After validation, this observation can aid in identification of high risk patients and designing strategies for mitigation of CVC loss.</p></sec><sec id="pbc26772-sec-8360"><label>P-430</label><title>The Feasibility of an Integrated Experiential Training Program with Coaching by Healthcare Professionals in Hong Kong Chinese Children with Cancer: A Phase II Study</title><p><underline underline-style="single">K.W.K. Lam</underline><sup>1</sup>, H.C.W. Li<sup>1</sup></p><p><italic><sup>1</sup>The Univeristy of Hong Kong, School of Nursing, hong kong, Hong Kong S.A.R</italic>.</p><p><bold>Background/Objectives</bold>: Literature review reflects children with cancer failing to attain the same physical activity levels that they had before contracting the disease. Scientific evidence supports that regular physical activity has beneficial effects, whereas physical inactivity induces a further increase in fatigue, muscle catabolism and atrophy. Nevertheless, increasing concern indicates the increased demand from families and children, posing specific challenges for implementing interventions during the unique intense treatment phase. This study aimed to examine the feasibility of an integrated experiential training program with coaching by healthcare professionals in promoting regular physical activity, reducing fatigue and enhancing quality of life among Hong Kong Chinese children with cancer.</p><p><bold>Design/Methods</bold>: A randomised controlled trial (RCT), two‐group pre‐test and post‐test, within and between subjects design was conducted. A total of 15 children with cancer (9‐ to 18‐year‐olds) was randomly allocated into the experimental group (N=8) and placebo‐control group (N=7). Each participant in the experimental group received home visits by a nursing student as a coach for 3 months. Those in the placebo control group received an amount of time and attention (home visits by research assistants) that mimics that received by the experimental group. The participants’ levels of cancer‐related fatigue, physical activity self‐efficacy, muscle strength, depression and quality of life were assessed at the time of recruitment and 3 months after. Semi‐structured interviews were also conducted.</p><p><bold>Results</bold>: No statistically significant result but positive trends were found among the outcome variables in the experimental group. Qualitative analysis also revealed that the informants were happy and satisfied to experience less fatigue, improvements in physical activity levels, self‐efficacy, muscle strength and mood. The integrated program was found to be feasible with no serious adverse effect.</p><p><bold>Conclusions</bold>: An integrated experiential training program with coaching by healthcare professionals was found to be feasible and safe among children with cancer.</p></sec><sec id="pbc26772-sec-8370"><label>P-431</label><title>Incidence and Prognosis of Septicemia after Chemotherapy: A Multicenter Acute Lymphoblastic Leukemia CCCG2015 Study</title><p>Y. Zhu<sup>1</sup>, <underline underline-style="single">C.K. Li</underline><sup>2</sup>, J. Tang<sup>3</sup>, X. Zhu<sup>4</sup>, J. Yu<sup>5</sup>, S. Hu<sup>6</sup>, H. Jiang<sup>7</sup>, C. Li<sup>8</sup>, X. Zhai<sup>9</sup>, X. Ju<sup>10</sup>, Y. Fang<sup>11</sup>, Q. Hu<sup>12</sup>, R. Jin<sup>13</sup>, X. Tian<sup>14</sup>, C. Liang<sup>15</sup>, N. Wang<sup>16</sup>, H. Jiang<sup>17</sup>, L. Sun<sup>18</sup>, K. Pan<sup>19</sup>, S. Shen<sup>3</sup></p><p><italic><sup>1</sup>Sichuan University west China second hospital, Hematology Oncology, Chengdu, China; <sup>2</sup>The Chinese University of Hong Kong, Paediatrics, Hong Kong, China; <sup>3</sup>Shanghai Jiaotong university school of medicine affiliated Shanghai children's medical center, Hematology Oncology, Shanghai, China; <sup>4</sup>Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Sciences Peking Union Medical College, Hematology Oncology, Tianjin, China; <sup>5</sup>Chongqing medical university affiliated children's hospital, Hematology Oncology, Chongqing, China; <sup>6</sup>Children's Hospital of Soochow University, Hematology Oncology, suzhou, China; <sup>7</sup>Guangzhou women and children health care center, Hematology Oncology, Guangzhou, China; <sup>8</sup>Southern medical university affiliated Nanfang hospital, Pediatrics, Guangzhou, China; <sup>9</sup>Children's hospital of Fudan university, Hematology Oncology, Shanghai, China; <sup>10</sup>Qilu Hospital of Shandong University, Pediatrics, Jinan, China; <sup>11</sup>Nanjing children's hospital affiliated to Nanjing medical university, Hematology Oncology, Nanjing, China; <sup>12</sup>Huazhong University of Science and Technology Tongji Medical college Tongji hospital, Hematology Oncology, Wuhan, China; <sup>13</sup>Huazhong University of Science and Technology Tongji Medical college union hospital, Pediatrics, Wuhan, China; <sup>14</sup>KunMing Children's Hospital, Hematology Oncology, Kunming, China; <sup>15</sup>Jiangxi provincial children's hospital, Hematology Oncology, Nanchang, China; <sup>16</sup>Anhui medical university second affiliated hospital, Pediatrics, Hefei, China; <sup>17</sup>Children's hospital affiliated to Shanghai jiaotong university, Hematology Oncology, Shanghai, China; <sup>18</sup>Qingdao university affiliated hospital, Hemnatology Oncology, Qingdao, China; <sup>19</sup>Xi 'an northwest women and children hospital, Hematology Oncology, Xian, China</italic></p><p><bold>Background/Objectives</bold>: Infection related mortality (IRM) is an important cause of treatment failure after chemotherapy. China Children's Cancer Group ALL2015 Study conducted a prospective multicenter clinical trial with chemotherapy stratified according to risk groups. This study aimed at analyzing incidence and prognosis of septicemia, and factors associated with IRM.</p><p><bold>Design/Methods</bold>: Regular reporting of adverse effects (AE) and serious adverse effects (SAE) are required, septicemia was pre‐defined AE and death as SAE. Annual audit of participating sites included random checking of septicemia episodes.</p><p><bold>Results</bold>: From 01/2015 to 12/2016, 2,543 subjects from 20 participating hospitals were recruited. A total of 290 patients (11.4%) were reported septicemia, male to female ratio was 55:45, median age 4 years. Timing of septicemia was induction 183 cases (63%), consolidation 36 cases (12.4%), interim maintenance/reinduction 71 cases (24.5%). Twelve patients died and IRM rate was 4.1% (12/290), 2 patients died during induction, 2 during consolidation and 8 during interim maintenance/reinduction. According to blood cultures, 50.2% were gram positive (Gpositive) (staphylococcus epidermidis 12.9%, staphylococcus aureus 4.9%, streptococcus pneumonia 3.4%, enterococcus 2.3%) and 47.5% were gram negative (Gnegative) (E Coli 12.6%, pseudomonas 8.8%, klebsiella pneumonia 8.4%, enterobacter cloacae 2.3%), 2.3% fungus (candida non‐albican). Among the 7 fatal cases, 5 were due to Gnegative and one due to Gpositive and one due to fungus). Interim maintenance/reinduction phase was associated with higher chance of IRM (P<0.05), there was no association with risk groups, gender and types of organisms.</p><p><bold>Conclusions</bold>: 11.4% of patients developed septicemia after chemotherapy, mortality rate was 4.1%. Early institution of broad spectrum during hospital stay at induction reduced IRM. Interim maintenance had higher IRM probably related to out‐patient management with possible delay in starting antibiotics. Gnegative septicemia had higher IRM. Education of parents and early attention for medical treatment during interim maintenance should be strengthened.</p><p>Supported by VIVA Children's Cancer Foundation (Hong Kong)</p></sec><sec id="pbc26772-sec-8380"><label>P-432</label><title>Feasibility and Experience with Ovarian Tissue Cryopreservation for Females Undergoing Gonadotoxic Treatment</title><p><underline underline-style="single">B. Lockart</underline><sup>1</sup>, K. Coyne<sup>1</sup>, T. Lautz<sup>1</sup>, M. Reimann<sup>2</sup>, M. Reynolds<sup>2</sup>, V. Scaccia<sup>1</sup>, K. Smith<sup>3</sup>, E. Rowell<sup>2</sup>, Y. Goseingfiao<sup>1</sup></p><p><italic><sup>1</sup>Lurie Children's Hospital, Hematology/Oncology, Chicago, USA; <sup>2</sup>Lurie Children's Hospital, Pediatric Surgery, Chicago, USA; <sup>3</sup>Northwestern University, Reproductive Medicine, Chicago, USA</italic></p><p><bold>Background/Objectives</bold>: Many children and adolescents diagnosed with cancer now survive into adulthood. With these improved outcomes, research demonstrates families are concerned about the impact of treatment on future fertility. In response to the increasing awareness of familial distress surrounding infertility from treatment, Ann & Robert H. Lurie Children's Hospital initiated a fertility preservation program in 2009. The program provides counseling, education, and fertility preservation to patients at risk for infertility due to cancer treatment or undergoing stem cell transplant for malignant and non‐ malignant conditions. Here, we report our experience with ovarian tissue cryopreservation (OTC) in patients receiving gonadotoxic treatment, including chemotherapy, radiation, or stem cell transplant.</p><p><bold>Design/Methods</bold>: We reviewed our data on the number of fertility preservation consults provided to female patients since the start of the fertility preservation program in 2009. Information on OTC performed at Ann & Robert H. Lurie Children's Hospital of Chicago from January 2010 to September 2017 is reported.</p><p><bold>Results</bold>: The number fertility preservation consults for female cancer patients increased annually from five in 2009 to 46 in 2016. Forty‐five females underwent OTC, with the number increasing from 3 in 2011 to 13 in 2016. The majority of patients underwent OTC prior to initiation of cancer treatment. Twenty‐four patients were pre‐pubertal (mean age 6.5 years, youngest patient five months of age) and 20 were post‐pubertal (mean age 15.2 years, oldest 22 years). No complications were noted after OTC. The number of tissue vials preserved range from four to 22. More tissue was preserved in post‐pubertal patients, than pre‐pubertal.</p><p><bold>Conclusions</bold>: Ovarian tissue cryopreservation is feasible in both pre‐ and post‐pubertal patients</p></sec><sec id="pbc26772-sec-8390"><label>P-433</label><title>Feasibility and Early Experience with Testicular Tissue Cryopreservation for Boys Undergoing Gonadotoxic Treatment</title><p><underline underline-style="single">B. Lockart</underline><sup>1</sup>, R. Brannigan<sup>2</sup>, K. Coyne<sup>1</sup>, E. Johnson<sup>3</sup>, T. Lautz<sup>4</sup>, M. Reimann<sup>5</sup>, E. Rowell<sup>4</sup>, V. Scaccia<sup>1</sup>, H. Valli<sup>6</sup>, K. Orwig<sup>6</sup>, Y. Gosiengfiao<sup>1</sup></p><p><italic><sup>1</sup>Lurie Children's Hospital, Hematology/Oncology, Chicago, USA; <sup>2</sup>Northwestern Medicine, Urology, Chicago, USA; <sup>3</sup>Lurie Children's Hospital, Urology, Chicago, USA; <sup>4</sup>Lurie Children's Hospital, Pediatric Surgery, Chicago, USA; <sup>5</sup>Lurie Children's Hospital, Pediaric Surgery, Chicago, USA</italic></p><p><italic><sup>6</sup>University of Pittsburgh, Magee Women's Research Institute, Pittsburgh, USA</italic></p><p><bold>Background/Objectives</bold>: Most children and adolescents diagnosed with cancer will survive into adulthood. With increased survival rates, research demonstrates that families are concerned about the impact of treatments on fertility. In response to increasing awareness of familial distress surrounding infertility from treatment, Ann & Robert H. Lurie Children's Hospital (LCH) initiated a fertility preservation (FP) service in 2009. The program provides counseling, education, and FP to patients at risk for infertility due to cancer treatment or undergoing stem cell transplant for malignant and non‐malignant conditions. In August 2015 LCH opened a testicular tissue cryopreservation (TTC) protocol. We aim to describe our early experience with TTC.</p><p><bold>Design/Methods</bold>: We reviewed our data on patients who underwent TTC at LCH from August 2015 to March 2017.</p><p><bold>Results</bold>: To date, 15 males (14 pre‐pubertal, 1 post‐pubertal) have undergone TTC at LCH. Mean age at TTC was 10.03 years (range 5 months to 18 years). Ten patients underwent TTC prior to initiation of cancer treatment. Testicular sperm extraction was attempted on two patients prior to TTC. Of the five patients who had received chemo, three were treated with 2.2 gr/m<sup>2</sup> or less of cyclophosphamide prior to TTC. Two patients received non‐gonadotoxic chemotherapy. Data on tissue yield was available for nine pre‐pubertal and two post‐pubertal patients. A mean of 11 vials of tissue per patient were obtained (range 4‐26). Undifferentiated spermatogonia stem cells were noted in all tissue. The testicular biopsy was well‐tolerated. One patient developed an incisional infection.</p><p><bold>Conclusions</bold>: Testicular tissue cryopreservation is safe and feasible in pre‐ and post‐pubertal males prior to and after initiation of chemotherapy. Viable undifferentiated spermatogonia stem cells were found in samples from all patients undergoing TTC at Lurie Children's Hospital.</p><p>Funds for testicular tissue processing and freezing were from the Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh.</p></sec><sec id="pbc26772-sec-8400"><label>P-434</label><title>Predictive Value of Procalcitonin and Interleukin‐6 for Bacterial Infection in Children with Cancer and Febrile Neutropenia</title><p><underline underline-style="single">E.A.H. Loeffen</underline><sup>1</sup>, H.T. van der Galiën<sup>1</sup>, W.J.E. Tissing<sup>1</sup></p><p><italic><sup>1</sup>University of Groningen‐ Beatrix Children's Hospital‐ University Medical Center Groningen, Department of Pediatric Oncology/Hematology, Groningen, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Only a third of children with cancer and febrile neutropenia have a bacterial infection, nevertheless standard care comprises hospitalization and intravenous antibiotics. Several biomarkers have been proposed as predictive markers for bacterial infection in this population. We aimed to evaluate the role of Interleukin‐6 (IL‐6) and Procalcitonin (PCT) in diagnosing bacterial infection in children with cancer and febrile neutropenia.</p><p><bold>Design/Methods</bold>: The study population was derived from a prospective database (2006‐2013, IL‐8 study) comprising children with cancer who presented with febrile neutropenia. From stored plasma samples (taken at admission and/or at 12‐24 hours) we determined the PCT and IL‐6 levels. Consequently, we explored their relation with presence of bacterial infection (positive blood culture, positive x‐thorax or clinical bacterial focus). We predefined cut‐off values, based on previous research, at 60 ng/L for IL‐6 and 0.25 ng/mL for PCT.</p><p><bold>Results</bold>: Seventy‐seven febrile neutropenic episodes in 55 children with cancer were included, in 18 episodes (23.4%) a bacterial infection was documented. Both at presentation and after 12‐24 hours, median values of IL‐6 as well as PCT were significantly higher in patients with a bacterial infection compared to patients without a bacterial infection. With both biomarkers above cut‐off values, sensitivity was 93% (with either one this was 100%). The identified low‐risk group comprised 41% of the population.</p><p><bold>Conclusions</bold>: PCT and IL‐6 are promising markers in identifying bacterial infection in children with cancer and febrile neutropenia. In a subsequent project, we will incorporate these biomarkers in a risk assessment model that we will test prospectively in a clinical trial.</p></sec><sec id="pbc26772-sec-8410"><label>P-435</label><title>Development of a Clinical Practice Guideline for Assessment, Prevention and Treatment of Pain in Children with Cancer: Phase 1</title><p><underline underline-style="single">E.A.H. Loeffen</underline><sup>1</sup>, A. Font‐Gonzalez<sup>2</sup>, R.L. Mulder<sup>2</sup>, L.L. Dupuis<sup>3</sup>, M.D. Van de Wetering<sup>2</sup>, L.C.M. Kremer<sup>2</sup>, F. Campbell<sup>4</sup>, W.J.E. Tissing<sup>1</sup>, O.B.O.T.G.W.G. Pain in Children with Cancer<sup>1</sup></p><p><italic><sup>1</sup>Beatrix Children's Hospital‐ University Medical Center Groningen‐ University of Groningen, Department of Pediatric Oncology/Hematology, Groningen, The Netherlands; <sup>2</sup>Emma Children's Hospital‐ Academic Medical Center, Department of Pediatric Oncology, Amsterdam, The Netherlands; <sup>3</sup>The Hospital for Sick Children, Department of Pharmacy and Research Institute, Toronto, Canada; <sup>4</sup>The Hospital for Sick Children, Department of Anesthesia and Pain Medicine, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: High‐quality evidence‐based guidelines for supportive care in children with cancer are needed. Pain in children with cancer has been identified as an area where many clinicians seek guidance. We aim to develop a clinical practice guideline (CPG) for pain in children with cancer with recommendations on 1) assessment of pain; 2) pharmacological prevention and treatment of a) tumor‐related pain, b) treatment‐related pain, and c) procedure‐related pain; and 3) physical and psychological prevention and treatment of a) tumor‐ and treatment‐related pain, and b) procedure‐related pain.</p><p><bold>Design/Methods</bold>: The international and inter‐professional guideline panel is comprised of a core group and six working groups and includes 44 individuals. In phase 1, clinical questions were formulated for each topic and prioritized (maximum 5 per working group) using GRADE methodology. The scope and possible outcomes for each clinical question were delineated. The critically important outcomes for decision making for each clinical question were then identified via electronic voting.</p><p><bold>Results</bold>: The six working groups prioritized a total of 25 clinical questions to be answered through systematic literature reviews. The number of critical outcomes differed per question, with a minimum of 4 and a maximum of 13.</p><p><bold>Conclusions</bold>: We have developed the framework for CPG development. In the next phase, systematic literature reviews will be undertaken and evidence‐to‐decision frameworks will be used to formulate recommendations. We expect to finalize the guideline in the spring of 2018.</p></sec><sec id="pbc26772-sec-8420"><label>P-436</label><title>Efficacy and Safety of Voriconazole Prophylaxis in Pedeatric Patients with Acute Myeloid Leukemia in Egypt</title><p>Y. Madney<sup>1,2</sup>, <underline underline-style="single">O. arafah</underline><sup>1,2</sup>, H. hafez<sup>1,2</sup>, L. Shalaby<sup>1,2</sup>, I. zaki<sup>1,2</sup>, H. El‐Mahalawy<sup>2</sup></p><p><italic><sup>1</sup>Children Cancer Hospital Egypt, Pediatric Oncology, Cairo, Egypt; <sup>2</sup>National Cancer Institute, Pediatric Oncology, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Patients with hematologic malignancies are at higher risk for invasive fungal infections (IFI) and the incidence of IFI is highest among patients with acute myeloid leukemia. Early detection and appropriate antifungal prophylaxis can help to decrease incidence of these infections and its related complications.</p><p><bold>Design/Methods</bold>: A double‐arms prospective and retrospective historical control arm study included 136 newly diagnosed Acute Myeloid Leukemia patients treated at the National Cancer Institute, Cairo university from 2011 to 2013. Prospective group (75 Patients) received primary voriconazole prophylaxis (prophylactic arm) and compared to 60 patients retrospective control (non prophylactic arm) regarding the infectious complications and incidence of fungal infection.</p><p><bold>Results</bold>: Median age was 5 ‐ 6 years. Almost all primary invasive fungal infections (IFI) occurred in lungs. Most of IFI occurred during induction phase of chemotherapy. Primary prophylaxis with voriconazole had highly statistically significant impact on reduction of incidence of invasive fungal infection between 2 groups (p value .001), 31 (50.8 %) of the 61 patients in non prophylactic arm and 5 (6.6 %) of the 75 patients enrolled in prophylactic arm developed invasive fungal infection. No statistically significant difference was detected between the 2 groups populations for age, gender, initial TLC, Initial monocytic count, risk stratification and previous hospitalization on incidence of invasive fungal infections. Fungal related mortality was reported in 8 patients /61 (13%) in non prophylactic arm compared to 2 patients/75 (2.6 %) in prophylactic arm. With median duration of follow up of 10 months, the overall survival and event free survival for the whole Group of patients at 3 years were 37.5% and 34.5% respectively. Voriconazole had an accepted toxicity profile.</p><p><bold>Conclusions</bold>: Anti fungal voriconazole prophyalaxis significantly reduce the incidence of fungal infections and fungal related mortality in pediatric acute myeloid leukemia patients However, its effect on overall survival is not as pronounced.</p></sec><sec id="pbc26772-sec-8430"><label>P-437</label><title>Impact of Antibacterial Levofloxacin Prophylaxis on Clinical Outcome and Blood Stream Infections during Treatment of Childhood Acute Myeloid Leukemia</title><p><underline underline-style="single">Y. Madney</underline><sup>1,2</sup>, O. arafa<sup>2</sup>, H. Hafiz<sup>1,3</sup>, I. zaky<sup>4</sup>, H. elmahalawy<sup>5</sup>, L. shalaby<sup>3</sup></p><p><italic><sup>1</sup>NCI, Pediatric Oncology, CAIRO, Egypt; <sup>2</sup>Children Cancer Hospital 57357, Pediatric Oncology, Cairo, Egypt; <sup>3</sup>Children Cancer Hospital 57357‐ Egypt, Pediatric Oncology, Cairo, Egypt; <sup>4</sup>Children Cancer Hospital 57357‐ Egypt, Radiology, Cairo, Egypt; <sup>5</sup>NCI, Clinical Microbiology, CAIRO, Egypt</italic></p><p><bold>Background/Objectives</bold>: Infections are important causes of morbidity and mortality in children undergoing antineoplastic chemotherapy especially Acute Myeloid Leukemia (AML) patients. The overall cumulative risk for bacteremia and invasive fungal infection (IFI ) increases during induction chemotherapy. Fluoroquinolones (FQLs) significantly reduced infection‐related mortality, fever, and clinically and microbiologically documented infections. However, the positive effect of antibiotic prophylaxis is associated with an increased risk of harboring FQLs‐resistant bacilli after treatment.</p><p><bold>Design/Methods</bold>: This is a comparative retrospective and prospective study that included 136 newly diagnosed Acute Myeloid Leukemia patients treated at the National Cancer Institute, Cairo University from 2011 to 2013. The prospective group (Group B) received primary Voriconazole and Levofloxacin prophylaxis and compared to the retrospective control(non prophylactic arm ) regarding the microbiological outcome and the correlation of bacteremia with IFI.</p><p><bold>Results</bold>: No statistically significant differences between both groups regarding rate of gram positive bacteremia (57.9 % in Group B, 58.6 % in group A, P value = 0.921) and gram negative bacteremia (38.9 % in Group B, 41.4 % in group A, P value = 0.7). Higher incidence of bacterial sepsis (50% in group B, 36 % in group A, P value .08) and bacterial sepsis released mortality (61% in group B, 36 % in group A, P value .07) seen in levofloxacin prophylaxis arm group.</p><p><bold>Conclusions</bold>: Levofloxacin prophylaxis was associated with increased bacterial sepsis episodes and bacterial sepsis mortality in our pediatric acute myeloid leukemia patients.</p></sec><sec id="pbc26772-sec-8440"><label>P-438</label><title>CT Somatom Force: A New First‐Line Modality to Investigate and Diagnose Chest Infections in Paediatric Oncology Patients</title><p><underline underline-style="single">M. Raju</underline><sup>1</sup>, S. Clarke<sup>2</sup>, C. Gowdy<sup>1</sup>, L. McDonald<sup>1</sup>, R. Skinner<sup>1</sup>, C.L. Chapple<sup>2</sup>, R. Hill<sup>3</sup></p><p><italic><sup>1</sup>Newcastle upon Tyne Hospitals, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom; <sup>2</sup>Newcastle upon Tyne Hospitals, Northern Medical Physics & Clinical Engineering, Newcastle upon Tyne, United Kingdom; <sup>3</sup>Northern Institute for Cancer Research, Wolfson Childhood Cancer Research Centre, Newcastle upon Tyne, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: The sensitivity and specificity of computer‐tomography (CT) imaging, as a diagnostic tool for investigating chest infections, is superior to plain chest x‐rays (CXR). However, greater radiation exposure, need for sedation and additional practicalities precludes the use of CT as a first‐line investigation. We investigated the clinical utility of, and radiation exposure resulting from, the new Siemens Somatom Force scanner.</p><p><bold>Design/Methods</bold>: We undertook a retrospective case‐review of patients with primary/relapsed acute leukaemia diagnosed after August 2012 (n=155), including 98 patients (63%) enrolled on the UKALL 2011 trial. Clinical episodes of suspected chest infections were defined as a febrile patient, investigated with CXR and CT chest. Radiological reports were reviewed, and radiation effective doses for each patient were estimated using conversion coefficients from the dose area product for CXR, and dose length product for CT.</p><p><bold>Results</bold>: Fifty‐nine separate episodes of CXR followed by CT chest were identified in 42/155 (27%) patients (median time between CXR and CT chest; 2 days, range 1‐15 days). Twenty‐one (36%) CT chests were performed on the Somatom Force scanner. CT imaging added clinically valuable information in 33/59 (56%) clinical episodes, and where data was available, subsequent treatment changes occurred in 17/41 patients (41.5%). Importantly, additional radiation delivered by the Somatom Force scanner following CXR was significantly less when compared to conventional CT (p<0.0001 unpaired t‐test; 0.89mSv mean, 0.04‐2.11mSv range versus 4.27mSv mean, 1.51mSv‐10.58mSv range, respectively).</p><p><bold>Conclusions</bold>: CT imaging provided treatment modifying information in >40% of acute leukaemia patients with suspected chest infections. The Somatom Force scanner enabled reduced investigation time, with significantly less radiation exposure compared to conventional CT. This versatile state‐of‐the‐art technology has clear potential as a first‐line investigation for chest infections in a selected population of immunocompromised patients, where early diagnosis and appropriately directed treatment may shorten hospital stay and improve outcomes.</p></sec><sec id="pbc26772-sec-8450"><label>P-439</label><title>A Study of Pediatric Cancer Patients Who Interacted with their School Through Information and Communication Technology (ICT) during Hospitalization: The Benefits of ICT Interaction</title><p><underline underline-style="single">T. Masako</underline><sup>1</sup>, S.I. Suenobu<sup>2</sup></p><p><italic><sup>1</sup>Oita University of Nursing and Health Sciences, Pediatric Nursing, Oita, Japan; <sup>2</sup>Oita University Faculty of Medicine, Pediatrics and Child Neurolgy, Yufu, Japan</italic></p><p><bold>Background/Objectives</bold>: This study focused on pediatric cancer patients who used ICT during long‐term inpatient care to communicate with their school and analyzed interviews with mothers to elucidate their experiences from hospital admission to re‐enrollment and the benefits of ICT interaction.</p><p><bold>Design/Methods</bold>: This study was conducted from Jan. 2012 to Oct. 2015. Participants were six mothers of children who underwent inpatient care for cancer and then re‐enrolled in their school. Three semi‐structured interviews lasting about 30 minutes each were held with each participant. The modified grounded theory approach was used for qualitative analysis. This study was approved by the research ethics committee of the hospital.</p><p><bold>Results</bold>: The analysis generated a total of 9 categories. The mothers talked about their [Confusion and difficulties at the time of hospital admission]. They were satisfied with the [Positive effects of the hospital school].For [Relations with the school], mothers consistently communicated with the school. Regarding [Effects of treatment], mothers described the stress of witnessing their child endure the consequences of chemotherapy. The [Benefits of interacting with the school] included interaction that instilled a daily routine that conformed to the school schedule. In [Assistance from nurses in preparation for re‐enrollment], mothers were satisfied with nurses’ joint conferences. [Mothers' concerns in anticipation of discharge] included worries about readjustment to school. [Support from the school] was generous in the sense that ICT interaction had prepared the school for the child's return and friends were cooperative in helping the child cope with school life. [Difficulties and responsibilities of mothers after discharge] included the difficulty of explaining their child's illness to others.</p><p><bold>Conclusions</bold>: The children's interactions with the school through ICT during hospitalization were a source of reassurance in the re‐enrollment process. ICT interaction was beneficial for the school because it helped prepare for the child's return.</p></sec><sec id="pbc26772-sec-8460"><label>P-440</label><title>Incidence of Central Line Associated Blood Stream Infections (CLABSI) in Peripherally Inserted Tunneled Central Venous Catheters (TCVL) Compared with Centrally Inserted TCVLS</title><p><underline underline-style="single">A. McCarthy</underline><sup>1</sup>, D.L. Spiers<sup>1</sup>, D.P. Moriarty<sup>1</sup>, V. Wallace<sup>1</sup></p><p><italic><sup>1</sup>Royal Belfast Hospital for Sick Children, Children's Oncology & Haematology, Belfast, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Central line associated bloodstream infection (CLABSI) is a frequent cause of morbidity in paediatric haematology‐oncology patients and is associated with significant healthcare costs. In our unit, single lumen tunneled central venous catheters (tCVC) are preferentially inserted into the brachial vein in the antecubital fossa. Traditionally placed central lines are utilised when an adequate vein cannot be found in the arm or when a multiple lumen line is required.</p><p><bold>Design/Methods</bold>: We aimed to (i) determine a baseline rate of CLABSI, (ii) to identify risk factors for infection and (iii) to examine the differences in rates of infection between insertion sites</p><p>A retrospective review of all patients with a tCVC inserted between 1<sup>st</sup> January 2009 and 31<sup>st</sup> December 2015 was undertaken. Infections were defined as possible, probable or definite, as per CDC guidelines. Logistic regression analysis was used to establish risk factors and Chi<sup>2</sup> tests to compare rates.</p><p><bold>Results</bold>: Out of 147 patients (mean age 6.5yrs; SD 4.5), 72 children had leukaemia and 75 solid tumours. Overall line infection rate was 0.65 per 1000 CVC days. Infection risk was higher in patients with haematological malignancy (OR 18.75; p<0.001) and with double‐lumen lines (OR 9.58; p<0.005). Subgroup analysis of children with single‐lumen lines and leukaemia showed a trend to lower rate of infection in arm lines (0.31 vs 1.03 per 1000 CVC days, p=0.06). No change in infection risk was seen with age, timing of insertion or neutropenia at time of insertion</p><p><bold>Conclusions</bold>: We observed a low rate of CLABSI. Risk factors for infection in our cohort were haematological malignancy and double‐lumen line. For single‐lumen arm lines, there was a very low rate of infection. Difference in infection rates with tCVC site has not previously been described, therefore prospective monitoring is required to explore this observation further.</p></sec><sec id="pbc26772-sec-8470"><label>P-441</label><title>The Use of Osteopathic Manipulative Treatment as a Preventive Supportive Care of Post‐Lumbar Puncture Headache: A French Pediatric Oncology Center Experience</title><p>C. Fort<sup>1</sup>, <underline underline-style="single">K. Michaux</underline><sup>1</sup>, I. Lucas<sup>2</sup>, A. Berthier<sup>2</sup>, P. Marec‐berard<sup>1</sup></p><p><italic><sup>1</sup>Institute of pediatric Onco‐Hematology IHOP, Pediatric Oncology, Lyon, France; <sup>2</sup>Institute of pediatric Onco‐Hematology IHOP, Institut supérieur d'osteopathie, Lyon, France</italic></p><p><bold>Background/Objectives</bold>: Post‐lumbar puncture headache (PDPH) is a frequent complication of lumbar puncture (LP) defined as postural headache occurring within 48 hours of the procedure and sometime accompanied by back pain, nausea, vomiting and dizziness. The leakage of cerebrospinal fluid through the dural defect produced by puncture is one of the etiologic hypothesis. Osteopathic Manipulative Treatments (OMT) on spinal column, in order to soften the dura mater before LP, could contribute to reduce symptoms.Our aim is to compare the incidence and severity of PDPH in children undergoing LP with or without preliminary OMT.</p><p><bold>Design/Methods</bold>: A prospective monocentric study included children undergoing LP for diagnosis or treatment from April to December 2016 in an oncologic unit. Every procedures were assigned with or without a preliminary OMT depending on the practitioners working day. Occurrence and duration of PDPH was assessed during 4 day by patient himself or family, using feedback form. Severity of symptoms was assessed by self‐administered visual analogical scales or hetero‐evaluation scales.</p><p><bold>Results</bold>: A total of 61 LP were studied (27 with OMT and 34 in the group control) on 45 children with a median age of 7 years [4‐12.25]. No difference was founded in PDPH incidence (70.4 % versus 70.5 %;p= 0,98). PDPH seemed to be less severe and shorter (37% of patients had back pain > 2 days without OMT versus 17.6% with OMT, p=0.087); and 14.8% had headache > 2 days without OMT versus 8.8% with OMT ; p=0.46). Dural and cranial dysfunctions were founded in more than 80% of cases.</p><p><bold>Conclusions</bold>: These results did not demonstrate a significant benefit in using OMT in prevention of PDPH, but a tendency to reduce intensity and duration of post LP symptoms. Dysfunctions were frequently observed in this population and OMT deserve to be better investigated as non‐pharmacologic supportive care in pediatric oncology.</p></sec><sec id="pbc26772-sec-8480"><label>P-442</label><title>Practical Support for Children Living with Cancer and Their Families: Increasing Adherance and Survival Rates</title><p><underline underline-style="single">L. Moore</underline><sup>1</sup></p><p><italic><sup>1</sup>CHOC Childhood Cancer Foundation SA, Gauteng South Region, Saxonwold, South Africa</italic></p><p><bold>Background/Objectives</bold>: A cancer diagnosis can cause financial stress to families and result in children not accessing health services at a paediatric oncology unit thus decreasing their chances of survival.</p><p>For 38 years, CHOC Childhood Cancer Foundation has been providing holistic care and support to children living with cancer and their families. Key to this is the successful implementation of a comprehensive practical support programme as a means of relieving the financial burden on a family, as well as increasing adherence to treatment cycles and increasing chances of survival.</p><p><bold>Design/Methods</bold>: Transport funds are issued daily to families from low‐income households. Alternatively accommodation is provided at CHOC houses for those who live very far. Both of these ensure that children can get to and from a treatment centre. Care bags containing toiletries, toys and a parent handbook are provided to families on admission to hospital. Information in the care bag guides parents through the treatment cycle and where to access relevant resources. On completion of a needs assessment families are provided with nutritional support in the form of a food parcel for when they return home.</p><p><bold>Results</bold>: Transport funds and accommodation play a significant role in ensuring adherence to and completion of treatment. Empowering families with knowledge helps them to better understand and cope with the arduous treatment cycle and therefore adhere to treatment. Food parcels ensure that children receive and maintain a healthy balanced diet during treatment. Anecdotal evidence and interviews with paediatric oncologists and CHOC beneficiaries from 5 different treatment centres in South Africa will be presented to show how practical support contributes towards increased adherence and chances of survival.</p><p><bold>Conclusions</bold>: Practical support, as part of a multidisciplinary approach to treatment, can reduce the financial burden placed on the family, increase adherence to treatment which can increase chances of survival for the child.</p></sec><sec id="pbc26772-sec-8490"><label>P-443</label><title>The Quest for Certainty Regarding Early Discharge in Paediatric Low Risk Febrile Neutropenia: A Multi‐Centre Focus Group Discussion Study Involving Patients, Parents, and Healthcare Professionals</title><p><underline underline-style="single">J. Morgan</underline><sup>1</sup>, R. Phillips<sup>1</sup>, L. Stewart<sup>1</sup>, K. Atkin<sup>2</sup></p><p><italic><sup>1</sup>University of York, Centre for Reviews and Dissemination, York, United Kingdom; <sup>2</sup>University of York, Department of Health Sciences, York, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: A recent systematic review found that outpatient care for children with low risk febrile neutropenia is safe, with low rates of treatment failure. A meta‐ethnography of qualitative studies suggested that early discharge of these patients may not be acceptable to key stakeholders. The current study aimed to explore experiences and perceptions of patients, parents and healthcare professionals involved in paediatric febrile neutropenia care in the United Kingdom.</p><p><bold>Design/Methods</bold>: Thirty‐two participants were included in eight focus group discussions in three different centres, purposively selected from a large national survey for differences in their service structure and febrile neutropenia management. Analysis was iterative, using a constant comparative method, with triangulation across centres and participant groups.</p><p><bold>Results</bold>: Participants described a quest for certainty, where they attempted to balance the uncertainty involved in understanding, expressing and negotiating risk with the illusion of certainty provided by strict protocols. Participants assessed risk using both formal and informal stratification tools, overlaid with emotional reactions to risk and experiences of risk within other situations. The benefits of certainty provided by protocols resulted in frustration at their strict constraints. The perceived benefits and harms of inpatient care that participants had previously experienced informed their appraisals of future treatment strategies. This work demonstrated how statistics identified in systematic reviews are interpreted and used by key stakeholders to assess risk differently, and how families in particular can view the harms of therapeutic options as different from the outcomes utilised within the literature.</p><p><bold>Conclusions</bold>: This study highlighted the previously underestimated harms of admission for febrile neutropenia and the paternalistic nature of decision making, along with the frustrations and challenges for all parties involved in caring for these children. It justifies a reassessment of current treatment strategies for these children and exploration of the introduction of shared decision making.</p></sec><sec id="pbc26772-sec-8500"><label>P-444</label><title>Etiology and Clinical Course of Pediatric Febrile Neutropenia in EL Salvador</title><p><underline underline-style="single">S. Mukkada</underline><sup>1</sup>, A. Rodriguez<sup>2</sup>, S. Fuentes Alabi<sup>3</sup>, R.F. Vasquez<sup>3</sup>, F. Marroquin<sup>3</sup>, E. Pineda<sup>3</sup>, P. Flynn<sup>1</sup>, H. Hakim<sup>1</sup>, M. Caniza<sup>1,4</sup>, R. Hayden<sup>2</sup>, G. Maron<sup>1</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Infectious Diseases, Memphis, USA; <sup>2</sup>St. Jude Children's Research Hospital, Pathology, Memphis, USA; <sup>3</sup>Hospital Nacional de Ninos Benjamin Bloom, Oncology, San Salvador, El Salvador; <sup>4</sup>St. Jude Children's Research Hospital, Global Pediatric Medicine, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Infection has been identified as one of the key drivers of morbidity and mortality in pediatric patients treated for cancer in low and middle income countries (LMIC). Identifying the causative organisms and clinical evolution of patients with febrile neutropenia has critical implications for empiric therapy in these settings however access to diagnostic testing, particularly for fungal and viral infections, is limited.</p><p><bold>Design/Methods</bold>: We prospectively ascertained the etiology and clinical outcomes of a group of pediatric cancer patients presenting with febrile neutropenia in El Salvador. Clinical, sociodemographic and laboratory predictors of adverse clinical outcomes were additionally collected.</p><p><bold>Results</bold>: We captured 240 febrile neutropenic episodes from November 2011 to June 2014. Patients were febrile prior to admission in 134 (56%) episodes; median delay to admission was 13.6 hours (IQR 7‐27 hours). Fever was categorized as being of unknown origin in 125 (52%) of episodes, with suspected or proven bacterial etiology in 30% (n=72), fungal in 3% (n=8), and viral etiology in 14% (n=34) of episodes. Microorganisms were recovered in 40 evaluable episodes, with bacteremia diagnosed in 22 episodes and a CVC associated bloodstream infection in 11 episodes. <italic>Escherichia coli</italic> was the organism most frequently isolated from blood culture (n=8), however, coagulase negative staphylococci were identified in 7 positive blood cultures. Mortality due to infection (n=1, 0.04%) and intensive care unit admission (n=12, 5%) were infrequent.</p><p><bold>Conclusions</bold>: In this LMIC setting, the etiology of febrile episodes is frequently unknown, however, morbidity and mortality are low, likely due to prompt empiric therapy. Increased access to diagnostic tests, particularly for viral and fungal organisms, may improve diagnostic precision, but their impact on clinical outcomes and resource use remains unknown. Further investigation, including cost effectiveness analyses, will be required to optimize management of febrile neutropenia in LMIC.</p></sec><sec id="pbc26772-sec-8510"><label>P-445</label><title>Identifying the Adverse Effects of Oncological Treatment in Pediatric Patients on Parents/Caregivers Perception: An Important Tool to Direct the Therapeutic Plan in Nutrition</title><p><underline underline-style="single">J. Nabarrete</underline><sup>1</sup>, A.P. Noronha Barrére<sup>1</sup>, M. Tanaka<sup>1</sup>, F. Lucio<sup>1</sup>, B. Laselva de Sá<sup>1</sup>, L.C. Almeida Silva<sup>1</sup>, S.M. Fraga Piovacari<sup>1</sup>, V. Odone Filho<sup>2</sup>, M. Nicastro<sup>1</sup></p><p><italic><sup>1</sup>Hospital Israelita Albert Einstein ‐ Centro de Oncohematologia, Serviço de Nutrição Clínica, São Paulo, Brazil; <sup>2</sup>Hospital Israelita Albert Einstein ‐ Centro de Oncohematologia, Medico Oncohematologista pediátrico, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: There are many symptoms that may contribute to decreased food intake during treatment, but not all of them distress the family of the same intensity. Outpatient follow‐up provides a greater moment to family participate in nutritional care. Identify which adverse effects are more impacting and which the better nutritional counseling in the management of them.</p><p><bold>Design/Methods</bold>: A prospective study was conducted in July 2015. Through a questionnaire applied to parents or caregivers when was investigated what symptoms impairs food intake of children and which nutritional counseling them prefer to be used to support the management of these symptoms.</p><p><bold>Results</bold>: A total of 19 questionnaires were answered, 68% were mothers, 16% were parents and 16% were other people. Among the most frequent diseases were 41% leukemia followed by 22.7% Lymphomas and 11% Non‐oncological diseases (e.g., Combined Immunodeficiency Syndrome). Decreased appetite was the symptom most cited (n=13), followed by nausea/vomiting (n=8), mucositis/pain at swallowing (n=7), dysgeusia (n=2), increased appetite (n=1) and alteration of the gastrointestinal tract (n=1). Individual verbal guidance was the nutritional counseling more mentioned, followed by practical nutrition workshop, written guidance and nutrition speeches. In addition, other forms of nutritional counseling were cited which the exchange of experiences between patients and the practical nutrition workshops for children. Guide on the inappetence, feeding in the phases of life and during the treatment and the presentation of recipes and menus appropriate to the age groups were suggestions of themes for news approaches to nutritional counseling.</p><p><bold>Conclusions</bold>: Decreased appetite is the most disturbing symptom during treatment and the best way to approach the management of nutritional therapy is individualized verbal guidance. This work was guiding the management of the diet plan in the oncopediatrics outpatient clinic, contributing to personalized and humanized care in Nutrition, involving and empowering patient/caregivers in the treatment.</p></sec><sec id="pbc26772-sec-8520"><label>P-446</label><title>Bacterial Infections in Children Treated for Cancer in South Africa</title><p><underline underline-style="single">G. Naidu</underline><sup>1</sup>, A. Izu<sup>2</sup>, R. Wainwright<sup>1</sup>, S. Poyiadjis<sup>1</sup>, D. MacKinnon<sup>1</sup>, B. Rowe<sup>1</sup>, S.A. Madhi<sup>3</sup></p><p><italic><sup>1</sup>University of the Witwatersrand and Chris Hani Baragwanath Academic Hospital, Paediatrics, Johannesburg, South Africa; <sup>2</sup>Medical Research Council, Meningeal and Respiratory Pathogens Research Unit, Johannesburg, South Africa; <sup>3</sup>Medical Research Council‐ Department of Science/ National Research Foundation: Vaccine Preventable Diseases‐ Faculty of Health Science‐ National Institute for Communicable Diseases‐ a Division of National Health Laboratory Service‐ Sandringham‐, Meningeal and Respiratory Pathogens Research Unit‐ University of the Witwatersrand, Johannesburg, South Africa</italic></p><p><bold>Background/Objectives</bold>: Introduction: Bacteria commonly cause infections in children with cancer. This is related to chemotherapy, stage of disease, immune dysfunction, neutropenia, malnutrition, surgery, and radiotherapy.</p><p>Aim: To prospectively delineate the bacterial epidemiology of infectious morbidity and mortality in children with cancer.</p><p><bold>Design/Methods</bold>: Methods: Febrile episodes in children treated for cancer were studied. A history, examination and a full blood count with differential and a blood culture was obtained.</p><p><bold>Results</bold>: Results 169 patients were enrolled, 82 (42.5%) with a haematological malignancy (HM) and 87 (51.5%) with a solid tumour (ST), 56.8% male, median age 68.5 months and 10.6% HIV‐infected. 77.5% had at least one microbiologically confirmed septic episode (MCSE), (87.8% HM vs 67.8% ST; p< 0.001) and 528 suspected septic episodes (SSE), with a mean of 3.1/patient (4 HM vs 2.3 ST; p<0.001). The incidence of Gram‐positive bacteraemia was (77.0 vs 43.7; p<0.001) and Gram‐negative bacteraemia was (74.5 vs 25.8; p<0.001) for HM and ST. The incidence of MCSE in children with high‐risk HM ((109) was 4.01 more than in medium‐risk HM (27; p<0.001). Children with metastatic ST had a higher incidence (71) of MSCE compared with localized ST (29; aOR: 2.49; p<0.001). Most children were severely malnourished (76.9% by MUAC and 56.8% by AMA). The most frequent GPB isolates were CONS (n=176; 59.1%), <italic>Streptococcus viridans</italic> (n=36; 12.1%), and <italic>Enterococcus faecium</italic> (n=27, 9.1%); and GNB isolates were <italic>Escherichia</italic> species (n=64; 26.9%) and <italic>Acinetobacter</italic> species (38; 16%), and <italic>Klebsiella</italic> species (28; 11.8%). There were 16.8 fungal MCSE/hundred child years, <italic>Candida albicans</italic> (n= 28; 62.2%) and <italic>Candida parapsilosis</italic> (n=12; 26.7%). Thirteen (7.6%) of the deaths were due to sepsis and all had a HM.</p><p><bold>Conclusions</bold>: Advanced disease (25% of ST and 61% of NHL had Stage 4 disease and 78% of children with ALL had high‐risk disease) and intensive treatment was independently associated with sepsis.</p></sec><sec id="pbc26772-sec-8530"><label>P-447</label><title>Evaluating the Effectiveness of Ketamine Plus Atropine as Anaesthesia for Intrathecal Chemotherapy and Bone Marrow Aspiration at Hospital, Vietnam</title><p><underline underline-style="single">H. Nguyen Thi Kim</underline><sup>1</sup>, H. Chau Van<sup>1</sup>, W. Kazuyo<sup>2</sup></p><p><italic><sup>1</sup>Hue Central Hospital, Hue Pediatric Center, Hue, Vietnam; <sup>2</sup>Asian Children Care's League ‐ Japan, CEO, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: Ketamine and atropine have increasingly been used in recent years as an effective form of deep sedation/anaesthesia in children in developed countries, but not in developing countries like Vietnam.</p><p>This pioneer trial aimed to evaluate the effectiveness of using ketamine plus atropine as anaesthetic agents for paediatric oncology procedures. From this study, we establish a protocol for anaesthesia in paediatric oncology procedures.</p><p><bold>Design/Methods</bold>: A descriptive and prospective study on 103 paediatric patients of both sexes (64 males and 39 females) aged 7 months to 14 years (median age: 4.0 ± 3.3 years) and with body weight between 4.5 to 40 kg was carried out from January 2015 to March 2017. The patients had been diagnosed with either acute lymphoblastic leukaemia or acute myeloid leukaemia. They underwent intrathecal chemotherapy and bone marrow aspirations for diagnostic as well as therapeutic purposes.</p><p><bold>Results</bold>: The total number of procedures was 381. Bone marrow aspiration was performed 163 times and intrathecal chemotherapy given 218 times. 99.7% procedures were successfully. The dose of ketamine and atropine used 1.83 ± 0.25 mg/kg and 0.100 ± 0.013 mg respectively. The time taken for anaesthesia to wear off was short: 8.5 ± 7.3 minutes. Only 0.26% experienced apnoea, hypotension; 3.1% convulsion; 0.9% nystagmus, and hyperactivity; 1.5% excess salivation, and dreaming; 3.2 % vomiting; none of the patients had laryngospasm or transient rash. Most of the patients’ parents were satisfied with the use of anaesthetics.</p><p><bold>Conclusions</bold>: This is a pioneer trial for children in Vietnam. 2 mg/kg intravenous ketamine and 0.1 mg atropine were found to be effective and suitable dose in children requiring deep sedation for painful procedures and produce only minimal side effects. We established a protocol with the above doses and continue to apply this in order to reduce pain, trauma, and complications and to practice safely.</p></sec><sec id="pbc26772-sec-8540"><label>P-448</label><title>Feasibility of Testing Physical Function in Children with Cancer during Intense Treatment in the Respect Study and Challenges in Clinical Practice</title><p><underline underline-style="single">M.K.F. Nielsen</underline><sup>1</sup>, J.F. Christensen<sup>2</sup>, K. Schmiegelow<sup>1,3</sup>, T. Thorsteinsson<sup>1</sup>, L.B. Andersen<sup>4,5</sup>, M. Faber<sup>1</sup>, J. Nersting<sup>1</sup>, H.B. Larsen<sup>1</sup></p><p><italic><sup>1</sup>Copenhagen University Hospital Rigshospitalet, Department of Pediatrics and Adolescent Medicine, Copenhagen, Denmark; <sup>2</sup>Copenhagen University Hospital Rigshospitalet, Centre of Inflammation and Metabolism / Centre for Physical Activity Research CIM/CFAS, Copenhagen, Denmark; <sup>3</sup>Institute of Clinical Medicine‐ Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark; <sup>4</sup>Norwegian School of Sport Sciences, Department of Sports Medicine, Oslo, Norway; <sup>5</sup>Campus Sogndal, Western Norway University of Applied Sciences, Røyrgata, Norway</italic></p><p><bold>Background/Objectives</bold>: Children with cancer exhibit reduced physical function during and following treatment. The “Rehabilitation including Social and Physical activity and Education in Children and Teenagers with Cancer” (RESPECT) study examines multimodal rehabilitation intervention initiated from diagnosis including physical activity intervention. Here we discuss feasibility and barriers of physical function evaluation.</p><p><bold>Design/Methods</bold>: Seventy‐five children (aged 6‐18 years [mean age: 11.3 ±3.1 y]), 61.3% boys diagnosed with cancer from the intervention group were included. At diagnosis and after three months, participants were scheduled to perform a test‐battery including timed up and go (TUG), sit‐to‐stand (STS), flamingo balance, handgrip strength, and cardiopulmonary exercise test (CPET) on a bicycle ergometer.</p><p><bold>Results</bold>: During the first 3 months 69 (92%) Of 75 children completed at least one test. Adherence rates were 66.7% for TUG, 71.3% for STS, 77.3% for balance and 80.7% for handgrip strength. CPET was associated with several barriers, and overall 25.3% of the tests were completed. Failure to complete CPETs was mainly (80.4%) due to medical restrictions (e.g. physician restrictions or side effects) with motivational and logistic reasons accounting for only 8 and 11.6%, respectively. In 607 completed tests one serious adverse event was observed, with one child who fainted briefly after CPET. Preliminary results show no change in VO<sub>2</sub>peak (mL/kg/min), and max watt (p>0.1). STS and balance trended to be impaired (P=0.07 and P=0.06 respectively) and a significant decrease in handgrip strength (p=0.03) and TUG (p=0.046) were observed.</p><p><bold>Conclusions</bold>: Evaluation of physical function in childhood cancer is safe and generally feasible and the children are motivated to participate. However strenuous tests such as CPET are accompanied by several barriers such as physician restrictions, side effects and logistic challenges. The preliminary results suggest that physical activity may prevent a further impairment of CPET during early treatment. Despite the intervention, strength and TUG declined.</p></sec><sec id="pbc26772-sec-8550"><label>P-449</label><title>Outcomes of Events to Support Pediatric Cancer Patients’ Siblings ‐ Through Collaboration with a Pediatric Hospital and Nursing University ‐</title><p><underline underline-style="single">J. Nonaka</underline><sup>1</sup>, S. Oka<sup>1</sup>, M. Yonayama<sup>1</sup>, M. Yamazaki<sup>1</sup>, K. Wada<sup>2</sup></p><p><italic><sup>1</sup>Kanagawa University of Human Services Faculty of Health & Social Work School of, Nursing, Yokosuka, Japan; <sup>2</sup>Nursing Care Children Fukushima Medical University School of Nursing, Nursing, Fukushima, Japan</italic></p><p><bold>Background/Objectives</bold>: This study examined the outcomes of sibling support events we held through collaboration with a hospital specializing in pediatrics and a nursing university.To examine the contents and outcomes of the events we held at a hospital specializing in pediatrics annually for 2 years to support pediatric cancer patients’ siblings.</p><p><bold>Design/Methods</bold>: Study design: A qualitative, descriptive study.</p><p>Data collection and analysis: The results of observation of siblings before and after the events, in addition to volunteers’ and families’ comments and impressions, were qualitatively and descriptively analyzed.</p><p>Ethical considerations: Before the start of each event were provided to obtain consent.</p><p><bold>Results</bold>: For the events, a sibling support program was developed upon deliberations among team members to clarify its purpose, particularly points to be conveyed and appropriate methods to convey them to siblings.The sibling support events mainly aimed to shine a spotlight on siblings, and provide them with an opportunity to express their emotions as a protagonist, and learn about a pediatric hospital through enjoyable play activities. The numbers of participants of the first and second events were 14 (8 males and 6 females) and 13 (3 males and 9 females), respectively, and their age ranged from 3 to 10 years. There were a total of 20 to 25 volunteers, including: nursing university faculty members and students; and CLS.</p><p><bold>Conclusions</bold>: Future challenges of sibling support:The sibling support program was mainly designed for relatively young children. Therefore, in the future, it may be necessary to: consider contents for other age groups, developmental tasks, and periods; use different media; and provide effective support in consideration of individual siblings’ situations. Furthermore, as a method to enhance their self‐affirmation and ‐efficacy, it may also be important to provide family support, and convey families’ message to siblings. In this respect, sibling support is likely to contribute to improved family functions.</p></sec><sec id="pbc26772-sec-8560"><label>P-450</label><title>Promoting Treatment Adherence Among Caregivers at the Paediatric Oncology Unit in a Teaching Hospital, Ghana</title><p><underline underline-style="single">P. Obeng</underline><sup>1</sup>, V. Paintsil<sup>1</sup>, J. Dogbe<sup>1</sup>, L. Osei‐Tutu<sup>1</sup>, B. Manlokiya<sup>1</sup>, C. Asiamah<sup>1</sup>, G. Acquah<sup>1</sup>, P. Yamoah<sup>2</sup>, A. Osei‐Nkrumah<sup>1</sup>, L. Adu‐Gyamfi<sup>1</sup>, R. Appiah<sup>1</sup>, A.A. Abruquah<sup>3</sup></p><p><italic><sup>1</sup>Komfo Anokye Teaching Hospital, Paediatric Oncology Unit‐ Child Health Directorate, Kumasi, Ghana; <sup>2</sup>Komfo Anokye Teaching Hospital, Department of Surgery, Kumasi, Ghana; <sup>3</sup>Kumasi Technical University, Faculty of Health‐ Department of Pharmaceutical Sciences, Kumasi, Ghana</italic></p><p><bold>Background/Objectives</bold>: Practical support bears the highest correlation with adherence. Studies suggest that structural or functional social support correlates with patient adherence to medical regimens. Caregivers of children with cancer may provide medical, financial, spiritual or physical support or a combination of all these to ensure their adherence to medications. The study objective was to find out the strategies adopted by caregivers to promote treatment adherence in paediatric oncology in Ghana to improve treatment outcomes.</p><p><bold>Design/Methods</bold>: The study was cross‐sectional prospective conducted at the Paediatric Oncology Unit (POU) at the Komfo Anokye Teaching Hospital (KATH), Ghana from October to December 2016. The POU serves about 30 patients every week. Fifteen patients out of 30 aged 12 years and below were recruited weekly for 10 weeks. A sample size of 150 was used for the study. Data on default, adherence and the strategies adopted by caregivers to improve treatment adherence were obtained after informed consent. Ethical approval was sought before the study was commenced.</p><p><bold>Results</bold>: Default rate was 98 (65.3%). Fifty‐two (34.7%) adhered to treatment of which 37 (71.2%) shared their strategies that enhanced treatment adherence.</p><p>The strategies for adhering to treatment from the caregivers perspective were financial and emotional support from family and friends 25 (67.6%), KATH POU 19 (51.4%), church 10 (27.0%) and colleague workers 8 (21.6%). Obtaining loans from banks 17 (45.9%), education and counseling from healthcare professionals at POU 8 (21.6%), motivation to save the children 7 (18.9%) and selling of property 5(13.5%) were also enumerated.</p><p><bold>Conclusions</bold>: Financial and emotional support, obtaining loans from banks, education and counseling from healthcare professionals at POU, motivation to save the children and selling of property are the strategies adopted by caregivers to promote treatment adherence. A further study on these strategies will inform outcome improvement interventions.</p></sec><sec id="pbc26772-sec-8570"><label>P-451</label><title>Risk Factors for Reluctance of Engagement in a Self‐Management Program Among Childhood Cancer Survivors</title><p><underline underline-style="single">M. Ogasawara</underline><sup>1</sup>, S. Saito<sup>2</sup>, A. Hayashibe<sup>1</sup></p><p><italic><sup>1</sup>Nagano Children's Hospital, Nursing, Azumino, Japan; <sup>2</sup>Nagano Children's Hospital, Hematology‐oncology, Azumino, Japan</italic></p><p><bold>Background/Objectives</bold>: The long‐term side effects in cancer survivors have been identified as a factor that reduces patient quality of life and potentially threatens survival. Accordingly, we have been conducting a self‐management transition program for childhood cancer survivors to provide a better understanding of their disease and the late effects related to treatment. Although the program teaches patients self‐management skills to become ready for care as adults, there has been difficulty with numerous patients due to reluctance to join. We therefore conducted a single‐institute study to investigate the causes of patient reluctance.</p><p><bold>Design/Methods</bold>: One hundred sixty‐six participants were recruited from Nagano Children's Hospital between June 2011 and March 2017. The inclusion criteria were: 1) discharge following intensive chemotherapy/radiotherapy for childhood cancer and 2) age >6 years and able to develop self‐management skills. Questionnaire surveys were conducted to determine patient reluctance to engage in the self‐management program and medical records were retrospectively analyzed for subject background. Statistical analysis was performed using the Χ<sup>2</sup> test or two‐tailed Fisher's exact test according to group size.</p><p><bold>Results</bold>: Of the 83 patients meeting the study inclusion criteria, 23 (28%) showed reluctance to engage in the program. Univariate analysis revealed that onset age <7 years (p<0.001), absence of guardian support (p<0.001), having received autologous stem cell transplantation (p<0.05), currently or with a history of receiving treatment related to late effects (p<0.01), embarrassment of physical condition (p<0.05), and cognitive or social development abnormality (p<0.05) were significantly associated with patient hesitance to participate in the self‐management program.</p><p><bold>Conclusions</bold>: Multiple risk factors contributed to patient reluctance of engagement in the self‐management transition program. Resolving these issues may improve patient compliance and facilitate the development of self‐management skills.</p></sec><sec id="pbc26772-sec-8580"><label>P-452</label><title>Potassium Supplementation and Corticosteroid‐Induced Neuropsychiatric Effects in Pediatric Oncology Patients</title><p><underline underline-style="single">H. Pariury</underline><sup>1</sup>, J. Willhoite<sup>1</sup>, J. Michlitsch<sup>1</sup>, A. Agrawal<sup>1</sup></p><p><italic><sup>1</sup>Childrens Hospital and Research Center Oakland, Pediatric Hematology Oncology, Oakland, USA</italic></p><p><bold>Background/Objectives</bold>: Glucocorticoids play an essential role in the treatment of multiple pediatric malignancies and are associated with an increase in behavioral disturbances. We aimed to investigate the efficacy of utilizing potassium chloride (KCl) supplementation to reduce corticosteroid‐induced neuropsychiatric effects among pediatric patients with acute lymphoblastic leukemia (ALL). Although utilized anecdotally at some institutions, no prior study has systematically reported data of potential therapeutic benefit.</p><p><bold>Design/Methods</bold>: The charts of pediatric patients with ALL who received KCl supplementation with the intent to reduce corticosteroid‐induced neuropsychiatric effects from 2012‐2016 were retrospectively reviewed, and those with baseline and follow‐up visits were analyzed. Primary outcome was the degree of behavioral disturbances pre‐ and post‐intervention, based on the subjective measure of the treating physician and parents.</p><p><bold>Results</bold>: Seventeen children were included with a median age of 5 years. 88.2% had pre‐B ALL and the majority were in maintenance therapy. Nine patients received dexamethasone; eight received prednisone. Patients received KCl, with a median dose of 0.53mEq/kg/day divided BID, in conjunction with days on corticosteroids. 76.5% of parents reported improvement in neuropsychiatric effects with KCl supplementation. No side effects were reported.</p><p><bold>Conclusions</bold>: Oral KCl supplementation appears beneficial in reducing corticosteroid‐induced psychiatric events in children with ALL, with no reported adverse effects. Other notable interventions for steroid‐induced neuropsychiatric symptoms include hydrocortisone and antipsychotics, medications with more potential secondary effects. Future prospective, randomized studies are necessary to better examine this effect with the goal of reducing the psychosocial impact of corticosteroids on patients and their families during ALL treatment.</p></sec><sec id="pbc26772-sec-8590"><label>P-453</label><title>Evaluation of Renal Function Using the Level of Urinary Neutrophil Gelatinase‐Associated Lipocaline is not Predictive of Nephrotoxicity Associated with Methotrexate‐Based Chemotherapy</title><p><underline underline-style="single">M. Pianovski</underline><sup>1</sup>, C. Almeida<sup>2</sup>, L. Litchvan<sup>1</sup>, D. Carmo<sup>1</sup>, T. Tormen<sup>1</sup></p><p><italic><sup>1</sup>Hospital Erasto Gaertner, Pediatric, Curitiba, Brazil; <sup>2</sup>Hospital de Clinicas ‐ HC/UFPR, Pediatric, Curitiba, Brazil</italic></p><p><bold>Background/Objectives</bold>: Methotrexate (MTX) is one of the most widely used anti‐cancer agents, and administration of high‐dose methotrexate (HDMTX) followed by folinic acid rescue is an important component in the treatment of a variety of childhood cancers. HDMTX can be safely administered to patients with normal renal function by the use of alkalinization, hydration and pharmacokinetically guided folinic acid rescues. Despite these measures, HDMTX‐induced renal dysfunction continues to occur. Prompt recognition and treatment of MTX‐induced renal dysfuntion are essencial to prevent potencially life‐threatening MTX‐associated toxicities, especially mucositis, myelosuppression and nephrotoxicity. Delay in the diagnosis of acute kidney injury (AKI) using convention biomarkers, like serum creatinine, has been one of the important obstacles in applying effective early interventions. Several new biomarkers are being evaluated in a quest for early diagnosis of AKI, among which neutrophil gelatinase‐associated lipocalin (NGAL) appears to be promising.This study evaluated and compared if urinary NGAL levels correlated with methotrexate induced nephrotoxicity.</p><p><bold>Design/Methods</bold>: Single‐center prospective study. Changes in serum creatinine and urinary NGAL were compared at 0 hour, 2 hours, 6 hours and 3 days after receiving HDMTX intravenous infusions.</p><p><bold>Results</bold>: Seventeen pediatric cancer patients receiving HDMTX chemotherapy were studied including 3 who developed injury, classified by <italic>Pediatric</italic><italic>Risk Injury Failure Loss End Stage Kidney (</italic>pRIFLE). No AKI was registered. Urinary NGAL did not increase during or after the HD‐MTX treatment.</p><p><bold>Conclusions</bold>: There was no AKI registered by pRIFLE criteria and so NGAL can not be used as an early biomarker for AKI in this situation.</p></sec><sec id="pbc26772-sec-8600"><label>P-454</label><title>Service Evaluation of the Clinical Value of Routinely Testing Stools for Rotavirus Antigen in a Regional Paediatric Oncology Unit</title><p>T. Akhtar<sup>1</sup>, J. Cargill<sup>2</sup>, C. Gerrard<sup>2</sup>, F. Shaw<sup>2</sup>, N. Cunliffe<sup>3</sup>, R. Cooke<sup>3</sup>, <underline underline-style="single">B. Pizer</underline><sup>1</sup></p><p><italic><sup>1</sup>Alder Hey Children's Hospital, Paediatric Oncology, Liverpool, United Kingdom; <sup>2</sup>Alder Hey Children's Hospital, Microbiology, Liverpool, United Kingdom; <sup>3</sup>Alder Hey Children's Hospital, Infectious Diseases, Liverpool, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Diarrhoea is common in paediatric oncology patients; caused by non‐infective or infective factors.</p><p>Rotavirus is historically the most common pathogen causing diarrhoea. However, although stool samples are commonly sent for virology, the value of testing in paediatric oncology patients with diarrhoea is unclear.</p><p>We conducted a service evaluation to estimate diagnostic yield of rotavirus testing in paediatric oncology patients. It was felt important to undertake this review following the introduction of UK‐wide rotavirus immunisation in July 2013.</p><p><bold>Design/Methods</bold>: Computerised microbiology records at Alder Hey Children's Hospital from January 2010 to December 2016 (seven years) were reviewed retrospectively to examine stool testing for rotavirus antigen detection in patents treated at a Regional Paediatric Oncology Unit. This review focused only on rotavirus, as testing for other viruses was not consistently undertaken. If repeat samples were submitted for testing within a two‐week period, it was assumed to be part of the same episode and testing was not performed.</p><p><bold>Results</bold>: A total of 1118 samples were reviewed. After rejecting repeat samples taken within two weeks, a total of 819 samples formed the basis for the analysis. Of these 819 samples, 46 (5.6%) were positive for rotavirus from a total of 38 patients (age 0‐19 years, 19 male; 19 female). The results by year (positives/numbers tested and percentages) were as follows: 2010 (15/141,10.6%), 2011 (10/143,6.9%), 2012 (6/132(4.5%), 2013 (8/158, 5.1%), 2014 (5/123,4.1%), 2015 (0/68,<0.1%), 2016(1/54,(1.9%).</p><p><bold>Conclusions</bold>: A comprehensive service evaluation of all stool tests performed for rotavirus performed in paediatric oncology patients during a 7‐year period has demonstrated that the incidence of rotavirus positivity has diminished since the introduction of rotavirus immunisation with only one positive test out of 122 samples in 2015/2016. Based on these results, we suggest there is very little utility for routine rotavirus testing in children and young people with cancer presenting with diarrhoea.</p></sec><sec id="pbc26772-sec-8610"><label>P-455</label><title>Invasive Fungal Infections in Hemato‐Oncology Pediatric Patients: A Eleven Year Review</title><p><underline underline-style="single">C. Mata Fernández</underline><sup>1</sup>, B. Ponce Salas<sup>1</sup>, H. Gonzalo Pascual<sup>2</sup>, E. Rincón López<sup>3</sup>, C. Garrido Colino<sup>1</sup>, B. Santiago García<sup>3</sup>, Y. Aguilar de la Red<sup>1</sup>, T. Hernández San Pelayo<sup>3</sup></p><p><italic><sup>1</sup>Hospital Gregorio Marañón, Pediatric Onco‐Hematology, 28009, Spain; <sup>2</sup>Hospital Gregorio Marañón, Pediatrics, 28009, Spain; <sup>3</sup>Hospital Gregorio Marañón, Pediatric Infectious Diseases, 28009, Spain</italic></p><p><bold>Background/Objectives</bold>: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in children with hematologic and malignant diseases.</p><p>Aim: To describe the epidemiology and outcome of IFIs in our hemato‐oncology unit during a eleven‐year period.</p><p><bold>Design/Methods</bold>: The medical records of pediatric patients admitted to our hemato‐oncology unit between 2006‐2016 with an IFI were reviewed. Clinical characteristics of mold and yeast infections, and their proportion over time were analyzed.</p><p><bold>Results</bold>: 24 patients were included (62.5% males, median age 6.2 [0.6‐11.9] years) in the study. Hematological malignancies were 41.7%, solid tumors 25%, and benign hematological conditions 29.2%% Overall, 31.7% of patients had undergone haematological stem cell transplant (HSCT),(90% allogenic), 20.8% had suffered graft versus host disease (GVHD),(60% acute), 45.8% of them were on antifungal prophylaxis (54.5% micafungin, 36.4% fluconazole).</p><p>Regarding outcomes, 33.3% needed PICU admission and 16.7% died.</p><p>Molds were the most common cause of IFI (62.5%, all bronchopulmonary disease), including 2 confirmed Aspergillus. Yeasts infections included 44.4% fungemias and 44.4% urinary infections, and were mostly caused by Candida albicans and Candida parapsilopsis. Patients with mold infections were older (9.32 vs 3.8 years; p=0.010), had higher initial PCR (8.85 vs 4.7mg/dl; p=0.016), higher incidence of HSCT (66.7% vs 0%;p>0.01) and GVHD (33.3% vs 0%;p=0.066), antifungal prophylaxis (73.3% vs 0%; p=<0.001), PICU admission (46.6% vs 11.1%,p=0.083) and mortality (26.7% vs 0%,p=0.066).</p><p>Comparing the first (2006‐2010, 12/24 patients) and second period (2011‐2015, 12/24 patients), the latter had an increased proportion of mold infections (33.3% vs 91.7%,p=0.007), which coincided with higher incidence of HSCT (25% vs 58.3%,p=0.225), GVHD (8% vs 33.3%,p=0.190), and antifungal prophylaxis (25% vs 66.7%,p=0.035).</p><p><bold>Conclusions</bold>: During the second period of time ( 2011‐2016) there has been an increased proportion of mold infections over yeast infections, with higher severity parameters, along with more intensive myeloablative chemotherapy regimens and an increased survival of these diseases in the last decades.</p></sec><sec id="pbc26772-sec-8620"><label>P-456</label><title>Prevalence of Malnutrition in Indian Children with Malignancies‐ A Retrospective Study</title><p><underline underline-style="single">P. Priya</underline><sup>1</sup>, A. Gupta<sup>1</sup>, R. Seth<sup>1</sup>, J. Sankar<sup>1</sup></p><p><italic><sup>1</sup>All India Institute Of Medical Sciences, Pediatrics, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Malnutrition is commonly seen in pediatric oncology patients particularly in resource poor countries.There is paucity of data on factors affecting nutritional status and treatment outcomes with malnutrition. The present study was done to estimate prevalence of malnutrition in children with malignancies, to ascertain the degree of malnutrition in hematological vs. non‐hematological malignancies,determine factors associated with malnutrition and follow malnourished children of various childhood cancer's for effect on final outcomes.</p><p><bold>Design/Methods</bold>: Retrospective review of records of children 6months to 15 years treated at the Oncology clinic at the All India Institute of Medical Sciences, a tertiary medical institute in India, between January 2014 to December2015 was done, Relevant data was retrieved and analysed. Children less than 6 months, with underlying genetic diagnosis/ Immunodeficiency,with associated malabsorption syndromes or chronic systemic diseases were excluded.</p><p><bold>Results</bold>: Total of 542(n=542) newly diagnosed children with malignancies were enrolled in the study period (M:F was 368:174). Children with Retinoblastoma constituted maximum number of patients (47%)followed by acute leukemia, lymphoma and others. Of the total, 36% children were underweight, 28% were stunted and 32% were wasted. Malnutrition in children with solid tumors was 37% and in children with hematological malignancies was 32% (p=0.27).45% children with advanced tumors were malnourished compared to 30% of children with early disease stage(p=0.001). Results were non‐ significant for effect of socioeconomic status and effect on treatment outcomes.</p><p><bold>Conclusions</bold>: Prevalence of malnutrition in various studies at diagnosis varied from 28‐36%. In our patients 36% children were underweight, 28% were stunted and 32% were wasted.Malnutrition is severe with advanced stage of the malignancies and also when there is lag period from onset of symptoms to starting treatment.Solid tumors are associated with greater degree of malnutrition. There is no significant effect of socioeconomic status on nutrition and there is no statistically significant effect of malnutrition on final outcomes.</p></sec><sec id="pbc26772-sec-8630"><label>P-457</label><title>Lifestyle Advice Provision to Teenage and Young Adult Cancer Patients: The Perspective of Health Professionals in the United Kingdom</title><p><underline underline-style="single">G. Pugh</underline><sup>1</sup>, R. Hough<sup>2</sup>, H. Gravestock<sup>3</sup>, A. Fisher<sup>4</sup></p><p><italic><sup>1</sup>University College London, Department of Behavioural Science and Health, London, United Kingdom; <sup>2</sup>University College Hospitals NHS Foundation Trust, Clinical Haematology, London, United Kingdom; <sup>3</sup>CLIC Sargent, Research and Policy, London, United Kingdom; <sup>4</sup>University College London, Department of Behavioural Health and Science, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: There are currently no health behaviour interventions available in the United Kingdom to support Teenage and Young Adult Cancer Survivors (TYACS) after a cancer diagnosis. Formative studies conducted by our group demonstrate that most UK TYACS desire age‐appropriate health behaviour information on physical activity, diet, smoking, alcohol consumption, and sun safety, delivered in multiple formats, at various time‐points throughout the cancer pathway. Health professionals were also identified as an important source of information for TYACS. However, little is known about health professionals’ provision of lifestyle advice to young people with cancer who are in their care.</p><p><bold>Design/Methods</bold>: An online survey was conducted to assess TYA health professionals awareness of lifestyle guidance and provision of lifestyle advice to TYACS in their care. Health professionals views on lifestyle information format and delivery were also explored.</p><p><bold>Results</bold>: Ninety‐five health professionals (44% nurses; 28% allied health professionals; 17% physicians) completed the survey. The majority (72%) of respondents were aware of some lifestyle guidance for cancer patients. However, less than half of TYA health professionals (46%) were able to successfully recall the source of the guidelines and less than a third (23‐27%) reported proving specific advice to the majority of their patients on some health behaviours. Many health professionals (38%) felt they were not the right person to provide advice and cited lack of resources as a key barrier to advice provision. The majority (95%) reported being interested in a resource containing relevant lifestyle information that could be given to young people with cancer.</p><p><bold>Conclusions</bold>: TYA health professionals’ awareness of lifestyle guidance and provision of advice regarding health behaviour is sub‐optimal. Clear and comprehensive guidance written specifically for TYA health professionals could overcome the reported barriers and improve professionals’ confidence in addressing and providing advice on lifestyle to young people with cancer.</p></sec><sec id="pbc26772-sec-8640"><label>P-458</label><title>Pain Experience Profile in Children with Cancer: Prospective Analysis of 2216 Treatment Days in a Developing Country</title><p><underline underline-style="single">K. Riad</underline><sup>1</sup>, M. Mohamed<sup>2</sup>, A. Morsy<sup>1</sup></p><p><italic><sup>1</sup>South Egypt Cancer Institute, pediatric oncology, Assiut, Egypt; <sup>2</sup>South Egypt Cancer Institute, Anesthesiology and Pain Management, Assiut, Egypt</italic></p><p><bold>Background/Objectives</bold>: Cancer in children is a potentially curable disease, How to deal with pain is an integral part of symptom management in pediatric cancer patients in general. Proper recognition of underlying pathophysiology and various causes of pain are so essential for pain management, and for ameliorating suffering in the realm of holistic care for children with cancer. The aim of this study is to address and meticulously analyze the spectrum of pain characteristics in children with cancer at an institutional university cancer center to unravel pain profile in these patients as an experience for a developing country</p><p><bold>Design/Methods</bold>: A hospital based, prospective study was conducted, involving pediatric cancer patients, who presented with pain due to cancer itself or its treatment in the period from 2013Jul to 2015 Jan. Evaluation of patients’ documented pain cycles for pain cause, type, and location & also for pain treatment characteristics was done.</p><p><bold>Results</bold>: A total of 286 pain cycles was documented comprising 2216 treatment days (range 3‐56 days). Disease‐related pain was the most frequent cause of pain in our study. Oral mucosa was the most frequent site for treatment‐related pain & strongly correlated with NHL diagnosis. Leukemia was strongly correlated with “the extremities” as a location of bone pain. Visceral pain was most often associated with lymphomas. Neuropathic pain was the least frequent type of pain, however, associated with higher initial pain intensity scores & longer pain cycle duration.</p><p><bold>Conclusions</bold>: Children with cancer in the developing countries still have more disease‐related pain than their counterparts in the developed countries. Pain experience may indirectly reflect presentations of childhood cancer, and could be a surrogate profile for tumor location, metastatic sites, the degree of treatment intensity, likewise the context of the disease state either at diagnosis, during treatment, or at progression.</p></sec><sec id="pbc26772-sec-8650"><label>P-459</label><title>Myocardial Changes in Childhood Cancer Patients Treated with Anthracyclines</title><p><underline underline-style="single">K. Riad</underline><sup>1</sup>, F. Ahmad<sup>2</sup>, R. Mohamed<sup>3</sup>, A. Ali<sup>1</sup>, A. Morsy<sup>1</sup>, H. Farghaly<sup>2</sup></p><p><italic><sup>1</sup>South Egypt Cancer Institute, Pediatric Oncology, Assiut, Egypt; <sup>2</sup>Children University Hospital, Pediatric Department ‐Cardiology Unite, Assiut, Egypt; <sup>3</sup>Assiut University Hospital, Clinical Oncology Department, Assiut, Egypt</italic></p><p><bold>Background/Objectives</bold>: Anthracycline‐induced cardiotoxicity in survivors of childhood cancer initially presenting as sub‐clinical cardiac abnormalities that, if left undetected or untreated, can lead to clinical cardiac dysfunction. The present study aimed to evaluate the early myocardial changes that develop with anthracycline therapy</p><p><bold>Design/Methods</bold>: In this prospective study the preanthracycline and 6‐months postanthracycline echocardiographic and electrocardiographic parameters were analyzed for cardiac dysfunction. The demographic information, including age, sex, type of anthracycline, and cumulative dose, were recorded, as well</p><p><bold>Results</bold>: In this study, 115 patients with childhood cancer, including 81 males (70.4%) and 34 females (29.6%) with the mean age of 11.1±3.8 years were enrolled. Their normal baseline and 6‐months postanthracycline echocardiographic and electrocardiographic parameters were compared for myocardial changes. Doxorubicin alone was used in 91 (79%) patients while daunorubicin alone in 24 (21%). Only 16 children (14%) received a high dose of anthracycline (cumulative dose > 300 mg/m2 ). QTc interval significantly prolonged 6‐months after chemotherapy than the baseline readings (P<0.001). There was a significant increase in the left ventricular dimensions, and all myocardial functional parameters were significantly deteriorated in children who received anthracycline (P<0.001). The incidence of cardiac dysfunction found more in female patients (20/28; 71.4%). Myocardial dysfunction was significantly higher among children who received a high cumulative dose of doxorubicin (P<0.001).</p><p><bold>Conclusions</bold>: The incidence of subclinical anthracycline‐related cardiac dysfunction is high. Children treated with anthracycline require a long‐term follow‐up to identify and establish optimal prevention and management strategies that balance oncologic efficacy with long‐term safety.</p></sec><sec id="pbc26772-sec-8660"><label>P-460</label><title>Correlation Between Multi‐Drug Resistant Organism Colonization and Blood Stream Infections in Children with Haematolymphoid Malignancies in a Low‐Middle Income Country</title><p><underline underline-style="single">N. Salifu</underline><sup>1</sup>, S. Desai<sup>1</sup>, B. Arora<sup>1</sup>, N. Periera<sup>1</sup>, M. Prasad<sup>1</sup>, G. Chinnaswamy<sup>1</sup>, T. Vora<sup>1</sup>, S. Biswas<sup>2</sup>, R. Kelkar<sup>2</sup>, G. Narula<sup>1</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Pediatric Oncology, Mumbai, India; <sup>2</sup>Tata Memorial Hospital, Microbiology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Colonization with multi‐drug resistant organisms (MDRO) is associated with a higher morbidity and mortality in children with cancer. The Expert Group of the 4<sup>th</sup> European Conference of Infections in Leukemia (ECIL4) developed guidelines for empirical antibiotic therapy in febrile neutropenic patients where ‘escalation’ or ‘de‐escalation’ strategies are employed based on colonization with drug‐resistant organisms among other factors. Our unit employed a “de‐escalation” policy based on colonization, due to a high incidence of MDRO blood‐stream infections (BSI). A retrospective audit of this practice was done to determine its usefulness.</p><p><bold>Design/Methods</bold>: Records from Jan‐2015 to Jul‐2016 were examined. Rectal swabs of all patients registered with haemato‐lymphoid malignancies were obtained within seven days of presentation. Blood cultures were taken during febrile episodes from peripheral veins. Central‐lines were also cultured, if present. Data was collated and analyzed with descriptive analytical tools.</p><p><bold>Results</bold>: Rectal swab positivity rate was 78.3% from 3,455 cultures. Incidence of MDRO and extended spectrum beta‐lactamase producing organisms (ESBLO) colonization in these was 32.0% and 36.6% respectively. Overall 6.63% of 4,490 blood cultures were positive. Paired positive rectal swabs with positive blood cultures were 253. MDRO colonization was seen in 90(35.6%) of the 253 culture pairs, while 95(37.5%) patients were colonized with (ESBLO). Forty‐six (51.1%) of patients with rectal MDRO colonization developed MDRO BSIs (p<0.05), while 12(13.3%) grew ESBLO. Significant association was also seen in 24(25.3%) patients colonized with ESBLO whose blood culture isolated organisms with same sensitivity (p<0.001). Thirty‐four (35.8%) patients colonized with ESBLO had BSIs with MDRO.</p><p><bold>Conclusions</bold>: There is a high incidence of MDRO and ESBLO colonization at presentation in pediatric hemato‐lymphoid malignancy patients at our center. In those developing BSIs with MDRO and ESBLO, baseline colonization status with these organisms was significantly correlated. A de‐escalation of antibiotics strategy would be justified in management of febrile neutropenia in our subject population.</p></sec><sec id="pbc26772-sec-8670"><label>P-461</label><title>The Utility of a Prognostic Scoring System in a Resource Limited Pediatric Oncology Setting: The Adaptation and Implementation of the Pediatric Early Warning Score</title><p><underline underline-style="single">H. Sankaran</underline><sup>1</sup>, V. Gopakumar<sup>2</sup>, P. Komoravolu<sup>1</sup></p><p><italic><sup>1</sup>Amrita Institute of Medical Sciences, Department of Medical Oncology, Ernakulam, India; <sup>2</sup>Amrita Institute of Medical Sciences, Department of Nursing, Ernakulam, India</italic></p><p><bold>Background/Objectives</bold>: The use of pediatric early warning score (PEWS) systems to identify deteriorating pediatric oncology patients in the developed world has been extensively studied and implemented. However, many PEWS systems are complex and difficult to implement in resource limited settings. A prospective study was performed to implement an adapted PEWS system and reduce pediatric code events.</p><p><bold>Design/Methods</bold>: Age‐dependent physiologic parameters and qualitative measures (heart rate, respiratory rate, respiratory distress, parental concern, comorbidity, oxygen need, consciousness) were used to design a PEWS system. The study period compared primary outcome measures 6 months before and after implementation of PEWS in October 2016. Primary outcome measures were defined as pediatric code events, and sepsis related ICU transfers for PEWS above 5. Sensitivity and specificity of the PEWS system were calculated at the end of the study period. Testing to determine health care provider recognition of abnormal age‐dependent physiologic parameters was conducted before and after implementation of the PEWS system.</p><p><bold>Results</bold>: 101 inpatient pediatric oncology admissions were available for analysis. Statistical significance could not be evaluated for the pediatric codes as after implementation there were no events compared to 4 events before implementation. The sensitivity of the PEWS system to identify patients requiring ICU admissions was 66.7% with a specificity of 100% using a PEWS cutoff of 4. Length of ICU stay significantly decreased (6.1 vs. 4.9 days, p=0.02) after implementation. Provider recognition of abnormal vital signs increased by 20% after implementation of the PEWS system.</p><p><bold>Conclusions</bold>: To our knowledge, this is the first PEWS system to be implemented in India. This study has demonstrated the feasibility and benefit of a PEWS system in the Indian environment. Further studies are being done decreasing the PEWS cutoff score to increase the sensitivity of this tool in our setting and making this generalizable to other hospitals in India.</p></sec><sec id="pbc26772-sec-8680"><label>P-462</label><title>Antibiotic Resistance in Paediatric Haematolgy and Oncology Patients –Glasgow Experience: Justification for Adding Aminoglycoside</title><p><underline underline-style="single">J. Sastry</underline><sup>1</sup>, I. Essa<sup>1</sup>, K. Harvey‐Wood<sup>1</sup>, A. Balfour<sup>1</sup></p><p><italic><sup>1</sup>Royal Hospital for Children, Haematology and Oncology, Glasgow, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Bacterial infections are a major obstacle to the treatment of febrile neutropenia in paediatric haemato‐oncology patients. Improvement in management strategies, including the use of broad‐spectrum antibacterial drugs targeting Gram‐negative bacteria, has reduced the mortality in neutropenic patients developing blood stream and other severe infections. However the development of multi‐resistant bacteria, such as<italic>pseudomonas aeruginosa</italic> and methicillin‐resistant <italic>Staphylococcus aureus</italic>, Vancomycin resistant enterococcus pose a major threat for such patients. This audit aims to determine the prevalence of antibiotic resistance in our unit, where first line agents used are Piperacillin and tazobactam(Tazocin) and gentamicin</p><p><bold>Design/Methods</bold>: We collected retrospectively, the results of microbiological tests from a variety of specimen including blood cultures and the sensitivities to various antibiotics of positive cultures, over a period of 22 months from January 2014 to October 2015. All paediatric haemato‐oncology patients admitted to the unit were included. The data was obtained from electronic records kept in the bacteriology department.</p><p><bold>Results</bold>: A total of 610 positive microbiological tests were noted during the audit period of which 207 showed resistance to one or more antibiotics (34%). 201 blood cultures were positive out of 2217 (9%). 88 of these had resistance to at least one drug (44%). A total of 126 positive cultures with sensitivity to Tazocin were recorded of which resistance was noted in 37(29%). 68 positive blood cultures had tazocin sensitivity reported of which 15 were resistant (22%). Meropenem sensitivity was reported in 121 positive cultures of which 22 were resistant (18%) Amikacin sensitivity was reported in 96 positive cultures of which 21 were resistant (22%).</p><p><bold>Conclusions</bold>: In view of the prevalence of high resistance to Tazocin, the addition of gentamicin is justified in our unit. Alternatively, single agent meropenem could be considered for those patients where gentamicin is contraindicated.Continued vigilance is essential to choose the appropriate empirical antibiotics</p></sec><sec id="pbc26772-sec-8690"><label>P-463</label><title>Prevalence of Fungal Infections in Paediatric Haemato‐Oncology Patients: Effectiveness of Selective Antifungal Prophylaxis, Glasgow Experience</title><p><underline underline-style="single">J. Sastry</underline><sup>1</sup>, L. Torrens<sup>1</sup>, K. Harvey‐Wood<sup>1</sup>, A. Balfour<sup>1</sup>, E. Davies<sup>1</sup></p><p><italic><sup>1</sup>Royal Hospital for Children, Haematology and Oncology, Glasgow, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Invasive fungal infections (IFIs) are an important concern in immunocompromised patients and treatment of these infections can be difficult once established. So emphasis has been placed on strategies of prevention, such as use of high efficient particulate air filter, isolation and use anti fungal prophylactic drugs. This audit was undertaken to study the prevalence of fungal infections among paediatric haemato‐oncology patients and to determine the effectiveness of unit's antifungal prophylaxis in preventing IFIs.</p><p><bold>Design/Methods</bold>: A retrospective audit involved all the immunocompromised patients treated in our unit with positive fungal culture or aspergillus PCR over a six month period between 1<sup>st</sup> February 2016 and 31<sup>st</sup> July 2016. The patients were identified using electronic databases from microbiology and virology department. A proforma was used to collect clinico‐pathological information from the hospital electronic patient records and case notes.</p><p><bold>Results</bold>: 107 positive fungal cultures and or aspergillus PCR tests were detected which translanted into 67 fungal infections from 42 patients (male 24, female 18). 62 of these were localised (muco‐cutaneous) and 5 were IFIs. 56 were candida (31 albicans, 9 parpsilosis, 6 lambica and 10 others), 3 saccharomyces, 1 aspergillus, 1 monilla and 6 yeast species. Specimen from where fungi were cultured or detected included surface swabs, urine, stools, blood and tissue. IFIs were noted in 3(7.5%) patients (lungs, blood and spleen). IFIs resulted in ICU admission, splenectomy, loss of CVAD and interruption of chemotherapy. 6 patients were on anti fungal prophylaxis and did not develop IFIs.</p><p><bold>Conclusions</bold>: Most fungal infections were superficial (muco‐cutaneous). IFIs were noted in minority of patients but resulted in adverse outcome. Children who were on anti fungal prophylaxis in this cohort, never developed IFIs although the number was small. Unit's antifungal policy needs to be aligned with international protocols, to prevent IFIs in those who are at significant risk.</p></sec><sec id="pbc26772-sec-8700"><label>P-464</label><title>Cost and Pattern of Use of Supportive Care for Pediatric Cancer Patients in Tanzania</title><p>M. Tesfaye<sup>1</sup>, A. Saxton<sup>2</sup>, M. Bhattacharya<sup>3</sup>, N. Masalu<sup>4</sup>, <underline underline-style="single">K. Schroeder</underline><sup>5</sup></p><p><italic><sup>1</sup>Duke University, Pediatric Hematology/ Oncology, Durham, USA; <sup>2</sup>Duke University, Surgery, Durham, USA; <sup>3</sup>Duke University, Medicine, Durham, USA; <sup>4</sup>Bugando Medical Centre, Oncology, Mwanza, Tanzania; <sup>5</sup>Duke University, Pediatric Hematology/ Oncology, raleigh, USA</italic></p><p><bold>Background/Objectives</bold>: Although supportive and preventive care play a crucial role in the successful management of childhood cancer, little is known about the use of these interventions in low resource settings and the costs associated with this treatment. This is essential information for the development of a pediatric cancer program. We examined the usage patterns and direct costs for supportive and preventive care for the treatment of children with cancer in Tanzania at the Bugando Medical Center, one of only two hospitals in the country treating pediatric cancer.</p><p><bold>Design/Methods</bold>: A retrospective chart review of hospital admissions and clinic visits from January 2010‐August 2014 was performed. Utilization and cost of preventive care (laboratory, imaging, and medications to evaluate and prevent chemotherapy toxicity) and supportive care (blood transfusions, antibiotics, and infection studies) were recorded. Conversions from the local currency (Tsh) to International Dollars (Intl. $) were performed. Tradable goods (i.e. medications) were converted using the prevailing exchange rate (2189.06Tsh/USD). Non‐tradable goods (clinical & lab supplies). were converted using purchasing power parity exchange rates obtained from the World Bank (779.205Tsh/Int $).</p><p><bold>Results</bold>: Files for 161 patients were available. For chemotherapy encounters, 82% had labs to monitor toxicity, 85% were prescribed anti‐emetics and only 27% received intravenous fluids. Only 25% of patients receiving cardio‐toxic chemotherapy had an echocardiogram. The mean cost incurred for preventive and supportive care was $153 and $43 per patient, respectively. Taken together, these accounted for less than 20% of total treatment costs.</p><p><bold>Conclusions</bold>: Our findings show that although there is a capacity to deliver supportive and preventive cancer care to pediatric patients in Tanzania, these services are not always routinely delivered to patients. The relatively low cost of these services demonstrate their merit to be included in pediatric cancer programs in low resource settings.</p></sec><sec id="pbc26772-sec-8710"><label>P-465</label><title>Use of and Beliefs About Integrative Medicine in a Pediatric Oncology Clinic: Parent and Adolescent/Young Adult Perspectives</title><p><underline underline-style="single">L. Schwartz</underline><sup>1</sup>, D. Henry‐Moss<sup>1</sup>, O. Natalie<sup>2</sup>, E. Butler<sup>1</sup>, P. Nirali<sup>1</sup>, L.P. Barakat<sup>1</sup>, M. Jun<sup>3</sup>, J. Tracey<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital of Philadelpia, Pediatrics/Oncology, Philadelphia, USA; <sup>2</sup>Philadelphia College of Medicine, Medicine, Philadelphia, USA; <sup>3</sup>Memorial Sloan Kettering Cancer Center, Integrative Medicine, New York, USA</italic></p><p><bold>Background/Objectives</bold>: Integrative Medicine (IM; e.g., massage, acupuncture, mediation, herbs) has been explored in adult oncology, but there is limited such research in pediatric oncology. Understanding use of complementary therapies in pediatric oncology, as well as beliefs, barriers, and support of IM, can help inform how these treatments are discussed with patients. We aimed to survey parents and adolescent/young adult patients (AYA) to gauge their use of and perspectives related to IM.</p><p><bold>Design/Methods</bold>: A convenience sample of patients 14‐24 yo and parents (not required to be matched dyads) provided information on demographics, treatment, and the use of and perceived benefit of 13 IM methods. The Attitudes and Beliefs about Complementary and Alternative Medicine (ABCAM) scale was used to rate expected benefits, perceived barriers, and subjective norms. Descriptive statistics were used to summarize scale scores and ratings of IM use. Chi‐squared and t‐tests were used to calculate relationships with IM use.</p><p><bold>Results</bold>: Parent participants (n=140) were 82% female, 70% non‐Hispanic white, and 81% had completed at least some college. Their children has Mage of 11 and 39% had completed treatment. AYA patients (n= 52) had a Mage of 19; 63% were male, 67% non‐Hispanic white, and 50% had completed treatment. Use of IM treatment since cancer diagnosis was 51% for parents and 60% for patients. Expressive arts therapy was the most commonly reported method among parents (26%) and patients (35%). Ratings of perceived benefit of IM were high. Parents endorsed wanting relaxation techniques for their children (79%); AYA patients were most interested in massage (64%). For parents, reporting IM use was associated with level of education (p=0.04) and subjective norm score (p=0.003). Benefits (p=0.001), barriers (p=0.02), and subjective norms (p=0.02) scores were associated with IM use for AYA patients.</p><p><bold>Conclusions</bold>: Use of IM is common in pediatric oncology and should be routinely discussed with patients.</p></sec><sec id="pbc26772-sec-8720"><label>P-466</label><title>Improving the Quality of Follow‐Up Care for Pediatric Cancer Survivors: A Mixed‐Methods Study on Preferences for Models of Survivorship Care</title><p><underline underline-style="single">C. Signorelli</underline><sup>1</sup>, C.E. Wakefield<sup>1</sup>, J.E. Fardell<sup>1</sup>, G. Michel<sup>2</sup>, J.M. Jones<sup>3</sup>, K.H. Turpin<sup>4</sup>, J. Emery<sup>5</sup>, J.K. McLoone<sup>1</sup>, R.J. Cohn<sup>1</sup></p><p><italic><sup>1</sup>Sydney Children's Hospital, Kids Cancer Centre, Randwick, Australia; <sup>2</sup>University of Lucerne, Department of Health Sciences and Health Policy, Lucerne, Switzerland; <sup>3</sup>Hudson Institute, Australian and New Zealand Children's Haematology/Oncology Group, Clayton, Australia; <sup>4</sup>Paediatric haematology/oncology, Department of Clinical Haematology/Oncology, Adelaide, Australia; <sup>5</sup>University of Melbourne, Victorian Comprehensive Cancer Centre, Melbourne, Australia</italic></p><p><bold>Background/Objectives</bold>: As the population of children surviving cancer grows, the importance of promoting essential, lifelong, survivorship‐focused care becomes critical. However, many survivors are disengaged from follow‐up care, mandating alternative models of care to encourage survivor engagement. To facilitate this, we explored survivors’ and parents’ preferences regarding the delivery of survivorship care.</p><p><bold>Design/Methods</bold>: Australian and New Zealand survivors and parents (of survivors aged less than 16 years) completed surveys and optional interviews on their follow‐up care preferences. We used multiple logistic regression to identify clinical/demographic associations with preferred survivorship care.</p><p><bold>Results</bold>: 403 survivors (mean age: 26.8years) and 207 parents (child mean age: 12.4years) completed surveys, complemented by 107 interviews. 46% of survivors were disengaged from care (not received cancer‐related care in last 2 years), and reported significantly greater dissatisfaction with the healthcare they were receiving (50% versus 16% of clinic attendees dissatisfied, χ2=43.529, <italic>p<0.001</italic>). Survivors preferred follow‐up clinic after‐hours (44.9%), and separate from pediatric patients (31.8%) and from patients on active treatment (27.2%). End of treatment, one, and five years post‐treatment completion were equally endorsed among survivors as the preferred timing to begin follow‐up care. Survivors’ treating oncologist was the most favored professional for follow‐up (62.5%), and primary care physicians were least preferred (10%). Survivors who were further from diagnosis (<italic>p=0.018</italic>), those who worried more about risk of recurrence (<italic>p=0.044</italic>), who reported fewer late effects (<italic>p=0.011</italic>) and had more unmet information needs (<italic>p=0.044</italic>) were more likely to prefer oncologist‐led versus primary‐ or nurse‐led survivorship care.</p><p><bold>Conclusions</bold>: Incorporating survivors’ preferences into future models of care may improve engagement in essential follow‐up, as well as satisfaction with care, ensuring survivorship needs are better met. This may help reduce the long‐term physical and psychosocial burden on survivors following treatment for pediatric cancer.</p></sec><sec id="pbc26772-sec-8730"><label>P-467</label><title>The Use of Complementary and Alternative Medicine Among the Pediatric Cancer Patients in Ankara University School of Medicine Pediatric Oncology Clinic</title><p>I. Bulut<sup>1</sup>, <underline underline-style="single">N. Tacyildiz</underline><sup>2</sup>, E. Unal<sup>3</sup>, H. Dincaslan<sup>4</sup>, G. Yavuz<sup>5</sup></p><p><italic><sup>1</sup>Ankara University Med School, Pediatrics, Ankara, Turkey; <sup>2</sup>Ankara Üniversity Faculty of Medicine, Pediatric Oncology, Ankara, Turkey; <sup>3</sup>Ankara University Med School, Pediatric Oncolgy, Ankara, Turkey; <sup>4</sup>Ankara University Med School, Pediatric Oncology, Ankara, Turkey; <sup>5</sup>Ankara University School Of Medicine ‐Ufuk University School of Medicine, Pediatric Oncology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: Complamantary Altarnative Medicine (CAM) is mostly traditional treatment modalities that most of the cancer patients may involve either informing their doctors or not. Since some of these treatment modalities may interfere with chemotherapy it is important to know if the patient is getting any of them.</p><p><bold>Design/Methods</bold>: Frequency and reasons of the use of CAM, types of CAM method, socio‐demographic characteristics of the patients that use CAM among the children that are being monitored with the diagnosis of cancer in Ankara University School of Medicine.</p><p>In this cross‐sectional study, between February‐November 2015, 139 pediatric cancer patients and their families were applied the survey form face‐to‐face when they are inpatient or outpatient clinic.</p><p><bold>Results</bold>: Mean age was 8.65±5.51(min:0.5,maks;18) years, 54.7% were male. The average age of patients which use CAM was 10.6±5.42, while mean age was 7.9±5.39(p<0.05) for didn't use CAM group. Patients with lower socio‐economic status were tend to use more CAM. Advanced staged patients were found to have increased frequency of the use of CAM. All patients participating this study have mentioned about praying. About 27% of the patients were using other CAM methods as well. The patients that used CAM mostly used honey (59.5%), bee pollen/milk (56.8%) and molasses (%45.9). Almost 38% of the families were found to have applied for religious help for their patients (Hodja reading holy passages which are believed to be beneficiary). About 38% of the patients using CAM have informed their doctor. The most common reason of not consulting to physicians was thought of possible rejection(78.3%).</p><p><bold>Conclusions</bold>: Most of patients are using CAM methods without the knowledge of physicians. None of the patients use CAM instead of medical treatment. All of the patients that admitted to hospital must be sufficiently informed,possible side effects of CAM and should given opportunity discuss with their doctors.</p></sec><sec id="pbc26772-sec-8740"><label>P-468</label><title>Improving Function in Pediatric Cancer Survivors: The Lasting Impact of the Stoplight Program</title><p><underline underline-style="single">L. Tanner</underline><sup>1</sup></p><p><italic><sup>1</sup>Children's Hospitals and Clinics of Minnesota, Physical Medicine and Rehabilitation Services, Minneapolis, USA</italic></p><p><bold>Background/Objectives</bold>: Survivors of pediatric acute lymphocytic leukemia (ALL) can have muscle strength deficits, symptoms of peripheral neuropathy, and range of motion limitations months to years after treatment. A proactive physical therapy intervention, The Stoplight Program (SLP) was implemented at a single institution with the goal of preventing and minimizing these deficits in body function and activity limitations. Children who completed the SLP during their ALL treatment tested within healthy norms for developmental age. In this follow‐up study, we continued to measure their function after treatment to evaluate the longer term impact of the SLP. The study objective was to measure body function and activity limitations in ALL survivors who completed the SLP and compare them to a historical control group of ALL survivors who completed their cancer treatment before the SLP was implemented</p><p><bold>Design/Methods</bold>: In this quasi‐experimental study, two cohorts of pediatric ALL survivors ages 5 to 18 years were assessed 18 to 24 months after completing ALL treatment. Measurements were administered by a physical therapist and included the Bruininks‐Oseretsky Test of Motor Proficiency and ankle range of motion (AROM). An independent‐samples t‐test was used to assess differences between groups and correlations were analyzed between AROM and motor tests results.</p><p><bold>Results</bold>: The historical control group and SLP intervention group did not differ significantly in mean age (9 years) or time off ALL treatment (20 months). The SLP group had significantly better AROM (p = .001) and scale scores for bilateral coordination (p = .05), running speed/agility (p = .01), and strength (p = .02). AROM had a positive correlation with survivors’ strength/agility percentile rank.</p><p><bold>Conclusions</bold>: The SLP is an innovative, proactive physical therapy intervention that continues to significantly impact children after ALL treatment. Creative approaches are needed to support the healthy development of children during and after cancer treatment.</p></sec><sec id="pbc26772-sec-8750"><label>P-469</label><title>Barriers to Effective Nursing Pain Management and Assessment of Children with Cancer on the Paediatric Oncology Unit, at the Korle‐Bu Teaching Hospital, Accra Ghana</title><p><underline underline-style="single">B. Tieku‐Ward</underline><sup>1</sup>, W. Eyiah‐Mensah<sup>1</sup></p><p><italic><sup>1</sup>Korle Bu Teaching Hospital, Department of Child Health, Accra, Ghana</italic></p><p><bold>Background/Objectives</bold>: The level of pain assessment and management among nurses is recently on the decline. This study sought to find out barriers to effective pain assessment and its management.</p><p><bold>Design/Methods</bold>: Ten nurses who are working at the pediatric oncology unit of Korle ‐Bu Teaching Hospital were randomly selected for this study.</p><p><bold>Results</bold>: Majority of the nurses, sixty percent was within the age bracket group thirty‐ one to fourty years. Eighty percent have obtained their bachelor's degree in nursing and majority has more than five years’ experience in oncology nursing. The research revealed that nurses are most abreast with the use of analgesics as pain management skills as to psychosocial and diversional therapy. Thus, unavailability of analgesics (morphine) because some parents cannot afford, is a barrier to effective pain management. Most often children are only assessed at the onset of their pain when they cry or verbalize it. Twenty percent of nurses noted that pain assessment tools are not readily available on the unit. Ninety percent of the nurses do not find the pain assessment procedure time consuming. Sixty percent perceive that the female patients exaggerate pain in order to get morphine, thus the fear for administering opioid. According to seventy percent of the nurses, doctors are not willing to prescribe morphine when suggested after a pain assessment and it is thus a barrier to further pain management and assessment.</p><p><bold>Conclusions</bold>: In conclusion, nurses need further education on early identification of pain in children and infants with cancer by the use of Behavioral Pain Assessment Scale (FLACC), since pain is effectively managed when detected early, as well as, to assess and manage pain consistently on the ward. Funds should be raised to support parents in purchasing morphine. Diversional therapy activities like puzzle games is encouraged in the unit.</p></sec><sec id="pbc26772-sec-8760"><label>P-470</label><title>Validation of the Oncological Pediatric Early Warning Score (O‐PEWS) on Critical Patients with Haemato‐Oncological Diagnosis</title><p><underline underline-style="single">A. Tondo</underline><sup>1</sup>, C. Rosa<sup>1</sup>, F. Melosi<sup>1</sup>, C. Favre<sup>1</sup>, C. Cecchi<sup>1</sup>, F. Trevisan<sup>1</sup>, V. Bertozzi<sup>1</sup></p><p><italic><sup>1</sup>Universita degli Studi di Firenze, Pediatric Oncology and Hematology Unit, Firenze, Italy</italic></p><p><bold>Background/Objectives</bold>: Patients with oncological‐haematological diagnosis are subject to potentially fatal complications. In the last years a scoring system has been developed, based on rapidly assessable clinical parameters, called Pediatric Early Warning Score (PEWS), to detect critical events in a timely manner and rapidly activate the emergency team. This study aims at finding an adaptation of this system for the pediatric patients with haemato‐oncological diagnosis, called Oncolgical‐PEWS (O‐PEWS), and evaluate its accuracy in reflecting the level of clinical impairment of the observed patients.</p><p><bold>Design/Methods</bold>: We modified the PEWS in order to include clinical parameters that reflect the neurocognitive, cardiovascular, respiratory and urinary state of the pediatric patients with haemato‐oncological diagnosis. A retrospective pilot study has been conducted on twenty‐six patients that required admission in the Pediatric Intensive Care Unit (PICU), measuring the O‐PEWS scores at admission and correlating those scores with the outcome.</p><p><bold>Results</bold>: The patients that were admitted in the PICU with a lower score (average O‐PEWS = 7/15) reached a better outcome. The survival rate proved lower (31% vs 69%) in patients with higher score at admission (average O‐PEWS = 9/15), correlating with negative prognostic factor such as use of mechanic ventilation and ultra‐filtration.</p><p><bold>Conclusions</bold>: This pilot study demonstrated that the Oncological‐PEWS is capable of predicting the clinical seriousness of the pediatric patients with haemato‐oncological diagnosis. We are now conducting a perspective multicenter observational study aiming at a more consistent validation of the O‐PEWS and of its ability of precociously identify all those patients that require an emergency consult and a potential take on responsability of the patient by the PICU.</p></sec><sec id="pbc26772-sec-8770"><label>P-471</label><title>Alternative and Complementary Medicine Use Among Pediatric Patients with Oncological Diseases in a Latinamerican Country</title><p><underline underline-style="single">M. Velazquez‐avina</underline><sup>1</sup>, A. Chena‐Sánchez<sup>1</sup>, J. Peñaloza‐González<sup>1</sup></p><p><italic><sup>1</sup>Hospital Juárez de México, Pediatric Oncology, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: Alternative/Complementary Medicine (ACM) refers to medical practices that are not in accordance with the standards of the medical community. ACM use is frequently used by patients with chronic or catastrophic diseases, but the treating physician ignores its use. The reported frequency of use in Mexico ranges from 30% to 84% according to various surveys.</p><p><bold>Design/Methods</bold>: We included patients from the Pediatric Oncology Service at our institution who had been receiving treatment for at least three months. A structured questionnaire was administered in person by a single interviewer (pediatric oncologist). We recorded the cancer type, ACM used, and parent/guardian age, and education level. We present descriptive statistics of the sample and clinical findings as means ± standard deviation, and proportion comparisons with Pearson's chi‐square test.</p><p><bold>Results</bold>: Of the 133 parents interviewed, 84.2% used some form of ACM. Herbs and minerals were the most frequently used (35.3%), followed by diet and nutrition (25.6%) and mind, body, and spirit (19.5%) therapies. The most frequent cancers were hematological malignancies in a proportion 3:1 versus solid tumors. The parents education level was not associated with more frequent ACM use, nor did mother's age. Father's age was significantly related to more frequent ACM use, especially if they were 40 years‐old or older.</p><p><bold>Conclusions</bold>: Our study population used very frequently ACM as an adjuvant therapy, in both, hematological and solid tumors. No subject attempted to abandon conventional treatment and rely solely on ACM. This study may lead to further studies that assess the results obtained from patients receiving ACM.</p></sec><sec id="pbc26772-sec-8780"><label>P-472</label><title>Infectious Disease Agents in Febrile Neutropenia in Patients with Childhood Cancer at a National Refrence Hospital</title><p><underline underline-style="single">M. Velazquez‐avina</underline><sup>1</sup>, M. Huitrón‐Hernández<sup>1</sup>, J. Peñaloza‐González<sup>1</sup></p><p><italic><sup>1</sup>Hospital Juárez de México, Pediatric Oncology, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: Approximately 80% of patients with childhood cancer and chemotherapy treatment will have an episode of febrile neutropenia (FN). The percentage of positive blood cultures is correlated with the risk of overall infection.</p><p>The purpose of the present study is to describe the percentage of positive blood cultures and the infectious disease agent.</p><p><bold>Design/Methods</bold>: We reviewed all blood cultures of patients with childhood cancer from August 2015 to December 2016 at our institution. We described percentages of negative or positive blood cultures and identified the disease agent in case of positive testing.</p><p>The demographic and clinical characteristics are described as means or proportions according to variable type.</p><p><bold>Results</bold>: We included 171 blood cultures. The patient average age was 10.4 years. In 52% of the cultures the result was negative, and 48% were positive. Fifty‐one percent of our patients were female and 49% were male. According to the type of cancer, high‐risk acute lymphoblastic leukemia represented 42.1% of our population, osteosarcoma 22.8%, 9.9% germ cell tumors and the rest were patients with Hodgkin disease and rhabdomyosarcoma.</p><p>Gram positive bacteria were isolated in 53.9% of positive cultures, and Gram negative bacteria in 46.1% of positive cultures. The most frequent Gram positive bacteria was <italic>Staphylococcus epidermidis</italic> followed by <italic>Staphylococus aureus</italic> and <italic>Staphylococcus hominis</italic>. The most frequent Gram negative bacteria was <italic>Escherichia coli</italic> followed by <italic>Klebsiella pneumoniae</italic>, and <italic>Acinetobacter baumanii</italic>. Gram positive bacteria were more frequently isolated in female patients, whereas Gram negative bacteria were most frequently isolated in male patients.</p><p><bold>Conclusions</bold>: The percentage of positive blood cultures in our practice is relatively high compared to other series. The most frequent infectious disease was a Gram positive agent. Although not statistically significant, we found a difference of disease agent according to gender.</p></sec><sec id="pbc26772-sec-8790"><label>P-473</label><title>Nutritional Status of Children with Cancer at Diagnosis in Brazil</title><p><underline underline-style="single">K. Viani</underline><sup>1</sup>, M. Neto Rafael<sup>1</sup>, G. Bouchabki<sup>1</sup>, A.C. Oliveira<sup>1</sup>, B. Manzoli<sup>1</sup>, V. Oliveira<sup>1</sup>, E. Ladas<sup>2</sup>, R. Barr<sup>3</sup>, V. Odone Filho<sup>4</sup></p><p><italic><sup>1</sup>Instituto de Tratamento do Câncer Infantil ITACI‐ Hematology‐Oncology Division ‐ Instituto da Criança do Hospital das Clínicas‐ Sao Paulo University Medical School, Nutrition, Sao Paulo, Brazil; <sup>2</sup>Columbia University, Division of Pediatric Hematology/Oncology/Stem Cell Transplant, New York, USA; <sup>3</sup>McMaster University and McMaster Children's Hospital‐ Hamilton Health Sciences, Department of Pediatrics, Hamilton, Canada; <sup>4</sup>Instituto de Tratamento do Câncer Infantil ITACI‐ Hematology‐Oncology Division ‐ Instituto da Criança do Hospital das Clínicas‐ Sao Paulo University Medical School, Department of Pediatrics, Sao Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: The relationship between nutritional status (NS) at diagnosis and survival in pediatric oncology has been described by several authors. Considering the overall importance of NS in these patients, the objectives of this study were: to determine the NS of children with cancer at diagnosis; compare the NS between patients with solid tumors (ST), hematological malignancies (HM) and central nervous system tumors (CNST); and compare the NS distribution by two different anthropometric parameters.</p><p><bold>Design/Methods</bold>: This is a retrospective cross‐sectional study. Data on weight, height and mid‐upper arm circumference (MUAC) measured within 7 days of diagnosis were collected from the nutrition service records of a hospital in Sao Paulo, Brazil. For comparison, NS was classified by both body mass index z scores (BMIz), using WHO growth charts, and MUAC percentiles. NS classifications by BMIz and MUAC were compared using the Chi‐square test.</p><p><bold>Results</bold>: We included 370 patients in the study, mean age 7.8(±5) years. The diagnoses distribution was: 56.5% (n=209) HM, 27.8% (n=103) ST and 15.7% (n=58) CNST. Overall, according to BMIz, 14% patients were below adequate, 79.8% adequate and 6.2% above adequate, whereas MUAC percentiles classified 12.4% as below adequate, 78.3% adequate and 9.32% above adequate, without statistical difference between the anthropometric parameters (p=0.726). Regarding patients with HM, ST and CNST, the groups were equivalent by BMIz (p=0.142). However they differed in MUAC percentiles (p=0.006). Although HM presented no divergence between BMIz and MUAC (p=0.698), more children with ST were under‐nourished by MUAC (24.7%) than BMIz (15.6%), p=0.075, while the reverse was true for CNST (MUAC 7.8%, BMIz 21.8%, p=0.011).</p><p><bold>Conclusions</bold>: The undernutrition prevalence in our study was 2 to 3 times higher than in the general population of Brazilian children/adolescents, especially in patients with ST and CNST. MUAC appears more sensitive than BMIz as indicator of undernutrition at diagnosis for patients with ST.</p></sec><sec id="pbc26772-sec-8800"><label>P-474</label><title>Screening of Vitamin D Deficiency in Children with cancer. Cause or Just a Consequence of Malignancy? L.P. Xalafova, R.S. Ismayilzade National Center of Oncology (NCO) of Azerbaijan</title><p><underline underline-style="single">L. Xalafova</underline><sup>1</sup>, R.S. Ismayilzade<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Clinic of the National Center of Oncology (NCO) of Azerbaijan, Baku, Azerbaijan</italic></p><p><bold>Background</bold>: Recent studies have identified an important function of vitamin D (VD) in regulation of cell proliferation and differentiation, and apoptosis. In addition vitamin D deficiency (VDD) has been linked to an increased cancer risk, prompting us to screening of VDD in children with cancer.</p><p><bold>Procedure</bold>: From 06.02.2015 to 28.02. 2017(24 months) in our center a survey was done of 191 children. Level of VD, age, sex, time of sampling and presence of malignant tumor were determined.</p><p>25‐hydroxyvitamin D (25‐OH‐D) concentrations in the serum were measured in all patients at the time of diagnosis and during treatment and levels were categorized as normal (>=30ng/ml), insufficient (20‐29ng/ml), or deficient (<20ng/ml). The timing of sample collection was classified into four seasons. The age ranged from 4 months to 21 years.</p><p><bold>Results</bold>: We evaluated a total of 191 patients for this study: 131(68.57%) had a diagnose malignancy and 60(31.41%) had non‐malignant disorders (NMD). VDD was detected in 101(77.1%) of the patients with malignancy. Particularly alarming was the fact that VDD in 14(13.86%) patients was detected prior to the start of treatment. VDI was identified in 19 cases (14.5%), and normal levels had only 11 patients (8.4%).The boys 59(58.42%) prevailed over girls 42(41.58%). More than 50% of VDD were determined in children aged 7‐15 years (54.46%). In 60 children with NMD VDD was determined in 32(53.33%) and VDI in 14(23.33%) cases.</p><p><bold>Conclusion</bold>: Azerbaijan is a country with 2700 sunny hours/year. Despite this, we discovered VDD cases in 77.1% of pediatric cancer patients and 53.33% of children with NMD in our survey. Further research is needed to determine whether the VDD is a cause of malignancy or just a consequence of it. Our study supports intake of vitamin D for possible prevention of cancer in children.</p></sec><sec id="pbc26772-sec-8810"><label>P-475</label><title>Verification of the Knowledge of Dietary Therapy of the Care Team: A Strategy of Continuing Education for a Pediatric Oncology Hospital</title><p><underline underline-style="single">L. Xavier Del Rio</underline><sup>1</sup>, M. Santos Murra<sup>2</sup>, N. Duran Leite<sup>2</sup></p><p><italic><sup>1</sup>Barretos Cancer Hospital, Nutrition, Franca, Brazil; <sup>2</sup>Barretos Cancer Hospital, Nutrition, Barretos, Brazil</italic></p><p><bold>Background/Objectives</bold>: There are many questions related to nutrition in the clinical practice of the multidisciplinary team. Investigating doubts and implementing interventions could be ways to address uncertainties and minimize errors related to nutritional support. The aims of the study was to investigate, evaluate and describe the knowledge related to nutrition in the nursing and nutrition and dietetics teams of a children's cancer hospital, before and after educational interventions.</p><p><bold>Design/Methods</bold>: The teams to be approached were defined, corresponding to cupbearers/ kitchen assistants and nurses/ nursing technicians of the Intensive Care Unit, Hematopoietic Stem Cell Transplantation and ward. Two questionnaires were prepared, one for each team, and applied on the first day (D1). Two interventions occurred at D7 and D14. Subjects such as neutropenia, types of diets and feeding routes, were discussed. A second questionnaire application occurred on the D75. The results were analyzed with the statistical package SPSS 21.0.</p><p><bold>Results</bold>: Forty‐seven professionals participated in this study. However, only fifteen performed the second questionnaire. The scores obtained by the nutrition and dietetics team in the first questionnaire were 2.0 to 6.0 points (poor to regular grades). The nursing team's scores were 1.0 to 5.0 points in the first moment (poor to bad grades). There was a significant increase (p <0.05) in scores of the second questionnaire for both teams, going from 5.0 to 7.0 (regular to good grades) for the first team and 3.0 to 9.0 (bad to great grades) for the second team. In comparison of the demographic characteristics of the nursing team, the sector and the working time were statistically different for those who answered the second questionnaire.</p><p><bold>Conclusions</bold>: Good retention rates have been demonstrated for those who participated of all stages of the study, but it is necessary to associate the theory with the practice performed by the teams.</p></sec></sec><sec id="pbc26772-sec-8820"><title>Treatment and Care ‐ Palliative Care</title><sec id="pbc26772-sec-8830"><label>P-476</label><title>Evaluation of the Acute Biochemical Changes in DLBCL Patients Treated with and Without Rituximab</title><p><underline underline-style="single">K. ali</underline><sup>1</sup></p><p><italic><sup>1</sup>National Institute of Blood Diseases and Bone Marrow Transplantation, Pharmacy, karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: The background of conducted study was to determine adverse implications on metabolic profile of DLBCL patients deal with CHOP and R‐CHOP. With a concise determination of the changes in metabolic profile correlated with dose intensity ratio, the findings of this study will be helpful in choices for the physician to discontinue therapy, delaying treatment or alternating regimen.</p><p><bold>Design/Methods</bold>: This was prospective study conducted at National Institute of blood diseases and bone marrow transplantation. In this study baseline readings of liver enzymes, urea, creatinine and electrolytes levels was taken and treated as control readings. Post‐treatment readings of aforesaid parameters were taken after 20 days. Means of above readings was calculated and compared with common terminology criteria for adverse events v3.0 2006 (CTCAE) to find the differences in biochemical parameters at baseline (control group) and 20 days post‐treatment (treatment group) to identify the types of toxicity (mild moderate or severe) as define by v3.0 2006 (CTCAE).</p><p><bold>Results</bold>: Among patients with CHOP therapy, significant difference of ALP (p‐value 0.009), direct bilirubin (p‐value 0.034) and SGPT (p‐value 0.004) was observed before and after the treatment whereas among patients with R‐CHOP no significant difference was observed in any biochemical analysis (p‐value >0.05).</p><p><bold>Conclusions</bold>: Despite the fact, subjects at baseline metabolic or biochemical investigation impairments should be corrected rigorously rather than post chemotherapy effects of CHOP or R‐CHOP cycles leads to the fatal or life threatening renal and hepatic toxicities. As far as safety is concern R‐CHOP is safest than CHOP in term of toxicities.</p></sec><sec id="pbc26772-sec-8840"><label>P-477</label><title>Parents' Lived Experiences of Losing a Child to Cancer; Like Being Covered in a Wet and Black Blanket</title><p><underline underline-style="single">M. Bjork</underline><sup>1</sup>, A. Sundler Johansson<sup>2</sup>, I. Hallström<sup>3</sup>, K. Hammarlund<sup>4</sup></p><p><italic><sup>1</sup>School of Health and Welfare, CHILD research group‐ Department of Nursing‐ Jönköping University, Jönköping, Sweden; <sup>2</sup>Faculty of Caring Science, Work Life and Social Welfare‐ University of Borås, Borås‐, Sweden; <sup>3</sup>Faculty of Medicine, Department of Health Sciences‐ Lund University, Lund, Sweden; <sup>4</sup>Division of Nursing, Department of Health and Learning‐ University of Skövde, Skövde, Sweden</italic></p><p><bold>Background/Objectives</bold>: To elucidate parents’ lived experiences of losing a child to cancer.</p><p><bold>Design/Methods</bold>: A hermeneutical phenomenological approach was chosen. Five parents were interviewed and one wrote down a narrative about the experiences of losing a child to cancer.</p><p><bold>Results</bold>: Through the analysis one essential theme was identified “Like being covered in a wet and black blanket”. In relation to the essential theme, six related themes emerged “Feeling conflicting emotions”, “Trying to get ready for the moment of death, “Parenting continues after death”, “Keeping the spirit alive”, “Working with the sorrow” and “Wanting to comprehend life into a new integrated whole”.</p><p><bold>Conclusions</bold>: Losing a child to cancer is one of the most painful situations a parent can live through. Life will forever be changed and the parents need to find ways to learn to live without the child. When giving palliative care to a child, the care needs to be holistic and focus both the child and its family. For staff, it is important to meet parents more than once after the child's death to be able to identify those in need for extensive support.</p></sec><sec id="pbc26772-sec-8850"><label>P-478</label><title>Teamwork at End‐of‐Life: Developing an Integrated Model</title><p><underline underline-style="single">S. Holm</underline><sup>1</sup></p><p><italic><sup>1</sup>Children's Medical Center, Psychiatry, Dallas, USA</italic></p><p><bold>Background/Objectives</bold>: (Abstract is part of a symposium submission: ‘Psychosocial Care Models for End of Life and Bereavement Support.') Preparing for the death of a child is exceptionally distressing for the family. To provide best end‐of‐life care, it's imperative that an institutional infrastructure exist to promote highly collaborative work. This project describes the development of an integrative interdisciplinary palliative care team within the oncology service at a large pediatric hospital and compares it to current standards of care. The purpose of the team was to improve quality of care for children at highest risk for death through cohesive assimilation of medical and psychosocial professionals already providing services in parallel.</p><p><bold>Design/Methods</bold>: Prior to developing this team, end‐of‐life care followed a traditional multidisciplinary model: the oncologist focused on medical aspects of care and referred to subspecialties for other concerns. Collaboration amongst subspecialties was inconsistent, leading to conflicting interventions, contradictory goals of care, and moral distress. In response to these difficulties, a group of experts developed an interdisciplinary approach to supporting families through end‐of‐life using an integrated care model.</p><p><bold>Results</bold>: An included case example to illustrates this integrated model of end‐of‐life care: an adolescent girl with metastatic alveolar Rhabdomyosarcoma; a parent with untreated paranoid schizophrenia. This highly integrated approach led to several improved outcomes: improved communication meant frequent crises were managed adequately, streamlined care prevented repeated/competing interventions, increased interdependence of psychosocial team members allowed for focus on self‐care, and unified goals led to a peaceful death experience.</p><p><bold>Conclusions</bold>: The ultimate goal of palliative care is to identify and ameliorate suffering and at end‐of‐life, this seems best achieved through the holistic care of a child and family by a well‐integrated team of specialists working toward consistent goals. Through developing this team, we learned that true interdisciplinary collaboration improved the experience of a child's death for the family and providers.</p></sec><sec id="pbc26772-sec-8860"><label>P-479</label><title>Palliative Radiotherapy for Pediatric Patients: Outcome Expectations</title><p><underline underline-style="single">B. Lee</underline><sup>1</sup>, D. Apkon<sup>2</sup>, J. Wolfe<sup>1,3</sup>, K. Marcus<sup>1,2,3</sup></p><p><italic><sup>1</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Radiation Oncology, Boston, USA; <sup>2</sup>Brigham and Women's Hospital, Radiation Oncology, Boston, USA; <sup>3</sup>Harvard Medical School, Radiation Oncology, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Palliative radiation therapy (pRT) for pediatric cancer patients is often used to treat pain, neurologic symptoms, and other conditions from progressive cancer that affect quality of life. The decision to pursue additional anti‐cancer therapy towards the end of their child's life may be a challenging one. The perceived risk versus benefit ratio may be altered depending on parental knowledge and expectations of pRT for their child. The goal of this study was to explore parental expectations of pRT and whether the outcome met their expectations.</p><p><bold>Design/Methods</bold>: Nineteen children referred for pRT were enrolled in a prospective IRB‐approved study. At the time of initial consultation, parents were counseled regarding the indication for pRT and the expected outcomes of treatment. At one to three months following treatment completion, a questionnaire was given to parents to evaluate how the results of treatment compared to their initial expectations of pRT. Descriptive statistics were used to analyze the results of the questionnaire.</p><p><bold>Results</bold>: Compared to their initial expectations for pRT, 56% reported that the outcome of pRT in their child was much better than expected. 33% reported slightly better results, 6% reported outcomes consistent with their expectations, and 7% reported that the results were slightly worse. No parents reported that the outcome was much worse than their expectations.</p><p><bold>Conclusions</bold>: Radiation therapy is an important modality in palliative care for children with end‐stage cancer. In this study, we found that the large majority of parents believed that the results of the pRT were better than expected. Our findings may be of value for future patients whose parents must make this difficult decision.</p></sec><sec id="pbc26772-sec-8870"><label>P-480</label><title>End of Life Care Experience at the Pediatric Oncology Unit at the Uganda Cancer Institute: What Role Can Oncology Nurses Play?</title><p><underline underline-style="single">I. Mulyowa</underline><sup>1</sup></p><p><italic><sup>1</sup>Uganda Cancer Institute, Oncology, Kampala, Uganda</italic></p><p><bold>Background/Objectives</bold>: Although the majority of childhood cancers are curable, this is not yet true for low resource countries. In Uganda, cancer care is only at the Uganda Cancer Institute.</p><p>Between Jan 1<sup>st</sup> and Dec 31<sup>st</sup>, there were <bold>4,321</bold> new cancer cases registered and about <bold>8%</bold> were among children. The mortality rate is <bold>70%</bold> annually, that is every <bold>3 in 5</bold> children diagnosed with cancer will not survive past one year after cancer diagnosis. Here, we review the factors contributing to poor outcomes and potential solutions.</p><p><bold>Design/Methods</bold>: Observation</p><p><bold>Results</bold>: Majority of the children present with advanced disease at cancer diagnosis. The chemotherapy is prescribed for palliative intent more frequently and high rates of complications are observed. Family involvement in decisions regarding the role of palliative chemotherapy at end of life is low. The concept of quality of life for cancer patients with advanced cancer is not well perceived among caretakers and some clinicians at UCI. Nurses play an integral role, identifying symptoms, providing care coordination, and assuring clear communication.</p><p><bold>Conclusions</bold>: Educational initiatives for patients, families and health‐care providers, are essential. The oncology nurses play a key role in the multidisciplinary team approach to paediatric patients at end of life care.</p></sec><sec id="pbc26772-sec-8880"><label>P-481</label><title>Palliative Care: Educational Intervention for Nurses in Lebanon: An Attempt</title><p><underline underline-style="single">M. Naifeh Khoury</underline><sup>1</sup>, M. Arevian<sup>1</sup>, G. El‐Khatib<sup>1</sup>, S. Fares<sup>1</sup></p><p><italic><sup>1</sup>American University of Beirut, Hariri School of NUrsing, beyrouth, Lebanon</italic></p><p><bold>Background/Objectives</bold>: <italic>Background</italic>: Palliative Care (PC), End –of‐Life (EOL) care is evolving worldwide and in Lebanon. PC provides as good or better outcomes than curative care alone, is cost effective, and alleviates pain and suffering for patients and caregivers. Nursing educators and leaders, internationally and nationally indicate need to include concepts of “PC” and “ EOL” care in curricula of professional nurses to cope with death and dying as potential outcome for patient. <italic>Purpose</italic>: Assess the effectiveness of PC continuing educational intervention for registered nurses (RNs) at American University Medical Center (AUBMC); recommend future educational programs.</p><p><bold>Design/Methods</bold>: <italic>Methods</italic>: Quasi experimental pre‐post‐test. <italic>Participants</italic>: Convenient sample of 45 “AUBMC” “RNs “dealing with “PC” and “ELO” care from different clinical units. <italic>Program</italic>: 0ne‐credit workshop, basics in” PC” and “ELO” Care. Local “PC” experts provided the program. Content adapted from the Education for Physicians of End of Life Care Curriculum (EPEC). Pre‐Post‐ test consisted 34 multiple choice questions<italic>. Analysis</italic>: Demographic characteristics summarized using descriptive statistics. Differences between pre‐post‐tests were measured by means and standard deviations (SD) using the paired t test. A two‐tailed test was used, p‐value less than 0.05 considered significant.</p><p><bold>Results</bold>: Results Thirty nine participants completed the pre‐post‐test: Mean pretest score was 48.53(SD = 9.23), range29‐65, post‐ test 70.05 (SD = 12.35), range 47‐88. Paired t test showed significant increase between pre and post test scores t (38) = 11.07, p < 0.001 with 95% confidence interval for the mean difference of (17.58, 25.45).</p><p><bold>Conclusions</bold>: <italic>Conclusion</italic>: provide structured workshops to “RNs” to for improving “PC” and “EOL” Care.</p></sec><sec id="pbc26772-sec-8890"><label>P-482</label><title>Implementation and Evaluation of a Pediatric Palliative Care Educational Program Intended for Nursing Staff of a National Reference Pediatric Hospital in Nicaragua</title><p>R. Ortiz<sup>1</sup>, <underline underline-style="single">N. Diaz</underline><sup>1</sup>, S. Saleh<sup>2</sup>, C. Maendley<sup>3</sup>, M. Chamorro<sup>4</sup>, C. Salazar<sup>4</sup></p><p><italic><sup>1</sup>Manuel de Jesus Rivera‐ La Mascota‐ Children's Hospital, Pediatric Hematology‐oncology, Managua, Nicaragua; <sup>2</sup>Sainte Justine Pediatric Hospital, Pediatrics, Montreal, Canada; <sup>3</sup>Centre Hospitalier Universitaire Vaudois, Pediatrics, Lausanne, Switzerland; <sup>4</sup>Manuel de Jesus Rivera‐ La Mascota‐ Children's Hospital, Pediatrics, Managua, Nicaragua</italic></p><p><bold>Background/Objectives</bold>: Pediatric Palliative Care (PPC) is unarguably essential in both Global North and South as it refers to universal Right to Health. Following the 2014 World Health Assembly's resolution on Palliative Care, Nicaragua launched in 2015 its first national Pediatric Palliative Care Program in collaboration with two NGO's Associazione per l'aiuto medico al Centro America and Médecins du Monde. Objectives include healthcare workforce training and essential drugs supply provision. Within this framework, a PPC educational program intended for nurses caring for children with life limitng diseases at the only national referral Children's Hospital in Managua was developed.</p><p><bold>Design/Methods</bold>: From November 2015 to December 2016, a trained nurse educator provided 8 educational basic courses on PPC to nurses of various departments of the pediatric hospital. Pre‐intervention tests and 6‐month post‐intervention tests were administered to nurses to assess change in general PPC knowledge. The highest possible test score was 18 points. Comparison of mean results between pre‐ and post‐tests was performed.</p><p><bold>Results</bold>: 54 nurses from 5 departments took part to the whole 8‐courses educational program. The mean pre‐test result was 10.45 points whereas mean post‐test result was 14.60 points. A 4.15‐point difference was observed between pre‐ and post‐test assessment of knowledge of participants.</p><p><bold>Conclusions</bold>: Marked difference between pre‐ and post‐ assessment demonstrate positive impact of this educational program. Above all, a raised awareness regarding need for palliative care was witnessed across the hospital as the demand for consultations increased notably. Education of health care professionals is essential to sustainable, efficient and quality provision of PPC. These positive outcomes open the doors now for additional theoretical and practical training for nurses as well as targeting other health care professionals involved in the care of pediatric palliative care patients. Finally, there is a need to review tools used to evaluate educational interventions in the field of palliative care.</p></sec><sec id="pbc26772-sec-8900"><label>P-483</label><title>End‐of‐Life Care for Children with Cancer: Medical Practitioners’ Training Needs Assessment in a Resource Poor Setting</title><p><underline underline-style="single">L. Osei‐tutu</underline><sup>1</sup>, E. Sarfo Frimpong<sup>2</sup>, V. Paintsil<sup>1</sup>, J. Dogbe<sup>1</sup></p><p><italic><sup>1</sup>Komfo Anokye Teaching Hospital, Child Health, Kumasi, Ghana; <sup>2</sup>Komfo Anokye Teaching Hospital, Research and Development Unit, kumasi, Ghana</italic></p><p><bold>Background/Objectives</bold>: The Paediatric Cancer Unit of the Child Health Department in the Komfo Anokye Teaching Hospital, KATH is one of two main childhood cancer treatment centers in Ghana. 113 new patients visited the Unit in 2016; 78(69%) required palliation and 39(34%) died. Most deaths, 33(84%) occurred in the hospital. We aimed to assess the end‐of‐life training needs of medical practitioners in the Department in the setting of paediatric cancers</p><p><bold>Design/Methods</bold>: Medical practitioners completed a survey assessing their participation, communication skills and practices in end‐of‐life care regarding paediatric cancer patients. Responses were ranked on five‐point Likert scales and analysed by simple proportions</p><p><bold>Results</bold>: 30 practitioners, 20 doctors and 10 nurses completed the survey. All participants reported ever undertaking some end‐of‐life care some end‐of‐life responsibilities. 12(60%) doctors and 5(50%) nurses reported not receiving any such formal training. All doctors reported not receiving any formal instructions on having follow‐up contact with families after patient deaths compared to 5(50%) of nurses surveyed. Most (80%) participants reported lacking formal instructions in seeking support for themselves regarding end‐of‐life situations. 12(60%) doctors and 7(70%) nurses did not “feel adequately trained to undertake withdrawal or limitation of life‐sustaining therapy” whereas only 9(18%) doctors and 4(40%) nurses “felt adequately trained to provide symptom management at the end of life.” 45–60% of participants reported adequate training and experience in communicating end‐of‐life issues to families while 15‐30% reported feeling knowledgeable, competent and comfortable in such communications. 40% doctors compared to 50% nurses reported adequate training and experience in providing spiritual support for dying children and their families. Only 15% of participants surveyed felt competent and comfortable including children in discussions about preparing for death</p><p><bold>Conclusions</bold>: Formal training in end‐of‐life care in the setting of paediatric cancers appears inadequate with significant gaps in communication skills, in withdrawing or limiting life‐sustaining therapy and symptom management</p></sec><sec id="pbc26772-sec-8910"><label>P-484</label><title>Palliative Care Practice in Pediatric Oncology: A Single Center Experience in France</title><p><underline underline-style="single">G.</underline><underline underline-style="single">Revon‐Riviere</underline><sup>1</sup>, J.C. Gentet<sup>1</sup></p><p><italic><sup>1</sup>Hopital Timone, Oncologie Pédiatrique, Marseille, France</italic></p><p><bold>Background/Objectives</bold>: Pediatric palliative care is a field of primary importance for improvement of quality of life of children with cancer. Our study aims to describe practice of palliative care in our institution by studying time from inclusion to death, treatments, length of hospitalization, location of death, use of community palliative services and symptoms in children dying of cancer.</p><p><bold>Design/Methods</bold>: This study is a retrospective, single center, chart review of every child treated in our institution and deceased between June 2014 and June 2016. Symptoms were assessed by chart examination three months before death. y.</p><p><bold>Results</bold>: 45 patients died of cancer in two years. 34 (75.5 %) have been discussed in palliative care staff and 25 (55 %) were actively treated by pediatric palliative care unit. Median duration of palliative phase was 4.3 months (range: 0.03‐29.80). 91 % of patients died in hospital. During that time, mean number of antineoplastic treatments was 1.8 per patient and 25 % were included in a clinical trial. Symptoms were in order of frequency: pain, fatigue, poor appetite and digestive disorders. Their prevalence was underestimated in medical charts.</p><p><bold>Conclusions</bold>: We report our palliative activity to allow improvement in practices and resource allocation. Availability of innovative treatment for palliative purpose is high. However, there is a great variability in duration of palliative care and use of palliative resources. Definition of a group of high‐risk children requiring early initiation of palliative care as well as standardization of palliative care assessments and interventions are necessary.</p></sec><sec id="pbc26772-sec-8920"><label>P-485</label><title>Consultation Team in Tertiary Hospital as a Pediatric Palliative Care Model in Developing Country– 5 Years Experience of a Single Institution in China</title><p><underline underline-style="single">J. Wang</underline><sup>1</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center, department of hematology/oncology, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: To evaluate the feasibility and effectiveness of palliative care consultation(PCC) team as a service model at an oncology unit in a pediatric tertiary hospital in China.</p><p><bold>Design/Methods</bold>: Our core palliative care consultation team consists of a pediatric oncologist, a pediatric oncology nurse and a social worker. Doctor is the leader of this interdisciplinary team who is responsible for a coordinated care plan development. Patients are referred to the team from other pediatric oncologists, and PCC team delivers palliative care services through outpatient clinic, consultation, 7*24 hours hotline and hospice room located in the observation ward. The team also provides teaching and support to the health care professionals.</p><p><bold>Results</bold>: A total of 50 patients and their families have been referred since 2012. The referral reasons were refractory pain (2 patients) and end‐of‐life care (48 patients). Diagnoses included leukemia and solid tumor. 28 boys and 22 girls aged from 14 months to 17 years. Among those patients for end‐of‐life care, 18 and 1 died at community hospital and oncology ward of our hospital separately. The role of PCC team for these cases was providing support to the local hospital and the colleagues at our oncology unit. Another 29 patients received the direct care of PCC team. 20 of them died at hospice room, and 9 died at home. The main symptoms during the last month were pain, anorexia, fatigue, dyspnea, fever, edema, infection, bleeding, depression, fear, anxiety and insomnia. The direct and indirect interventions of PCC team showed the positive impact on suffering relief and death preparation.</p><p><bold>Conclusions</bold>: The palliative care consultation team is closely attached and provides professional support to the conventional health care. It is well‐functioning and cost saving. We conclude that this model may play an important role of pediatric palliative care in developing country where the medical resources are insufficient.</p></sec></sec><sec id="pbc26772-sec-8930"><title>Treatment and Care ‐ Psychosocial (PPO)</title><sec id="pbc26772-sec-8940"><label>P-486</label><title>Who Should Inform on Children Quality of Life in Paediatric Oncology? Systematic Review and Meta‐Analysis of Agreement Between Respondents</title><p><underline underline-style="single">C. Abate</underline><sup>1,2</sup>, C. Laverdière<sup>2,3</sup>, M. Krajinovic<sup>2,3</sup>, D. Sinnett<sup>2,3</sup>, S. Sultan<sup>1,2</sup></p><p><italic><sup>1</sup>Université de Montréal, Psychology, Montreal, Canada; <sup>2</sup>CHU Sainte‐Justine, Hematology‐Oncology, Montreal, Canada; <sup>3</sup>Université de Montréal, Pediatrics, Montreal, Canada</italic></p><p><bold>Background/Objectives</bold>: Quality of life (QOL) is an essential component of care for children with cancer and for young survivors and is often informed by parents or significant others. Assessing QOL reliably is difficult due to divergent child and parent ratings. A systematic review and meta‐analysis was performed to synthesize the size of differences between child and parent ratings on QOL at all stages of the cancer and to identify moderators of the differences between ratings.</p><p><bold>Design/Methods</bold>: A systematic search of PubMed, PsycINFO, EMbase, CINALH and reference lists revealed pertinent articles published until December 2016. Eligibility criteria included QOL ratings of patients <19 years old during or after cancer treatment and at least one of their parents with a validated instrument. Two independent reviewers extracted data and conducted quality assessments with standardized tools, in line with PRISMA recommendations. Random effects meta‐analyses compared self‐assessed and parent‐assessed QOL across scores and subscores: overall, physical, psychosocial. We computed effect sizes with 95% confidence intervals. Additional analyses of differences between QOL ratings and cancer diagnosis, cancer trajectories, and instruments are underway.</p><p><bold>Results</bold>: Forty‐two articles were eligible out of a possible 1,139. Twenty‐six percent of studies recruited children during treatment, 29% after treatment and 45% included mixed samples. They describe 4,325 children and 4,485 parents who differ on age at diagnosis, time since diagnosis, cancer types and QOL measures. Median ICC for overall QOL was 0.58 (quartile range=0.48‐0.72) and median Cohen's <italic>d</italic> was 0.23 (quartile range=0.14‐0.44). Preliminary analyses yield a mean moderate effect size between child and parent ratings. Moderation studies indicated that differences are associated with child age, child gender, clinical history, and parental mood.</p><p><bold>Conclusions</bold>: Disagreements among children and their parents highlight the importance of gathering QOL assessments from multiple respondents to identify vulnerable patients. Future research should explain disagreements and develop new methods to interpret multiple reports.</p></sec><sec id="pbc26772-sec-8950"><label>P-487</label><title>The Childhood Cancer Mobile APP</title><p><underline underline-style="single">A. Filander</underline><sup>1</sup>, U. Persson<sup>1</sup>, M. af Sandeberg<sup>1</sup>, L. Pettersson<sup>1</sup>, G. Cleve<sup>1</sup></p><p><italic><sup>1</sup>Karolinska University Hospital, Astrid Lindgren Childrens Hospital‐ Pediatric Oncology, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: A family in shock because their child is diagnosed with cancer need to learn to understand the disease and treatment, a prerequisite for them to feel confident in taking care of their child. Health care is legally obliged to provide adequate information during a time when it is extremely difficult to absorb. For many years families at the children's cancer unit got their own folder with information about childhood cancer, unit routines and instructions how to act if the child should exhibit acute symptoms. The problem, however, was to keep the information updated. The childhood cancer mobile APP was developed as a complement to the verbal information, to make it possible to get answers when the questions arise at home, to avoid mixed messages from healthcare staff and to help parents to inform other close persons.</p><p><bold>Design/Methods</bold>: A special group of various clinical professions was formed to work with the APP together with the hospitals' Innovation Centre and an enterprise platform. The text in the information folder was updated and context and wording discussed in frequent meetings. Feedback from patients and relatives was gathered through workshops, questionnaires and mail. Significant parts was translated into the four most common foreign languages: English, Spanish, Somali and Arabic, and processed in workshops for interpreters and parents.</p><p><bold>Results</bold>: The APP was soon used by the majority of families at the unit and is constantly developed.</p><p><bold>Conclusions</bold>: The childhood cancer APP meet a considerable need for parents, relatives and staff. It is crucial to take help from experts on platform construction.</p></sec><sec id="pbc26772-sec-8960"><label>P-488</label><title>Bridging the Gap Between Treatment and End of Life for Pediatric Patients with Cancer</title><p><underline underline-style="single">S. Flowers</underline><sup>1</sup>, J. Hansen‐Moore<sup>1</sup>, T. Young‐Saleme<sup>1</sup>, C. Russell<sup>1</sup>, M. Gardner<sup>1</sup></p><p><italic><sup>1</sup>Nationwide Children's Hospital, Pediatric Psychology, Columbus, USA</italic></p><p><bold>Background/Objectives</bold>: This abstract is part of a symposium submission from APA/Division 54 Hematology/Oncology/BMT SIG entitled Psychosocial Care Models for End of Life and Bereavement Support</p><p>Nationwide Children's Hospital is the largest children's hospital in the United States. Our Psychosocial Oncology Team developed a model of care to enhance care for dying children. It embodies a collaborative approach with integration of medical, psychosocial, and palliative services for comprehensive, coordinated, and integrated programing. This model assesses and treats emotional and symptom burden, facilitates communication, provides anticipatory guidance and support to patients/families, while facilitating staff communication and support.</p><p><bold>Design/Methods</bold>: Our program addresses specialized needs of dying children in a collaborative team approach. Patients are assessed and treated via a large comprehensive psychosocial team of providers. Anticipatory grief support is facilitated by relationships focused on continuity of care, medical decision‐making, care conferences, and end‐of‐life conversations. We assist with patient/family communication with family‐centered rounds, advanced care planning, and legacy building. Palliative/Oncology Rounds, team huddles, documentation, and death notification protocols were developed to improve staff communication. Additionally, we provide support for staff following patient deaths through debriefings/remembrances.</p><p><bold>Results</bold>: In large programs with multiple providers, it is often challenging to know who is providing specific services, while ensuring that families are receiving needed care. By increasing communication between and within teams, we ensure support, enhance/streamline services, and delineate service provision.</p><p><bold>Conclusions</bold>: The Psychosocial Oncology Team at NCH has improved communication among medical, psychosocial, and palliative team members to enhance opportunities and provide support around a child's death. In a field with a high level of burnout and stress, open communication and support among team members can serve to enhance the well‐being and service provided to patients, and also reduce staff distress. A comparison between our model and the Psychosocial Standards of Care related to palliative care and bereavement follow‐up will be reviewed.</p></sec><sec id="pbc26772-sec-8970"><label>P-489</label><title>Risk Factors and Reasons for Loss to Follow‐Up Among Families of Children with Lymphoma in Malawi</title><p><underline underline-style="single">C. Stanley</underline><sup>1</sup>, T. van der Gronde<sup>1</sup>, K. Westmoreland<sup>1</sup>, S. Ande<sup>1</sup>, A. Amuquandoh<sup>1</sup>, S. Itimu<sup>1</sup>, A. Manda<sup>1</sup>, I. Mtete<sup>2</sup>, M. Butia<sup>2</sup>, A. Mpasa<sup>2</sup>, S. Wachepa<sup>2</sup>, P. Wasswa<sup>2</sup>, P. Kazembe<sup>2</sup>, N. El‐Mallawany<sup>2</sup>, S. Gopal<sup>1</sup></p><p><italic><sup>1</sup>UNC Project Malawi / Kamuzu Central Hospital, Cancer Program, Lilongwe, Malawi; <sup>2</sup>Baylor Children's Foundation, Oncology, Lilongwe, Malawi</italic></p><p><bold>Background/Objectives</bold>: Lymphoma is the commonest pediatric cancer in sub‐Saharan Africa (SSA). A principal contributing factor to suboptimal outcomes is frequent loss to follow‐up (LTFU). However, risk factors and reasons for LTFU among families of children with lymphoma in SSA are not clear. Our aim was to assess risk factors and reasons for LTFU among pediatric lymphoma patients in Malawi.</p><p><bold>Design/Methods</bold>: We conducted a mixed methods study among children <18 years old with newly diagnosed lymphoma, prospectively enrolled between 2013 and 2016 in Lilongwe, Malawi. All children received standardized diagnosis and treatment, and were followed for up to two years. LTFU was defined as failure to attend a prescribed chemotherapy visit within four weeks, or post‐treatment visit within three months. Child, guardian, and household characteristics associated with LTFU were assessed using Cox models. Semi‐structured interviews were conducted with primary caregivers of children experiencing LTFU.</p><p><bold>Results</bold>: Seventy‐two children were newly diagnosed with lymphoma, of whom 56 (78%) had Burkitt and 16 (22%) Hodgkin lymphoma. Forty‐nine (68%) were male, median age was 10.6 years (interquartile range [IQR] 7.9–13.0), and 26 (36%) were LTFU. Lack of guardian formal education and travel time ≥4 hours to clinic were independently associated with LTFU, with adjusted hazard ratio (aHR) 3.8 [95% confidence interval (CI) 1.5‐8.9, p=0.005] and aHR 2.9 (95% CI 1.2‐6.9, p=0.019), respectively. The most frequent reasons for LTFU mentioned by guardians were community influence, suboptimal clinic environment, logistical challenges, transport costs, treatment side effects and toxicities, loss of hope, alternative healers, and beliefs about cure.</p><p><bold>Conclusions</bold>: LTFU was driven more by guardian or household characteristics than child characteristics. These findings highlight families at risk for LTFU, and opportunities to improve retention in care for pediatric cancer patients in SSA.</p></sec><sec id="pbc26772-sec-8980"><label>P-490</label><title>Psychosocial Care Models for End of Life and Bereavement Support</title><p><underline underline-style="single">J. Hoag</underline><sup>1</sup>, K. Bingen<sup>1</sup></p><p><italic><sup>1</sup>Medical College of Wisconsin, Department of Pediatrics, Milwaukee, USA</italic></p><p><bold>Background/Objectives</bold>: This proposed symposium represents collaboration amongst the Hematology/Oncology/Blood and Marrow Transplant (BMT) Special Interest Group of the Society of Pediatric Psychology, American Psychological Association. In 2015, the Standards for Psychosocial Care for Children with Cancer were published in a landmark special edition of Pediatric Blood & Cancer. Two standards dealt with palliative care and bereavement. While a minimum of care has been established, it remains unclear how institutions are using these guidelines within their existing infrastructure to improve or refine their practice model. Therefore, the objective of this symposium is to describe the psychosocial care models for end of life and bereavement support across three institutions of varying sizes, resources, and geographical diversity to aid in our understanding of current practices.</p><p><bold>Design/Methods</bold>: The proposed presentations reflect various approaches to collaborative care across disciplines at end of life to facilitate honest and respectful communication with patients and families, improve family‐centered advance care planning, and assist with memory making. Presenters will also discuss bereavement follow‐up in their institution for families, as well as staff.</p><p><bold>Results</bold>: Descriptive program data will be presented, including hospital and patient demographics, composition of palliative and bereavement teams, timing of introductions and interventions, and program evaluation. Barriers to implementation will be addressed.</p><p><bold>Conclusions</bold>: This symposium highlights that there are various ways to implement the standards for psychosocial care for providing end of life and bereavement care for children with cancer and their families.</p><p>Authors of corresponding abstracts: Stacy Flowers, Jeffrey Karst, and Suzanne Holm</p></sec><sec id="pbc26772-sec-8990"><label>P-491</label><title>Psychosocial Functioning and Risk Factors for Siblings of Children with Cancer: An Updated Systematic Review</title><p><underline underline-style="single">K. Long</underline><sup>1</sup>, V. Lehmann<sup>2</sup>, A. Carpenter<sup>3</sup>, C. Gerhardt<sup>2</sup>, A. Marsland<sup>4</sup>, M. Alderfer<sup>5,6</sup></p><p><italic><sup>1</sup>Boston University, Psychological and Brain Sciences, Boston, USA; <sup>2</sup>Nationwide Children's Hospital, Center for Biobehavioral Health, Columbus, USA; <sup>3</sup>Boston University, Department of Psychological and Brain Sciences, Boston, USA; <sup>4</sup>University of Pittsburgh, Psychology, Pittsburgh, USA; <sup>5</sup>Nemours Children's Health System, Center for Healthcare Delivery Science, Wilmington, USA; <sup>6</sup>Thomas Jefferson University, Sidney Kimmel Medical College, Philadelphia, USA</italic></p><p><bold>Background/Objectives</bold>: Despite increased research, our understanding of siblings’ psychosocial adjustment to cancer remains limited. This updated systematic review summarizes main findings and limitations of the current sibling literature, provides clinical recommendations, and offers future research directions.</p><p><bold>Design/Methods</bold>: Searches of MEDLINE/Pubmed, CINAHL, and PsycINFO yielded 1731 articles published since 2008 related to siblings, psychosocial functioning, and pediatric cancer. Of these, 103 (64 quantitative, 35 qualitative, and four mixed methods) met inclusion criteria. They were rated for scientific merit, and findings were extracted and synthesized</p><p><bold>Results</bold>: While mean levels of anxiety, depression, and general adjustment (e.g., symptoms of internalizing, externalizing, or general distress) are similar across sibling and comparison samples, many siblings report moderate/severe levels of cancer‐related posttraumatic stress. School‐aged siblings display poorer academic functioning and more absenteeism than peers; their peer relationships are similar to those of comparisons. Findings regarding quality of life are mixed. Adult siblings may have a higher risk for cardiovascular disease and engaging in risky or heavy drinking than comparisons. Risk factors for poor adjustment include low social support, poorer family functioning, lower income, nonwhite race, and shorter time since diagnosis, but findings are inconsistent. Qualitative studies report themes of siblings’ maturity, compassion, and autonomy, along with strong negative emotions, uncertainty, family disruptions, limited parental support, school problems, altered friendships, and unmet needs. Conclusions are limited because longitudinal studies are lacking, siblings are often considered controls for patients/survivors, and sample characteristics (e.g., age, race/ethnicity, time since cancer diagnosis) are rarely considered.</p><p><bold>Conclusions</bold>: Despite methodological limitations, the literature indicates a strong need for sibling psychosocial care focused on identifying at‐risk siblings, facilitating family communication about cancer, and bolstering siblings’ social support, cancer‐related knowledge, and cancer involvement. Future research that implements longitudinal designs and focuses on mechanisms and moderators of siblings’ adjustment would inform optimal timing and targets of siblings’ psychosocial care.</p></sec><sec id="pbc26772-sec-9000"><label>P-492</label><title>Post‐Traumatic Stress Symptoms and Family Risk Among Adolescents and Young Adults with Differentiated Thyroid Cancer: Prospective Psychosocial Screening of an Underserved Cancer Population</title><p><underline underline-style="single">A. Psihogios</underline><sup>1</sup>, J. Baran<sup>1</sup>, J. Pizza<sup>1</sup>, S. Mostoufi‐Moab<sup>1</sup>, A. Bauer<sup>1</sup>, L. Barakat<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital of Philadelphia, Pediatrics, Philadelphia, USA</italic></p><p><bold>Background/Objectives</bold>: Approximately 25% of AYA with cancer report elevated post‐traumatic stress symptoms (PTSS). AYA with differentiated thyroid cancer (DTC) are often excluded from psychosocial research and clinical initiatives due to their good prognosis and treatment outside of cancer centers. To enhance understanding of adaptation, this study describes clinical rates of AYA and caregiver PTSS and family risk, and correlates with PTSS.</p><p><bold>Design/Methods</bold>: AYA with DTC (<italic>n</italic>=45, <italic>M</italic> age=15.0, 91.3% female, 85.1% White) and a caregiver (<italic>n</italic>=44, 70.2% mothers) completed questionnaires at diagnosis (T1) and 12 months later (T2), including the PTSD Checklist‐Civilian 6 (PTSS), Psychosocial Assessment Tool (family risk), and PedsQL (HRQOL). We evaluated clinically significant rates of PTSS and family risk by assessing responses above established cut points. Multiple regressions and MANOVAs examined relationships between PTSS and correlates.</p><p><bold>Results</bold>: Among AYA, 23.8% and 11.1% reported clinically significant PTSS at T1 and T2. Among caregivers, 22.0% and 26.7% reported clinically significant PTSS, and 36.6% and 35.0% endorsed family risk associated with intervention needs at T1 and T2. Mean AYA HRQOL was 77.6 and 82.5 at T1 and T2. Paired t‐tests showed no significant changes in PTSS and family risk from T1 to T2. Lower HRQOL (β=.72, <italic>p</italic><.001) was associated with more AYA PTSS at T1, and AYA with at least one complication reported greater PTSS at T2 (<italic>F</italic>=5.29, <italic>p</italic>=.04). Higher family risk was associated with greater caregiver PTSS at T1 (β=.40,<italic>p</italic>=.001) and T2 (β=.81, <italic>p</italic>=.001).</p><p><bold>Conclusions</bold>: Comparable to other childhood cancer samples, a subset of AYA with DTC and caregivers are at‐risk for clinical levels of PTSS. The persistence of PTSS in the year post‐diagnosis, combined with family risk, highlight the importance of conveying psychosocial screening to AYA treated in the endocrine setting. AYA HRQOL was similar to other newly diagnosed cancer patients at T1, and may be targeted to reduce PTSS.</p></sec><sec id="pbc26772-sec-9010"><label>P-493</label><title>An Investigation of Parent and Child Sleep Patterns on an In‐Patient Oncology Unit</title><p>B. Russell<sup>1</sup>, G. Narendran<sup>2</sup>, S. Lee<sup>3</sup>, L. Tomfohr<sup>1</sup>, <underline underline-style="single">F. Schulte</underline><sup>4</sup></p><p><italic><sup>1</sup>University of Calgary, Psychology, Calgary, Canada; <sup>2</sup>University of Calgary, Medicine, Calgary, Canada; <sup>3</sup>University of Guelph, Psychology, Guelph, Canada; <sup>4</sup>University of Calgary, Oncology, Calgary, Canada</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer patients and their parents often stay in hospital for extended periods of time and report disruptions in sleep. This study aims to examine objective and subjective measures of sleep quality in pediatric cancer patients and their parents, receiving overnight oncology care.</p><p><bold>Design/Methods</bold>: Sixteen patients (11 male; mean age=13.47 years) and 14 parents have participated. For three consecutive days, patients and parents each wore an actigraphy watch and completed a daily Sleep Diary. Patients also completed the Child Depression Inventory, Multidimensional Anxiety Scale for Children, Child Sleep Habits Questionnaire, Pediatric Quality of Life (PedsQL) Multidimensional Fatigue Scale, and PedsQL Generic Core. Parents additionally completed the State Trait Anxiety Inventory for Adults, Abbreviated Pittsburgh Sleep Quality Index, Proxy PedsQL Mulidimensional Anxiety Scale, Proxy PedsQL Generic Core, and a daily Profile of Mood States Questionnaire.</p><p><bold>Results</bold>: Preliminary findings indicate that 80% of pediatric oncology patients self‐report symptoms of sleep disruption and/or fatigue based upon measures of Child Sleep Habits, Anxiety and Sleep Quality. Additionally, the PedsQL Multifatigue Scale indicated that all 16 children reported greater general, cognitive and sleep/rest fatigue in comparison to published norms.</p><p><bold>Conclusions</bold>: Data obtained from this research will help to identify ways to decrease the effects of an important physiological consequence of current cancer care practices. Research into sleep disturbances in hospitalized pediatric cancer patients and parents will aid in a better understanding of the developmental frameworks that guide intervention/prevention programs, providing benefit to and optimization of child and parent health during their hospital stay.</p></sec><sec id="pbc26772-sec-9020"><label>P-494</label><title>Home Physical Activity Intervention to Improve Cognitive Late Effects in Children Treated with Radiation for Brain Tumors: Pilot Feasibility and Efficacy Data</title><p><underline underline-style="single">P. Wolters</underline><sup>1</sup>, B. Abel<sup>1</sup>, S. Martin<sup>1</sup>, K. Smith<sup>2</sup>, M.A. Toledo‐Tamula<sup>3</sup>, B. Drinkard<sup>2</sup>, K. Chen<sup>4</sup>, A. Kramer<sup>5</sup>, A. Schembri<sup>6</sup>, J. Han<sup>7</sup></p><p><italic><sup>1</sup>National Cancer Institute, Pediatric Oncology Branch, Bethesda, USA; <sup>2</sup>National Institutes of Health, Clinical Center, Bethesda, USA; <sup>3</sup>Leidos Biomedical Research Inc, Clinical Research Directorate/Clinical Monitoring Research Program‐ NCI Campus at Frederick, Frederick‐ Maryland 21702, USA; <sup>4</sup>National Institute of Diabetes and Digestive and Kidney Diseases, Diabetes‐ Endocrinology‐ and Obesity Branch, Bethesda, USA; <sup>5</sup>Northeastern University, Mechanical and Industrial Engineering, Boston, USA; <sup>6</sup>Cogstate‐ Inc., Clinical Science, Melbourne, Australia; <sup>7</sup>University of Tennessee Health Sciences Center, Department of Pediatrics, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Cranial radiation therapy (CRT) for pediatric brain tumors contributes to neurocognitive late effects. Cognitive rehabilitation interventions are sorely needed. Studies indicate that physical activity (PA) improves CRT‐damaged brain mechanisms and cognitive functions. The aim of this pilot randomized controlled trial (RCT) was to assess the feasibility and preliminary efficacy of a novel home PA intervention in children treated with CRT for brain tumors.</p><p><bold>Design/Methods</bold>: Children 8‐17 years, >two years post‐CRT, with cognitive late effects were randomized to the Immediate Intervention Group (IIG), which followed a 12‐week home program to increase PA then maintained PA for 12 weeks, or the Delayed Intervention Group (DIG), which monitored usual PA for 12 weeks followed by the 12‐week program. Psychologists taught Acceptance and Commitment Therapy techniques to facilitate PA engagement. Participants used accelerometers and a website to track and reward moderate‐to‐vigorous PA (MVPA). Both groups underwent fasting blood draws (to measure circulating growth factors), treadmill evaluations, and cognitive assessments before and after the first 12 weeks, and repeat cognitive assessments after the second 12 weeks, including Cogstate computerized tests (normative mean=100;SD=15). Participants repeated Cogstate tests immediately after treadmill evaluations.</p><p><bold>Results</bold>: All six children (mean age=13.8 years, 10‐17) enrolled (IIG=3;DIG=3) completed the pilot study. From baseline to during the 12‐week program, 6/6 increased weekly MVPA (total means 41 to 130 minutes). After the treadmill evaluations, 5/6 had improved Cogstate visual memory scores (total means 107 to 118). The IIG showed greater increase in visual memory scores post‐intervention compared to after the DIG 12‐week post‐control period (14 versus 5 points). On 5‐point Likert scales, participants reported liking the program (mean=4) and finding it helpful (mean=4).</p><p><bold>Conclusions</bold>: These pilot data suggest feasibility of an innovative home PA intervention in children treated for brain tumors and provides preliminary evidence of increased MVPA and potential cognitive benefit to support a larger RCT.</p></sec></sec><sec id="pbc26772-sec-9030"><title>Treatment and Care ‐ Nursing</title><sec id="pbc26772-sec-9040"><label>P-495</label><title>Developing Resources on Positive Attitudes and a Sense of Purpose to Gain Resilience in Adolescents with Cancer</title><p><underline underline-style="single">I. Akiko</underline><sup>1</sup>, K. Kamibeppu<sup>1</sup></p><p><italic><sup>1</sup>Graduate School of Health Sciences & Nursing Faculty of Medicine, The University of Tokyo</italic></p><p><bold>Background</bold>: Adolescents with cancer (AWC) show the strengths of a positive attitude and sense of purpose. The resources refer to maintain peers, school life, social relationships, and a normal life. The purpose of this study was to develop the resources on the positive attitude and the purpose to gain resilience in the AWC.</p><p><bold>Methods</bold>: Yin's descriptive case study was used. The study was approved by the institutional review board. The semi‐structured interview guide was performed face‐to‐face by an author in a private room. The cancer experience, coping strategies, hope, and social support in the 4 phases (the early inpatient, the inpatient, the near discharge, and the outpatient) were asked. The interview was lasted between 45 to 70 minutes.</p><p><bold>Results</bold>: The 9 participants comprised; 6 males and 3 females, 12 to 18 years old, and 1 to 17 months of being an outpatient. The interview data was classified in the resources on the positive attitude and the purpose in the 4 phases. The results were exhibited the graphical patterns in the newly diagnosed AWC and the other one. The average of the patterns was shown in the temporal patterns. The wave of the positive attitude was higher than it of the purpose. The positive attitude encountered the gently wave path with low, up, and down between the 4 phases. The purpose was the steep one with up between in the inpatient and the near discharge. The resources were found that the parent(s) and the friends were used more than the others. The parent(s) worked more in the early inpatient phase and the friends did more after the phase.</p><p><bold>Conclusions</bold>: The AWC used the resources depends on the phases. They had fewer resources to make the purpose. The some interventions may need them to make the purpose and to improve the resilience.</p><p><bold>Keywords</bold>: adolescents with cancer, resilience, resources, positive attitudes, a sense of purpose</p></sec><sec id="pbc26772-sec-9050"><label>P-496</label><title>Technology Solutions to Promote Medication Adherence: Perceptions of Parents of Childhood Cancer Patients</title><p><underline underline-style="single">C. Baggott Do not use</underline><sup>1</sup></p><p><italic><sup>1</sup>Stanford University, Cancer Clinical Trials Office, Palo Alto, USA</italic></p><p><bold>Background/Objectives</bold>: Children with cancer require complex home medication regimens, typically facilitated by their parents. Despite the critical nature of these drugs, nonadherence to these regimens is commonplace, related to intentional factors (e.g., avoidance of toxic effects) or unintentional factors (e.g., forgetfulness, medication errors). Medication non‐adherence has been linked to poor outcomes among children with cancer. A thorough and accurate assessment of patients’ medication use is essential. When collected in real‐time, these data can: promote early detection of untoward symptom patterns; identify patient/family misconceptions of medication regimen details; identify patients/families who struggle with medication adherence; and provide required data for. clinical trials. The current practice of interviewing parents to elicit drug use over the prior weeks is time consuming and prone to recall errors. Furthermore, this practice does not provide feedback on medication use patterns. While numerous technology solutions (e.g., smartphones, smartwatches, electronic pillboxes) are available to promote medication adherence, their efficacy has not been evaluated. In a sample of parents of childhood cancer patients, the primary objective of this project is to determine the challenges in existing medication administration/recording practices and the optimal features to include in technology solutions for medication tracking.</p><p><bold>Design/Methods</bold>: Parents of children who are receiving chemotherapy for cancer will participate in semi‐structured interviews to elicit their perceptions of challenges in medication adherence and their views on technology available and potential technology solutions to facilitate medication tracking and promote adherence to medication regimens. The sample will consist of 15 mothers or fathers whose children have received chemotherapy for at least 6 months and remain on treatment at the time of the interview.</p><p><bold>Results</bold>: Results will be summarized in poster format.</p><p><bold>Conclusions</bold>: Eliciting views of challenges and solutions for medication tracking from parents of childhood cancer patients may inform strategies to promote successful adoption of technology solutions to promote medication adherence.</p></sec><sec id="pbc26772-sec-9060"><label>P-497</label><title>Paying it Forward: The Shared Knowledge of Pediatric Nursing Care from the United States to the West Bank Palestine and Beyond</title><p><underline underline-style="single">J. Bartholomew</underline><sup>1</sup>, M. Freha<sup>2</sup></p><p><italic><sup>1</sup>Children's Mercy Hospital, Hematology/Oncology, Kansas City, USA; <sup>2</sup>Huda Al Masri, Pediatric Oncology, Beit Jala, Palestinian Authority</italic></p><p><bold>Background/Objectives</bold>: Due to political and economic forces, children with cancer in Palestine had essentially no access to care. In 2013, the vision to develop a regional pediatric oncology center became a reality. A collaborative effort to maximize the care available to these children was established between Kansas City (KC), United States and Beit Jala (BJ), Palestinian Territory.</p><p><bold>Design/Methods</bold>: A series of training sessions by nurses from KC were provided. Initially nursing education focused on the oncologic diseases that were anticipated to be seen and the emergent care that would be needed. As the center in BJ developed, nursing education progressed to infection control, safe handling of agents and patient supportive care. The focus most recently has shifted to the development of nursing policies and procedures to provide consistent care and in the strengthening of interdisciplinary communication. A questionnaire was provided to the nurses at Huda Al Masri Pediatric Cancer Department to assess nursing care and level of comfort both prior to and post the educational sessions related to:</p><p>Chemotherapy safety</p><p>Supportive care</p><p>Patient/family education</p><p>Consistency of care</p><p>Team communication</p><p><bold>Results</bold>: The questionnaire clearly demonstrated the confidence in nursing care that has developed through the educational interventions provided by KC. Nurses at Huda Al Masri acknowledge the ability to safely provide care, educate the patients and families on the diagnosis and treatment side effects and advocate for their patients in a receptive team environment</p><p><bold>Conclusions</bold>: Knowledge gained regarding oncologic diagnoses, processes, treatments and emergency management has increased nursing ability to confidently provide quality care. The success of this BJ program is now being replicated in Gaza.</p></sec><sec id="pbc26772-sec-9070"><label>P-498</label><title>Care Plan for Mucositis in Thalassemia Patients after Haploidenticalhematopoietic Stem Cell Transplantation</title><p><underline underline-style="single">J. Chanapai</underline><sup>1</sup>, P. Aimsirirak<sup>1</sup>, S. Suksalee<sup>1</sup>, P. Nakvijit<sup>1</sup>, S. Ritthisong<sup>1</sup>, N. Wongsingrad<sup>1</sup>, S. Pakakasama<sup>2</sup>, P. Chiraporn<sup>1</sup></p><p><italic><sup>1</sup>Samitvej Children's hospital, Pediatric onco/Hemato and HSCT, Bangkok, Thailand; <sup>2</sup>Mahidol university, Pediatric Oncology, Bangkok, Thailand</italic></p><p><bold>Background/Objectives</bold>: Background; Mucositis is a common complication in patient' underwent hematopoietic stem cell transplantation (HSCT).</p><p>Mucositis is graded from mild sympyoms to severe pain and unable to eat causing nutritional insufficiency. Care plan for mucositis may help to relief patients' suffering and improve their nutrition status.</p><p><bold>Objective</bold>: To develop care plan for mucositis in thalassemic patients after heploidentical Hematopoietic stem cell transplantation(HSCT)</p><p><bold>Design/Methods</bold>: Methods; We retrospectively analyzed frequency and severity of mucositis in patients with Thalassemia after haploidentical Hematopoietic stem cell transplantation(HSCT) and developed care plan using the collected data of mucositis.</p><p><bold>Results</bold>:
<list list-type="order" id="pbc26772-list-0021"><list-item><p>There were 18 severe beta ‐ thalassemic patients,with a median age of 7.3 years (range 2.1‐27 years), receiving hematopoietic stem cells from mothers or fathers at our insttute between January 2015 and December 2016.</p></list-item><list-item><p>The preparative regimen included rabbit antithymocyte globulin, fludarabine and intravenous busulfan.</p></list-item><list-item><p>All of patients developed mucositis with severity of grade3 (n=8) and grade 4 (n =10).</p></list-item><list-item><p>We recorded mucositis grading everyday and found that patient suffered withmucositis during the first 2 weeks after HSCT. Grade 1 occurred between day +2 and +4, grade 2 between day +2 and +6, grade 3 between day +6 and +12 and grade 4 between day +8 and +16. Using this data, we have planned for our nursing care as(1) evaluating nutrition intake and support since day +1, (2) changing oral is intravenous medications since day +6, (3) considering parenteral nutrition since day +6,(4) weaning parenteral support and encouraging oral intake since day +16. As a result, the median length of stay was only 22 days.</p></list-item></list></p><p><bold>Conclusions</bold>: Using data of mucositis,We successfully developed and used our care plan for mucositis in Thalassemia patients undergoing Hematopoietic stem cell transplantation(HSCT).</p></sec><sec id="pbc26772-sec-9080"><label>P-499</label><title>Prevention of Severe Incontinence‐Associated Dermatitis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant</title><p><underline underline-style="single">K. Coish</underline><sup>1</sup>, K. Ridgway<sup>1</sup>, B. patteson<sup>1</sup>, A. mahoney<sup>1</sup>, E. Postell<sup>1</sup>, S. malone<sup>1</sup></p><p><italic><sup>1</sup>Children's National Health System, Heme/Onc/HSCT unit, Washington‐ DC, USA</italic></p><p><bold>Background/Objectives</bold>: Hematopoietic stem cell transplants (HSCT) registered nurses in our institution noted an increased incidence of severe incontinence‐associated dermatitis (IAD), defined by perianal excoriation, in diapered patients undergoing HSCT. Myeloablative preparative regimens required for HSCT induce prolonged neutropenia, increased risk of infection, and delayed wound healing, increasing the risk of skin breakdown. This preventable complication causes increased pain, costs, and length of stay.</p><p><bold>Design/Methods</bold>: Cyanoacrylate liquid skin barrier has been used with positive outcomes to treat and expedite healing of IAD. Through an interdisciplinary quality improvement (QI) project, our HSCT team implemented prophylactic use of cyanoacrylate on incontinent patients undergoing HSCT. Patients who met eligibility and consented began prophylactic perianal cyanoacrylate use upon admission for their myeloablative preparatory regimen. Use of cyanoacrylate continued through engraftment. Incontinent patients receiving thiotepa were excluded until adhesive products were permissible. Skin and Wound Team members provided education to staff and caregivers on application of cyanoacrylate. Providers added cyanoacrylate application to orders on eligible and consenting HSCT patients.</p><p><bold>Results</bold>: Sixty seven percent of patients who met criteria participated in the preventative application of cyanoacrylate to the perianal area. No perianal breakdown was observed on these four patients during their HSCT admission. The remaining two patients (33%), who did not to consent to cyanoacrylate, experienced severe IAD necessitating wound consultation and intravenous pain medication. One patient developed incontinence after admission, prompting immediate implementation of preventative cyanoacrylate. This patient did not develop IAD.</p><p><bold>Conclusions</bold>: The use of cyanoacrylate in vulnerable pediatric patients can prevent life‐threatening infection due to skin breakdown. This succesful quality initiative is innovative and cost‐effective. This project can be expanded to meet the needs of other incontinent patients at risk for severe IAD.</p></sec><sec id="pbc26772-sec-9090"><label>P-500</label><title>Improving Patient Care for Hispanic Pediatric Oncology Patients with Limited English Proficiency</title><p>T. Flatt<sup>1</sup>, <underline underline-style="single">T. Torres</underline><sup>1</sup></p><p><italic><sup>1</sup>Children's Mercy Hospital, Pediatric Hematology/Oncology, Kansas City, USA</italic></p><p><bold>Background/Objectives</bold>: Caregivers of pediatric oncology patients with limited English proficiency face challenges as they navigate the English speaking medical system in the US. Our objective is to present bilingual materials that have improved patient care and compliance.</p><p><bold>Design/Methods</bold>: This is a description of materials that have been successfully utilized to improve patient care services and medical compliance for Hispanic caregivers with limited English proficiency. The materials will be demonstrated in the poster.</p><p><bold>Results</bold>: Bilingual patient face sheets that include cancer diagnosis, central line details, oncology contact information and strict instructions regarding time to collect blood cultures and initiate antibiotics for patients with cancer are provided to caregivers for medical visits outside of our facility. Many patients live long distance from our main hospital with no on‐site language interpreter and this tool has decreased triage time and shortened time to obtain antibiotics for patients with fever and neutropenia. Bilingual medication calendars and medication lists have improved compliance including adherence to oral chemotherapy. A bilingual oncology essentials entailing side effects to monitor at home and parameters for when to contact provider services. The use of bilingual pill boxes (made by our medical team) have proven instrumental in medication adherence in complicated experimental therapeutic protocols that do not permit deviation from the protocol.</p><p><bold>Conclusions</bold>: Appropriate bilingual materials can improve patient care access, decrease triage times, time to antibiotic administration and improve medication compliance.</p></sec><sec id="pbc26772-sec-9100"><label>P-501</label><title>Role of Nursing Care in the Management of Burkitt's Lymphoma Patient During Inpatient Stay after First Cycle of Intense Chemotherapy Copadm Post Complications</title><p><underline underline-style="single">R.N. Gill</underline><sup>1</sup>, H. Khan<sup>1</sup>, N. Patrus<sup>1</sup>, A.N. Gill<sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Memorial Cancer Hospital and Research Center, Pediatric Oncology/Hematology Inpatient department, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: This Study permits us to know the nursing care convention gave by nurses at Shaukat Khanum Memorial Cancer Hospital and Research Center to the patient with Burkitt lymphoma got first cycle of COPADM. Nurses are challenged by the complexity of the therapy regimen & the management of acute and long term effects & toxicities. Nursing care include symptoms management,encouragement and support to the patients during hospital stay</p><p><bold>Design/Methods</bold>: We retrospectively investigated nursing notes of 30 patient of Burkitt's lymphoma patients received first cycle COPADM at Shaukat Khanum Memorial Cancer Hospital and Research Center during the year December 2016 to Jan 2017. Information including age, sex, financial status & duration of hospital stay. Common issues experienced were completely examined. Nurse's notes were evaluated in regards to motivational and dietary advising.</p><p><bold>Results</bold>: 30 patients reviewed 28 were male. Median age of diagnosis was 14 years. All of these patients were admitted though EAR after 5‐7 days of post COPADM. During hospital stay, Nurse to patient proportion was 1:6. Span of Hospital stay was 10‐14 days. Symptoms persisting for 7 days or more included Oral Mucositis (56%), Nausea (46%), Diarrhea (29%), fever (25%). Oral intake was decreased in 62% (n=19) primary contributing element was oral mucositis (n=18), nausea vomiting (n=14) abdominal discomfort (n=8) and disliking the food (n=6). Persistent nursing care including regular oral care and counseling for dietary improvement. 62% patients (n=19) were encountered by psychological disturbance, eminent reasons were social separation, home sickness, fear of disease progression & long term toxicities of chemotherapy. Frequent counseling session by attending nurses were conducted with active listening, employing play therapy (n=12), provision of Cartoon Movies (n=19) & story books (n=10)</p><p><bold>Conclusions</bold>: Individual assessment and dedicated efforts by nursing staff can facilitate these patients to cope with the problems encountered after receiving first cycle of intense chemotherapy COPADM.</p></sec><sec id="pbc26772-sec-9110"><label>P-502</label><title>The Feasibility of a Tool to Systematically Evaluate Nursing Care Needs of Children with Cancer and Utilization of Nursing Resources</title><p><underline underline-style="single">H. Hansson</underline><sup>1</sup>, G. Petersen<sup>1</sup>, M. Madsen<sup>1</sup>, P. Roland<sup>1</sup>, A.B. Christensen<sup>1</sup>, M. Nøddeboe<sup>1</sup></p><p><italic><sup>1</sup>Copenhagen University Hospital ‐ Rigshospitalet, Paediatric Haematology and Oncology Department, Copenhagen, Denmark</italic></p><p><bold>Background/Objectives</bold>: As a result of more intensive and complex treatment regimens, our patients have increasing multi‐faceted needs for nursing care. We developed a tool called PIMI to systematically document and measure nursing care needs of children with cancer and the use of nursing resources. The objective of this study was to assess the feasibility of the tool and the balance between nursing care needs and the amount of nursing resources the needs demand.</p><p><bold>Design/Methods</bold>: PIMI is recorded daily and comprises two parts: 1) a classification in which the patient's needs for nursing care are evaluated and placed in one of six care categories, which refers to an optimal number of nurses needed to meet the patient's needs, and 2) a comparison of the optimal number of nurses with the actual number of nurses available. The inter‐rater reliability was studied and it will be statistically validated in 2017. Data were collected for 179 days at our pediatric hematology oncology ward with 21‐inpatient beds between February and December 2016 and were analyzed with descriptive statistics.</p><p><bold>Results</bold>: The ward had 150 days (84%) below the optimal nursing staffing, 3 days on the optimal level, and 26 days (14%) above the level. The daily average was: 17 in‐patient children (range 9‐23), the optimal number of nurses needed: 10 (range 5‐16), the actual number of nurses in nursing care: 8 (range 5‐11), and number of nurses in nursing care with < 1 year of experience: 2 (range 0‐6).</p><p><bold>Conclusions</bold>: PIMI is easy and accurate to use. The results document that the children's needs for nursing care do not match with the actual staffing level. PIMI can be used to the daily allocation of nurses based on the children's nursing care needs, and to manage nursing resources most appropriate in the long‐term.</p></sec><sec id="pbc26772-sec-9120"><label>P-503</label><title>A Meta‐Analysis and Systematic Review of the Effect of Low‐Level Laser Therapy in Pediatric Chemotherapy‐Induced Oral Mucositis</title><p><underline underline-style="single">M. He</underline><sup>1</sup>, N. Shen<sup>2</sup>, J. Sun<sup>2</sup></p><p><italic><sup>1</sup>Shanghai Children's Medical Center, Hematology and Oncology, Shanghai, China; <sup>2</sup>Shanghai Children's Medical Center, Nursing Department, Shanghai, China</italic></p><p><bold>Background/Objectives</bold>: Background</p><p>Oral mucositis is one of the most frequent complications after chemotherapy, occurring in approximately 52% to 80% of children receiving treatment for cancer. Recently, it has been suggested that the use of low‐energy laser could reduce the grade of oral mucositis and alleviate the symptoms. Most of recommendations were made for adult patients, not pediatric patients. Data about effect of low‐level laser therapy in pediatric patients is limited.</p><p>Objective</p><p>To synthesize the available clinical evidences on the effects of low‐level laser therapy (LLLT) in the prevention and treatment of chemotherapy‐induced oral mucositis (OM).</p><p><bold>Design/Methods</bold>: A meta‐analysis was performed using trials identified through Pubmed (1966 to March 2017), EMbase (1980 to March 2017), Cochrane Library (up to 2016), CNKI (in Chinese, 1980 to March 2017). Data on occurrence, duration and severity of oral mucositis were collected. All randomized controlled studies and clinical controlled studies comparing LLLT to routine qualified prevention or treatment during or after chemotherapy were critically appraised and analyzed.</p><p><bold>Results</bold>: We found 5 qualified clinical trials with a total of 295 pediatric patients; methodological quality was acceptable. After meta‐analysis, there was a significant preventive effect of LLLT with a relative risk at 0.34 (95% CI, 0.12 to 0.99) for grade II or higher OM to occur, but no significant preventive effects with a relative risk at 0.82 (95% CI, 0.60 to 1.11) for all OM to occur. After prophylactic LLLT, the OM severity could decrease significantly, with combined effect size ‐0.54 (95% CI, ‐1.87,‐0.03). No meta‐analysis could be done with the effect of LLLT on treatment of OM</p><p><bold>Conclusions</bold>: Recommendation could be made to support LLLT on prevention of OM in pediatric patients. Effect of LLLT on treatment of OM could be promising, to decrease pain and duration. Future research should identify the proper characteristics of LLLT and determine feasibility in the clinical setting.</p></sec><sec id="pbc26772-sec-9130"><label>P-504</label><title>Developing Resources to Gain Resilience in Adolescents with Cancer</title><p><underline underline-style="single">K. Kamibeppu</underline><sup>1</sup></p><p><italic><sup>1</sup>Graduate School of Health Sciences & Nursing Faculty of Medicine‐ The University of Tokyo, Department of Family Nursing, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: Positive health is defined as developing strengths and resources to gain resilience. The resources refere to maintaining peers, school life, social relationships, and a normal life. The purpose of this study was to develop the resources to gain the positive attitude and the purpose (resilience) in adolescents with cancer (AWC).</p><p><bold>Design/Methods</bold>: Yin's descriptive case study was used. The data were analyzed with the pattern‐matching logic. This study was approved by the institutional review board. The physicians identified potential participants from their appointment list. The semi‐structured interview guide and Social Network Map were used to assess. The tools were performed face‐to‐face by an author in a private room and lasted between 45 to 90 minutes and occurred while the participants were waiting for the results of a blood test. The interview proceeded from a broad and safe question to a specific and sensitive one. The participants were asked about the cancer experience, positive coping, hope and social support. The same researcher conducted the all interviews. The demographic and the health information were obtained form the patient charts.</p><p><bold>Results</bold>: The 9 participants comprised 6 malls and 3 females. Five of them were newly diagnosed, and 4 had experienced relapse. the ages pf the newly diagnosed participants reed from 13 to 17 years, and the participants who had relapsed were aged between 12 and 17 years.</p><p><bold>Conclusions</bold>: The positive attitude and the purpose were related to the resources.</p></sec><sec id="pbc26772-sec-9140"><label>P-505</label><title>The Scope of Practice for Advanced Practice Nurses Working with Short Term Global Health Programs</title><p><underline underline-style="single">P. Johnson</underline><sup>1</sup></p><p><italic><sup>1</sup>Children's Mercy Hospital, Hematology/Oncology, Kansas City, USA</italic></p><p><bold>Background/Objectives</bold>: Advanced practice registered nurses (APRNs) are an essential part of the US health care system and many seek to volunteer for short term global health programs to further expand their worldviews and provide care to marginalized populations. The International Council of Nurses (ICN) created a Scope of Practice and a Code of Ethics to be followed for APRNs practicing internationally, however this is not widely known. In addition, many countries do not fully recognize the APRN role and what healthcare services they can or cannot provide.</p><p><bold>Design/Methods</bold>: The purpose of the project was to explore APRNs perceptions of their scope of practice and current international standards of practice. A 21 item Survey Monkey© in 2016, was conducted among members of the American Academy of Nurse Practitioners International Special Interest group who had participated in international short term global health programs. Participants were asked about scope of practice used with international practice, awareness of practice guidelines and ethical dilemmas encountered regarding scope of practice.</p><p><bold>Results</bold>: Nineteen respondents qualified for the survey. Half were family nurse practitioners and had participated in five or more trips internationally. Over 50% believed they were recognized as an APRN but many of the countries listed do not recognize APRNs. Over 60% followed their US scope of practice. Some expressed concerns about the number of patients to be seen with limited resources but 90% expressed a love of the work did not feel ethically challenged. Ethics of practice ranged from national guidelines to personal beliefs.</p><p><bold>Conclusions</bold>: As APRNs participate more in short term global health programs, mindfulness of the host and country expectations regarding scope of practice and national recognition of their role. Continued discussion of international roles of APRNs will help increase access to vulnerable populations and reduce stress to the providers.</p></sec><sec id="pbc26772-sec-9150"><label>P-506</label><title>A Case Study Approach to Understanding the Value of Blogging for Social Support in Parents of Children Who Have Completed Cancer‐Directed Treatment</title><p><underline underline-style="single">M. Killela</underline><sup>1</sup>, S. Santacroce<sup>2</sup></p><p><italic><sup>1</sup>University of North Carolina at Chapel Hill, Nursing, Raleigh, USA; <sup>2</sup>University of North Carolina at Chapel Hill, Nursing, Chapel Hill, USA</italic></p><p><bold>Background/Objectives</bold>: Completion of cancer‐directed treatment contains a very stressful transition for children with cancer and their families. The stress associated with this time period is amplified when the social supports that are associated with regular hospitalizations and outpatient visits are less frequent and thus a gap in the social network of families is created. The use of social media presents a possible source of support to fill this gap. This exploratory study aims to qualify the types of support evident in one family's publicly available online blog detailing their experiences in the period following completion of cancer‐directed treatment.</p><p><bold>Design/Methods</bold>: By implementing Schaefer's theory of social support, which differentiates among emotional support, information support, and tangible support (1981), this paper used directed content analysis to scrutinize blog posts written in the six‐months following cancer‐directed treatment completion and to sort the content by social support domain.</p><p><bold>Results</bold>: The most common form of social support observed was information support in two categories: information about medical procedures and information about family life. The second most common form of social support was emotional support, which was divided into expression of fear and stress associated with both disease recurrence and the quest to achieve a new normal. Lastly, the third form of social support, tangible support, was the least common and expressed mostly in terms of gratitude for such support.</p><p><bold>Conclusions</bold>: This paper serves to provide information necessary for future studies in developing a nursing intervention to widely distribute blogging as a means of improving social support among parents and caregivers of children who have completed cancer‐directed treatment.</p></sec><sec id="pbc26772-sec-9160"><label>P-507</label><title>A Study on Preparation Utilizing a Picture Book at Hospitalization: for Patients of 3‐10 Years Old</title><p><underline underline-style="single">N. Nakagaki</underline><sup>1</sup></p><p><italic><sup>1</sup>Wayo Women's University, Nursing, Ichikawa, Japan</italic></p><p><bold>Background/Objectives</bold>: The purpose of this study is to make clear how preparation utilizing a picture book influenced the children's coping ability when being admitted to a hospital.</p><p><bold>Design/Methods</bold>: The subjects of this study were eight children of 3‐10 years old with leukaemia. During the children's hospitalization, nurses explained children the necessity of their hospitalization, visiting hour, hospital life and various staff using a picture book. Time of the explanation was 20‐30 minutes. They were hospitalized for the first time in a C ward for a hospitalization period of 3‐7 days. Data was collected on the 1st day, the 2nd day and the last day of the hospitalization by means of participation observational method. The children's reactions toward hospitalization were observed. We analyzed and coded the children's reaction focusing on the state of their hospital life. The coded results were classified to subcategories, categories and then core categories.</p><p><bold>Results</bold>: The derived 7 core categories are as follows:</p><p>[Children made up their mind to be staying in the hospital by joining preparation during hospitalization.] [They made an effort in order to get over loneliness staying away from their family.] [They could spend their hospital life depending on nurses.] [They spent the hospitalization with the relaxed feelings] [They had positive feelings toward the hospital life] [They could positively receive medical practice.] [They persevered in the hospitalization and had the feeling of achievement.]</p><p><bold>Conclusions</bold>: Children became able to imagine a hospitalization life somehow because they received preparation with their family's cooperation. Children were able to communicate with a nurse by sharing a picture book in preparation for hospitalization. Therefore children could build mutual trust relationship with a nurse and entrust a nurse with their hospital life. We consider children can evade prospective critical situation in hospitalization by receiving preparation utilizing a picture book.</p></sec><sec id="pbc26772-sec-9170"><label>P-508</label><title>The Actual Situation of Preventive Measures Against Exposure to Anticancer Drugs in Japan</title><p><underline underline-style="single">J. Ogawa</underline><sup>1</sup>, M. Kudo<sup>2</sup>, M. Baba<sup>3</sup>, T. Watanabe<sup>4</sup>, K. Sakuta<sup>2</sup>, Y. Ohara<sup>2</sup></p><p><italic><sup>1</sup>Shukutoku University, School of Nursing&Nutrition, Chiba, Japan; <sup>2</sup>Chiba Children's Hospital, Nursing, Chiba, Japan; <sup>3</sup>Teikyo University Medical Center, Nursing, Ichihara, Japan; <sup>4</sup>Chiba University Hospital, Nursing, Chiba, Japan</italic></p><p><bold>Background/Objectives</bold>: A guideline on preventing occupational exposure to anticancer drugs was published in 2016 in Japan. It is, however, insufficient to cover the pediatric oncology area. This study aimed to find the perception of occupational exposure among pediatric oncology nurses.</p><p><bold>Design/Methods</bold>: The original questionnaires about the preventing occupational exposure were mailed to nurses working for 104 hospitals (3 nurses from each hospital) where cancer children were treated.</p><p><bold>Results</bold>: Got 107 nurses (34.3%) responded including 86 nurses (80%) who reported they have hospital rules for occupational exposure. And found 78 nurses (73%) take some preventing measures for disposal of child excreta and 60 nurses of them educate family caregivers of children about preventing exposure.</p><p>Eighty‐seven nurses (81%) take preventing measures for handling linen contaminated with excreta, while only 38 nurses (36%) explain about doing the laundry or taking laundry home to families. Specific exposure measures concerning the handling of excreta and linen were various, such as wearing only gloves and using some of personal protective equipment.</p><p>Fifty‐five nurses (51%) clean children at the time of diaper changing. 19 nurses (18%) apply ointment for protecting themselves from exposure before administrating anticancer drug to children.</p><p>Seventy‐seven nurses (71%) responded that they put on gloves for protection at the time of oral anticancer drug administration, and 64 nurses (60%) explain family caregivers about its importance. 55 nurses(51%) take preventing measures for handling empty bags of oral anticancer drugs.</p><p><bold>Conclusions</bold>: It's clear that preventing exposure to anticancer drugs for medical staff in pediatric oncology ward is not sufficient and need for guidelines specialized in childhood cancer treatment because patient's siblings or mother who gets pregnant are much more vulnerable than ordinal adults.</p></sec><sec id="pbc26772-sec-9180"><label>P-509</label><title>The Introduction and Collaboration of Pharmacy Technicians to the Drug Adminsitration Process with Nurses Increases Saftety and Releases Time to Care</title><p><underline underline-style="single">H. Petts</underline><sup>1</sup></p><p><italic><sup>1</sup>Birmingham Childrens Hospital, Haematology/ Oncology, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: The complexity, number and cost of medications within oncology has continued to rise.</p><p>Nurses in a busy 27 bedded Principal Treatment Centre were reporting they were spending less time with patients at the bedside and more time in the drug preparation rooms. Families commented they always knew where to find a nurse; in the drug preparation room. This was compounded by the Trust's drug administration policy required 2 trained staff for the whole process.</p><p>The project sought to explore the possibility of pharmacy technicians being part of this traditional nurse's role (from preparation of a drug trolley and medicines through to the documentation of the administration being complete) thus releasing nurse's time to care in a health‐ economy where paediatric nurse recruitment was challenged. Further objectives were to improve timely delivery of medicines; reducing avoidable medicines waste and integrate the pharmacy role into the paediatric oncology ward team;ncreasing efficiency.</p><p><bold>Design/Methods</bold>: Initial observational studies were undertaken to identify the busiest time of day for intravenous and oral drug administration.This time was used to focus the initial intervention with the aim of maximum impact. A training package was disseminated for the technicians and checklists introduced based on monographs.</p><p><bold>Results</bold>: Each oral drug round undertaken by the nurse + pharmacy technician has reduced from an average of taking 61minutes to 41 minutes releasing time for “nurses to care”.</p><p>Additionally there was a reduction of 1‐3 medication/ prescribing errors/ near miss incidents per day.</p><p><bold>Conclusions</bold>: The pharmacy technician – nurse combination to oral and intravenous medication administration has improved the patient / staff experience and released nurse's time.</p><p>There continues to be a high incident reporting culture within the clinical area but the overall associated harm level has reduced and a proactive protocol driven approach to safety of medications has been embedded.</p></sec><sec id="pbc26772-sec-9190"><label>P-510</label><title>Symptom Patterns in Children Recovering from Hematopoietic Stem Cell Transplant</title><p><underline underline-style="single">C. Rodgers</underline><sup>1</sup>, M. Highberger<sup>2</sup>, K. Voigt<sup>2</sup>, K. Powers<sup>3</sup></p><p><italic><sup>1</sup>Duke University, School of Nursing, Durham, USA; <sup>2</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>3</sup>Ann & Robert H. Lurie Children's Hospital, Stem Cell Transplant, Chicago, USA</italic></p><p><bold>Background/Objectives</bold>: Hematopoietic stem cell transplantation (HSCT) causes frequent and distressing symptoms that continue through the first 100 days post HSCT, known as the acute recovery phase. Current HSCT symptom research focuses on symptom prevalence at specific points in time with little evidence regarding the complexity of symptoms and their changes over time. The primary aim of the study is to identify symptom trajectory patterns among adolescents during acute HSCT recovery.</p><p><bold>Design/Methods</bold>: A repeated measures design was used to elicit symptoms experiences from 55 adolescents, age 10‐19 years, who received an allogeneic HSCT. After signed consent/assent, demographic information was obtained from the medical record and adolescents completed the Memorial Symptom Assessment Scale (MSAS) prior to HSCT. Adolescents completed the MSAS again at one, two, and three months post HSCT.</p><p><bold>Results</bold>: Data collection will be completed in June. Symptom trajectories will include symptom frequency, severity, and distress and evaluations will occur separately for these three symptom characteristics. Descriptive statistics and standard linear regressions will be used to examine the data over time.</p><p><bold>Conclusions</bold>: Findings from this study will allow healthcare providers to easily recognize and even anticipate their patients’ symptoms during acute HSCT recovery. These providers can have meaningful symptom discussions with their patients to provide anticipatory guidance and promote strategies that can best help patients manage their symptoms.</p><p>This study was funded by Alex's Lemonade Stand Foundation.</p></sec><sec id="pbc26772-sec-9200"><label>P-511</label><title>Feasibility of Measuring Carotid‐Femoral Pulse Wave Velocity (PWV) During Clinical Visits to Estimate Risk for Cardiovascular Disease (CVD) in New Survivors of Childhood Cancer</title><p><underline underline-style="single">S. Santacroce</underline><sup>1</sup>, J. Crandell<sup>1</sup>, J. Bai<sup>2</sup>, J. Blatt<sup>3</sup>, S. Gold<sup>3</sup></p><p><italic><sup>1</sup>The University of North Carolina at Chapel Hill, School of Nursing and Lineberger Comprehensive Cancer Center, Chapel Hill, USA; <sup>2</sup>Emory University, Nell Hodgson Woodruff School of Nursing, Atlanta, USA; <sup>3</sup>The University of North Carolina at Chapel Hill, School of Medicine and Lineberger Comprehensive Cancer Center, Chapel Hill, USA</italic></p><p><bold>Background/Objectives</bold>: Carotid‐femoral pulse wave velocity (PWV) is an accurate non‐invasive means to estimate arterial stiffness and thus risk for CVD in adults. The study purpose was to examine feasibility of measuring PWV during clinical visits to estimate risk for CVD in children who recently completed cancer therapy and relate PWV measurements to reference values.</p><p><bold>Design/Methods</bold>: Included: children aged 8‐19 years and 1‐4 months post treatment with treatment regimen that incorporated anthracyclines. Excluded: children with history of another medical condition (e.g., diabetes) known to heighten risk for CVD. A SphygmoCor Px device (Atcor, Sydney Australia) interfaced with a laptop computer was used to conduct PWV measurements. Trained professionals performed anthropometric measurements (e.g., weight, height, blood pressure, surface distance carotid site to jugular notch and jugular notch to femoral site) and entered them into the laptop for PWV calculation. PWV measurements were discarded and repeated if heart rate varied >10% between carotid and femoral site captures.</p><p><bold>Results</bold>: Most of the 23 participants were male (52%), white (82%), and non‐Hispanic (74%) with mean age of 12.26 ±3.16 years and mean time since treatment 2.30 ±1.06 months. The device tonometry probe failed during preparations in clinic for the first data collection. We had a second probe on hand and experienced no further technical issues. All participants lay quietly on an exam table and otherwise cooperated with PWV measurements. Femoral site captures were challenging but achieved for the 5 participants (22%) with body mass index (BMI) z‐scores >2. Plots compare PWV measurements to reference values for healthy children by sex and age, and show associations between PWV and BMI z‐scores.</p><p><bold>Conclusions</bold>: Measurement of PWV during clinical visits for children who recently completed cancer therapy is feasible. PWV measurements have potential to both inform and evaluate precision interventions to control risk for CVD in new survivors of childhood cancer.</p></sec><sec id="pbc26772-sec-9210"><label>P-512</label><title>Establishment of A Guideline to Facillitate Adjustment on School Reentry for Children with Cancer in Japan</title><p><underline underline-style="single">G. Sayaka</underline><sup>1,2</sup>, S. Hitoshi<sup>1</sup>, M. Kimikazu<sup>3</sup></p><p><italic><sup>1</sup>Tohoku University Graduate School of Medicine, Department of Child Health Nursing, miyagi, Japan; <sup>2</sup>National Center for Child Health and Development, Nursing Department, tokyo, Japan; <sup>3</sup>National Center for Child Health and Development, Children's Cancer Center, tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: Children and adolescents with cancer face the difficulty to return to schools after completion of the therapy. There is no standard guideline for supporting to school reentry for children with cancer in Japan.In this study, we aim to develop a guideline for assessing the support of school reentry for children with cancer, providing equality in this situation in Japan.</p><p><bold>Design/Methods</bold>: First, we identified 39 papers from an online literature retrieval system of past 10 years using search words such as “childhood cancer,” “chronic disease,” and “school reentry”, and collected fundamental information to establish a guideline. Five experts in medical care or educational research on children with cancer evaluated those papers using the Delphi method. Subsequently, a semi‐structured interview was conducted with 6 clinical nurses who specialize in pediatric cancer care, to confirm the validity of the guideline.</p><p><bold>Results</bold>: Although the supporting program of school reentry provided by hospitals in Japan varied, the basic elements were common. In addition to scheduling of the conference, and preparing requesting letters, we find it very important to affirm consensus between patients and their parents in the individual reentry plan.</p><p>The conference should be held with doctors and nurses in charge, class teachers and supervisors, and patient and parents soon after the completion of initial treatment and at two to four weeks before discharge. The points to be addressed in the meeting included the information of disease to the concerned people at school, and methods to facilitate adjustment to classmates, those concerned with schools, and the healthcare personnel involved.</p><p><bold>Conclusions</bold>: A guideline will provide concrete methods of school reentry for children with cancer to patients, parents, medical staffs, and educators, which will lead to fulfilling support for pediatric cancer patients.</p></sec><sec id="pbc26772-sec-9220"><label>P-513</label><title>Working for the Child´S Best by Creating a Sheltered Place During Chemotherapy for Paediatric Leukaemia</title><p><underline underline-style="single">C. Sjöberg</underline><sup>1</sup>, I.M. Carlsson<sup>1</sup>, P. Svedberg<sup>1</sup>, J. Källstrand Eriksson<sup>1</sup>, J. Nygren<sup>1</sup></p><p><italic><sup>1</sup>Halmstad University, School of health and Welfare, Halmstad, Sweden</italic></p><p><bold>Background/Objectives</bold>: Leukaemia is the most common cancer form for children worldwide. The disease encroaches on the child's daily life and influence on their living conditions and lifestyle. In addition to the disease itself, the treatment is an unpleasant experience that can cause pain, nausea and suffering. During treatment, the children stays at the hospital for long and frequent periods, which has a significant effect on their everyday life. Improvement and increased quality of care for children throughout their cancer trajectory is important and could lead to a better experience for children and reduced suffering related to the treatment.The objective was to explore the caring environment in accordance to sedation for chemotherapy in paediatric leukemia.</p><p><bold>Design/Methods</bold>: The study followed the approach of grounded theory and were based on interviews with practitioners involved in the paediatric oncology care process such as paediatricians (n=2), anaesthetists (n=2), child‐nurses (n=3) and nurse anaesthetists (n=5).</p><p><bold>Results</bold>: The main concern that emerged was “<italic>creating a sheltering place</italic>”, which means that all healthcare professionals works for the child´s best by providing sedation for chemotherapy at the children´s department instead of the operation theatre. The sheltering place consists of a familiar place, nearby the child´s hospital bed. The sheltering place creates an atmosphere that is embracing, calm and protects the child from the outside world. By reducing environmental difficulties and de‐dramatizing the event the sheltering place provides a temporary opportunity to feel safe and protected, which decreases the child´s anxiety and fear, and adapts the situation to the children´s needs. In doing so, the sheltering place minimizes the interference of the caring process on the child´s daily life.</p><p><bold>Conclusions</bold>: Working for the child´s best by creating a sheltering place during sedation for chemotherapy promotes adoption of a child‐centred approach.</p></sec><sec id="pbc26772-sec-9230"><label>P-514</label><title>How Hospital Environment Influences Children's Cancer Nursing in Japan</title><p><underline underline-style="single">M. Uchida</underline><sup>1</sup>, S. Takeuchi<sup>1</sup>, F. Shirai<sup>2</sup>, Y. Ohara<sup>3</sup>, N. Takenouchi<sup>4</sup>, M. hirata<sup>5</sup>, M. Adachi<sup>1</sup>, Y. Takahashi<sup>1</sup>, J. Nonaka<sup>6</sup>, J. Ogawa<sup>7</sup>, M. MOri<sup>8</sup></p><p><italic><sup>1</sup>Nagano College of Nursing, School of Nursing, Komagane, Japan; <sup>2</sup>Nagano College of Nursing, School ob Nursing, Komagane, Japan; <sup>3</sup>Chiba Children's Hospital, Department of Nursing, Chiba, Japan; <sup>4</sup>Kanagawa Children's Medical Center, Department of Maternal & Child Health, Yokohama, Japan; <sup>5</sup>St. Luke's International Hospital, Department of Nursing, tokyo, Japan; <sup>6</sup>Kanagawa University of Human Service, Child Health Nursing, Yokosuka, Japan; <sup>7</sup>Shukutoku University, School of Nursing & Nutrition, chiba, Japan; <sup>8</sup>University of Human Environments, Child Health Nursing, Okazaki, Japan</italic></p><p><bold>Background/Objectives</bold>: A Japanese Society of Pediatric Oncology Nursing study group developed “Nursing Care Guidelines for Children with Cancer 2012” to standardize children's cancer nursing in Japan in 2012.</p><p>In addition, we examined the degree of importance and the frequency of each nursing practice based on the guidelines to evaluate this guideline in 2016. As a result, nurses recognized that almost all nursing practices on the guideline were important. However, nurses felt difficulties implementing a few nursing care despite their recognition.</p><p>This study examines factors influencing nursing practice to improve children's cancer nursing in Japan.</p><p><bold>Design/Methods</bold>: We sent two different of questionnaires to 216 wards where children with cancer were hospitalized. The questionnaire is composed of the following two categories.</p><p>1. On frequency of nursing practice</p><p>Asked how frequently they bring their practice into action based on the 46 items in the Guidelines.</p><p>2. On their hospital environment</p><p>Asked how their team is composed, the arrangement of certified nurse specialist, and physical environment for children in their wards.</p><p>We analyzed answers from 56 wards that completely answered questions from two categories, in order to see the relationship between the frequency of nursing practice and their hospital environment. Out of this 56 wards, 43 were university hospitals, 7 were children's hospitals and 5 were general hospitals.</p><p>For data analysis, we conducted a Mann‐Whitney‐U test using SPSS statistics Ver.21.</p><p><bold>Results</bold>: We found that the following 4 hospital environment factors especially have strong influences to the frequency of the nursing practice.
<list list-type="simple" id="pbc26772-list-0022"><list-item><label>–</label><p>The arrangement of certified nurse specialist</p></list-item><list-item><label>–</label><p>The presence of “Nursing Care Guidelines 2012”in their wards</p></list-item><list-item><label>–</label><p>The presence of long‐term follow‐up system for children with cancer</p></list-item><list-item><label>–</label><p>The presence of teen room</p></list-item></list></p><p><bold>Conclusions</bold>: From the results, some of the influencing factors on the nursing practice have been revealed. Enhancing those factors in their wards will raise the quality of the nursing practice.</p></sec></sec><sec id="pbc26772-sec-9240"><title>Treatment and Care ‐ Biology and Pathology</title><sec id="pbc26772-sec-9250"><label>P-515</label><title>Characterization of the Immune Infiltrate in Pediatric Solid Tumors by Flow Cytometry</title><p>V. Botafogo<sup>1</sup>, C. Ferreira‐Facio<sup>1</sup>, P. Ferrão<sup>1</sup>, L. Castro<sup>1</sup>, E. de Oliveira<sup>1</sup>, <underline underline-style="single">M.C. Canellas</underline><sup>1</sup>, D. Vieira‐Lopes<sup>1</sup>, J. Almeida<sup>2</sup>, A. Orfao<sup>2</sup>, E. Sobral da Costa<sup>1</sup></p><p><italic><sup>1</sup>Federal University of Rio de Janeiro, Pediatric Institute IPPMG, Rio de Janeiro, Brazil; <sup>2</sup>University of Salamanca, Cancer Research Center, Salamanca, Spain</italic></p><p><bold>Background/Objectives</bold>: Interactions between cancer and immune cells can influence treatment response and patients´ prognosis. The proposed strategy aims at characterizing the infiltrating immune cells in solid tumors and in metastatic sites from pediatric patients with cancer using Multiparameter Flow Cytometry (MFC).</p><p><bold>Design/Methods</bold>: Eighty‐seven samples were obtained at diagnosis from 67 patients suspicious of pediatric cancer ‐ 44.8% males and 55.2% females. A MFC panel of markers was used for the identification and characterization of tumor and immune cells. The Mann‐Whitney U test was used for continuous variables (SPSS, version 21.0, Chicago, IL).</p><p><bold>Results</bold>: Fifty‐six patients (83.6%) had cancer and 11 (16.4%) had inflammatory/reactive diseases. Within solid tumors we found a reversed CD4/CD8 T‐cell ratio in neuroblastic (median:0.82; n=10); adrenal (median:0.68; n=2); renal (median:0.55; n=4) and germ cell tumors (median:0.55; n=8). Conversely, CD4/CD8 ratio was ≥1 in soft tissue sarcomas (median:1.2; n=7); Nasopharyngeal carcinomas (median:1.0; n=3) and inflammatory/reactive masses (median:1.9; n=6). There was a statistically significant difference (p<0.05) between the percentage of T cells in soft tissue sarcomas – median:3.0% (1.0 – 11.8) ‐ and nasopharyngeal carcinomas – median:32.9% (15 – 36.8); and also between nasopharyngeal carcinomas and germ cell tumors – median:6.2% (0.2 – 36.7). Concerning BM samples (n=27), BM infiltrated with neuroblastic tumors (n=9) had significantly more total T cells ‐ median:7.6% (3.0 – 39.0) ‐ than non‐infiltrated BM of patients with neuroblastic tumors (n=11) – median:5.4% (2.0 – 10.8) and also than reactive/inflammatory BM – median:5.4% (4.1 – 6.5).</p><p><bold>Conclusions</bold>: Our data showed that there are different patterns of T cell tumor infiltration according to disease categories. Such differences can relate to distinct patterns of tumor aggressiveness. In addition, infiltrating neuroblastic cells seem to induce an increase of total T cells in BM. Further investigation is necessary to elucidate the role of these differences.</p></sec><sec id="pbc26772-sec-9260"><label>P-516</label><title>Antitumor Activity of Flubendazole in a Neuroblastoma Tumor Model</title><p><underline underline-style="single">E. Cecen</underline><sup>1</sup>, Z. Altun<sup>1</sup>, S. Aktas<sup>1</sup>, E. Serinan<sup>1</sup>, E. Kolatan<sup>2</sup>, H. Evin<sup>1</sup>, O. Yılmaz<sup>2</sup></p><p><italic><sup>1</sup>Dokuz Eylül University, Basic Oncology, izmir, Turkey; <sup>2</sup>Dokuz Eylül University, Department of Laboratory Animal Science, izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is the most common extra‐cranial solid tumor in children. Half of all patients presenting with neuroblastoma have metastatic disease at the time of diagnosis, and their overall prognosis has been poor despite intensive therapy. Flubendazole had been demonstrated to exert activity against leukaemia, myeloma and neuroblastoma cells. The aim of the study was to investigate antitumor activity of flubendazole in a neuroblastoma.</p><p><bold>Design/Methods</bold>: The effects of flubendazole on the C1300 neuroblastoma cell line were measured <italic>in vitro</italic> by using MTT assay. C1300 cells were injected subcutaneously to nude mice. Twenty male 4‐week‐old mice were used (5 mice each group). All the mice were divided into 4 groups. Group I; Control group, Group II; Flubendazole group (50 mg/kg/day), Group III; Cisplatin group (16 mg/kg/day), Group IV; Flubendazole+cisplatin group. Each group was treated every 3 days and the next day sacrificed. Sections were stained with hematoxylin and eosin (H&E). The electrically evoked auditory brainstem response (EABR) was evaluated in all mice. Statistical analysis was performed using SPSS. The significance of the data was analyzed using Kruskal‐Wallis and Mann‐Whitney‐U and <italic>p</italic>‐values of <italic>p</italic> < 0.05 were considered significant.</p><p><bold>Results</bold>: Ld50 doses of flubendazole were determined and 50 mg/kg flubendazole was administered accordingly. The rates of necrobiyosis in tumors were evaluated. Tumor necrosis were higher in the group II, III and IV, when compared to the group I (control) (p=0.029). Rates of tumor necrosis at group I, II, II and IV were %5, %46.25, %48.95, %70, respectively. In all groups, except for the control group, serum creatinin levels were increased.</p><p><bold>Conclusions</bold>: Flubendazole showed no more toxic effect than cisplatin and led to cell death at similar levels with cisplatin. Application of these data to clinical practice requires further studies.</p></sec><sec id="pbc26772-sec-9270"><label>P-517</label><title>Low Phase Angle (PA) Values of the Electrical Bioimpedance Analysis (BIA) in Pediatric Patients with Cancer</title><p><underline underline-style="single">A. GAROFOLO</underline><sup>1</sup>, K.J.T. GUEDES<sup>1</sup>, P. MAIA‐LEMOS<sup>1</sup></p><p><italic><sup>1</sup>IOP/GRAACC/UNIFESP, Pediatric, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: PA is direct measure of cell stability and can be interpreted as indicator of membrane integrity and predictor of body cell mass and as a prognosis indicator of survival in clinical situations. Its use is described as valid even in situations with oscillations in the hydration state. To know the PA values obtained through the BIA in patients with cancer and to characterize the sample for this indicator, and to compare PA values with reference values in the healthy pediatric population.</p><p><bold>Design/Methods</bold>: Pilot cross‐sectional study with pediatric patients diagnosed with malignant neoplasm. The study used BIA which describes the response of living organisms to an externally applied current. It is a measure of opposition to the flow of the applied current through tissues.</p><p><bold>Results</bold>: Thirty‐three patients (45% on chemotherapy and/or radiotherapy, 33% new cases and 21% on hematopoietic stem cell transplants) were evaluated, with an average of 10 years, 19 (57.6%) were male, with no difference for age between genders. Tumors of the central nervous system (33%) and leukemias (21%) were the main diagnoses in the study. Disease recurrences accounted for 15% of the total. 39 % were underweight and 51% were overweight. The BMI for the total sample was 17.5 ± 6.1. AF had a mean of 4.79 ± 1.5, (4.78 for females and 4.8 for males). Compared to the healthy pediatric population, oncological patients present lower AF means (5.5 vs 4.8).</p><p><bold>Conclusions</bold>: Despite the small number of the sample, a PA lower than that found in the healthy pediatric population was demonstrated. Studies have shown that low PA values in critically ill patients are associated with poor nutritional status, poorer clinical outcome and higher mortality.</p></sec><sec id="pbc26772-sec-9280"><label>P-518</label><title>SNPS in Micrornas Associated with Vincristine Induced Neurotoxicity in Spanish Children with Acute Lymphoblastic Leukemia</title><p>M. Umerez<sup>1</sup>, Á. Gutierrez‐Camino<sup>1</sup>, <underline underline-style="single">M. García‐Ariza</underline><sup>2</sup>, A. Sastre<sup>3</sup>, N. García de Andoin<sup>4</sup>, A. Echebarria‐Barona<sup>2</sup>, I. Astigarraga<sup>2</sup>, A. Navajas<sup>5</sup>, A. Garcia‐Orad<sup>1</sup></p><p><italic><sup>1</sup>University of the Basque Country, Genetics‐ Physical Anthropology and Animal Physiology, Leioa, Spain; <sup>2</sup>University Hospital Cruces, Department of Pediatrics, Bilbao, Spain; <sup>3</sup>University Hospital La Paz, Department of Oncohaematology, Madrid, Spain; <sup>4</sup>Universitary Hospital Donostia, Department of Paediatrics, San Sebastián, Spain; <sup>5</sup>BioCruces Health Research Institute, BioCruces Health Research Institute, bilbao, Spain</italic></p><p><bold>Background/Objectives</bold>: Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, often causes sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation. Several studies associated peripheral neurotoxicity with polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it is well known that these genes are regulated by microRNAs (miRNAs) and SNPs in miRNAs could modify their levels or function. Therefore, the aim of this study was to determine whether SNPs in miRNAs could be associated with VCR‐induced neurotoxicity.</p><p><bold>Design/Methods</bold>: The association analysis was performed in a cohort of 155 Spanish children with B‐ALL treated with LAL/SHOP protocol. We selected all the SNPs described in pre‐miRNAs with a MAF>1% (213 SNPs in 206 miRNAs) that could regulate VCR PK/PD genes. Genotyping was performed with VeraCode GoldenGate platform.</p><p><bold>Results</bold>: Statistically significant association was found between 8 miRNA SNPs and neurotoxicity during induction phase. The most significant result in this study was found for the rs12402181 in the seed region of miR‐3117, in which A variant allele showed a decreased risk of peripheral neurotoxicity. This miRNA could target ABCC1 and RALBP1 VCR transport genes.</p><p><bold>Conclusions</bold>: In the present study we detected a SNP in the seed region of in miR‐3117, which could alter ABCC1 and RALBP1 VCR transport genes expression and consequently affect VCR‐induced neurotoxicity in patients with pediatric B‐ALL.</p><p>This project was supported by Basque Government (IT989‐16).</p></sec><sec id="pbc26772-sec-9290"><label>P-519</label><title>Expression of Wilms Tumor 1 and CD31 in Non‐Involuting Congenital Hemangioma</title><p><underline underline-style="single">Q. Shu</underline><sup>1</sup>, Y. Shu<sup>1</sup>, Y. Liu<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital‐ Zhejiang University School of Medicine, Department of Surgery, Hangzhou, China</italic></p><p><bold>Background/Objectives</bold>: To analyze the clinicopathological features of the Non‐involuting congenital hemangioma (NICH), and to evaluate the expression of Wilms tumor 1 (WT1) and CD31 in NICH.</p><p><bold>Design/Methods</bold>: Thirty‐eight patients from our hospital who were diagnosed with NICH during January 2014 and May 2016 were included in this study. The control group included 38 patients who were diagnosed with vascular malformations (VM). Based on the appearance of the hemangiomas (flat or slightly bossed), NICHs were divided into two groups: bossed group and plaque‐like group. The pathological characteristics and the expression of WT1 and CD31 were analyzed.</p><p><bold>Results</bold>: The 38 NICH cases included 27 males and 11 females, aged 1Y6M to 10Y3M (mean 4Y10M). Immunohistochemical study showed cytoplasmic staining of WT1 in NICH, positive in the endothelial cells and pericytes. There was significant difference in the positive rate of WT1 expression between NICH and VM (Fisher exact probability test, P<0.01). CD31 was intensely and diffusely expressed in all NICHs, including the small vessels of the lobules, irregular stellate vessels and the anomalous vessels in the fibrous tissues between the lobules. No difference in the positive rate of CD31 expression between NICH and VM was observed. The expression levels of both WT1 and CD31 in the plaque‐like group were significantly higher than those of the bossed group (Person χ2=10.481 and 10.596, respectively, P<0.05). The expression of WT1 positively correlated with CD31 in NICH (Person correlation test, r=0.384, P<0.05).</p><p><bold>Conclusions</bold>: For NICH, bossed type was more common. WT1 and CD31 were expressed in all NICH specimens, with different expression levels between the plaque‐like type and the bossed type. Expression of WT1 in NICH positively correlated with CD31.</p></sec><sec id="pbc26772-sec-9300"><label>P-520</label><title>Charaterization of the Involvement of DNA Methylation Changes in Osteosarcomas</title><p>D. Onofre Vidal<sup>1</sup>, M. Quintero Escobar<sup>2</sup>, A. van Helvoort Lengert<sup>1</sup>, E. Boldrini<sup>3</sup>, S.R. Morini da Silva<sup>4</sup>, L.F. Lopes<sup>3</sup>, <underline underline-style="single">M. Maschietto</underline><sup>2</sup></p><p><italic><sup>1</sup>Barretos Cancer Hospital, Molecular Oncology Research Center, Barretos, Brazil; <sup>2</sup>Brazilian Center for Research in Energy and Materials CNPEM, National Laboratory of Biosciences LNBio, Campinas, Brazil; <sup>3</sup>Barretos Children's Cancer Hospital, Barretos Children's Cancer Hospital, Barretos, Brazil; <sup>4</sup>Barretos Cancer Hospital, Department of Pathology, Barretos, Brazil</italic></p><p><bold>Background/Objectives</bold>: Osteosarcoma comprises 5% of the tumors in children and adolescents. It is an aggressive disease with metastatic patients evolving with very poor clinical outcomes. We hypothesized that DNA methylation changes could be associated with the mechanisms involved with transformation and progression in osteosarcomas.</p><p><bold>Design/Methods</bold>: We profiled DNA methylation in 28 chemotherapy‐naive samples from patients with osteosarcomas and nine normal bone tissues using the Illumina HumanMethylation 450K Beadchip arrays. Methylation data were corrected for technical bias and cellular composition effects.</p><p><bold>Results</bold>: Supervised comparison using a Bayesian framework linear model identified 3,146 differentially methylated CpG sites (DMSs, pvalue<0.01 and methylation differences >10%) between osteosarcoma and bone samples, with the majority of CpG sites (n=1,997, 63%) showing an hypermethylated state in osteosarcoma samples. In addition, bumphunter analysis identified 95 differentially methylated regions (DMRs). We found that tumors exhibited an hypermethylated state of the DMR that controls PTEN expression. PTEN down‐regulation was associated to increased tumor growth in osteosarcoma cells. At DMS and DMR levels, methylation changes identified here were enriched to chromatin assembly and remodeling, DNA packing and gene transcriptional control suggesting that DNA methylation may be involved with osteosarcoma disease. They were also enriched for skeletal system morphogenesis and development potinting to the involvement of DNA methylation with the disruption of mechanism that control bone cell differentiation.</p><p><bold>Conclusions</bold>: Our analysis revealed that DNA methylation changes might be associated with cellular transformation in osteosarcoma. These changes may be controlling expression of genes related to biological processes involved with disruption of the correct cell differentiation and transformation. Finally, osteosarcoma showed a tendency to an hypermethylated state compared to normal bone samples.</p></sec><sec id="pbc26772-sec-9310"><label>P-521</label><title>Changes in DNA Methylation May be Associated with Progression of Wilms Tumors</title><p>J.V.S. Guerra<sup>1</sup>, R.M. Azevedo<sup>2</sup>, P.A. Faria<sup>3</sup>, B. De Camargo<sup>2</sup>, <underline underline-style="single">M. Maschietto</underline><sup>1</sup></p><p><italic><sup>1</sup>Brazilian Center for Research in Energy and Materials CNPEM, National Laboratory of Biosciences LNBio, Campinas, Brazil; <sup>2</sup>Research Center National Institute of Cancer, Department of Pediatric Hematology and Oncology Program, Rio de Janeiro, Brazil; <sup>3</sup>Research Center National Institute of Cancer, Department of Pathology, Rio de Janeiro, Brazil</italic></p><p><bold>Background/Objectives</bold>: Wilms tumors (WTs) have a relapse rate of ∼25%, from which long‐term survival remains approximately 50%. Blastemal predominant WT have a higer risk of relapsing and was associated with resistance to chemotherapy and capacity of forming distant metastasis. DNA methylation changes could be associated with the mechanisms involved with Ws progression and resistance. We aimed to identify the underlying mechanisms involved with metastasis formation in WT.</p><p><bold>Design/Methods</bold>: A comprehensive DNA methylation using the Illumina 450K Beadchip arrays was applied to matched kidney, WT blastemal component and metastatic tissues from patients treated under SIOP 2001 protocol. Methylation data was corrected for technical effects and cellular composition.</p><p><bold>Results</bold>: A Bayesian framework linear model considering intra‐patients and inter‐groups comparisons identified 904 differentially methylated positions (DMPs, adjP<0.05) WT, kidney and metastasis. The methylation pattern of these DMPs showed that whilst WT displayed an hypomethylation profile compared to kidney, metastatic samples had an hypermethylated profile compared to both. DMPs were enriched manl biological processes involved wih embronic development, morphogenesis and cellular differentiation. They were also related to genes enriched for pathways related to metabolism, mTOR and PI3K‐AKT signaling pathways. Several genes with a role in nephrogenesis and disrupted in WT appeared as differentially methylated in our analysis, in agreement with the literature. To identify the most differentially methylated regions (DMRs), a Gaussian kernel algorithim from DMRcate was applied to WT and kidney tissues. This analysis showed 36 DMRs between WT and kidney samples, which were located next to 28 genes, including CYP26C1 that catalyze reactions involved in drug metabolism.</p><p><bold>Conclusions</bold>: Altogether, we found that Wilms tumors exhibited an hypomethylated state compared to normal kidney, and both were hypomethylated compared to metastatic samples. These methylation changes could be controlling the expression of genes associated with Wilms tumor progression.</p></sec><sec id="pbc26772-sec-9320"><label>P-522</label><title>Identification of Receptor Tyrosine Kinases and Downstream Signaling Pathways as Possible Therapeutic Targets Using Phosphoprotein Arrays</title><p><underline underline-style="single">J. Neradil</underline><sup>1,2,3</sup>, P. Macigova<sup>1</sup>, M. Sramek<sup>1</sup>, K. Melicharkova<sup>2,3</sup>, P. Mudry<sup>2</sup>, R. Veselska<sup>1,2,3</sup>, J. Sterba<sup>2,3</sup></p><p><italic><sup>1</sup>Masaryk University, Dept. of Experimental Biology, Brno, Czech Republic; <sup>2</sup>University Hospital Brno and School of Medicine‐ Masaryk University, Department of Pediatric Oncology, Brno, Czech Republic; <sup>3</sup>St. Anne's University Hospital, International Clinical Research Center, Brno, Czech Republic</italic></p><p><bold>Background/Objectives</bold>: The main aim of our study is to identify activity of the RTK signaling pathways as well as of the downstream signaling pathways in pediatric refractory and/or relapsed solid tumors. Primary samples of tumor tissue taken from the individual patients, as well as paired samples (i.e., primary tumor sample and relapsed tumor sample) are analyzed in detail to find the possible targets for personalized biological therapy using monoclonal antibodies and low‐molecular‐weight inhibitors.</p><p><bold>Design/Methods</bold>: The experimental approaches include the RTK and MAPK phosphorylation protein arrays to determine patterns of activity in these two groups of signaling transducers. These arrays allowed us to identify activities of 49 human RTKs and 24 downstream signaling molecules.</p><p><bold>Results</bold>: Till now (March 2017), we analyzed 157 samples in total. 88 patients have examined primary tumors only, 31 patients both primary and relapsed tumors and 7 patients have analyzed three subsequent tumor samples. According to ICCC‐3 classification, the most frequent tumor types were soft tissue sarcomas, CNS tumors and bone tumors. This number of samples allowed us to perform also a detailed analysis of RTK and downstream signaling profiles that clearly showed that histogenetically different groups of tumors clearly differ also in their cell signaling activities. Furthermore, we can also demonstrate the changes in cell signaling pattern after administration of low‐molecular‐weight inhibitors during the course of the disease in patients suffering with rhabdomyosarcoma, Maffucci syndrome or multiple infantile myofibromatosis.</p><p><bold>Conclusions</bold>: To summarize, our obtained results bring completely new information concerning the changes in RTK and downstream activity patterns associated with the course of disease that may be important for determination of personalized therapy for these children.</p><p>Supported by the project No. 16‐34083A from the Ministry of Healthcare of the Czech Republic.</p></sec><sec id="pbc26772-sec-9330"><label>P-523</label><title>Childhood Tumours with a High Probability of Being Part of a Tumour Predisposition Syndrome; Reason for Referral for Genetic Consultation</title><p><underline underline-style="single">F. Postema</underline><sup>1</sup>, S. Hopman<sup>1</sup>, C. Aalfs<sup>2</sup>, L. Berger<sup>3</sup>, F. Bleeker<sup>2</sup>, C. Dommering<sup>4</sup>, M. Jongmans<sup>5</sup>, T. Letteboer<sup>6</sup>, M. Olderode‐Berends<sup>3</sup>, A. Wagner<sup>7</sup>, R. Hennekam<sup>8</sup>, H. Merks<sup>1</sup></p><p><italic><sup>1</sup>Academic Medical Center, Pediatric Oncology, Amsterdam, The Netherlands; <sup>2</sup>Academic Medical Center, Clinical Genetics, Amsterdam, The Netherlands; <sup>3</sup>University Medical Centre Groningen, Genetics, Groningen, The Netherlands; <sup>4</sup>VU University Medical Centre, Clinical Genetics, Amsterdam, The Netherlands; <sup>5</sup>Radboud University Medical Centre, Human Genetics, Groningen, The Netherlands; <sup>6</sup>University Medical Centre Utrecht, Genetics, Utrecht, The Netherlands; <sup>7</sup>Erasmus Medical Centre, Clinical Genetics, Rotterdam, The Netherlands; <sup>8</sup>Academic Medical Center, Pediatrics, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 20 childhood tumours that in themselves should be a reason to refer a child for genetic consultation.</p><p><bold>Design/Methods</bold>: We performed a PubMed search to review the incidence of TPSs in children for 74 tumour types listed in the International Classification of Childhood Cancer third edition (ICCC3). The results were discussed during a national consensus meeting with representative clinical geneticists from all six academic paediatric oncology centres in The Netherlands. A TPS incidence of 5% or more was considered a high probability and therefore in itself a reason for referral to a clinical geneticist.</p><p><bold>Results</bold>: The literature search resulted in data on the incidence of a TPS in 23 tumours. For 20/23 tumour types a TPS incidence of 5% or higher was reported. In addition, during the consensus meeting the experts agreed that children with any carcinoma should always be referred for clinical genetic consultation as well, as it may point to a TPS.</p><p><bold>Conclusions</bold>: We present an overview of 20 paediatric tumours with a high probability of a TPS; this will facilitate paediatric oncologists to decide which patients should be referred for genetic consultation merely based on type of tumour.</p></sec><sec id="pbc26772-sec-9340"><label>P-524</label><title>Concentrations of Plasma‐Free Amino Acids in Pediatric Cancers</title><p><underline underline-style="single">A. Synakiewicz</underline><sup>1</sup>, M. Sawicka‐Zukowska<sup>2</sup>, N. Adrianowska<sup>3</sup>, G. Galezowska<sup>4</sup>, J. Ratajczyk<sup>4</sup>, A. Owczarzak<sup>5</sup>, T. Stachowicz‐Stencel<sup>1</sup></p><p><italic><sup>1</sup>Medical University of Gdansk, Department of Pediatrics‐ Hematology and Oncology, Gdańsk, Poland; <sup>2</sup>Medical University of Bialystok, Department of Pediatric Oncology and Hematology‐, Bialystok, Poland; <sup>3</sup>Medical University of Lodz, Department of Pediatrics‐ Oncology‐ Hematology and Diabetology, Lodz, Poland; <sup>4</sup>Medical University of Gdansk, Department of Environmental Toxicology, Gdańsk, Poland; <sup>5</sup>Medical University of Gdansk, Department of Clinical Nutrition, Gdańsk, Poland</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer remains one of the main cause of death in the pediatric population because of its low detection rate in the early stage. No single substance is known to be sensitive and specific enough to detect cancer cells and play a role as an early biomarker. Malignant neoplastic diseases are metabolic conditions with unique metabolism, thus amino acids and level alterations in plasma are considered to play a role in carcinogenesis and further course of the disease.</p><p><bold>Design/Methods</bold>: Seventy seven children with cancer, including 47 with hematological malignancies (leukemias, non‐Hodgkin and Hodgkin lymphomas) and 30 with solid tumors (nephroblastoma, neuroblastoma, soft tissue sarcomas, malignant brain tumor, germ cell tumors) were enrolled in this multicenter study. 22 plasma‐free amino acids were determined by highperformance liquid chromatography with fluorometric detection.</p><p><bold>Results</bold>: The results revealed significant differences between children with cancer and healthy control.</p><p><bold>Conclusions</bold>: This report suggest that plasma‐free amino acid profiling may be used in cancer diagnoses and may be considered as an early tumor biomarker. Further study in this specific group is necessary to verify the metabolic patterns characteristic of pediatric cancer.</p></sec><sec id="pbc26772-sec-9350"><label>P-525</label><title>A Retrospective Analysis of Molecular Profiling of Pediatric Solid Tumors Using OmniSeq Comprehensive</title><p><underline underline-style="single">L. Wiltsie</underline><sup>1</sup>, A. Papanicolau‐Sengos<sup>2</sup>, C. Morrison<sup>2</sup>, K. Kelly<sup>1</sup>, M. Barth<sup>1</sup></p><p><italic><sup>1</sup>Roswell Park Cancer Institute, Pediatrics, Buffalo, USA; <sup>2</sup>OmniSeq LLC, Pathology, Buffalo, USA</italic></p><p><bold>Background/Objectives</bold>: Tumor molecular profiling holds the promise of personalized diagnostic, prognostic and therapeutic decision making. Due to cost and limited availability, molecular profiling data of pediatric tumors is limited. A small number of centers have performed large scale, genome wide screening for molecular alterations in pediatric tumors identifying about 30‐40% of pediatric tumors with potentially actionable alterations. OmniSeq Comprehensive, a New York State approved next‐generation sequencing assay, utilizes a targeted approach to molecular profiling that screens tumor DNA and RNA to identify somatic variants in 144 genes focusing on genomic alterations known to be associated with cancer.</p><p><bold>Design/Methods</bold>: We analyzed OmniSeq Comprehensive profiling of high risk solid tumors and brain tumors from pediatric patients treated in Buffalo, NY from July 2016 to March 2017. All results were reviewed at an ongoing Pediatric Molecular Tumor Board.</p><p><bold>Results</bold>: Tumor samples from 21 patients age 2 months‐22 years were analyzed. Results were available within 2 weeks of obtaining a sample for testing in each case. At least one variant was identified in 17/21 (81%) of patients with a mean of 1.6 variants/patient. Eight patients (38%) had a variant considered potentially actionable. Six patients (29%) had a lesion targetable with an agent in clinical trials, but did not meet eligibility requirements. In one patient with inflammatory myofibroblastic sarcoma, molecular testing identified an ALK gene fusion, not identified by FISH, that aided in identifying the diagnosis and led to targeted therapy with crizotinib as first line therapy.</p><p><bold>Conclusions</bold>: OmniSeq Comprehensive identified actionable variants in children with high risk solid and brain tumors at a rate similar to published results for genome wide molecular profiling approaches. The results of this pilot study highlight the potential role of a more cost effective, targeted approach to molecular profiling in pediatric oncology patients.</p></sec></sec><sec id="pbc26772-sec-9360"><title>Imaging</title><sec id="pbc26772-sec-9370"><label>P-526</label><title>Value of PET/CT in Treatment Response to Chemotherapy in Musculoskeletal Tumors</title><p><underline underline-style="single">R. Lopez‐Almaraz</underline><sup>1</sup>, M. Garcia‐Ariza<sup>1</sup>, J.M. De Pedro Olabarri<sup>1</sup>, U. Gonzalez Camacho<sup>1</sup>, A. Echebarria Barona<sup>1</sup>, R. Adan Pedroso<sup>1</sup>, T. Rodriguez Inchausti<sup>2</sup>, I. Astigarraga Aguirre<sup>1</sup></p><p><italic><sup>1</sup>Hospital Universitario Cruces, Pediatric Hematology and Oncology Unit, Cruces‐ Bilbao, Spain; <sup>2</sup>Hospital Universitario Cruces, Nuclear Medicine Service, Cruces‐ Bilbao, Spain</italic></p><p><bold>Background/Objectives</bold>: To evaluate the correlation between anatomopathological (AP) tumour necrosis in musculoskeletal tumours and the morpho‐metabolic response observed in 18F‐FDG PET/CT.</p><p><bold>Design/Methods</bold>: Retrospective descriptive study. We collected data on pediatric new diagnoses of bone and soft tissue sarcomas (STS) in a tertiary hospital in the last 3 years (January 2014‐January 2017).</p><p><bold>Results</bold>: Seventeen patients were newly diagnosed during those years: 6 (35%) with Ewing sarcoma (ES), 5 (30%) Osteosarcoma (OS) and 6 STS, of which 5 (83%) were Rhabdomyosarcomas (RMS). Within the (ES 5/6 patients underwent PET/CT. Two presented a complete morpho‐metabolic response coinciding with a 100% AP tumor necrosis. Two others presented a very good partial response in the imaging test, with tumour necrosis being 96 and 98% respectively. The last patient presented a partial response in PET/CT; but could not undergo surgery for its inoperability. In the case of the 5 OS; only two PET/CT scans were performed at the pre‐surgical evaluation. these presented partial response in PET‐CT and had a necrosis of 34% and 65% respectively. In the STS, PET/CT was performed in 4 of 6 patients: one with complete response; but could not undergo surgery because of its high surgical risk. In the other three patients, PET/CT showed a good partial response with complete necrosis in two and partial necrosis in the other.</p><p><bold>Conclusions</bold>: In our series, PET/CT is a valuable diagnostic tool for the initial extension study and to evaluate the chemotherapy response of bone and soft tissue tumors. Further studies are needed to demonstrate their degree of direct correlation with tumour necrosis of histological pieces.</p></sec><sec id="pbc26772-sec-9380"><label>P-527</label><title>First FDG PET/MRI Experience of Gazi University in Pediatric Oncology</title><p><underline underline-style="single">C. Karadeniz</underline><sup>1</sup>, L.U. Besli<sup>2</sup>, U.Ö. Akdemir<sup>3</sup>, U. Aydos<sup>3</sup>, F.G. Pinarli<sup>1</sup>, A. Okur<sup>1</sup>, M. Özçelik<sup>3</sup>, I.N. Karabacak<sup>3</sup>, U. Kocak<sup>4</sup>, O. Atay Kapucu<sup>3</sup></p><p><italic><sup>1</sup>Gazi University School of Medicine, Pediatric Oncology, Ankara, Turkey; <sup>2</sup>Istanbul University Cerrahpaşa School of Medicine, Nuclear Medicine, Istanbul, Turkey; <sup>3</sup>Gazi University School of Medicine, Nuclear Medicine, Ankara, Turkey; <sup>4</sup>Gazi University School of Medicine, Pediatric Hematology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: PET/MRI has recently been introduced as an alternative to PET/CT and pediatric patients are expected to be one of the main target groups for PET/MRI, which has considerably less ionizing radiation compared to PET/CT. The aim of our study is to compare FDG PET/CT and PET/MRI in our group of pediatric oncological patients in terms of anatomical correlation of FDG positive lesions.</p><p><bold>Design/Methods</bold>: Total 31 pediatric oncological patients were included in our study. The median age was 9 years (range: 6 months‐15 years). Nine patients were diagnosed for lymphoma (2 of them were Hodgkin lymphoma), 4 neuroblastoma, 3 rhabdomyosarcoma, 3 ALL, 4 Langerhans cell histiocytosis, 2 Ewing sarcoma, 2 ovarian cancer, 1 glioblastoma multiforme, 1 pelvic germ cell tumor, 1 renal clear cell carcinoma and 1 conjunctival squamous cell carcinoma. Total 39 sequential FDG PET/CT (GE Discovery ST) and PET/MRI (GE Signa PET/MR) examinations were performed on the same day after injection of mean 3,3 mCi (122 MBq) FDG. PET/MRI was performed first in 5 patients and PET/CT was obtained first in the rest of the patients. All images were evaluated by 2 nuclear medicine physicians separately.</p><p><bold>Results</bold>: On lesion based analysis, total 16 sequential PET/CT and PET/MRI examinations were concordantly negative. Among 47 FDG positive lesions in 18 sequential PET/CT and PET/MRI examinations (maximum 5 lesions/patient), 37 were positive with both CT and MRI. Remaining 10 FDG positive lesions (2 central nervous system, 4 bone marrow, 2 lymph nodes, 2 soft tissue lesions) could not be differentiated using CT although it could be demarcated using MRI.</p><p><bold>Conclusions</bold>: PET/MRI showed better anatomical correlation in FDG positive lesions compared to PET/CT in our pediatric patients. Therefore FDG PET/MRI, with reduced ionizing radiation and better contrast resolution in soft tissue and bone marrow, may be a preferred alternative to PET/CT in the pediatric population.</p></sec><sec id="pbc26772-sec-9390"><label>P-528</label><title>Diffusion‐Weighted Magnetic Resonance Imaging Shows A Critical Difference Between Supratentorial and Infratentorial Pediatric Ependymoma</title><p><underline underline-style="single">J. Murray</underline><sup>1</sup>, H. Head<sup>2</sup>, A. Hoeft<sup>1</sup>, L. Margraf<sup>3</sup></p><p><italic><sup>1</sup>Cook Children's Health Care System, Hematology & Oncology Center, Fort Worth, USA; <sup>2</sup>Cook Children's Health Care System, Radiology, Fort Worth, USA; <sup>3</sup>Cook Children's Health Care System, Pathology, Fort Worth, USA</italic></p><p><bold>Background/Objectives</bold>: Magnetic resonance imaging (MRI) features differ between various childhood brain tumors. Advanced MRI techniques including diffusion‐weighted imaging (DWI) can add vital information to conventional sequences, potentially crucial in creating an appropriate differential diagnosis. Ependymoma, the third most common malignant brain tumor in youth, remains challenging with respect to an imaging differential diagnosis. We have recognized a critical difference in DWI characteristics between supratentorial (ST) and infratentorial (IT) ependymomas in children.</p><p><bold>Design/Methods</bold>: Following IRB approval, we re‐reviewed the MRIs and neuropathology from 30 consecutively diagnosed children with intracranial ependymomas, 2007‐2016, abstracting for tumor location (ST vs IT), diffusion characteristics and tumor grade. Chi‐square and Cramer's V tests were applied.</p><p><bold>Results</bold>: The mean age at diagnosis was 5 years (18 boys, 12 girls). Eighteen patients had IT tumors and 12 had ST tumors. Ten tumors had anaplastic histology (WHO grade III) and 20 had classic histology (WHO grade II). Eleven tumors showed restricted diffusion on DWI, and 19 did not (13 facilitated diffusion and 6 were equivalent to surrounding brain). All tumors that showed restricted diffusion were ST; none were IT. Of the 11 restricting tumors, 3 had anaplastic histology. Of the 13 non‐restricting tumors, 4 had anaplasia. The relationship between tumor location and restricted diffusion was significant and strongly associated (χ2(1) = 26.053, p = 0.000, Cramer's V= 0.932).</p><p><bold>Conclusions</bold>: Diffusion‐weighted imaging can supplement conventional MRI sequences in formulating a critical differential diagnosis in children with brain tumors. Our analysis shows a dramatic difference in diffusion characteristics between ST and IT ependymomas, independent of tumor grade. Supratentorial tumors tend to show restricted diffusion, but IT tumors, irrespective of grade, do not restrict. We postulate that there are physiologic tumor microenvironmental factors that account for this observation. Awareness of DWI differences in ependymoma may be helpful in refining the initial differential diagnosis.</p></sec><sec id="pbc26772-sec-9400"><label>P-529</label><title>Correlation of Brown Fat to Disease State in Lymphoma Patients</title><p>S. Servaes<sup>1</sup>, <underline underline-style="single">L. States</underline><sup>1</sup>, A. Ntoulia<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital of Philadelphia and The University of Pennsylvania, Radiology, Philadelphia, USA</italic></p><p><bold>Background/Objectives</bold>: The purpose of our study was to determine if there is a relationship between the depiction of brown adipose tissue (BAT) with positron emission tomography/computed tomography (PET/CT) in pediatric patients with Hodgkin lymphoma and the disease and season.</p><p><bold>Design/Methods</bold>: In total, 126 PET/CT studies of 41 subjects (25 boys and 16 girls) with ages ranging from 6‐22 years with diagnosed Hodgkin lymphoma were retrospectively reviewed. The uptake and anatomic distribution of BAT were evaluated at PET/CT scans in every subject at the time of initial diagnosis and after completion of chemotherapy. Comparisons regarding the presence of BAT at these two time intervals were performed between each subject using McNemar's test. Correlations of BAT presence with children's gender, anthropometric data (body mass index and height), examination parameters (FDG and Glucose) as well as season were performed.</p><p><bold>Results</bold>: 80/126 (63.5%) of PET/CT studies showed no disease activity, whereas in 46/126 (36.5%) of PET/CT presence of Hodgkin lymphoma disease was identified. Among patients with no active disease, in 23/80 (28.8%) PET/CT studies there were high BAT uptake, whereas among patients with active disease more BAT uptake was observed in 8/46 (17.4%) examinations. This difference was marginally significant (p=0.05). There was no significant relationship between BAT uptake and the season that PET/CT study was performed (p=0.74). Finally BAT uptake was not associated with examination parameters including the FDG dose (p=0.06).</p><p><bold>Conclusions</bold>: Our findings show a marginal correlation between the BAT uptake and the disease state. However, contrary to what other studies have demonstrated, in our study BAT uptake was not associated to the season that the PET/CT examination was performed and the FDG dosage.</p></sec><sec id="pbc26772-sec-9410"><label>P-530</label><title>Laparoscopy as a Primary Investigatory Tool in Pediatric Abdominal Massess</title><p><underline underline-style="single">O. Zakaria</underline><sup>1</sup></p><p><italic><sup>1</sup>King Faisal University, College Of Medicine, Al Ahsa, Saudi Arabia</italic></p><p><bold>Background / Objectives: BACKGROUND</bold>: Abdominal masses still pose as a major challenge for pediatrcialn and surgeons.</p><p><bold>AIM OF THE WORK</bold>: This study was designated to evaluate the role of diagnostic laparoscopy in investigating equivocal pediatric masses that had undergone other imaging modalities.</p><p><bold>Design/Methods</bold>: A combined prospective and retrospective multicentric study for the period of 13 years from January 2005 to December 2016.</p><p>Inclusion Criteria: all children from 3 months of age to 15 years were studied.</p><p>Exclusion Criteria: those who have a documented diagnosis through other imaging modalities including sonographic and or CT guided biopsy. All patients underwent multiport diagnostic laparoscopy for biopsy from the mass. All specimens were hispatologically assessed using H&E staining, some specimens were immunohistochemically studied, patients mean follow up was 3.6 years.</p><p><bold>Results</bold>: A total of 132 of patients were recruited in this study they were 69 males and 63 girls with the male to female ratio of1.1:1 the age ranged from 3 month up to 15 years with the mean age 0f 2.7 ± 0.8. Out of the total studied group 54 patients were diagnosed as neuroblastoma with the percentage of 40.9% while 66 were having nephroblastoma while the remaining 12 (9.1%) were having non‐Hodgkin's abdominal lymphoma. All patients did not show any complications related to the procedure. Patients mean follow up was 3.6 years. Most of cases (121) with different diagnosis were clinically staged as grade I to grade II (91.7%). Neither intraoperative or post operative complications were recorded during this technique. The mean operative time was recorded to be 72 mins ± 20 in the earliest group; yet, it has declined to be 32 ± 12 mins in the latest group due to the advancement of the learning curve.</p><p><bold>Conclusions</bold>: Laparoscopy is an accurate, safe and should be used as the sole tool for biopsing solid abdominal tumors in pediatrics.</p></sec><sec id="pbc26772-sec-9420"><label>P-531</label><title>Reliability of Elastographic Sonography in Predicting Pediatric Cervical Lymph Node Malignancy</title><p><underline underline-style="single">O. Zakaria</underline><sup>1</sup></p><p><italic><sup>1</sup>King Faisal University, College Of Medicine, Al Ahsa, Saudi Arabia</italic></p><p><bold>Background/Objectives</bold>: Preliminary studies suggest that ultrasonographic (US) elastography may be useful in differentiating benign and malignant cervical lymph nodes, thereby informing decisions to perform a biopsy and facilitating follow‐up.</p><p>The current study aimed to evaluate the accuracy and reliability of US elastography in distinguishing malignant pediatric malignant cervical lymphadenopathy from benign lesions.</p><p><bold>Design/Methods</bold>: A total of 177 lymph nodes in 128 children with the age ranging form 11months to 12 years ; they were 77 males and 51 females with a ratio of 1.5:1. A preliminary diagnosis primary head and neck cancer were examined by B‐mode sonography, power Doppler ultrasound and elastography. Elastographic patterns were determined on the distribution and percentage of the lymph node area with low elasticity (hard), with pattern 1 being an absent or very small hard area to pattern 5, a hard area occupying the entire lymph node. Patterns 3–5 were considered metastatic. Ultrasound guided aspiration cytology was done for 107 lymph nodes.</p><p><bold>Results</bold>: The majority 154 (87%) of metastatic lymph nodes had elastography pattern 3–5. This finding was observed in only 6 (3.4) % of the benign lymph nodes (P < 0.001). The elastography pattern had sensitivity of 87.3%, specificity of 96.5%, PPV of 98.2%, NPV of 73.1% and overall accuracy of 91.9% in differentiation between benign and malignant lymph nodes. On the other hand, for the B mode criteria, the best accuracy was given to abnormal hilum (73%). The accuracy of power Doppler ultrasound pattern was 65.8%.</p><p><bold>Conclusions</bold>: The accuracy of sonoelastography is higher than other sonographic modalities in elucidating the pathology and diagnosis of cervical lymphadenopathy distinguishing between benign and malignant lesions. This may replace the lymph node biopsies in the future. Moreover, The integration of lymph node sonoelastography in the follow up of patients with known head and neck cancer may reduce the number of biopsies.</p></sec></sec><sec id="pbc26772-sec-9430"><title>Epidemiology ‐ Pathway of Care</title><sec id="pbc26772-sec-9440"><label>P-532</label><title>Training of Childhood Cancer Ambassadors: A Nurse‐Led Capacity Building Project to Improve Early Diagnosis of Childhood Cancer in Northwest Cameroon</title><p><underline underline-style="single">G. Afungchwi</underline><sup>1</sup>, K. Francine<sup>2</sup>, P. Hesseling<sup>3</sup>, V. Njamnshi<sup>4</sup>, P. Nana<sup>2</sup>, J. Kaah<sup>4</sup></p><p><italic><sup>1</sup>Cameroon Baptist Convention Health Services, Childhood Cancer Program, Bamenda, Cameroon; <sup>2</sup>Mbingo Baptist Hospital, Pediatric oncology, Mbingo, Cameroon; <sup>3</sup>Tygerberg children's hospital‐ Stellenbosch University, Department of Childhealth, Cape Town, South Africa; <sup>4</sup>Banso Baptist Hospital, Pediatric Oncology, Kumbo, Cameroon</italic></p><p><bold>Background/Objectives</bold>: In resource poor countries, many children with cancer are diagnosed at late stages, which makes cure impossible(Awadelkarim et al. 2012; Sullivan et al. 2014).Childhood cancer symptoms are usually missed by community health professionals due to their unfamiliarity with these signs. Even when referred with suspicion of cancer, lack of transportation means becomes a major cause of delay(Afungchwi et al., 2016). The objective of this project was to promote early diagnosis and prompt treatment of childhood cancers through the use of trained ambassadors and mobile money.</p><p><bold>Design/Methods</bold>: Health professionals and prominent traditional healers for 6 health districts were invited to their respective district health services for training. The training included topics on biology of cancer, the early warning signs of childhood cancer, and the availability of care for children with cancer in Cameroon. Three trainees from each health district were selected as Childhood cancer Ambassadors and provided with mobile phones and mobile money accounts to transport every suspected patient to the treatment centre.</p><p><bold>Results</bold>: 133 health care providers (including 20 traditional healers) were trained, and 18 ambassadors selected and equipped for referrals. There was a 33.8 percentage point increase(p<0.001) in knowledge about childhood cancers among trainees and the proportion of trainees providing health education on childhood cancers to their communities is expected to increase from 14% to 100%(p<0.001). A total of 9,000 childhood cancer warning signs leaflets were distributed. The cost of training was €27.2 per trainee.</p><p><bold>Conclusions</bold>: The SanofiEspoir MCM Awards has provided an opportunity to build capacity for childhood cancer early diagnosis in Northwest Cameroon. This project has the potential to become a formal surveillance model for childhood cancers and, if expanded to cover the entire region, would create a net through which no child with cancer could filter undiagnosed.</p></sec><sec id="pbc26772-sec-9450"><label>P-533</label><title>Challenges Faced in Pediatric Hematology/Oncology in a Developing Country: The Children's Hospital Lahore Pakistan Experience</title><p><underline underline-style="single">A. Ahmad</underline><sup>1</sup>, N. Tahira<sup>1</sup>, M. Sadiq<sup>1</sup>, M.Y. Kazi<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital and Institute of Child Health, Paediatric Haematology/Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: In Punjab Pakistan for a 200 million population there are very few dedicated pediatric hematology/oncology centers resulting in delayed diagnosis and poor management of majority these children. Objective of this study was to evaluate the challenges faced in pediatric hematology/oncology services in resource limited settings like the Children's Hospital Lahore which is a 60 bedded unit with bed occupancy of 200% and 300 new admissions per month and over 1000 new childhood cancer cases each year.</p><p><bold>Design/Methods</bold>: Retrospective review of 140 cases enrolled and died in the department from January to December 2016 for their epidemiology, diagnosis, treatment, stay in hospital and cause of death and analyzed with SPSS17.</p><p><bold>Results</bold>: Among 140 patients analyzed 106/140(76%) were below 10 years with M: F ratio 2.3:1.71/140 (51%) had their diagnosis established at admission while 131/140(93%) had their diagnosis confirmed before they died. Only 50% cases had their definite treatment started before they died.36% were diagnosed as ALL,38% with solid malignancies,9% B‐Thalassaemia Major, 9% Aplastic Anemia, 4% AML and 4% others like MDS, Factor VII deficiency. Febrile neutropenia and sepsis was the major killer in 95/140(68%) while 45/140(32%) died due to relapse or progression of disease. When cause of death analyzed for type of diagnosis (p‐value: 0.022) and stay in hospital (p‐value: 0.001) and definite treatment given or not (p‐value: 0.000) while 93% cases were diagnosed before death but only 50% cases were started on the treatment(p‐value:0.016). 16% cases died within 24 hrs of admission while 58% stayed up to 2 weeks 50% of cases has to travel >100 KM to reach the Children's Hospital Lahore.</p><p><bold>Conclusions</bold>: There is an urgent need of capacity building with more centers and trained health professionals, implementation of effective infection control measures and efficient psycho social support for these families to decrease the morbidity and mortality in this center.</p></sec><sec id="pbc26772-sec-9460"><label>P-534</label><title>Differential Survival Rates in State Funded and Privately Funded Paediatric Oncology Units in Johannesburg, South Africa</title><p><underline underline-style="single">K. Bennett</underline><sup>1</sup>, J. Geel<sup>1</sup>, N. Beringer<sup>2</sup></p><p><italic><sup>1</sup>Faculty of Health Sciences ‐ University of the Witwatersrand‐ Wits Donald Gordon Medical Centre‐ Charlotte Maxeke Johannesburg Academic Hospital, Department of Paediatric Oncology, Johannesburg, South Africa; <sup>2</sup>Faculty of Health Sciences ‐ University of the Witwatersrand‐ Charlotte Maxeke Johannesburg Academic Hospital, Department of Paediatric Oncology, Johannesburg, South Africa</italic></p><p><bold>Background/Objectives</bold>: Data on survival rates of children with cancer is only available from two South African centres. The reported rate of 52% is lower than that reported in similar upper‐middle income settings in South America and Eastern Europe. The aim of this study was to analyse survival rates of all children with cancer treated in two large referral centres in both the state and private setting.</p><p><bold>Design/Methods</bold>: This retrospective review included all children, (0‐15years) diagnosed with a malignancy at two pediatric oncology units between January 2012 and December 2016. The treatment regimens in both units were identical, the same doctors worked in both settings and all diagnoses were confirmed histologically. Descriptive statistics and Kaplan‐Meier analyses with Cox regression modeling are presented.</p><p><bold>Results</bold>: There were 599 children, 107 of whom presented from outside South Africa. Median follow up was 1.3 years (IQR 0.4 to 2.7). The most common cancers were leukaemias (24.4%), brain tumors (17.7%) and lymphomas (14%). The HIV incidence was 6%. Two‐year overall survival was calculated to be 60%. The highest survival rates were in children with Hodgkin Lymphoma, retinoblastoma and nephroblastoma, while the lowest were noted in children with osteogenic sarcoma and neuroblastoma. Children treated at the private institution had higher two‐year survival rates than those in the state funded hospital (68% vs 55% p=0.0004).</p><p><bold>Conclusions</bold>: Two‐year overall survival rates were higher for children treated in the privately funded unit. This may reflect differential access to specialist care and earlier referral in the private setting.</p></sec><sec id="pbc26772-sec-9470"><label>P-535</label><title>Incidence of Malignant Solid Tumor in an Adolescent Population in an Equatorian Children Hospital</title><p><underline underline-style="single">A. Borja</underline><sup>1</sup>, M.J. Pesantez<sup>1</sup>, D. Franco<sup>2</sup></p><p><italic><sup>1</sup>Hospital Axxis, Oncología Pediatrica, Quito, Ecuador; <sup>2</sup>Hospital Metropolitano, Pathology, Quito, Ecuador</italic></p><p><bold>Background/Objectives</bold>: Approximately thirty percent of all pediatric cancers in children and adolescents are solid tumors, most frequent types Brain Tumor, Wilms Tumor, Neuroblastoma, Hepatoblastoma and Osteosarcoma. The differences between solid tumors in childhood and adulthood are well delimited but not in the transition period. Under 15 years old, brain tumors are the most common form of solid tumors, however, according to WHO, between 10 to 15 years old a higher incidence of Osteosarcoma, Ewing tumor and lymphoma was found compared to children. This shows noticeable changes in solid tumor distribution when children reach adolescence.</p><p>Objetive: To determine incidence of solid malignant tumor in adolescents at Children Hospital in Ecuador from January 2007 to August 2013.</p><p><bold>Design/Methods</bold>: Descriptive, retrospective study including 406 patients between 9years11months and 14years11months old. Inclusion criteria was diagnostic of Malignant solid tumor confirmed by Pathology area.</p><p><bold>Results</bold>: Of 406 patients, fifty six (13.5%) were admitted by Malignant solid tumor. Most of them were males (63 %) and the mean age at diagnosis was 11.5 years old. CNS tumor had the highest incidence (50%) followed by Lymphoma 14%, Osteosarcoma 9%, Germ Cell tumor 9%, Ewing Sarcoma 5%, Neuroblastoma 5%, Hepatic Adenocarcinoma 2%, undifferentiated tumors and others 6%. Distribution by type is similar to epidemiology of malignant solid tumor described by literature however selection bias is possible due to enroll of population admitted in this pediatric hospital only.</p><p><bold>Conclusions</bold>: CNS tumors were most common malignant tumors found. Osteosarcoma appear to be less frequent compared to international series. In addition, a greater number than expected of males were diagnosed. Although epidemiology and distribution of solid tumor in children and adolescents are different, evidence has shown that higher survival incomes in adolescents could be expected by better psychological support and accurate treatment in specialized pediatric centers despite of this differences in the epidemiology.</p></sec><sec id="pbc26772-sec-9480"><label>P-536</label><title>Impact of Acute Methotrexate‐Induced Neurotoxicity on Therapy Among Pediatric Patients with Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">H. Danysh</underline><sup>1</sup>, A. Brown<sup>1</sup>, O. Taylor<sup>1</sup>, J. Brackett<sup>1</sup>, P. Lupo<sup>1</sup>, I. Moore<sup>2</sup>, M.C. Hooke<sup>3</sup>, M. Hockenberry<sup>4</sup>, M. Scheurer<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Department of Pediatrics, Houston, USA; <sup>2</sup>University of Arizona, College of Nursing, Tucson, USA; <sup>3</sup>University of Minnesota, School of Nursing, Minneapolis, USA; <sup>4</sup>Duke University, School of Nursing, Durham, USA</italic></p><p><bold>Background/Objectives</bold>: Acute methotrexate‐induced neurotoxicity (MTX‐NT) among pediatric patients with acute lymphoblastic leukemia (ALL) often results in treatment interruption, potentially reducing treatment efficacy. Despite its clinical significance, the effects of MTX‐NT on subsequent treatment have not been well‐described. Therefore, we evaluated the impact of acute MTX‐NT on delays and modifications to MTX treatment among pediatric patients with ALL.</p><p><bold>Design/Methods</bold>: We identified patients treated on ALL protocols who had reached maintenance therapy at Texas Children's Hospital and University of Arizona in 2012‐2017 (n=158). MTX‐NT was defined as the occurrence of NT‐related symptoms (e.g., seizure, aphasia) after receiving MTX and led to a change in MTX therapy. Difference in time from diagnosis to start of maintenance, cumulative intravenous MTX dose, and number of intrathecal MTX courses between end of induction and start of maintenance were compared by MTX‐NT status using multiple linear regression and adjusting for age at diagnosis, sex, ethnicity, and ALL risk stratification.</p><p><bold>Results</bold>: On average, patients were 8.3 years of age at diagnosis (range: 2.5‐18.0). The majority was male (57%), Hispanic (58%), and assigned to high or very high risk treatment arms (56%). A total of 25 patients (16%) experienced acute MTX‐NT, of which three (12%) subsequently relapsed or died during follow‐up. After adjusting for demographics and risk group, those who experienced acute MTX‐NT received a 2.7 g/m<sup>2</sup> lower dose of intravenous MTX (95% confidence interval [CI]: 0.4‐5.0; p=0.024) and 2.4 fewer intrathecal MTX courses (95% CI: 1.6‐3.3; p<0.001) by the start of maintenance therapy compared to those without MTX‐NT. The occurrence of MTX‐NT did not significantly delay the start of maintenance therapy (p=0.680).</p><p><bold>Conclusions</bold>: MTX‐NT during post‐induction chemotherapy for pediatric ALL results in patients receiving significantly less intravenous and intrathecal MTX. Future work is needed to determine whether modifications to therapy following acute MTX‐NT compromise treatment efficacy or outcomes, including relapse and survival.</p></sec><sec id="pbc26772-sec-9490"><label>P-537</label><title>Incidence of Childhood Leukemia in Costa Rica from 2001 to 2013: An International Perspective</title><p><underline underline-style="single">F. Erdmann</underline><sup>1,2</sup>, T. Li<sup>3</sup>, G. Luta<sup>3</sup>, J. Schüz<sup>2</sup>, A.M. Mora<sup>4</sup></p><p><italic><sup>1</sup>Danish Cancer Society Research Center, Unit of Survivorship, Copenhagen, Denmark; <sup>2</sup>International Agency for Research on Cancer, Section of Environment and Radiation, Lyon, France; <sup>3</sup>Georgetown University, Department of Biostatistics‐ Bioinformatics and Biomathematics, Washington‐ DC, USA; <sup>4</sup>Universidad Nacional, Central American Institute for Studies on Toxic Substances, Heredia, Costa Rica</italic></p><p><bold>Background/Objectives</bold>: Higher childhood cancer incidence rates, particularly for leukemia, have been reported in high‐income countries compared to low and middle‐income countries. However, estimating childhood cancer incidence globally is hampered by a lack of reliable data from developing countries, including those from the Latin American region. Costa Rica is one of the few developing countries with a long‐term nationwide population‐based cancer registry, enabling the analysis of high‐quality incidence data on childhood leukemia.</p><p><bold>Design/Methods</bold>: Data on incident leukemia in children under 15 years of age reported to the National Cancer Registry of Costa Rica between 2001 and 2013 were analyzed by leukemia type, age at diagnosis, gender, and region.</p><p><bold>Results</bold>: During the 13‐year period, a total of 832 children with leukemia were reported, resulting in an overall age‐standardized incidence rate (ASR) of 58.1/million. The male‐to‐female ratio was 1.2. The highest age‐specific rate was observed in children aged 1‐4 years (97.7/million). The most frequent leukemia type was lymphoid leukemia; with an ASR of 49.1/million the observed rate ranked among the highest in the world. A very low rate was observed for leukemia in infants, largely driven by the low lymphoid leukemia rate. With respect to geographical differences, higher leukemia rates were observed in the Huetar Atlantica (69.2/million) and Huetar Norte (68.1/million) regions. Both regions are characterized by extensive agricultural fields.</p><p><bold>Conclusions</bold>: The patterns of childhood leukemia incidence in Costa Rica were closer to those reported from high‐income countries than to those reported from other developing countries. Further research is needed to investigate which factors may drive the high overall leukemia rate, the low rate observed in infants as well as regional differences. Our study suggests using caution when interpreting global incidence differences, since our observations from a developing country with well‐established pediatric oncology clinics and nationwide registration showed only small differences to incidence patterns from high‐income countries.</p></sec><sec id="pbc26772-sec-9500"><label>P-538</label><title>Epidemiology of Childhood Cancers in Upper Egypt: Five Years Experience of the Largest Cancer Institute Outside the Capital</title><p><underline underline-style="single">A. Farrag</underline><sup>1</sup>, M.H. Ghzally<sup>2</sup></p><p><italic><sup>1</sup>South Egypt Cancer Institute‐ Assiut University, Department of Pediatric Oncology, Assiut, Egypt; <sup>2</sup>Faculty of Medicine‐ Assiut University, Department of Pediatrics, Assiut, Egypt</italic></p><p><bold>Background/Objectives</bold>: Most previous epidemiological studies have focused on patients in developed countries, or capitals and large cities of developing countries. People in rural areas in developing countries may have different genetic, environmental and life style issues.</p><p><bold>Design/Methods</bold>: This retrospective study was performed through review of charts of newly diagnosed children with cancer who started treatment between 2006 and 2010 in the Department of Pediatric Oncology in South Egypt Cancer Institute (SECI). Analyzed data included: age, sex, diagnosis and stage of the disease, response to initial course of therapy, date of relapse if occurred, and last clinical results of treatment.</p><p><bold>Results</bold>: Between 2006 and 2010, 502 children (291 males and 211 females, 1.4:1) with malignancy started therapy in SECI. The median age at first presentation was 5.2 years (2 months‐18 years). Diagnoses were commonly leukemia (49%), lymphomas (24%), solid tumors (24%) and rarely brain tumors (1%). At presentation, 62% of patients with acute lymphoblastic leukemia (ALL) were considered high risk group, 86% of patients with non‐Hodgkin lymphoma (NHL) presented in late stages (III‐IV), and 90% of neuroblastoma patients presented in stage IV. After initial courses of therapy, 53%, 19%, 43% and 0% of patients with ALL, Acute myeloid leukemia (AML), NHL, and neuroblastoma, respectively, were in complete remission. During initial courses of chemotherapy 21%, 52%, 18% and 2% of patients with ALL, AML, NHL, and neuroblastoma, respectively, died. About 85% of patients were compliant with therapy. Overall, the relapse rate was 14%, median time from diagnosis till relapse was 7 (1‐43) months. Deaths were mainly therapy related (60%). Five years overall and event free survival were 0.45 ± 0.03 and 0.36 ± 0.03, respectively.</p><p><bold>Conclusions</bold>: It is essential to establish country based cancer registries in developing countries to enable own plans.</p></sec><sec id="pbc26772-sec-9510"><label>P-539</label><title>Early Diagnosis Improvement of Child Cancer in South of Brazil</title><p><underline underline-style="single">C. Fiori</underline><sup>1</sup>, A. Carla Rosa<sup>1</sup></p><p><italic><sup>1</sup>Hospital do Câncer de Cascavel‐UOPECCAN, Pediatric Oncology, Cascavel, Brazil</italic></p><p><bold>Background / Objectives: Introduction</bold>: Childhood cancer is a rare disease, but the second leading cause of death between 5 to 19 years old. Otherwise, the cure rate reaches 70% if diagnosed early. Precoce detection considerably reduces the complications of the treatment, and contribute to increase the cure.</p><p><bold>Objective</bold>: Evaluate the degree of tumor involvement in children and adolescents with cancer after training health professionals.</p><p><bold>Design / Methods: Methodology</bold>: Health professionals being trained since 2008, in partnership with the Ronald McDonald Institute, through the Early Diagnosis of Cancer Children and Adolescents Program. There were analyzed children younger than 19 years old attended from January 2008 to December 2016, at Cancer Hospital of Cascavel, Paraná, Brazil. The Leukemias were considerated – Low Risk(LR) and High Risk( HR) according to age and leukometry at diagnosis: <bold>LR</bold>: > 12 months and < 10 years old, < 50.000 leukocytes / mm3. <bold>HR</bold>: < 12 months and > 10 years old, > 50.000 leukocytes / mm3. In solid tumors are considerated by stage: <bold>LR</bold>: I/II and <bold>HR</bold>: III/IV.</p><p><bold>Results: Results</bold> 449 patients were attended in the period from 2008 to 2016, of which 248 (55%) were considered High Risk and 201 (45%) Low Risk. There was a predominance of HR over LR per year, from 2009 to 2013. From 2014 until 2016, a predominance of LR over HR.</p><p><bold>Conclusions: Comments</bold>: The preliminary analysis of the data allows us to observe that children and adolescents with cancer have advanced disease at diagnosis. After 2014, we observed change in staging diagnosis of patients who are coming up with more localized disease. It is possible that this change in the between Low Risk and High Risk disease from 2014 may be related to the training activities as a result of the Early Diagnosis Program developed in the West, Northwest and Southwest of Paraná since 2008.</p></sec><sec id="pbc26772-sec-9520"><label>P-540</label><title>Pediatric Population‐Based Cancer Registries in Central America: Insights Shaping Health Policy and Epidemiological Research</title><p><underline underline-style="single">S.</underline><underline underline-style="single">Fuentes</underline><underline underline-style="single">Alabi</underline><sup>1</sup>, G. Claudia<sup>2</sup>, M. Carranza<sup>1</sup>, T. Balcarcel<sup>2</sup>, F. Moreno<sup>3</sup>, M. Metzguer<sup>4</sup>, C. Rodriguez‐Galindo<sup>5</sup>, L. Frazier<sup>6</sup></p><p><italic><sup>1</sup>Hospital Nacional de Niños Benjamin Bloom, Pediatric Oncology, San Salvador, El Salvador; <sup>2</sup>Unidad de Oncologia Pediatrica ‐ UNOP, Pediatric Oncology, Guatemala, Guatemala; <sup>3</sup>Registro Oncopediatrico Hospitalario de Argentina‐ROHA, Hospital Based Pediatric Cancer Registry, Buenos Aires, Argentina; <sup>4</sup>St. Jude Children's Research Hospital, Global Pediatric Medicine‐ International Outreach Program, Memphis‐TN, USA; <sup>5</sup>St. Jude Children's Research Hospital, Global Pediatric Medicine‐International Outreach Program, Memphis‐TN, USA; <sup>6</sup>Dana‐Farber Cancer Institute, Pediatric Oncology, Boston‐MA, USA</italic></p><p><bold>Background/Objectives</bold>: Population‐based cancer registries (PBCR) provide a measure of incidence and survival rate—essential for rational health care planning and further epidemiologic research. Before 2014, the incidence of pediatric cancer in Guatemala and El Salvador (G & ES) was estimated based on international models. Since 2014, G & ES has engaged in a systematic collection of data which has yielded an epidemiological profile of childhood cancer that will impact health care systems.</p><p><bold>Design/Methods</bold>: In 2014, the Registro Oncologia Pediatrica‐Central America (ROP‐CA) was initiated in G & ES to provide PBCR for children 0‐14y. In each country, a cancer registrar identifies cases through search of pathology and laboratory reports, medical and radiation records. Neither registries currently have access to death certificates. All cases are recorded using the International Classification of Disease‐Oncology, version 3. Using the International Classification of Childhood Cancer, the age‐adjusted incidence rates per 10^6 population are calculated and standardized to world population. Incidence rates in G & ES were compared to rates of Argentina.</p><p><bold>Results</bold>: The overall incidence in El Salvador was 91.2/10^6 and in Guatemala 71.8/10^6, compared to an incidence of 125/10^6 in Argentina. The expected vs. observed incidence in Guatemala is 56% and in El Salvador, 71%. In both countries, the incidence was lower than expected for neuroblastoma, retinoblastoma, renal tumors, germ cell tumors and brain tumors; incidence of hepatic tumors was higher than expected.</p><p><bold>Conclusions</bold>: The ROP‐CA has demonstrated that the number of children accessing pediatric cancer care is lower than would be expected–likely due to limited access to primary care, lack of recognition of disease in primary care, or competing mortalities. The identification of these factors has already influenced strategies to improve access to care services for the control of childhood cancer.</p></sec><sec id="pbc26772-sec-9530"><label>P-541</label><title>Texas Children's Cancer and Hematology Center's Global Hope (Hematology‐Oncology Pediatric Excellence)</title><p><underline underline-style="single">K. Wilson‐Lewis</underline><sup>1</sup>, E. Ishigami<sup>1</sup>, J. Slone<sup>2</sup>, C. Allen<sup>2</sup>, J. Lubega<sup>2</sup>, P. Wasswa<sup>2</sup>, A. Anderson<sup>2</sup>, N. El‐Mallawany<sup>2</sup>, G. Airewele<sup>2</sup>, E. Fruge<sup>2</sup>, N. Kagoro<sup>2</sup>, S. Pons<sup>1</sup>, R. Weinstein<sup>1</sup>, P. Mehta<sup>2</sup>, D. Poplack<sup>2</sup></p><p><italic><sup>1</sup>Texas Children's Hospital, Cancer and Hematology Centers, Houston, USA; <sup>2</sup>Baylor College of Medicine, Pediatrics, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Approximately 300,000 children per year develop cancer globally. In Sub‐Saharan Africa (SSA) the majority die due to lack of or incorrect diagnosis, lack of access to medications and inadequate healthcare infrastructure. In contrast, over 80% of children diagnosed with cancer in the U.S. are cured. This inequity compels us to improve pediatric cancer care in SSA.</p><p><bold>Design/Methods</bold>: The Texas Children's Cancer and Hematology Centers (TXCH) and Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) have created a comprehensive program called Global HOPE (Hematology‐Oncology Pediatric Excellence) aimed at building capacity and improving Pediatric Hematology/Oncology (PHO) infrastructure in selected SSA countries.</p><p>Through partnering with local governments and key stakeholders, Global HOPE implements a country‐specific model based on local need. With a focus on in‐country capacity building, Global HOPE educates a broad array of healthcare roles in SSA to support the delivery of high‐quality, comprehensive, multi‐disciplinary care. This comprehensive model is aimed at addressing the clinical care, research, education and administrative goals that will create a sustainable model to improve health care access and outcomes, and stakeholder and community involvement, in an environment of operational excellence.</p><p><bold>Results</bold>: Since 2007, across four SSA countries, Global HOPE has increased the capacity of local healthcare workforce by training over 1500 healthcare workers and improved the care of children with cancer or blood disorders demonstrating improved outcomes in each of its sites, including increased case identification through improved diagnostics, increased number of children receiving care and better access to medications.</p><p><bold>Conclusions</bold>: Global HOPE represents a first step towards the ultimate, transformational goal of cure equity for children with cancer and blood disorders in SSA delivered by a locally sustainable workforce and infrastructure.</p></sec><sec id="pbc26772-sec-9540"><label>P-542</label><title>Development of the Joint Children's Cancer Hospital Egypt (CCHE‐57357) Dana‐Farber Boston Children's Hospital Pediatric Oncology Fellowship Program</title><p>M. Zamzam<sup>1</sup>, H. Hanafy<sup>2</sup>, <underline underline-style="single">R. Khedr</underline><sup>2</sup>, S. Abouelnaga<sup>3</sup>, M. Abdelbaki<sup>4</sup>, L. Goumenrova<sup>5</sup>, L. Lehmann<sup>6</sup>, K. Houlahan<sup>7</sup>, M. Kieran<sup>8</sup>, P. Pruden<sup>9</sup></p><p><italic><sup>1</sup>National Cancer Institute ‐ Cairo University / Children's Cancer Hospital Egypt CCHE 57357, Pediatrics Oncology, Cairo, Egypt; <sup>2</sup>National Cancer Institute ‐ Cairo University / Children's Cancer Hospital Egypt CCHE57357, Pediatrics Oncology, Cairo, Egypt; <sup>3</sup>National Cancer Institute ‐ Cairo University /Children's Cancer Hospital Egypt CCHE57357, Pediatrics Oncology, Cairo, Egypt; <sup>4</sup>Nationwide Children's Hospital, Pediatrics Oncology, Colmbus ‐ Ohio, USA; <sup>5</sup>Dana Farber / Boston Children Cancer Institute, Pediatric Neurosurgical Oncology, Boston, USA; <sup>6</sup>Dana Farber / Boston Children Cancer Institute, Pediatric Oncology/BMT, Boston, USA; <sup>7</sup>Dana Farber / Boston Children Cancer Institute, Nursing Department, Boston, USA; <sup>8</sup>Dana Farber / Boston Children Cancer Institute, Pediatric Oncology / Neuroncology, Boston, USA; <sup>9</sup>Children's Cancer Hospital Egypt CCHE 57357, Nursing Department, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Children diagnosed with cancer in low‐ and middle‐income countries (LMIC) have inferior outcomes compared to those in high income countries. While some of these issues can be resource availability, a major problem is the quality of training and traditional methods of clinical practice where decision making is centered on the most senior person on the team. To ensure real change, highly‐trained locally based specialists with a strong emphasis on problem‐solving and critical thinking using evidence‐based approaches are needed.</p><p><bold>Design/Methods</bold>: The Children's Cancer Hospital Egypt (CCHE‐57357) and Dana‐Farber Boston Children's Hospital (DFBCH) at Harvard Medical School developed a 30 month pediatric oncology fellowship training program following the American Academy of Pediatrics fellowship guidelines.The primary objective of the program was to implement a shared education model to develop highly educated physicians who are able to follow evidence‐based approaches and committed to sustained practice in LMIC.</p><p><bold>Results</bold>: DFBCH staff provide ongoing education to the fellows through visits to CCHE‐57357 every 2‐3 months, weekly video sessions with the fellows for case presentation and journal clubs, and weekly conference calls with the fellowship program staff to ensure that the goals and objectives for each fellow and the program are met.Each of the current 15 fellows spend 6 weeks/year in Boston participating in evidence‐based multi‐disciplinary based rounds; the remainder of the curriculum takes place at CCHE‐57357 and incorporates an array of individual, small group and e‐learning modules specifically created for the program. Three classes of fellows have been enrolled and the senior class will graduate in spring of 2017.</p><p><bold>Conclusions</bold>: Training of fellows following the same standards as those applied to North American candidates is feasible and has the potential to advance the quality of education and expertise in LMIC. By focusing on the education of the next generation of clinicians, the opportunity to implement many of the important principles of clinical care can be realized.</p></sec><sec id="pbc26772-sec-9550"><label>P-543</label><title>Presentation of Children with Cancer to a Pediatric Oncology Unit in Mangaluru, India</title><p><underline underline-style="single">H. Lashkari</underline><sup>1</sup>, R. Shenoy<sup>2</sup>, N. Kamath<sup>3</sup>, J. K<sup>3</sup>, S. Rao<sup>4</sup>, M. Faheem<sup>3</sup>, M. Kishore<sup>2</sup>, S. Nayak<sup>2</sup>, S. Prabhu<sup>2</sup>, S. dsa<sup>5</sup>, H. MM<sup>6</sup>, K. Bhat<sup>6</sup></p><p><italic><sup>1</sup>Kasturba Medical College, Paediatrics, Mangalore, India; <sup>2</sup>Kasturba Medical College Hospital, Pediatrics, Mangalore, India; <sup>3</sup>Kasturba Medical College Hospital Manipal University, Pediatrics, Mangalore, India; <sup>4</sup>Kasturba Medical College Hospital‐ Manipal University, Pediatrics, Mangalore, India; <sup>5</sup>Kasturba Medical College Hospital Mangalore, Pediatrics, Mangalore, India; <sup>6</sup>Kasturba Medical College, Pediatrics, Mangalore, India</italic></p><p><bold>Background/Objectives</bold>: It is essential to know the routes of presentation and time prior to diagnosis in primary and secondary care to avoid delay in diagnosis which plays an important role in better survival strategy in childhood cancers.To describe average time taken for a child with cancer to present and to get diagnosed in an oncology unit.</p><p><bold>Design/Methods</bold>: It is retrospective cohort study of children diagnosed with cancer between the 1<sup>st</sup> Jan 2014 and 31st Dec 2016 at Pediatric oncology unit, KMC Hospital Mangalore, India. Time to presentation (TTP) was defined as time from initial symptoms to time seen by a pediatrician. Time to diagnosis (TTD) was defined as time from initial symptoms to diagnosis at our pediatric oncology unit. Patient pathways to diagnosis were mapped and routes for different cancers were compared.</p><p><bold>Results</bold>: Total 148 children were registered with childhood cancer during this period. The data of 104 children aged between 0 to 16 yrs diagnosed during this period were collected. The majority of them were boys (68). Acute leukemia was diagnosed in 67 cases and TTP varied between 2 to 45 days. Nearly two third (40/67) presented within 2 weeks of onset of symptoms. The TTD varied between 7 to 180 days with mean of 36 days in leukemia group. In solid tumor group TTP was 1 to 60 days, whereas TTD varied between 8 to 105 days with an average of 42 days. Acute lymphoblastic leukaemia (ALL) with skeletal manifestations had longest TTD (180 days). Lymphoma had TTD of 105 days with TTP of 45 days.</p><p><bold>Conclusions</bold>: The majority of children diagnosed with cancer presented via referral from pediatricians, with the route varying between tumor types.This is part of ongoing study which is looking into the challenges in diagnosing cancer, identifying a wide range of non‐disease related factors potentially delaying the diagnosis.</p></sec><sec id="pbc26772-sec-9560"><label>P-544</label><title>The Pediatric East African Clinical Oncology Consortium (PEACOC)</title><p><underline underline-style="single">J. Lubega</underline><sup>1</sup>, P. Scanlan<sup>2</sup></p><p><italic><sup>1</sup>Uganda Cancer Institute, Pediatric Oncology, Kampala, Uganda; <sup>2</sup>Muhimbili National Hospital, Pediatrics, Dar es Salaam, Tanzania</italic></p><p><bold>Background/Objectives</bold>: The survival of children with cancer in East Africa is poor due to shortages of dedicated and standardized pediatric cancer services, skilled multi‐disciplinary workforce, and locally appropriate evidence‐based pediatric cancer management guidelines. PEACOC is a cooperative group of pediatric cancer centers in the six member states of the East African Community to sustainably improve the outcomes of children with cancer in the region.</p><p><bold>Design/Methods</bold>: PEACOC was created in November 2016 at Ocean Road Cancer Hospital, Dar es Salaam (Tanzania) by the pediatric oncology expert working under the auspices of the East Africa Regional Oncology Center of Excellence that is funded by member state loans from the African Development Bank. The Expert Working Group (EWG) noted the following as the topmost challenges of pediatric oncology across all centers in East Africa: 1) Late presentation of patients with advanced tumors and with life‐threatening complications; 2) Inconsistent access to chemotherapy; 3) Poor access to blood products for transfusion; 4) Poor access to radiotherapy; 5) Lack of local evidence‐based treatment and supportive care guidelines; 6) Lack of dedicated infrastructure and personnel. To foster regional collaboration and sharing resources, the EWG agreed to form PEACOC to include all pediatric cancer units in East Africa and various international collaborators.</p><p><bold>Results</bold>: PEACOC will evaluate current pediatric cancer units in East Africa including treatment guidelines, tumor‐specific epidemiology, care funding, research activity, tertiary and specialist skills development. The Consortium will then adapt current regional practices to best international practices to develop guidelines for the region.</p><p><bold>Conclusions</bold>: PEACOC will conduct cooperative group clinical trials, establish a harmonized regional pediatric cancer registry, conduct pediatric cancer training programs, and benchmark quality of pediatric cancer care in the region.</p></sec><sec id="pbc26772-sec-9570"><label>P-545</label><title>Strategic Planning for Expansion: Children's Cancer Hospital Egypt 57357</title><p><underline underline-style="single">F. Makka</underline><sup>1</sup>, B. Lee<sup>2</sup>, I. Albanti<sup>3</sup></p><p><italic><sup>1</sup>Harvard University School of Public Health, Health Management, Boston, USA; <sup>2</sup>Harvard University School of Public Health, Global Health, Boston, USA; <sup>3</sup>Dana Farber Cancer Institute, Global Health Institute, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer is a global health problem. While low‐and middle‐income countries (LMIC) plan to initiate or expand pediatric oncology services, guidance from published literature is limited due to its focus on high‐income countries and academic medical centers. As the largest pediatric oncology hospital in the world, the Children's Cancer Hospital Egypt (CCHE) strives to provide free care to all without discrimination. High demand has pushed CCHE to start the process of expanding its space and services. Our project explored the expansion strategy at CCHE while considering its local context, with the goal of creating a generalizable resource for other LMIC to reference.</p><p><bold>Design/Methods</bold>: We used qualitative research methods in the form of in‐depth Interviews with 24 key informants, including members of senior management, staff at CCHE and community members. The interviews were conducted over two weeks in January 2017, with each session lasting 45‐60 minutes. Findings were structured into a process map, a stakeholder analysis, a SWOT analysis, and a final report.</p><p><bold>Results</bold>: CCHE faces many challenges in its progress, from the flotation of the Egyptian currency to spatial restrictions of its expansion. Throughout the interviews, we identified several major attributes that were instrumental in helping them overcome these barriers: visionary leadership, strong international collaborations, early investment in external consultants to bring in world‐class best practices, and an emphasis on extensive planning.</p><p><bold>Conclusions</bold>: Many of the challenges present in the CCHE expansion are also likely to be faced by other pediatric oncology facilities in LMIC seeking to expand their own pediatric oncology units. We believe that such facilities may benefit from the findings of our study.</p></sec><sec id="pbc26772-sec-9580"><label>P-546</label><title>The Slovak Clinical Cancer Registry of Children and Adolescents: Rationale, Organization and Incidence in Years 2000‐2012</title><p><underline underline-style="single">M. Makohusová</underline><sup>1,2,3</sup>, E. Kaiserová<sup>1</sup>, M. Colombet<sup>2</sup>, E. Bubanská<sup>4</sup>, I. Oravkinová<sup>5</sup>, T. Stančoková<sup>4</sup>, J. Puškáčová<sup>1</sup>, A. Kolenová<sup>1</sup>, E. Steliarova‐Foucher<sup>2</sup></p><p><italic><sup>1</sup>Children's University Hospital, Department of Pediatric Hematology and Oncology, Bratislava, Slovak Republic; <sup>2</sup>International Agency for Research on Cancer, Section of Cancer Surveillance, Lyon, France; <sup>3</sup>University of SS. Cyril and Methodius, Department of Chemistry‐ Faculty of Natural Sciences, Trnava, Slovak Republic; <sup>4</sup>Children's University Hospital‐ Slovak Medical University, Department of Pediatric Oncology and Hematology, Banská Bystrica, Slovak Republic; <sup>5</sup>University Children s Hospital‐ Pavol Jozef Safarik University, Department of Pediatric Hematology and Oncology, Kosice, Slovak Republic</italic></p><p><bold>Background/Objectives</bold>: The aim of the study was to report on the cancer incidence and time trends in children and adolescents (age‐range 0‐19) registered in the Slovak Clinical Cancer Registry of Children and Adolescents during the period 2000‐2012.</p><p><bold>Design/Methods</bold>: The data are collected from three regional pediatric treatment centers. All malignant, some benign and borderline malignancies were included. This population‐based cancer registry with national coverage records detailed clinical information on diagnosis, treatment and follow‐up of patients. The tumours were classified using International Classification of Childhood Cancer, edition 3. Official population figures were used to calculate incidence rates.</p><p><bold>Results</bold>: In 2000‐2012, 2,071 cases were registered (age‐range 0‐19 years). For the age‐range 0‐14 (N=1,626), the age‐standardized (World standard) annual incidence rate (ASR) was 144.6 per million person‐years; the most frequent were leukaemias (ASR=44.4), followed by CNS tumours (ASR=31.7), lymphomas (ASR=15.4) and neuroblastomas (ASR=13.0; N=125). Age‐specific incidence rates were the highest among infants (239.3; N=171), lower at age 1‐4 years (181.6; N=516), 5‐9 (112.0; N=424), 10‐14 years (116.1; N=515) and the lowest at age 15‐19 years (86.0; N=445). The average annual increase over the study period in the age 0‐14 was 1.68% (P=0.01) overall and increased for neuroblastoma by 6.66% (P=0.02).</p><p><bold>Conclusions</bold>: Observed incidence rates for children aged 0‐14 years are comparable with those reported from countries of Eastern Europe and from the National cancer registry of Slovakia (NOR). The low rate reported for adolescents is due to data incompleteness. Continuous monitoring of the time trends is needed. For the future, it is important to put in place a mechanism of data exchange with the national registry for cancers of all ages (NOR), to improve data quality and completeness in both sources and provide reliable and detailed data for research and public health.</p><p><bold>Acknowledgement</bold>: National Scholarship Program of the Slovak Republic</p></sec><sec id="pbc26772-sec-9590"><label>P-547</label><title>Demographic Survey on Pediatric Cancer Patients in Japan after the Election of Childhood Cancer Core Hospitals</title><p><underline underline-style="single">K. Matsumoto</underline><sup>1</sup>, T. Takimoto<sup>2</sup>, A. Saito<sup>3</sup>, A. Oara<sup>4</sup>, K. Horibe<sup>3</sup>, E. Hiyama<sup>5</sup></p><p><italic><sup>1</sup>National Center for Child Health and Development, Children's Cancer Center, Tokyo, Japan; <sup>2</sup>National Center for Child Health and Development, Clinical Epidemiology Research Center for Pediatric Cancer, Tokyo, Japan; <sup>3</sup>National Hospital Organization Nagoya Medical Center, Clinical Research Center, Nagoya, Japan; <sup>4</sup>Toho University School of Medicine, Department of Pediatrics, Tokyo, Japan; <sup>5</sup>Hiroshima University, Department of Pediatric Surgery, Hiroshima, Japan</italic></p><p><bold>Background/Objectives</bold>: In Japan there used to exist about 200 hospitals that cared childhood cancer arising about 2500 patients yearly. In 2013, with the aim of further integration and to provide uniform accessibility to pediatric cancer treatment, the Ministry of Health, Labour and Welfare elected 15 core hospitals in seven regional blocks in Japan. The aim of this study is to determine the demographic profile of childhood cancer patients in Japan before and after the election of 15 core hospitals.</p><p><bold>Design/Methods</bold>: We collected data from the published registry of the Japanese Society of Pediatric Hematology/Oncology, which would cover approximately 80% of the patients with cancer in Japan. The collected data were analyzed to reveal the change before and after the election of the core hospitals.</p><p><bold>Results</bold>: In 2016, there exist 150 hospitals that cared pediatric cancer patients in Japan. Among them, 55% were university hospitals and 10% were children's hospitals. Twenty‐five percent of the hospitals that cared more than 20 cases per year (high‐volume center) covered 57% of the cancer patients in Japan. The core hospitals were elected from the high volume centers, and covered 32% of pediatric cancer patients.</p><p>The number of hospitals that could care leukemia/lymphoma patients decreased from 175 in 2012 to 143 in 2015. High volume centers of eukemia/lymphoma covered 23.8% patients in Japan, which was increased from 13.8% before the election of core hospitals. Also, the number of hospitals that could care solid tumors, including brain tumor, decreased from 139 in 2012 to 129 in 2015. The coverage rate of solid tumor patients by high volume centers of solid tumors increased from 31.0% to 41.2%.</p><p><bold>Conclusions</bold>: Integration of the pediatric patients with solid tumors and hematological malignancies is realizing in Japan after the election of 15 core hospitals.</p></sec><sec id="pbc26772-sec-9600"><label>P-548</label><title>Burden of Pediatric Solid Tumors Management in South‐East Asia Countries</title><p><underline underline-style="single">C. Monsereenusorn</underline><sup>1,2</sup>, P. Friedrich<sup>3</sup>, P. Alcasabas<sup>4</sup>, C. Lam<sup>3</sup>, C. Rodriguez‐Galindo<sup>3</sup></p><p><italic><sup>1</sup>Phramongkutklao Hospital and College of Medicine, Department of Pediatrics, Bangkok, Thailand; <sup>2</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Department of Pediatric Oncology, Boston‐ MA, USA; <sup>3</sup>St.Jude Children's Research Hospital, Department of Global Pediatric Medicine, Memphis‐ TN, USA; <sup>4</sup>Philippines General Hospital, Department of Pediatrics, Manila, Philippines</italic></p><p><bold>Background/Objectives</bold>: Pediatric solid tumor treatment require complex multidisciplinary care. The objective of this study is to identify barriers to effective treatment of pediatric solid tumors in South‐East Asia (SEA) and will inform the development targeted strategies to improve outlook for children with solid tumors in SEA.</p><p><bold>Design/Methods</bold>: Physicians were received an individualized email‐specific link of survey. Questions in the survey included topic: patients, care team, hospital/infrastructure, abandonment and barriers to treatment. Analysis will be done from countries as classified by the World Bank Method as low (LIC), low‐middle (LMIC), upper‐middle (UMIC), and high income countries (HIC).</p><p><bold>Results</bold>: The survey was sent to 66 physicians. 17 responses (25.8%) from 17 centers (7 countries) had been received. Neuroblastoma is the most common disease that presenting with late presentation in SEA, followed by osteosarcoma, Ewing sarcoma, other soft tissue sarcomas. In terms of laboratory, Methotrexate level is still not available in 50% of centers and 2 countries. More than 50% of solid tumor cases have been encountered with inconclusive diagnosis by pathology. Infection is still a leading cause of death among SEA countries. For surgery, limb sparing surgery is performed in less than 50% of cases, with higher rate in UMIC (P=0.045). However, external prostheses are seldom available, in particular in LMIC (P=0.023). The rate of abandonment was highest for bone tumors, soft tissue sarcomas and neuroblastoma. The most important barriers for solid tumor treatment are financial constraints, followed by commute, infection, abandonment, fear from surgery, radiation and lacking of legal support.</p><p><bold>Conclusions</bold>: Barriers to effective treatment of pediatric solid tumors in SEA are late presentation, limited resources for laboratory and pathology, inadequate supportive care, limited accessibility of limb sparing surgery and prosthesis and treatment abandonment. These results will inform the development of specific strategies to solve these barriers in pediatric solid tumors treatment in SEA.</p></sec><sec id="pbc26772-sec-9610"><label>P-549</label><title>Evaluation of Maternal and Perinatal Characteristics and Risk of Langerhans Cell Histiocytosis in Texas, 1995‐2011</title><p><underline underline-style="single">E. Peckham‐Gregory</underline><sup>1</sup>, K. McClain<sup>1</sup>, C. Allen<sup>1</sup>, M. Scheurer<sup>1</sup>, P. Lupo<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics‐ Hematology‐Oncology Section, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with a median diagnosis age of 30 months. In studies of pediatric malignancies, maternal and perinatal characteristics have been successfully evaluated to determine the impact of inborn variation on disease risk. Therefore, we reviewed population‐based registry data to determine if these factors influence the risk of LCH.</p><p><bold>Design/Methods</bold>: The study population included children with LCH born in Texas (n=164) for the period 1995‐2011 who were identified from the Texas Cancer Registry. Birth certificate controls were randomly selected at a ratio of 10:1 for the same period matched on birth year. We evaluated the impact of factors identified from vital records including: gestational age, birthweight, and parental race/ethnicity. Unconditional logistic regression was used to generate adjusted odds ratios (aOR) with 95% confidence intervals (CI) evaluating the association between selected factors and the risk of LCH.</p><p><bold>Results</bold>: Overall, non‐Hispanic Black mothers were less likely to give birth to offspring who developed LCH compared to non‐Hispanic White (NHW) mothers (aOR: 0.50; 95% CI: 0.24‐1.03). However, Hispanic mothers were at increased risk of giving birth to offspring who developed LCH (aOR: 1.58; 95% CI: 1.07‐2.35). Furthermore, the risk of LCH was stronger among children born from two Hispanic parents compared to children born from two NHW parents (aOR: 1.83; 95% CI: 1.15‐2.90). Mothers born in Mexico versus the U.S. and who resided along the U.S.‐Mexico border were less likely to give birth to offspring who developed LCH (aOR: 0.66; 95% CI: 0.41‐1.07 and aOR: 0.54; 95% CI: 0.29‐0.98, respectively).</p><p><bold>Conclusions</bold>: Maternal and parental race/ethnicity were strongly associated with LCH risk. Further, mothers who resided along the U.S.‐Mexico border at time of infant birth, and Mexico‐born mothers, were less likely to give birth to offspring who developed LCH. These findings highlight novel risk factors that warrant assessment in future studies.</p></sec><sec id="pbc26772-sec-9620"><label>P-550</label><title>Spectrum of Malignancies in Patients with Neurofibromatosis (NF): Experience from the First Greek NF‐Center</title><p><underline underline-style="single">K. Roka</underline><sup>1</sup>, M.C.S. Filippidou<sup>1</sup>, E. Kokkinou<sup>2</sup>, M. Tsipi<sup>3</sup>, M. Themistocleous<sup>4</sup>, I. Nikas<sup>5</sup>, K. Stefanaki<sup>6</sup>, M. Tzetis<sup>3</sup>, R. Pons<sup>2</sup>, A. Kattamis<sup>1</sup></p><p><italic><sup>1</sup>Athens Medical School, Division of Pediatric Hematology‐Oncology‐ First Department of Pediatrics, Athens, Greece; <sup>2</sup>Athens Medical School, First Department of Pediatrics, Athens, Greece; <sup>3</sup>Athens Medical School, Medical Genetics, Athens, Greece; <sup>4</sup>Aghia Sophia Childrens Hospital, Department of Neurosurgery, Athens, Greece; <sup>5</sup>Aghia Sophia Childrens Hospital, Radiology Department, Athens, Greece; <sup>6</sup>Aghia Sophia Childrens Hospital, Pathology Department, Athens, Greece</italic></p><p><bold>Background/Objectives</bold>: Neurofibromatosis(NF) type‐1(NF1) and type‐2(NF2) are distinct genetic‐clinical‐syndromes in which affected individuals develop both benign and malignant tumors that predominantly affect the nervous‐system. In order to standardize and improve the clinical‐care of patients with NF, the first national‐center of reference was established in 1/1/2016.</p><p><bold>Design/Methods</bold>: To describe the spectrum of malignancies in patients with NF examined from January 2016 until February 2017 in our NF‐reference‐center. Clinical diagnosis of NF1 was based on National‐Institutes of Health diagnostic‐criteria(NIH,1988), while for NF2 on National‐Neurofibromatoses‐Foundation‐Criteria (NNFF,1997). Patients were evaluated from a multidisciplinary‐team including neurologist, dermatologist, oncologist, ophthalmologist as well as psychologist. Genetic‐counseling was provided in all the families and regular follow‐up for the patients was arranged.</p><p><bold>Results</bold>: During the study‐period 51 patients(age 6mo‐17y, median 8,79y) were examined and included in the analysis. Clinical diagnosis of NF1 had 48 patients, while 3 of NF2. Molecular‐testing for NF1 was performed in all the patients, with NF1 confirmed in 27 patients(3 de‐novo‐mutations), while in 21 patients evaluation is still ongoing. Among the 51 patients, there were 4 families with 2 affected children, while 7 patients were referred due to positive family‐history. Optic‐Pathway‐Gliomas(OPGs) were found in 19 patients with NF1(39,6%), of whom 9 had visual deterioration during follow‐up and received chemotherapy. Two siblings with NF1 and OPGs presented with non‐reversible blindness. Pilocytic‐astrocytomas were diagnosed in two patients, located in posterior‐fossa and left parietal‐lobe, respectively. Neurofibromas were diagnosed in 4 patients(8.33%), one with plexiform‐neurofibroma and metastatic‐malignant‐peripheral nerve‐sheath‐tumor also and one with a large cervical neurofibroma causing mild‐respiratory distress. Bilateral vestibular‐schwannomas causing mild‐deafness with previous history of two resected meningiomas were observed in two out of three patients with NF2. Indication for oncologic intervention was needed in 27,4% of the patients.</p><p><bold>Conclusions</bold>: Establishment of a Multidisciplinary‐Center for Neurofibromatosis can improve clinical‐care by providing necessary multidimensional‐approach and contributing to early diagnosis and timely therapeutic intervention.</p><p><italic>The author thanks Special Account for Research Grants and National and Kapodistrian University of Athens for funding to attend the meeting</italic></p></sec><sec id="pbc26772-sec-9630"><label>P-551</label><title>Organization of Medical Care for Children with Cancer in the Regions of the Russian Federation: The Results of External Audit</title><p><underline underline-style="single">M. Rykov</underline><sup>1</sup>, V. Polyakov<sup>1</sup></p><p><italic><sup>1</sup>Institute of Pediatric Oncology and Hematology FSBSI “N.N. Blokhin RCRC”, General oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The study presents the analysis of the external audit results of the delivery of medical care in children with cancer conducted in the regions of the Russian Federation: Central, North‐West, North‐Caucasian, Volga and South Federal Districts.</p><p><bold>Design/Methods</bold>: The authors analyzed the clinical histories of children with solid tumors who received specialized treatment in the oncology departments of the Regional Children's Hospitals in the period of 2011–2015, and evaluate the available equipment and existing competence of the staff.</p><p><bold>Results</bold>: The study revealed 374 patients (194 (51.9%) boys and 180 (48.1%) girls) aged 0 ‐ 17 years (mean age 5.4 years) with malignant tumors. The number of hospitalizations ‐ 1534, the total number of patient days ‐ 22762, average ‐ 14.8. Patients with I stage of disease ‐ 23 (6.1%), with II ‐ 112 (30%), with III ‐ 89 (23.9%) and with IV ‐ 146 (39%), with an unknown stage ‐ 4 (1%). Clinical guidelines have been violated in the treatment of 46 (12.3%) patients.</p><p><bold>Conclusions</bold>: It seems reasonable to develop recommendations that justify the expediency of the individual stages of the treatment of patients in different regions of the Russian Federation in accordance with their distance from the federal center, the size and density, as well as the incidence of child population in order to ensure optimal routing of patients and improve the Commission. It is also necessary to strengthen the oncology alertness of primary care physicians (pediatricians) for early detection of cancer, including during routine inspections.</p></sec><sec id="pbc26772-sec-9640"><label>P-552</label><title>Duration Between the First Symptom and Exact Diagnosis Time in Childhood Cancer</title><p><underline underline-style="single">B. Sevinir</underline><sup>1</sup>, M. Demirkaya<sup>1</sup>, M. Ertekin<sup>1</sup>, G. Kalay<sup>1</sup></p><p><italic><sup>1</sup>Uludag University Medical Faculty, Pediatric Oncology, BURSA, Turkey</italic></p><p><bold>Background/Objectives</bold>: Early diagnosis promotes prognosis in childhood cancers.Our aim is to evaluate the duration between the first symptom and exact diagnosis time in children diagnosed as lymphomas or solid tumors.</p><p><bold>Design/Methods</bold>: The data of 759 patients applied to Uludağ University Medical Faculty Department of Pediatric Oncology who diagnosed as lymphoma or solid tumor during January 2005 to November 2014 was retrospectively analysed.The time from the first complaints to the apply of a physician,the time from admission to get a diagnose and total time from the first complaints to the final diagnosis were determined.These datas were compared with age, sex and diagnosis.</p><p><bold>Results</bold>: Median age was 84 months.The most common diagnosis were lymphomas(22%), brain tumors (18.3%) and germ cell tumors (10.8%). The patients’ were firstly apply to 67.5% pediatricians, 5.3% general practitioners, 29% other specialties. Median time of the duration between the first admission was 15 days. Median time of the referral of the patient to the oncology centers is 8 days and median diagnose time of the patients was 10 days. Median time between the onset of symptoms and the final diagnosis was 55 days (3‐1254 days). The first admission time of the patiens diagnosed non‐Hodgkin lymphoma (p=0.030), Hodgkin lymphoma (p=0.003), osteosarcomas (p=0.005), soft tissue sarcomas(p=0.009) and thyroid carcinomas (p=0.001) were more than 15 days. The first admission time of the patients were significantly less than 15 days who diagnosed neuroblastoma (p=0.001), renal tumors(p=0.005) and hepatoblastomas (p=0.016). The referral time of the patients with Hodgkin's lymphomas (p=0.003) and osteosarcomas (p=0.016) were more than 8 days.The admission time was longer than 15 days in adolescent patients.Time to diagnosis was longer in patients who addmited to physians other than pediatricians or pediatric surgeons(p=0.024).</p><p><bold>Conclusions</bold>: In our study the referral and diagnose times are prolonged especially the physicians who rarely examine children.</p></sec><sec id="pbc26772-sec-9650"><label>P-553</label><title>A Comprehensive Model for Developing a Pediatric Cancer Health System in Ethiopia: A Five‐Year Experience</title><p><underline underline-style="single">A. Shad</underline><sup>1</sup>, J. Broas<sup>2</sup>, D. Korones<sup>3</sup>, D. Hailu<sup>4</sup>, M. Bonilla<sup>5</sup>, C. Rodriguez‐Galindo<sup>6</sup>, W. Bekele<sup>7</sup>, S. Weitzman<sup>8</sup>, J. Challinor<sup>9</sup></p><p><italic><sup>1</sup>Children's Hospital at Sinai, Pediatrics‐ Pediatric Hematology/Oncology, Baltimore, USA; <sup>2</sup>The Aslan Project, Non‐Profit Organization, Washington DC, USA; <sup>3</sup>Wilmot Cancer Institute – University of Rochester Medical Center, Pediatrics‐ Pediatric Hematology/Oncology, Rochester, USA; <sup>4</sup>Tikur Anbessa Specialized Hospital, Pediatric Hematology/Oncology, Addis Ababa, Ethiopia; <sup>5</sup>Jimma University Specialized Hospital, Pediatric Hematology/Oncology, Jimma, Ethiopia; <sup>6</sup>St. Jude Children's Research Hospital, Global Pediatric Medicine, Memphis, USA; <sup>7</sup>Newark Beth Israel Medical Center, Pediatric Hematology/Oncology ret., Newark, USA; <sup>8</sup>The Hospital for Sick Children, Haematology/Oncology, Toronto, Canada; <sup>9</sup>School of Nursing – University of California San Francisco, Physiological Nursing, San Francisco, USA</italic></p><p><bold>Background/Objectives</bold>: In 2012, despite an estimated 6,000 cases of pediatric cancer annually, Ethiopia had no qualified pediatric oncologists, pediatric oncology nurses, or oncology pharmacists and no dedicated infrastructure. Children with cancer were intermixed with the general pediatrics population and palliative care/pain medications were rarely offered during treatment. To address these issues, The Aslan Project, a US non‐governmental organization (NGO), introduced a pilot project for building a pediatric cancer system at Tikur Anbessa Specialized Hospital (TASH) in 2012. In 2015, with St. Jude's support, Aslan opened a second Ethiopian site, Jimma University Specialized Hospital (JUSH), serving an area of 15 million people with no prior pediatric oncology capacity.</p><p><bold>Design/Methods</bold>: Aslan's model focuses on human resource (HR) capacity building (fellowship training), infrastructure development, and family/psychosocial support. Initially, at TASH, Aslan provided nearly full financial support for the project. At JUSH, Aslan refined its model to enhance local partner ownership and improve HR training through partnerships with high‐functioning LMIC institutions. Aslan prioritizes advocacy and relationship building with the Federal Ministry of Health (FMOH).</p><p><bold>Results</bold>: The TASH unit is robust; in November 2016, it had 729 patient visits collectively on in‐ and out‐patient service, and family support has reduced treatment abandonment substantially. JUSH has treated 50+ children since August 2016 and administered 600+ doses of chemotherapy with no significant error. The FMOH has prioritized childhood cancer, forming a National Task Force for Pediatric Cancer, and WHO, SIOP, and CCI are engaged within the country. Other Ethiopian hospitals have adopted Aslan's model, and training continues in all specialties.</p><p><bold>Conclusions</bold>: Full engagement of all stakeholders – the government, major institutions, and NGOs – is critical, largely through building of trust and joint ownership of the project. Continual refinement of the model is necessary to adapt to the needs/capacity of partner institutions. Aslan's model may be replicated successfully within other LMICs.</p></sec><sec id="pbc26772-sec-9660"><label>P-554</label><title>Launching Pointe: Use of Branding and Social Media to Promote Pediatric Oncology Education and Training Opportunities</title><p><underline underline-style="single">J. Slone</underline><sup>1</sup>, M. Zobeck<sup>1</sup>, J. Libes<sup>2</sup>, R. Kunkel<sup>3</sup>, N. Ranasinghe<sup>4</sup>, J. Geel<sup>5</sup></p><p><italic><sup>1</sup>Baylor College of Medicine/Texas Children's Hospital, Pediatrics, Houston, USA; <sup>2</sup>University of Illinois College of Medicine, Pediatrics, Peoria, USA; <sup>3</sup>Arkansas Children's Hospital, Pediatrics, Little Rock, USA; <sup>4</sup>Thomson Reuters, London, United Kingdom; <sup>5</sup>University of the Witwatersrand‐ Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, Johannesburg, South Africa</italic></p><p><bold>Background/Objectives</bold>: Training a pediatric oncology workforce is essential to providing optimal treatment to children with cancer in low‐ and middle‐income countries (LMICs). While training opportunities exist, information on them is often difficult to find. In an effort to promote global childhood cancer education, we aimed to improve upon a previous initiative to consolidate information for providers by developing a new and enhanced web site with a social media campaign to increase awareness.</p><p><bold>Design/Methods</bold>: The International Society of Paediatric Oncology‐Paediatric Oncology in Developing Countries Education and Training Working Group (SIOP‐PODC ET WG) launched an online database of training programs in October 2014. To better engage stakeholders, the site was re‐branded as the Paediatric Oncology International Network for Training and Education (POINTE) and launched a new website at www.cancerpointe.com. A social media campaign on Facebook, Twitter and LinkedIn accompanied the new site's launch in October 2016. Google Analytics was utilized to monitor website traffic and reach of both sites.</p><p><bold>Results</bold>: In the first five months after www.cancerpointe.com was launched, page views increased compared to the same time period of the initial site by 53% (5051 vs. 3291) and the site was accessed from 13 more countries (95 countries vs. 82 previously). With a social media campaign that included 320 Facebook likes and 58 Twitter followers in the first five months, social media referrals accounted for 13.9% of referrals to the new site. Without a similar campaign, only 1.8% of traffic of the first site originated from social media.</p><p><bold>Conclusions</bold>: Rebranding and launching a social media campaign has effectively increased web traffic and exposed new training opportunities to healthcare providers in LMICs. While data is lacking regarding impact on patient care, we believe this initiative and the programs added to the site have the ability to greatly improve the quality of education and training.</p></sec><sec id="pbc26772-sec-9670"><label>P-555</label><title>Causes of Death In Pediatric Cancer Patients in Mexico</title><p><underline underline-style="single">L.</underline><underline underline-style="single">Velasco‐Hidalgo</underline><sup>1</sup>, M. Zapata‐Tarrés<sup>1</sup>, F. Arreguín‐González<sup>2</sup>, N.A. López‐Facundo<sup>3</sup>, R. Cárdenas‐Cardós<sup>1</sup>, B. Almazan‐García<sup>2</sup>, I. Tejocote‐Romero<sup>3</sup>, R. Rivera‐Luna<sup>1</sup>, A. Benito‐Resendiz<sup>2</sup></p><p><italic><sup>1</sup>Instituto Nacional de Pediatría, Pediatric Oncology Department, Mexico City, Mexico; <sup>2</sup>Centro Médico Nacional 20 de Noviembre ISSSTE, Pediatric Oncology Department, Mexico City, Mexico; <sup>3</sup>Hospital Materno Infantil ISSEMYM, Pediatric Onology Department, Estado de México, Mexico</italic></p><p><bold>Background/Objectives</bold>: Worldwide a higher survival rate is reported in pediatric patients with cancer, due to: early diagnosis, better support treatment and early detection of complications. In a middle income country like Mexico, the mortality of pediatric patients with cancer is still high.</p><p><bold>Design/Methods</bold>: The aim was to know the frequency and the main causes of death in pediatric patients with cancer registered in three public health institutions in Mexico from January 2007 to December 2015.</p><p><bold>Results</bold>: Two thousand three hundred twenty‐seven patients were registered in the study period, of which 378 (16.4%) died. One hundred and twenty patients were diagnosed with leukemia and the rest with solid tumors. Fifty‐three point fifteen percent were male. In patients with acute lymphoblastic leukemia, the treatment phase with the highest number of deaths was in induction (48%), and the main cause of death was toxicity (58.1%). In patients with solid tumors the treatment phase in which the highest number of deaths occurred was neoadjuvance. 44% died from toxicity and 23% from disease progression. There were 437 toxicity events in 258 patients with solid tumors, of which 14.6% of the patients had septic shock as the cause of death. The time of diagnosis to death in patients with leukemia was 18.4 months compared to patients with solid tumors where it was 13.49 months (P=0.04)</p><p><bold>Conclusions</bold>: Most patients with acute leukemia who die are secondary to toxicity in the induction phase. The main cause of death in patients with solid tumors is toxicity and disease progression. Mortality in patients with solid tumors occurs earlier. Particular attention should be paid to the early detection of complications, to avoid mortality from these causes in a middle income country.</p></sec><sec id="pbc26772-sec-9680"><label>P-556</label><title>Pediatric Cancer Treatment Abandonment in Botswana: A Lower than Expected Abandonment Rate</title><p><underline underline-style="single">M. Zobeck</underline><sup>1</sup>, T. Gilliland<sup>2</sup>, A. Slone<sup>1</sup>, P. Semetsa<sup>3</sup>, M. Raletshegwana<sup>3</sup>, M. Scheurer<sup>1</sup>, P. Mehta<sup>1</sup>, J. Slone<sup>1</sup></p><p><italic><sup>1</sup>Texas Children's Hospital/Baylor College of Medicine, Pediatrics, Houston, USA; <sup>2</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>3</sup>Princess Marina Hospital, Pediatrics, Gaborone, Botswana</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer treatment abandonment (TA) is a major cause of preventable morbidity and mortality in low‐ and middle‐income countries (LMICs). Recent publications estimate that Sub‐Saharan Africa (SSA) has an average TA of 28%, but few comprehensive hospital‐based studies have been published. TA for Botswana has not been measured previously. Our objective was to determine the prevalence of TA for pediatric cancer patients at the tertiary referral center in Botswana and investigate predisposing factors for TA from the available literature.</p><p><bold>Design/Methods</bold>: Since 2007, the Botswana Ministry of Health and Wellness has partnered with Baylor College of Medicine/Texas Children's Hospital to operate the only pediatric hematology‐oncology program in the country at Princess Marina Hospital (PMH). We analyzed data from the Botswana Pediatric Oncology Database for children diagnosed with a malignancy at PMH between January 1, 2008 and December 31, 2015.</p><p><bold>Results</bold>: Of the 185 patients in the cohort, seven met criteria for abandonment (3.8%) and two (1.1%) had abandonment as their final outcome. Of those who abandoned, four (57.1%) of the patients were female, five (71.4%) had solid tumors including two (28.6%) osteosarcomas and two teratomas. Median time to abandonment from diagnosis was 9.14 weeks. No statistically significant risk factors for TA were identified, including living outside the capital city, possessing private medical aid, HIV status, metastases at diagnosis, and solid tumor outside the central nervous system.</p><p><bold>Conclusions</bold>: It was found that the TA at PMH in Botswana is low compared to a recently published average of estimated TA of SSA countries, although precise comparison is difficult due to the limited data available for the region. More research is needed at the hospital and country levels to better quantify the magnitude of the problem and to facilitate inter‐country comparisons that explore the regional and national risk factors for TA at a given center.</p></sec></sec><sec id="pbc26772-sec-9690"><title>Late Effects</title><sec id="pbc26772-sec-9700"><label>P-557</label><title>Renal Dysfunction in Survivors of Egyptian Children with Solid Tumors</title><p><underline underline-style="single">E.R. Abdel Khalek</underline><sup>1</sup>, L. Sherief<sup>2</sup>, M. Almalky<sup>3</sup>, N. Khalifa<sup>4</sup>, M. Abdel Monem<sup>2</sup></p><p><italic><sup>1</sup>Faculty of Medicine‐ Zagazig University, Pediatrics, Cairo, Egypt; <sup>2</sup>Faculty of Medicine‐Zagazig University, Pediatrics, Zagazig, Egypt; <sup>3</sup>Faculty of Medicine ‐ Zagazig University, Pediatrics, Zagazig, Egypt; <sup>4</sup>Faculty of Medicine‐Zagazig University, Clinical Pathology, Zagazig, Egypt</italic></p><p><bold>Background/Objectives</bold>: Pediatric cancer survivors have a nine‐fold risk to renal injury compared to healthy children. Little is known about long‐term renal dysfunction in this vulnerable group.</p><p>The aim of this work is to detect early chronic Kidney dysfunction (CKD) in Survivors of Egyptian Children with Solid Tumors in order to prevent any developing renal impairment.</p><p><bold>Design/Methods</bold>: We investigated 50 children (aged 3‐15 years) cured from different solid tumors, 1 to 4 years after ending the treatment. Twenty healthy age and sex‐matching children were added as a control group. All participants were subjected to history taking, physical assessment, and laboratory investigations including urine analysis, serum creatinine, and BUN. Estimated glomerular filtration rates (GFR) were calculated and chronic kidney disease was diagnosed accordingly. In addition, serum Cystatin‐C (Cys‐C) and neutrophil‐gelatinase‐associated Lipocalin (NGAL) were determined.</p><p><bold>Results</bold>: Survivors of solid tumors showed evidence of subclinical CKD as compared to the control group after an average of 2.1 years after cessation of therapy. The creatinine level between cases and control was insignificant (p‐022). The (GFR) has a median of 95.87 versus 120.55 (mL/min/1.73 m2) (p‐0.006), serum Cystatin‐C has a median of 0.99 versus 0.75 mg/l (p‐0.025). NGAL level has a median of 381 versus 225 pg. /ml for the control group. There is a significant positive correlation between serum Cys‐C and serum NGAL. (p< 0.001) and a Negative correlation between Cys‐C (p‐0.029) and NGAL (p‐0.006) with (GFR)</p><p><bold>Conclusions</bold>: Subclinical renal dysfunction could be found in survivors. Both NGAL and cystatin C altogether connected with measured GFR. They have a higher diagnostic accuracy than serum creatinine in discriminating normal from an early stage of renal injury. Re‐assessment of the renal function in survivors can help us to promote the health of the Survivors.</p></sec><sec id="pbc26772-sec-9710"><label>P-558</label><title>Survivor's Assistance Program: Continuing Psychological Support for Children and Young Adults after the Completion of their Cancer Treatment</title><p><underline underline-style="single">H. Anis</underline><sup>1</sup>, A. Dhaliwal<sup>1</sup>, K. Bhattacharya<sup>1</sup></p><p><italic><sup>1</sup>CanKids... Kidscan, Pediatric Psycho‐oncology Program, New Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Cancer is a significant stressor for patients and their families but after the completion of their treatment, some survivors, siblings and caregivers develop persistent traumatic stress reactions. Experiencing these post‐traumatic stress symptoms is often part of the process of coming to terms with a life‐threatening event,some survivors and their parents, however, require more intensive therapeutic interventions and approaches to re‐enter in the society with enhanced psychological adjustment and emotional well‐being.</p><p><bold>Design/Methods</bold>: In May 2016 Cankids has initiated a Survivor's Assistance Program which aims to identify, understand and rectify the unique needs and challenges of survivors and their parents that reduces the experience of trauma and issues of survivorship. This program is a combination of special interventions that provide the survivors and their caregivers in distress with one‐on‐one therapeutic interventions and Sharing and Caring Sessions to enhance their psychological well being.</p><p><bold>Results</bold>: However, survivors reported to possess higher risk of depression, low self esteem, marital and fertility issues, mood swings, acceptance, and some degree of anxiety over the possibility of a recurrence, serious psychiatric disorders such as Obsessive Compulsive Disorder, Bipolar Disorder, and Schizophrenia were found to be uncommon. Parents were concerned about relapse, sibling issues and mood swings of the survivors. Based on the pre and post intervention assessment, they reported greater benefits after participating in these cognitive and behavioral stress management interventions and showed positive psychological responses such as less anxiety and fear, enhanced self‐esteem, greater feelings of relief, peacefulness and purposefulness in their lives.</p><p><bold>Conclusions</bold>: It must be recognized that cancer survivors do appear to possess slightly higher risk for major depression and other psychological complications which continues to exist across the survivorship trajectory.This kind of ongoing cognitive and behavioural stress management interventions not only helps in identifying issues but also resolves the psychological complications related to surviviorship for positive outcomes.</p></sec><sec id="pbc26772-sec-9720"><label>P-559</label><title>Creation of a Survivorship Clinic for Oncology Pediatric Patients in Medical National Center 20 De Noviembre Issste, A Third Level Hospital in Mexico City</title><p><underline underline-style="single">F.</underline><underline underline-style="single">Arreguin</underline><sup>1</sup>, B. Alma<sup>2</sup>, B.R. Eduardo<sup>2</sup>, A.G. Blanca<sup>3</sup>, R.C. Julieta<sup>2</sup>, S.B. Ruben<sup>4</sup>, P.C. Soledad<sup>4</sup>, D.M. Martha<sup>4</sup></p><p><italic><sup>1</sup>Centro Medico Nacional “20 de Noviembre” ISSSTE, Pediatric Oncology, Mexico City, Mexico; <sup>2</sup>Centro Medico Nacional 20 de Noviembre ISSSTE, Pediatric Oncology, Mexico, Mexico; <sup>3</sup>Centro Medico Nacional 20 de Noviembre ISSSTE, Pediatric Oncology, Pediatric Oncology, Mexico; <sup>4</sup>Centro Medico Nacional 20 de Noviembre, Pediatric Oncology, Mexico, Mexico</italic></p><p><bold>Background/Objectives</bold>: Over the last 30 years the survival rate in childhood cancer has improved all around the world. Currently, eight of every ten children will survive ≥5 years beyond their diagnosis, but they will have adverse healthrelated and quality‐of‐life outcomes as a sequealae of their cancer treatment. The ISSSTE (Institute of Security and Social Service for State Workers) is a third level institute in Mexico city that takes care of 11% of Mexico`s total population and the Medical National Center 20 de Noviembre (CMN 20 de Noviembre) is the main reference hospital for ISSSTE´S cancer pediatric patients. We receive around 120 new cases/year. In March 2016 we created the first Survivorship Pediatric Cancer Clinic as a national strategy for these vulnerable population.</p><p><bold>Design/Methods</bold>: CMN 20 de Noviembre is the main reference third level hospital for adults and children with severe conditions, so there is a complete routine health care clinicians of all medical specialties. We implemented a risk‐based model based on the Childhood Cancer Survivor Study adjusted to a low income country and opened Mexico´s first Surveillance Clinic for pediatric cancer patients.</p><p><bold>Results</bold>: We recluted 128 cancer survivors, with a female predominance (71% vs 57%). Adolescents were the most frequent group (14‐17 years old). The most common late effects were altered pituitary disfunction, overweight and obesity, metabolic syndrome, neurocognitive deficits, scoliosis, ovarian disfunction, infertility, neurosensory deficits and renal insufficiency</p><p><bold>Conclusions</bold>: The ideal approach to childhood cancer survivor care involves a risk‐based model with routine health care and a personalized plan of surveillance. It is difficult in a low income country to do this follow up so we need to strengthen the relation with primary care doctors, follow practice guidelines for early detection of cancer treatment morbidity and work with expertise groups in order to maximize quality of life outcomes. More data is needed.</p></sec><sec id="pbc26772-sec-9730"><label>P-560</label><title>Sarcopenic Obesity in Long Term Survivors of Acute Lymphoblastic Leukemia (ALL)</title><p><underline underline-style="single">R. Barr</underline><sup>1</sup>, T. Farncombe<sup>2</sup>, L. Beaumont<sup>3</sup>, A. Cranston<sup>4</sup>, V. Yakemchuk<sup>2</sup>, C. Marriott<sup>2</sup></p><p><italic><sup>1</sup>McMaster University, Pediatrics, Hamilton‐Ontario, Canada; <sup>2</sup>Hamilton Health Sciences, Nuclear Medicine, Hamilton, Canada; <sup>3</sup>McMaster University, Nuclear Medicine, Hamilton‐Ontario, Canada; <sup>4</sup>Hamilton Health Sciences, Pediatrics, Hamilton, Canada</italic></p><p><bold>Background/Objectives</bold>: Sarcopenic obesity (a gain in fat mass with loss of lean‐especially skeletal muscle‐mass) has been reported to occur early in the treatment of ALL, and ascribed mainly to the influence of glucocorticosteroids. This apparent paradox risks the double jeopardy of the metabolic and frailty syndromes during survivorship, with the associated adverse effects on overall health and survival that result from the added burdens of morbidity and premature aging. We sought to determine whether this clinical phenotype persists in long term survivors.</p><p><bold>Design/Methods</bold>: A cohort of 75 adolescents and young adults, who were more than 10 years from diagnosis, were enrolled in a study of bone health and body composition<sup>*</sup>. All had been treated on Dana Farber Cancer Institute protocols. Measures of fat mass, lean body mass, appendicular lean mass (ALM) and their corresponding indices (I=mass/height<sup>2</sup>) were provided by dual energy X‐ray absorptiometry (Hologic Discovery A model) which also gave values for bone mineral content and density. Skeletal muscle mass (SMM) was derived from the equation SMM (kg) = (1.19 × ALM [kg])‐1.65.</p><p><bold>Results</bold>: On the basis of the fat mass index (FMI) 68% of the females and 88% of the males were overweight or obese (the obese proportions being 15% and 21% respectively). All but one subject had a low SMM. Based on a positive Z score for FMI and a negative Z score for ALMI, 44% of the subjects met the definition of sarcopenic obesity (discordance between fat mass and lean mass).</p><p><bold>Conclusions</bold>: Sarcopenic obesity is prevalent in long term survivors of ALL. Given the attendant risks of premature aging and mortality, this finding offers encouragement to research into prevention and amelioration of the clinical phenotype, so improving overall health and extending survival.</p><p>*Barr R et al. BMJ Open 2015; 5: e006191</p></sec><sec id="pbc26772-sec-9740"><label>P-561</label><title>Sensorineural Hearing Loss After IMRT for Nasopharyngeal Carcinoma: Is Paediatric Cochlea Radioresistant?</title><p><underline underline-style="single">A. Bindal</underline><sup>1</sup>, S. Laskar<sup>1</sup>, N. Khanna<sup>1</sup>, S. Chaudhary<sup>2</sup>, T. Vora<sup>3</sup>, G. Chinnaswamy<sup>3</sup>, S. Kembhavi<sup>4</sup>, S. Shah<sup>5</sup>, M. Ramadwar<sup>6</sup>, S. Qureshi<sup>7</sup>, M.A. Muckaden<sup>8</sup>, P. Kurkure<sup>3</sup></p><p><italic><sup>1</sup>Tata Memorial Centre, Radiation Oncology, Mumbai, India; <sup>2</sup>Tata Memorial Centre, Medical Physics, Mumbai, India; <sup>3</sup>Tata Memorial Centre, Pediatric Oncology, Mumbai, India; <sup>4</sup>Tata Memorial Centre, Radiodiagnosis, Mumbai, India; <sup>5</sup>Tata Memorial Centre, Nuclear Medicine, Mumbai, India; <sup>6</sup>Tata Memorial Centre, Pathology, Mumbai, India; <sup>7</sup>Tata Memorial Centre, Surgical Oncology, Mumbai, India; <sup>8</sup>Tata Memorial Centre, Radiation Oncology/ Palliative Medicine, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: To evaluate sensorineural hearing loss (SNHL) in children with nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiation therapy (IMRT) and cisplatin based chemotherapy (CTh).</p><p><bold>Design/Methods</bold>: From 2005 to 2015, 95 children with NPC were treated with neoadjuvant cisplatin based CTh followed by IMRT to nasopharynx (70.2Gy/33fr) and neck nodal regions and adjuvant CTh, and evaluated for late auditory toxicity in the form of SNHL. Post treatment audiograms were available for 33 children (66 ears). A total of 55 pure tone audiograms more than 6 months post RT were evaluated retrospectively and the SNHL grade noted on a scale of 0 to IV according to SIOP ototoxicity criteria. Chemotherapy doses and mean cochlear doses were analysed for association with grade III/IV ototoxicity.</p><p><bold>Results</bold>: The median audiological follow‐up was 24 months. SIOP grade 0,I,II,III and IV ototoxicity was observed in 45(68.2%), 0(0%), 6(9.1%), 9(13.6%) and 6(9.1%) ears respectively, with grade III/IV accounting for 22.7% of cases. All except three of our patients received a cumulative cisplatin dose of 400mg/m<sup>2</sup>, and no threshold cisplatin dose was observed to correlate with ototoxicity. The average cochlear D<sub>mean</sub> was 54.6±10 Gy. For patients who developed grade III/IV SNHL it was 57.8±8.2Gy. Using the Pearson Chi Square test a cochlear D<sub>mean</sub> threshold of >58 Gy was observed to be associated with higher incidence of developing grade III/IV SNHL (p=0.045), while the dose of 45Gy failed to show any significant association (p=0.24).</p><p><bold>Conclusions</bold>: Severe ototoxicity was seen in 22.7% of ears in children receiving radiation and chemotherapy and was significantly more in those receiving a mean cochlear dose of more than 58 Gy. Suggested thresholds for radiation doses to cochlea and cumulative cisplatin doses, from adult studies, may not be applicable in paediatric population. Prospective studies are required to determine the cochlear tolerance doses in children.</p></sec><sec id="pbc26772-sec-9750"><label>P-562</label><title>The Effect of Vitamin D Levels and Fok 1 VDR Gene Polymorphism on Long Term Bone Health in Pediatric Cancer Survivors</title><p>N. Çetingül<sup>1</sup>, <underline underline-style="single">Z. Önder Siviş</underline><sup>1</sup>, S. Özen<sup>2</sup>, H. Onay<sup>3</sup>, D. Gökşen<sup>2</sup>, Z. Burak<sup>4</sup>, A. Oral<sup>4</sup>, M. Kantar<sup>1</sup>, S. Aksoylar<sup>1</sup>, F. Özkınay<sup>3</sup></p><p><italic><sup>1</sup>Ege University Faculty of Medicine, Pediatric Oncology, Izmir, Turkey; <sup>2</sup>Ege University Faculty of Medicine, Pediatric Endocrinology, Izmir, Turkey; <sup>3</sup>Ege University Faculty of Medicine, Medical Genetics, Izmir, Turkey; <sup>4</sup>Ege University Faculty of Medicine, Nuclear Medicine, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: 25‐Hydroxy‐vitamin D (25‐OH D) insufficiency is common in healthy children and adolescents, with the prevalence being %14‐49 in the general population. Survivors of childhood cancer are at increased risk for a variety of adverse medical outcomes. Potential risk factors for imparied 25‐OH D status in this population include poor diet, exposure to chemotherapy, steroids, radiotherapy. Vitamin D performs its effect via the nuclear vitamin D receptor (VDR), which shows an extensive polymorphism. We studied the frequencies of the Fok 1 VDR gene polymorphism and the status of 25‐OH D and their correlation with bone mineral density (BMD).</p><p><bold>Design/Methods</bold>: This study included 100 pediatric cancer survivors in the Ege University, Dept. of Pediatric Oncology. All of them were subjected to full history taking and clinical examination. The peripheral venous blood were took from each patient for genomic DNA extraction (Fok 1 gene), serum 25‐OH D, calcium, phosphorus, alkaline phosphatase, parathormone levels and obtained urine calcium/creatine and measured bone mineral density (BMD). Fok 1 gene polymorphism results were compared with a control group of Turkish healthy people.</p><p><bold>Results</bold>: The diagnosis of patients was 28% leukemia, 31% lymphoma, and 41 % solid tumor. Median age of patients at cancer diagnosis was 7.8 years, during to the study was 16.9 years. In 72% of the patients were patients 25‐OH D insufficient and deficient. The Fok 1 gene polymorphism was found in 54% of them. In 44% of BMD measure was osteopenia and osteoporosis. Patients with solid tumors were most affected, despite of their lack of routine exposure to steroids.</p><p><bold>Conclusions</bold>: In pediatric cancer survivors the frequency of Fok 1 gene polymorphism was similar to control group. The prevalance of 25‐OH D insufficiency and deficiency in cancer survivors were high according to general population. Prospective studies evaluating on long term bone health in survivors of cancers are required.</p></sec><sec id="pbc26772-sec-9760"><label>P-563</label><title>Life Threatening and Fatal Late Effects in Long Term Survivors of Childhood Cancer‐Data from after Completion of Treatment (ACT) Clinic</title><p><underline underline-style="single">G. Chinnaswamy</underline><sup>1</sup>, M. Prasad<sup>1</sup>, V. Dhamankar<sup>1</sup>, T. Vora<sup>1</sup>, G. Narula<sup>1</sup>, P. Kurkure<sup>1</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Department of Pediatric and Medical Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Long term survivors of childhood cancer(CCSs) are known to have a higher prevalence of life threatening and fatal health conditions(NCI CTCAE grade 4/5) compared to the normal population. These include second malignant neoplasms(SMN), benign second neoplasms(SN) and late recurrences. Although these have been described in large cohorts from the US and Europe, no data is available from LMIC.</p><p><bold>Design/Methods</bold>: A total of 1838 CCSs have been enrolled into the After Completion of Therapy(ACT) clinic of our hospital since 1991. Survivors are kept under follow up based on primary disease, treatment received and expected long term toxicities. Data regarding SMN/SN, recurrences and deaths was obtained from the database.</p><p><bold>Results</bold>: 1838 CCSs with a median age of 18 years(5‐53) have been followed up over a median duration 10 years(5‐40). Nearly 50% are lost to long term followup at various stages. 91(5%) CCSs were detected to have grade 4/5 toxicities‐37 late recurrences, 33 SMN, 14 SN and additional 7 deaths. The commonest tumors to have late recurrences are Hodgkin lymphoma(HL), ALL and Ewing sarcoma, mean time to recurrence being 7.3 years, multiple recurrences in some and high subsequent mortality (>30%). The most common SMNs were carcinomas of thyroid and parotid, others being Ewing sarcoma and osteosarcoma., with mean time to develop being 13.2 years(3‐38). The commonest SNs were schwannomas and meningiomas and in ALL and HL survivors. There were 22 documented deaths‐3 due to late organ toxicities(renal failure, cardiac failure and moyamoya disease),10 following recurrence, 5 in SMN and 4 unrelated deaths(Rheumatic heart disease, accident, malaria and dengue).</p><p><bold>Conclusions</bold>: With increasing survival there is a need for long term surveillance of CCSs for both late recurrences and second malignancies. Ascertaining the true number of these very long term toxicities needs rigorous follow up, which is a challenge given the health system network in LMICs.</p></sec><sec id="pbc26772-sec-9770"><label>P-564</label><title>Human Papillomavirus (HPV) Vaccination Rates Among Childhood Cancer Survivors in South Texas</title><p><underline underline-style="single">L. Embry</underline><sup>1</sup>, A. Brennan<sup>2</sup>, A. Shay<sup>3</sup>, A. Grimes<sup>1</sup></p><p><italic><sup>1</sup>UTHSCSA, Pediatrics, San Antonio‐ TX, USA; <sup>2</sup>UTHSCSA, School of Medicine‐ MS4, San Antonio‐ TX, USA; <sup>3</sup>UT Health School of Public Health in San Antonio, Department of Health Promotion & Behavioral Sciences, San Antonio, USA</italic></p><p><bold>Background/Objectives</bold>: Initiatives targeting uptake of human papillomavirus (HPV) vaccination improved rates nationally, however HPV‐related diseases remain a significant health concern. Although childhood cancer survivors are at increased risk for HPV‐related disease (particularly those with a history of stem cell transplantation (SCT) or radiation therapy), they are not a targeted group in population‐based initiatives. In South Texas, HPV vaccination uptake is among the lowest in the state. Study aims included evaluation of (1) HPV vaccination rates among pediatric cancer survivors in South Texas, and (2) demographic and clinical factors associated with HPV vaccine uptake in this population.</p><p><bold>Design/Methods</bold>: Retrospective chart reviews of 210 childhood cancer survivors identified patients who were potentially eligible to receive HPV vaccination from 2006 through 2016. Review of vaccine records through Texas ImmTrac vaccine registry and electronic clinical records verified HPV vaccination status. Demographic and clinical variables collected included DOB, gender, race/ethnicity, cancer diagnosis, and cancer treatment.</p><p><bold>Results</bold>: Of 210 records reviewed, 156 survivors were deemed vaccine‐eligible. Of these, 21 (13.5%) received at least one vaccine, but only 9 (5.7%) completed the 3‐dose series. Of the 84 females, 19% initiated with 10.7% completing the series. However among the 72 males, only 6.9% initiated with no completions. Approximately 76% of the sample was Hispanic/Latino. Among them, 17 patients initiated the vaccine series but only 7 completed. Rates of initiation and completion were also low in white and black patients. Furthermore, patients who received high‐risk therapies (radiation, SCT) did not have increased uptake of the HPV vaccine compared to patients receiving only chemotherapy.</p><p><bold>Conclusions</bold>: HPV vaccination rates among childhood cancer survivors in South Texas is lower than in the general population, both regionally and nationally. Given the increased susceptibility to secondary HPV‐related malignancies, this study demonstrates a clear need for enhanced efforts to increase HPV vaccination rates in this at‐risk population.</p></sec><sec id="pbc26772-sec-9780"><label>P-565</label><title>Investigating the Mechanisms of Methotrexate Neurotoxicity in Patients with Childhood Leukemia and Long‐Term Survivors</title><p><underline underline-style="single">V. Forster</underline><sup>1</sup>, J. Carr‐Wilkinson<sup>2</sup>, D. Tweddle<sup>2</sup>, S. Nakjang<sup>2</sup>, S. Choufani<sup>1</sup>, W. Rosanna<sup>1</sup>, F. Van Delft<sup>2</sup></p><p><italic><sup>1</sup>Peter Gilgan Centre for Research and Learning‐ The Hospital for Sick Children, Genetics and Genome Biology, Toronto, Canada; <sup>2</sup>Newcastle University, Northern Institute for Cancer Research, Newcastle upon Tyne, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Adverse neurological events are common (4‐20%) during treatment for pediatric acute lymphoblastic leukaemia (ALL) and include seizures, stroke like syndrome and leukoencephalopathy. In addition, chronic neurotoxicity is emerging as a worrying late effect of treatment with long‐term survivors experiencing decreased executive function, processing speed and memory function. Survivors are also at increased risk of experiencing learning difficulties, social withdrawal issues and inattention hyperactivity disorders. Methotrexate, an anti‐folate chemotherapy agent, is a mainstay of pediatric leukemia treatment regimens globally and is widely implicated as a cause of these neurological side effects. We hypothesise that methotrexate disrupts DNA methylation via effects on S‐adenosyl methionine, a key methylation component that has previously been described to be involved in regulation of genes involved in myelination.</p><p><bold>Design/Methods</bold>: Using both neural cell lines and oligodendrocytes derived from induced pluripotent stem cells (iPSC) treated with methotrexate, we assayed for changes in DNA methylation and consequential effects on gene expression using whole‐genome methylation arrays and RNAseq, respectively. Genes with corresponding methylation and expression changes were selected for confirmation of expression by real‐time qPCR and assessment of protein levels.</p><p><bold>Results</bold>: We identified methylation and concomitant expression changes in genes involved in neurodevelopmental pathways and neurological disorders. Of particular interest was dose‐dependent demethylation and consequential increase in gene expression of <italic>IRS1</italic>, a vital component of insulin signalling pathways, highly expressed in neural tissue and implicated in regulating cognitive performance. We also detected altered methylation within the <italic>PLP1</italic> gene, which encodes the most major protein component of myelin. We identified that increased <italic>PLP1</italic> methylation after methotrexate treatment in iPSC‐derived oligodendrocytes resulted in a corresponding reduction in <italic>PLP1</italic> transcript levels and PLP1 protein.</p><p><bold>Conclusions</bold>: Our work provides insight regarding the biological mechanisms behind methotrexate‐induced neurological side effects, implicating altered insulin signalling and myelination pathways as potential causative factors in neurotoxicity.</p></sec><sec id="pbc26772-sec-9790"><label>P-566</label><title>Mental Health of Long Term Survivors of Childhood and Young Adult Cancer</title><p><underline underline-style="single">A.J. Friend</underline><sup>1</sup>, R. Feltbower<sup>1</sup>, A. Glaser<sup>1</sup>, E. Hughes<sup>2</sup>, K. Dye<sup>3</sup></p><p><italic><sup>1</sup>University of Leeds, School of Medicine, Leeds, United Kingdom; <sup>2</sup>University of Southampton, School of Medicine, Southampton, United Kingdom; <sup>3</sup>St George's‐ University of London, School of Medicine, London, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Survivors of young people's cancer are known to have increased risk of psychological distress including cognitive difficulties, however little is known about emotional and behavioural problems. We aimed to collate evidence of the prevalence of mental health problems in long‐term survivors of childhood cancer.</p><p><bold>Design/Methods</bold>: A standard systematic review was performed,excluding papers on cognitive function. We searched the PubMed, Embase/OVID, CINAHL and Web of Science databases using the following strategy:
<table-wrap id="nlm-table-wrap-3" xml:lang="en" orientation="portrait" position="anchor"><table frame="hsides" rules="groups"><col align="left" span="1"></col><col align="left" span="1"></col><tbody><tr><td align="left" rowspan="1" colspan="1"></td><td align="left" rowspan="1" colspan="1">(child OR children OR childhood OR teen OR teenage* OR adolescent* OR “young adult”)</td></tr><tr><td align="left" rowspan="1" colspan="1">AND</td><td align="left" rowspan="1" colspan="1">(cancer OR leukaemia OR tumour OR tumor)</td></tr><tr><td align="left" rowspan="1" colspan="1">AND</td><td align="left" rowspan="1" colspan="1">survivor</td></tr><tr><td align="left" rowspan="1" colspan="1">AND</td><td align="left" rowspan="1" colspan="1">“Mental health” or “mental illness” or “psychiatric” or “psychological” or “emotional” or “behavioural” or “behavioral”</td></tr><tr><td align="left" rowspan="1" colspan="1">AND</td><td align="left" rowspan="1" colspan="1">“late effects” or “long term”</td></tr></tbody></table><permissions><copyright-holder>John Wiley & Sons, Ltd.</copyright-holder><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions></table-wrap></p><p><bold>Results</bold>: Initial search results returned over 1500 papers, after discarding papers covering cognitive function and those exploring interventions rather than prevalence, 324 papers remained. We found reports of increased antidepressant use and higher rates of psychological distress in long term survivors of CYP's cancer compared to controls, although many of these were siblings of survivors, who are likely to have their own difficulties.The majority of data came from self‐reports, which are associated with high risk of bias. There was also data from hospital admissions for mental health problems and analysis of prescribing data from primary care. We found no papers reporting on primary care‐diagnosed mental health problems, despite this being the most common place for mental illness to be diagnosed and treated in many settings.</p><p><bold>Conclusions</bold>: There is a need to more accurately ascertain the prevalence of mental health problems in this group. Data from primary care would significantly improve our understanding of this issue. This would be essential for future service planning. We hope our future work linking primary care records to cancer registries will go some way to addressing this gap in knowledge.</p></sec><sec id="pbc26772-sec-9800"><label>P-567</label><title>Pharmacogenetic Analysis of Treatment–Related Toxicities for Hepatoblastoma Patients in Japan</title><p><underline underline-style="single">E. Hiyama</underline><sup>1</sup>, S. Kumura<sup>2</sup>, S. Kuriahra<sup>1</sup>, M. Kawashima<sup>1</sup>, Y. Ueda<sup>1</sup>, Y. Onitake<sup>3</sup></p><p><italic><sup>1</sup>Hiroshima University Hospital, Peditric Surgery, Hiroshima, Japan; <sup>2</sup>Hiroshima University, Natural Science Center for Basic Research and Development, Hiroshima, Japan; <sup>3</sup>Kure Medical Center, Peditric Surgery, Kure, Japan</italic></p><p><bold>Background/Objectives</bold>: Cisplatin and anthracycline are the most widely used anticancer agents against hepatoblastoma (HB). The Japanese Study Group for Pediatric Liver Tumor (JPLT)‐2 study (1999‐2012) was to evaluate the efficacy of cisplatin/pirarubicin (CITA regimen) for HB. Avoidance of treatment‐related ototoxicity, cardiotoxicity, and secondary malignancy effects is important to improve long‐term outcomes for childhood HB.</p><p><bold>Design/Methods</bold>: In JPLT‐2 study, 360 HB children were eligible for inclusion. Among them, we evaluated late effects including ototoxicity, cardiotoxicity, maldevelopment and secondary malignancy in survived cases. Among them, in 186 patients whose germline DNA samples were available under informed consent, genotyping was performed using the Illumina Human Omni Express Exome‐8 v.1.3 BeadChip (Illumina). A linkage disequilibrium (LD)‐based single‐nucleotide polymorphism (SNP) selection strategy was 60 used to identify a minimal set of informative variants. Associations between SNPs and toxicities were assessed using logistic regression. Ototoxicity was determined by audiometry and/or auditory brain‐stem response. Cardiotoxicity was mainly determined by standardized echocardiography.</p><p><bold>Results</bold>: Among the 186 survived cases tested these SNP analysis, 64 ototoxicity, 17 cardiotoxicity, 36 maldevelopment and 8 secondary malignancies were determined. The dose of cisplatin and/or pirarubicin seemed to be correlated with their occurrence but not significantly. We identified inherited genetic variations in three SNPs including 6 SNPs including ACYP2 associated with ototoxicity and in two SNPs associated with cardiotoxicity. Moreover, we find out candidates of genetic variations correlated with maldevelopment or secondary malignancy.</p><p><bold>Conclusions</bold>: The risk variant in these SNPs strongly predisposed these patients to toxicities including ototoxicity and cardiac toxicity using chemotherapy. These results point to new biology underlying the late toxic effects of palatinum/anthoracyclin agents. We should pay biological assessment for next protocol avoiding these toxic effects of chemotherapeutic agents.</p></sec><sec id="pbc26772-sec-9810"><label>P-568</label><title>Rare Outcomes Encountered In the Care of Childhood Cancer Survivors: Piloting a Methodology to Create Clinical Practice Guidelines</title><p><underline underline-style="single">L.B. Kenney</underline><sup>1</sup>, B. Ames<sup>2</sup>, D. Williams<sup>3</sup>, A. Michaud<sup>1</sup>, N. Ullrich<sup>4</sup>, P. Manley<sup>1</sup></p><p><italic><sup>1</sup>Dana‐Farber /Boston Children's Hosptial, Pediatric Oncology, Boston, USA; <sup>2</sup>Dartmouth Hitchcock Medical Center, Pediatric Hematology Oncology, Hanover, USA; <sup>3</sup>Boston Children's Hospital, Clinical Research Center, Boston, USA; <sup>4</sup>Boston Children's Hospital, Neurology, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Many of the clinical issues encountered in the long‐term follow‐up care of childhood cancer survivors are unique to this population. Studies investigating management of these outcomes are often not available. We piloted a consensus‐based, modified Delphi‐approach methodology to develop regional guidelines for the care of survivors and to identify areas of clinical disagreement.</p><p><bold>Design/Methods</bold>: Members of the Consortium for New England Childhood Cancer Survivors (CONNECCS) were surveyed to identify clinical challenges encountered in care of survivors. Five vignettes on neurologic outcomes were developed based on most frequent clinical issues described. A purposeful sample of 30 was chosen to represent specialty and general physicians from geographically diverse CONNECCS institutions. A systematic review of the medical literature to identify risk factors and interventions was completed; a summary of evidence was made available to participants. A modified Delphi approach required three rounds of anonymous survey data collection to establish practice norms and systematically build consensus among expert participants.</p><p><bold>Results</bold>: All 30 participants completed the round 1 survey with 25 open‐ended questions addressing practice norms related to 5 clinical scenarios. Responses were coded and a modal management option for each question was described. The round 2 survey asked participants to agree/disagree with the modal management options and to provide rational for their responses. All 30 responded. Of the 25 management questions, participants reached consensus on 3 (>90% agreement), conditional agreement on 11 (>90%), and disagreement on 11 (>10%). Round 3 questionnaire attempts to negotiate consensus in areas of disagreement by sharing summarizes of rationale provided by participants for their management decisions.</p><p><bold>Conclusions</bold>: Regional experts can be successfully recruited and retained to develop clinical practice guidelines to manage rare outcomes encountered in the care of childhood cancer survivors using a modified Delphi methodology. Areas where management is controversial can be identified for further research.</p></sec><sec id="pbc26772-sec-9820"><label>P-569</label><title>Radiation‐ Associated Pulmonary Diffusion, Restrictive and Obstructive Abnormalities as a Function of Age in Pediatric Cancer Survivors</title><p><underline underline-style="single">F. Khan</underline><sup>1</sup>, A. Williams<sup>2</sup>, D. Weiner<sup>3</sup>, S. Dhakal<sup>4</sup>, L. Constine<sup>4</sup></p><p><italic><sup>1</sup>University of Rochester, School of Medicine, Rochester, USA; <sup>2</sup>University of Rochester, James P Wilmot Cancer Center, Rochester, USA; <sup>3</sup>Children's Hospital of Pittsburgh, Pediatric Pulmonology, Pittsburgh, USA; <sup>4</sup>University of Rochester, Radiation Oncology, Rochester, USA</italic></p><p><bold>Background/Objectives</bold>: Pulmonary dysfunction is a prevalent and potentially debilitating late effect of radiation therapy (RT) used to treat children with cancer. We postulated that age, as a surrogate for respiratory developmental status, might be associated with vulnerability to pulmonary injury.</p><p><bold>Design/Methods</bold>: Sixty‐one children treated at our institution with lung radiation who had undergone pulmonary function testing (PFT) between 1995‐2016 were analyzed. Data collection included age at treatment (radiation, chemotherapy, surgery), radiation dose and location, spirometry and plethysmography results. PFTs were normalized according to age, gender, height, and ethnicity and transformed into standardized z‐scores. Obstructive disease was defined as zFEV1/FVC<‐1.645, restrictive as zTLC<‐1.645 and abnormal diffusion as zDLCO<‐1.645. We determined the incidence of obstructive, restrictive, or diffusion abnormalities in our population and estimated the relative risk of developing pulmonary abnormalities.</p><p><bold>Results</bold>: At a mean age of 24 years (range 12‐31) and time from diagnosis of 9 years (range 1‐20), the cumulative incidence of any pulmonary abnormality was 34.4%. The incidence of diffusion abnormalities, obstructive, and restrictive disease was 19.6%, 18% and 8.1% respectively. Those <5 years and 5‐13 years at RT had more diffusing, restrictive, and obstructive abnormalities than those >13 years. Compared to patients >13 years, those <5 years and 5‐13 years at RT had a significantly increased risk of an abnormal PFT as follows: OR 7.71 (95% CI: 1.17, 51.06) and 3.51 (95% CI: 1.06, 11.57) respectively, p<0.035, although statistical significance was lost after adjustment for bleomycin use and time since RT. Further, this association remained when examining each type of abnormality (p>0.05).</p><p><bold>Conclusions</bold>: Pulmonary function abnormalities were common among our cohort of childhood cancer survivors treated with lung radiation. Diffusion and obstructive disease were more common than restrictive disease. Younger age at treatment is associated with an increasing risk of developing pulmonary dysfunction, presumably due to developmental immaturity.</p></sec><sec id="pbc26772-sec-9830"><label>P-570</label><title>Vision Loss in Pediatric Oncology Due to NF1, Retinoblastoma and Childhood Brain Tumors. Recommendations for Psychological Intervention</title><p><underline underline-style="single">J. Korzeniewska</underline><sup>1</sup>, B. Dembowska ‐ Bagińska<sup>1</sup></p><p><italic><sup>1</sup>The Children's Memorial Health Institute, Pediatric Oncology, Warsaw, Poland</italic></p><p><bold>Background/Objectives</bold>: Vision loss in context of pediatric oncology is due to neurofibromatosis (NF1), retinoblastoma or brain tumors. In which cases vision loss could be partial or total, occurs immediately or as a progressive disease, touch children in various ages and level of development. Symptoms of vision loss are variable and determine different ways of early intervention and psychological support.</p><p><bold>Design/Methods</bold>: Whole oncological population in our center we search for vision deficits and assessed their special needs, determined by specific mechanism of sensory loss. We prepared recommendation for psychological procedures, including: challenges in the assessment of this population, the most effective vision functional assessment, psychological early rehabilitation and stimulation, psychological support for parents in decisions making about their child's treatment, rehabilitation and education.</p><p><bold>Results</bold>: As a dynamic disease NF1 causes progression of optic pathway gliomas and decreasing vision ability. Symptoms and grade of vision loss due to childhood brain tumors depend on localization of lesion, e.g. posterior fossa tumor – double vision, strabismus, nystagmus; frontal lobe – risk of total vision loss; occipital lobe – cortical visual impairment (CVI) or total vision loss (legal blindness); chiasma of optic nerves – hemianopia, loss of peripheral vision (tunnel vision). In our sample we observed also that relation between localization of brain damage (as a consequence of tumors) and vision loss is complex and mechanism is not clear. Retinoblastoma as a progressive disease caused gradual vision loss. Patients are adapted to this limitation and do not show significant behavior disturbances as the consequences of lack of sight. Child is too small to give feedback how is sighing. Same behaviors and reactions connected to vision loss are misdiagnosed, delayed diagnose and confused caregivers.</p><p><bold>Conclusions</bold>: Vision impairment in oncological population is specific and requires special psychological procedures and early intervention, started at the time of treatment.</p></sec><sec id="pbc26772-sec-9840"><label>P-571</label><title>Physical Activity Behavior in Children and Adolescents Before, During and After Cancer Treatment</title><p><underline underline-style="single">M. Neu</underline><sup>1</sup>, S. Stössel<sup>1</sup>, V. Rustler<sup>2</sup>, R. Söntgerath<sup>3</sup>, J. Däggelmann<sup>2</sup>, K. Eckert<sup>4</sup>, V. Kramp<sup>3</sup>, F.T. Baumann<sup>5</sup>, W. Bloch<sup>2</sup>, J. Faber<sup>1</sup></p><p><italic><sup>1</sup>University Medical Center Mainz, Center for Pediatric and Adolescent Medicine‐ Department of Pediatric Hematology/Oncology/Hemostaseology, Mainz, Germany; <sup>2</sup>German Sport University Cologne, Institute of Cardiovascular Research and Sports Medicine‐ Department of Molecular and Cellular Sport Medicine, Cologne, Germany; <sup>3</sup>Leipzig University Hospital, Department of Pediatric Oncology‐ Hematology and Hemostaseology, Leipzig, Germany; <sup>4</sup>University of Heidelberg, Institute of Sport and Sport Science, Heidelberg, Germany; <sup>5</sup>University Hospital of Cologne, Department I of Internal Medicine‐ Center of Integrated Oncology Köln Bonn, Cologne, Germany</italic></p><p><bold>Background/Objectives</bold>: Childhood Cancer is associated with various disease‐ and treatment‐related sequelae on physical, psychological and social levels. Previous studies showed reduced physical activity levels in survivors after childhood cancer treatment (CCT) which may have considerable impact on child development, quality of life, social participation and cardiovascular health. The aim of this study was to evaluate physical activity behavior (PA) in children and adolescents before, during and after intensive CCT.</p><p><bold>Design/Methods</bold>: In this prospective multicenter study, 114 children and adolescents formerly treated for any type of cancer were enrolled (mean age 11.7 (4.17‐19.7) years). PA was assessed after completion of intensive treatment phase (time since diagnosis 3.7 (0.6‐14) years) using an adapted version of the PA questionnaire from the German KiGGS‐Study. The questionnaire included items asking for the level and intensity of PA before and during CCT, and at time of study participation, i.e. after completion of intensive CCT. Results were compared to 37 healthy controls (mean age 11.9 (5.4‐17.3) years).</p><p><bold>Results</bold>: Compared to time before CCT, patients reported significantly lower PA levels during and after CCT, evaluated by a visual analog scale (p<0.05). Healthy controls reported higher PA levels than patients after CCT (p<0.05). Time of PA spent at a low intensity level was lower after CCT than before (p<0.05). 31.1% of patients did not participate in sport club activities before CCT and 51.1% after CCT whereas 2.7% of healthy controls did not participate.</p><p><bold>Conclusions</bold>: In conclusion, children and adolescents treated for cancer report modified PA behavior during and after CCT in comparison to time before CCT as well as in comparison to healthy controls. Further studies are needed to investigate the consequences of physical inactivity during and after CCT and to examine subsequently how physical activity behavior can be influenced positively.</p></sec><sec id="pbc26772-sec-9850"><label>P-572</label><title>Neuropsychological Outcome of Different Treatments for Young Children with Medulloblastoma, Ependymoma and PNET: Multicenter Trial HIT 2000</title><p><underline underline-style="single">H. Ottensmeier</underline><sup>1</sup>, P.G. Schlegel<sup>2</sup>, J.E. Wolff<sup>3</sup>, M. Eyrich<sup>4</sup>, B.O. Juhnke<sup>5</sup>, K. von Hoff<sup>5</sup>, S. Frahsek<sup>1</sup>, G. Fleischhack<sup>6</sup>, A. von Bueren<sup>7</sup>, C. Friedrich<sup>8</sup>, M. Mynarek<sup>5</sup>, A. Resch<sup>8</sup>, M. Warmuth‐Metz<sup>9</sup>, J. Krauss<sup>10</sup>, R.D. Kortmann<sup>11</sup>, U. Bode<sup>12</sup>, J. Kuehl†<sup>1</sup>, S. Rutkowski<sup>5</sup></p><p><italic><sup>1</sup>University of Wuerzburg Children´s Hospital, Department of Pediatric Oncology, Wuerzburg, Germany; <sup>2</sup>University of Wuerzburg Children´s Hospital, Department of Pediatric Oncology‐ Comprehensive Cancer Center Mainfranken, Wuerzburg, Germany; <sup>3</sup>Cleveland Clinic Children´s Hospital, Department of Pediatric Hematology Oncology, Cleveland, USA; <sup>4</sup>University Medical Center Wuerzburg, Department of Pediatric Hematology and Oncology, Wuerzburg, Germany; <sup>5</sup>University Medical Centre Hamburg‐Eppendorf, Department of Pediatric Hematology and Oncology, Hamburg, Germany; <sup>6</sup>University of Essen, Pediatrics III Oncology, Essen, Germany; <sup>7</sup>University Hospital of Geneva, Department of Pediatrics and Adolescent Medicine Division of Pediatric Oncology, Geneva, Switzerland; <sup>8</sup>University Children´s Hospital Rostock, Department of Hematology Oncology, Rostock, Germany; <sup>9</sup>University Medical Center Wuerzburg, Department of Neuroradiologie‐ Hit 2000 National Refenrence Center, Wuerzburg, Germany; <sup>10</sup>University Medical Center Wuerzburg, Department of Pediatric Neurosurgery, Wuerzburg, Germany; <sup>11</sup>University of Leipzig, Department of Radiotherapy, Leipzig, Germany; <sup>12</sup>University of Bonn, Department of Pediatric Oncology, Bonn, Germany</italic></p><p><bold>Background/Objectives</bold>: Background: Medulloblastoma (MB), Ependymoma (ED) and Primitive neuroectodermal tumors (PNET) in young children in are associated with an unfavorable mental outcome after multimodal treatment. Therefore, craniospinal radiotherapy (CSI) is often delayed or replaced by intrathecal methotrexate (MTX<sup>i.th</sup>) and systemic Chemotherapy (CH‐T).</p><p><bold>Design/Methods</bold>: Procedures: Between October 2007 and March 2017 n = 327 surviving children treated within the HIT 2000 protocol at age of < 4 years were prospectively assessed by two neuropsychologist from the Wuerzburg team. The following tests were systematically applied: Kaufman Assessment Battery for Children (K‐ABC) measuring the Mental Processing Composite (MPC), the Coloured Progressive Matrices (CPM), the Developmental Test of Visual Motor Integration (VMI), the Tapping Test (TP) und der Continuous Performance Test (CPT‐K). Data of n = 206 patients were included in this analysis.</p><p><bold>Results</bold>: Results Children were stratified according to diagnosis (MB, ED, PNET), M‐status (M0, M+) and clinical response. The average IQ of all patients was: MPC IQ 84.96; SD 1.63. However, the values differed largely among the various treatment groups.</p><p>As examples, the results of MB M+ patients (treated with systemic chemotherapy and the following RT) are shown:</p><p>DMB M+ good responder <italic>no</italic> CSI, MPC IQ 86</p><p>DMB M+ poor responder CSI, MPC IQ 61</p><p>CMB M+ good responder <italic>no</italic> CSI, MPC IQ 89</p><p>CMB M+ poor responder CSI, MPC IQ 62</p><p>EP II infratentorial local RT, MPC IQ 97</p><p>EP III infratentorial local RT, MPC IQ 93</p><p>Interestingly, patients with infratentorial ED were found to have a K‐ABC within normal age range.</p><p><bold>Conclusions</bold>: Conclusions In this longitudinal assessment of the HIT 200 cohort, we found that multimodal therapy without CSI in MB patients resulted in improved mental outcome as measured by K‐ABC. <italic>This neuropsychological follow‐up project was supported by the German Childhood Cancer Foundation</italic>.</p></sec><sec id="pbc26772-sec-9860"><label>P-573</label><title>Dose Metrics and Memory Performance in Children Treated for Brain Tumor</title><p><underline underline-style="single">K. Raghubar</underline><sup>1</sup>, M. Lamba<sup>2</sup>, K. Cecil<sup>3</sup>, K. Yeates<sup>4</sup>, E.M. Mahone<sup>5</sup>, M.D. Ris<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>2</sup>University of Cincinnati College of Medicine, Radiation Oncology, Cincinnati, USA; <sup>3</sup>University of Cincinnati College of Medicine, Radiology, Cincinnati, USA; <sup>4</sup>Hotchkiss Brain Institute‐ University of Calgary, Psychology, Calgary, Canada; <sup>5</sup>Kennedy Krieger Institute, Neuropsychology, Baltimore, USA</italic></p><p><bold>Background/Objectives</bold>: Advances in radiation oncology provide new opportunities to study neurocognitive outcomes of radiation therapy (RT) in pediatric patients treated for brain tumor. Specifically, these advances allow for the consideration of the multidimensionality inherent to individualized RT treatment planning when examining the relationship between RT and neurocognitive outcomes. The present study investigates the relationship between biophysical and physical dose metrics, as well as their relation to neurocognitive ability, namely learning and memory.</p><p><bold>Design/Methods</bold>: This study is based on a subsample (<italic>n</italic> = 20) of participants from a longitudinal, prospective, multi‐site study (BRISC: Brain Radiation Investigative Study Consortium). Participants included in this study were diagnosed between the ages of 5 and 16 years and received RT following surgical intervention. Detailed dose reconstruction metrics were collected, and results from neuropsychological evaluations completed on average 29 months post‐treatment are reported. Physical (mean dose, prescribed dose, max dose) and biophysical (generalized equivalent uniform dose, integral biological effective dose) dose metrics for the whole brain, and right and left hippocampus were evaluated and correlated with learning and memory subtests from the Children's Memory Scale.</p><p><bold>Results</bold>: Biophysical dose metrics were highly correlated with the physical metric of mean dose (all Spearman's ρ correlations > .82) but not prescribed dose. Although prescribed dose was uncorrelated with measures of learning and memory, biophysical metrics and mean dose correlated with most measures; and lateralizing findings were obtained.</p><p><bold>Conclusions</bold>: These preliminary findings suggest limited advantage of biophysical dose metrics over physical metrics of mean dose when calculated for specific regions of brain. Implications for evaluating and understanding the relation between RT and neurocognitive functioning are discussed.</p></sec><sec id="pbc26772-sec-9870"><label>P-574</label><title>The Risk of Subsequent Malignancies Among Survivors of Pediatric Thyroid Cancer</title><p><underline underline-style="single">W.M. Rashed</underline><sup>1,2</sup>, M.H. Adly<sup>1</sup>, M. Sobhy<sup>2</sup>, M.A. Rezk<sup>2</sup>, M. Ishak<sup>2</sup>, A. El Shafie<sup>2</sup>, M. Ali<sup>2</sup>, A. Alfaar<sup>3</sup></p><p><italic><sup>1</sup>Children's cancer Hospital‐Egypt‐57357, Research, Cairo, Egypt; <sup>2</sup>Armed Forces College of Medicine, Research, Cairo, Egypt; <sup>3</sup>Charité‐Universitätsmedizin Berlin, Medicine, Berlin, Germany</italic></p><p><bold>Background/Objectives</bold>: Thyroid carcinoma is a very rare tumor in pediatric, it accounts for only 3% of all newly diagnosed childhood carcinomas in the United States according to the SEER database. The incidence rates of thyroid carcinoma of children from 0 – 4 years of age is 0.4 per 100 000, and up to 1.5 per 100 000 for adolescents aged from 15 to19 years. It was reported from large cohort studies that thyroid carcinoma is associated with an increased risk of second primary malignancies after treatment. We aim to assess the risk of subsequent malignancies among survivors of pediatric thyroid cancer.</p><p><bold>Design/Methods</bold>: We used US SEER (Surveillance Research Program, National Cancer Institute, Bethesda, MD, USA) database to perform this study. SEER*STAT version 8.3.4 was used to extract data from SEER public‐use database. The cohort for this analysis consisted of pediatric cancer patients aged less than 20 years diagnosed with a primary thyroid cancer and identified by site code ICD‐0‐3: C739, reported to a SEER 9 database between 1973 and 2013 To identify subsequent malignancies in this population, a query was performed to obtain all additional records of a new tumor diagnosis for each patient. Subsequent malignancies occurring 5 years or more after the original thyroid cancer diagnosis were included except thyroid cancer as a second malignancy.</p><p><bold>Results</bold>: A total of 38 patients diagnosed primarily with thyroid carcinoma with 42 incidence of subsequent malignancies as 4 patients developed third malignancy. Females represents 89.4% while males represent 10.5%. The subsequent malignancies of pediatric cancer survivors diagnosed with thyroid cancer includes many sites but high percent in both Female breast (21.3%) and Salivary gland (13.2%).</p><p><bold>Conclusions</bold>: Thyroid cancer is a rare tumor in childhood. The risk of developing second malignancy between pediatric cancer survivors mandates the presence of precise plan of longer follow‐up.</p></sec><sec id="pbc26772-sec-9880"><label>P-575</label><title>Cardiovascular Function in Adult Survivors of Pediatric Cancer</title><p><underline underline-style="single">I. Schmid</underline><sup>1</sup>, B. Reiner<sup>2</sup>, J. Müller<sup>2</sup>, A. Hager<sup>3</sup>, A. Kühn<sup>3</sup>, R. Oberhoffer<sup>4</sup>, P. Ewert<sup>3</sup>, J. Weil<sup>3</sup></p><p><italic><sup>1</sup>Dr. von Hauner Children's Hospital‐ Ludwig Maximilian University, Pediatric Hematology and Oncology, Munich, Germany; <sup>2</sup>Deutsches Herzzentrum München and Institute of Preventive Pediatrics‐ Technical University of Munich, Department of Pediatric Cardiology and Congenital Heart Disease, Munich, Germany; <sup>3</sup>Deutsches Herzzentrum München‐ Technical University of Munich, Department of Pediatric Cardiology and Congenital Heart Disease, Munich, Germany; <sup>4</sup>Institute of Preventive Pediatrics‐ Technical University of Munich, Department of Pediatric Cardiology and Congenital Heart Disease, Munich, Germany</italic></p><p><bold>Background/Objectives</bold>: Adult survivors of pediatric cancer are at high risk developing late cardiovascular events. The most important risk factor is the cumulative dose of anthracycline therapy. The goal of this prospective study was to detect any alterations regarding vascular structure, function and exercise capacity based on the dose of anthracyclines given.</p><p><bold>Design/Methods</bold>: 51 survivors of pediatric cancer (25 male) diagnosed at a median age of 12 years were examined at an average age of 22 years (16‐43 y) between 03/2015 and 01/2017. Patients with a cumulative dose of >250 mg/m² anthracyclines were compared to patients with 100‐250 mg/m² anthracyclines. All patients were asymptomatic and in NYHA class 1. To quantify dysfunction of the left ventricle, ejection fraction (EF) was determined by echocardiography. As cardiac biomarker, the plasma N‐terminal pro‐brain natriuretic protein (NT‐proBNP) level was measured. In addition, cardiopulmonary exercise test was performed to detect limitations in exercise capacity.</p><p><bold>Results</bold>: EF was reduced (EF <55%) in 17% of male and 16% of female survivors. There was no difference between the groups with high and moderate anthracycline dosage. NT‐proBNP was elevated (NT‐proBNP >100 ng/ml) in 20% of male and in 46% of female survivors. NT‐proBNP was significantly higher in the group with high compared to the group with moderate anthracyclines (p=0.03). There was no association between NT‐proBNP and EF. Cardiopulmonary exercise capacity was significantly lower in the group with high than with moderate anthracycline dosage (p=0.005).</p><p><bold>Conclusions</bold>: EF, NT‐proBNP levels and cardiopulmonary exercise tests are important parameters to detect early impairment of cardiovascular function in asymptomatic survivors of childhood cancer.</p><p>Irene Schmid and Barbara Reiner contributed equally to this work.</p></sec><sec id="pbc26772-sec-9890"><label>P-576</label><title>Late Effects of Treatment in Survivors of Childhood Cancers: Experience from India</title><p><underline underline-style="single">R. Seth</underline><sup>1</sup>, S. Seth<sup>2</sup>, A. Singh<sup>1</sup>, S. Sapra<sup>1</sup></p><p><italic><sup>1</sup>ALl India Institute of Medical Sciences, Pediatrics, Delhi, India; <sup>2</sup>ALl India Institute of Medical Sciences, Cardiology, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: Background: With improved survival of childhood cancer, long‐term cancer survivors are increasing. Few studies have assessed the long‐term morbidity after childhood cancer treatment in developing countries.</p><p>Objectives: To study the prevalence and spectrum of late effects of cancer treatment in pediatric cancer survivors.</p><p><bold>Design/Methods: Methodology</bold>: Evaluation of the first 300 patients who completed 5 years of follow‐up in the after treatment completion clinic was done. Details of primary diagnosis, treatment received and current clinical status was noted. The spectrum of late effects was ascertained by appropriate investigations.</p><p><bold>Results</bold>: Hematological malignancies comprised 25% of total cases.Commonest primary diagnosis comprised acute lymphoblastic leukemia (ALL), retinoblastoma and Hodgkin lymphoma. The median age at evaluation and follow‐up were 14 years and 8.5 years respectively. 23% (69) of the survivors had a minimal disability (growth retardation or underweight), 13% (39) had moderate disabilities needing medical attention (HbSAg positive, myocardial dysfunction, Azoospermia and hypothyroidism) while 2 % (1) had major/ life threatening disabilities (mental retardation, liver disease, mortality). Eleven patients relapsed on follow‐up: of these five patients expired. Two second malignancies were recorded in our cohort of patients during the period of follow‐up.</p><p><bold>Conclusions</bold>: Late effects are a concern however severe disability (grade 3‐5) is seen in only 2% survivors: most can be tackled. Lifelong follow‐up of childhood cancer survivors is recommended to define accurately cancer‐related morbidity, occurrence of a secondary neoplasm, facilitate timely diagnosis and implement remedial or preventive interventions that optimise health outcomes.. Awareness towards the existence of late effects of cancer therapy is required among parents, patients and health professionals</p></sec><sec id="pbc26772-sec-9900"><label>P-577</label><title>Subsequent Glioma in Survivors of Paediatric Neoplasms</title><p><underline underline-style="single">L. Shats</underline><sup>1</sup>, M. Belogurova<sup>1</sup>, S. Ozerov<sup>2</sup>, A. Ektova<sup>3</sup>, M. Rizhova<sup>4</sup>, I. Doronina<sup>5</sup>, O. Vizhlukova<sup>5</sup>, E. Grishina<sup>6</sup>, A. Rudneva<sup>7</sup>, E. Erega<sup>8</sup>, O. Zheludkova<sup>9</sup>, A. Pshonkin<sup>2</sup>, E. Kumirova<sup>2</sup></p><p><italic><sup>1</sup>Saint‐Petersburg State Paediatric Medical University, Division of Oncology‐ Paediatric Oncology and Radiotherapy, St. Petersburg, Russia; <sup>2</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Division of Neurooncology, Moscow, Russia; <sup>3</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Pathology Department, Moscow, Russia; <sup>4</sup>N.N. Burdenko Neurosurgical Institute‐ Russian Academy of Medical Sciences, Division of Pathology, Moscow, Russia; <sup>5</sup>Paediatric Hospital of Murmansk, Department of Paediatric Oncology‐ Haematology and Endocrinology, Murmansk, Russia; <sup>6</sup>Children's Republican Clinical Hospital, Departmant of Paediatric Oncology and Haematology, Kazan, Russia; <sup>7</sup>Dmitry Rogachev National Research Center of Pediatric Hematology‐ Oncology and Immunology, Consultation Department, Moscow, Russia; <sup>8</sup>Children's Regional Hospital, Paediatric Oncology and Haematology, Khabarovsk, Russia; <sup>9</sup>Russian Scientific Center of Radiology, Department of Neuro‐Oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Multimodal therapy has improved survival for most childhood tumours.The development of neoplasms subsequent to therapeutic cranial irradiation is a rare but serious and potentially fatal complication.</p><p><bold>Design/Methods</bold>: The analysis included 16 patients (pts) with subsequent glioblastoma (SG) from several institutions who underwent cranial or neck irradiation (1 case) to treat their primary disease (acute lymphoblastic leukaemia ‐ 12 pts, medulloblastoma‐ 2 pts, choroid plexus papilloma ‐ 1 pt, lymphoma ‐ 1 pt.). All gliomas arose within the previous radiation fields and satisfied the widely used criteria for the definition of radiation induced neoplasms. The median RT dose administered was 18 Gy with the dosage ranges being 12‐36 Gy. Total body irradiation(TBI) was used in one patient with Ph‐positive ALL during bone marrow transplantation. Median latency period was 7 years until diagnosis of SG. The majority of SG (13 of 16 [81%]) occurred during the initial 9 years of follow‐up, only 3 were diagnosed after 10 years. Patients underwent surgery resection followed by standard fractionated local radiation and chemotherapy.</p><p><bold>Results</bold>: A Kaplan‐Meier analysis was used to illustrate the overall survival (OS) curves. OS rate was 37.5±12.9% and 15.0±9.7% at 1 and 2 years respectively.</p><p><bold>Conclusions</bold>: In case that paediatric neoplasms are treated by standard fractionated radiation or TBI is used, radiation‐induced gliomas should be considered as possible long‐term side effect. And the patients should be followed for a long term, even longer after the period of risk for relapse of the primary cancer has passed.</p></sec><sec id="pbc26772-sec-9910"><label>P-578</label><title>The ApoE Genotype and White Matter Lesions in Childhood Non‐CNS Tumor Survivors</title><p><underline underline-style="single">C. Sleurs</underline><sup>1</sup>, J. Lemiere<sup>1</sup>, G. Vercruysse<sup>1</sup>, L. Vandenwyngaert<sup>1</sup>, V. Labarque<sup>1</sup>, S. Jacobs<sup>1</sup>, S. Sunaert<sup>2</sup>, S. Deprez<sup>2</sup>, A. Uyttebroeck<sup>1</sup></p><p><italic><sup>1</sup>University Hospitals Leuven, Pediatric Oncology, Leuven, Belgium; <sup>2</sup>University Hospitals Leuven, Radiology, Leuven, Belgium</italic></p><p><bold>Background/Objectives</bold>: ApoE is the cholesterol transporter, playing an important role in neuronal plasticity. Given the lack of evidence about neurodevelopment in childhood cancer patients, this study aims to explore potential brain lesions in survivors and the link with cognition and the ApoE4 allele.</p><p><bold>Design/Methods</bold>: We acquired neurocognitive data for survivors of pediatric solid non‐CNS tumors (n=34) and age‐matched controls (n=34) [16‐35] years. Patients were treated since 2000. Neuropsychological assessments included intelligence, verbal and auditory memory, attentional measures. T2*‐weighted FLAIR images were investigated for white matter lesions. DNA samples were examined for the ApoE polymorphism. First, we compared behavioral scores on objective assessments (WAIS, AVLT, RVDLT, ANT) and subjective questionnaires (STAI, CFQ, BRIEF), with depression (BDI) and SES as covariates. The risk for white matter lesions within the patient group was predicted by the ApoE genotype (i.e. by the presence vs. absence of allele ε2 and ε4). Cognitive scores within the patient group were compared between the Apoε4 patient subgroups, as well as between the white matter lesion (present vs. absent) subgroups.</p><p><bold>Results</bold>: Cognitive scores appeared lower for WAIS working memory (<italic>F</italic>=6.866, <italic>p</italic>=.012), WAIS processing speed (<italic>F</italic>=6.942, <italic>p</italic>=.011), RVDLT total (F=8.982, p=.004), BRIEF working memory (F=6.149, p=.017) and PedSQL total score (<italic>F</italic>=6.314, p=.015). WM lesions were present in 23.5% of patients (vs. .02% of controls). The risk of WM lesions predicted by the Apoε4 allele, resulted in a correct categorization of 37.5% as lesion patient (Model: χ²= 8.708, <italic>p</italic>=.003). Neither of both factors were related to cognition.</p><p><bold>Conclusions</bold>: Survivors of solid tumors mainly complain about working memory, and also showed lower objective scores for processing speed, visual memory and QoL. The heterogeneity of WM lesions suggest that the impact on cognition is different, depending on the location and type of lesion. The ApoE genotype could be a potential biomarker for such lesions.</p></sec><sec id="pbc26772-sec-9920"><label>P-579</label><title>Sonographic Image of Solitary Kidney in Wilms Tumor Survivors</title><p><underline underline-style="single">J. Stefanowicz</underline><sup>1</sup>, M. Kosiak<sup>2</sup>, E. Adamkiewicz‐Drożyńska<sup>3</sup>, A. Balcerska<sup>2</sup>, A. Kurylak<sup>4</sup></p><p><italic><sup>1</sup>Gdansk Medical University, Department of Pediatrics‐ Hematology and Oncology, Gdańsk, Poland; <sup>2</sup>Medical University of Gdansk, Department of Family Medicine, Gdansk, Poland; <sup>3</sup>Medical University of Gdansk, Department of Paediatrics‐ Haematology‐ Oncology, Gdansk, Poland; <sup>4</sup>Department of Paediatrics‐ Haematology and Oncology. Ludwik Rydygier Collegium Medicum in Bydgoszcz. Nicolaus Copernicus University in Torun., Department of Paediatrics‐ Haematology and Oncology, Department of Paediatrics‐ Haematology and Oncology, Poland</italic></p><p><bold>Background/Objectives</bold>: Study presents analysis of sonographic and laboratory parameters of solitary kidneys and prevalence of chronic kidney disease (CKD) in Wilms tumor survivors (WTs).</p><p><bold>Design/Methods</bold>: 53 WTs who completed treatment for Wilms tumor (WT) and 44 healthy individuals were enrolled to the study.</p><p>Study protocol consists of: completing medical history, sonographic examination of solitary kidney, estimation of glomerular filtration rate (eGFR) with Schwartz or MDRD formula, albumin urine excretion (ACR), blood pressure measurement.</p><p><bold>Results</bold>: Sonographic sings of kidney damage were observed in 21 (39,6%) WTs. Hypertrophy of solitary kidney occurred in 71,7% of cases. Mean volume of solitary kidney was 77% of volume of sum of two kidneys in control group. Mean eGFR in WTs group was 117 ± 19,5 ml/min/1,73m<sup>2</sup> vs 131 ± 12,8 ml/min/1,73m² in control group (p<0,05). Six WTs (11,3%) had value of eGFR below 90ml/min/1,73m<sup>2</sup>. Increased albumin urine excretion (ACR > 30mg/g) was observed in 7 WTs ( 13,2%) and in 3 (6,8%) individuals in control group.</p><p><bold>Conclusions</bold>: Sonographic image of solitary kidney in WTs differs from sonographic image in control group. The most frequently detected abnormality are hyperechoic rings around renal pyramids. There was no difference in sonographic image of solitary kidney according to chemotherapy. Sonographic examination in WTs ought to be performed not only to detect eventual tumor recurrence but also to assess risk of CKD and progressive deterioration of renal function.</p><p>Persons involved in writing the paper do not report a conflict of interest.</p></sec></sec><sec id="pbc26772-sec-9930"><title>Childhood Cancer International (CCI)</title><sec id="pbc26772-sec-9940"><label>P-580</label><title>Family Members’ Perceptions Towards Equity and Quality in Accessing Health Care Services at Children's Cancer Hospital Egypt: A Mixed Methods Study</title><p><underline underline-style="single">M. Alattas</underline><sup>1</sup>, A. Hamdy<sup>2</sup>, S. Elmeniawy<sup>2</sup>, A. Elhaddad<sup>3</sup>, A. Abdelfattah<sup>3</sup>, M. Zamzam<sup>4</sup>, I. Albanti<sup>5</sup></p><p><italic><sup>1</sup>Boston University School of Public Health, Global Health, Boston, USA; <sup>2</sup>Children's Cancer Hospital Egypt 57357, Quality, Cairo, Egypt; <sup>3</sup>Children's Cancer Hospital Egypt 57357, Pediatric Oncology, Cairo, Egypt; <sup>4</sup>Children's Cancer Hospital Egypt 57357, Healthcare Sciences Academy, Cairo, Egypt; <sup>5</sup>Dana Farber Cancer Institute, The Global Health Initiative, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Patients’ experience within the health care system in terms of equity and quality influences their perception to access. This project explores the referral mechanism at Children's Cancer Hospital Egypt 57357 (CCHE) in Cairo and assesses perceptions of family members towards equity, quality, and other dimensions associated with access to pediatric oncology care.</p><p><bold>Design/Methods</bold>: This is a single site mixed methods study. Data were collected through in‐depth interviews using a structured interview guide which included probes, close‐ended and open‐ended questions. A sample size of 100 family members were randomly selected and interviewed. A focus group with 5 mothers and 1 father was conducted to expand on parents’ opinion on the referral process and overall experience.</p><p><bold>Results</bold>: Respondents reported the following factors when deciding to seek care at CCHE</p><p>1) Experience outside CCHE: Dissatisfaction with healthcare providers’ knowledge, attitudes and behaviors; fragmented system; and under equipped hospitals.</p><p>2) Perceived quality of CCHE services: Advanced, specialized facility; effective treatment; high survival rate.</p><p>3) Reputation of CCHE: Trust in CCHE and brand awareness (word of mouth, television ads, doctors’ recommendations).</p><p>4) Equity: CCHE's mission for equal access and free of charge treatment.</p><p><bold>Conclusions</bold>: Efficient patient centred referral process is a vital element of high quality care service. Our recommendations include suggestions to increase engagement of families into care, incorporate family members’ feedback into quality improvement efforts, collaborate with national existing cancer centers to streamline the referral system and access, plan an outreach program for health care providers in rural areas to improve their communication skills, conduct follow‐up surveys to expand on the public perception towards different access elements.</p></sec><sec id="pbc26772-sec-9950"><label>P-581</label><title>The Cost of Childhood Cancer Treatment in Jordan</title><p><underline underline-style="single">I. Sultan</underline><sup>1</sup>, A. Al‐Nassan<sup>1</sup>, A. Mansour<sup>2</sup>, S. Gupta<sup>3</sup>, S. Horton<sup>4</sup>, N. Bhakta<sup>5</sup></p><p><italic><sup>1</sup>King Hussein Cancer Center, Department of Pediatrics, Amman, Jordan; <sup>2</sup>King Hussein Cancer Center, Department of Radiology, Amman, Jordan; <sup>3</sup>Hospital for Sick Children, Division of Hematology/ Oncology, Toronto, Canada; <sup>4</sup>University of Waterloo School of Public Health and Health Systems, Global Health Economics, Ontario, Canada; <sup>5</sup>St. Jude Children's Research Hospital, Department of Global Pediatric Medicine, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Over the past 15 years, King Hussein Cancer Center (KHCC) has established a multidisciplinary cancer care program and become an important regional hub for oncology. Each year, the center treats over 3500 new cancer patients from both Jordan and its surrounding regions. KHCC provides state‐of‐the‐art medical equipment and services, including 8 operating rooms, 170 beds, and 18 intensive care units, including 6 dedicated pediatric ICU beds. Emerging data from KHCC has shown outcomes for many pediatric malignancies treated by the hospital are approaching those seen in high‐income countries (HICs). The cost of childhood cancer treatment in upper middle‐income countries (UMIC) like Jordan, however, has not been well investigated. The aim of this research is to determine the cost of operating a national childhood cancer treatment center in Jordan to help prioritize future interventions for childhood cancer treatment and provide an analytic framework to model future costing analyses elsewhere.</p><p><bold>Design/Methods</bold>: We will conduct a cross‐sectional study to evaluate the expenses of childhood cancer treatment covered by the budget and financing model in Jordan. Expenditures will be categorized by Personnel, Room and Board, Outpatient Clinic, Pharmacy, Pathology, Surgery, Radiation, and Imaging. To estimate the unit cost per bed, we will multiply the World Health Organization table of unit costs for a Tertiary Hospital, the average length of stay at KHCC (days) and the total number of inpatient visits per year.</p><p><bold>Results</bold>: We will calculate total costs based on annual cases diagnosed and admitted at KHCC. Cost‐effectiveness will be assessed by comparing costs with Disability‐Adjusted Life‐Years estimated from center‐specific outcomes data.</p><p><bold>Conclusions</bold>: Both the cost and cost‐effectiveness results of this study will inform policy makers and other stakeholders in Jordan with planning, implementation and prioritization for childhood cancer treatment programs. The described methods also provide a template for other UMICs to conduct similar analyses.</p></sec><sec id="pbc26772-sec-9960"><label>P-582</label><title>Building an Advocacy Campaign “Go Gold India” for Childhood Cancer to be a Child Health Priority in India</title><p><underline underline-style="single">K. Chawla</underline><sup>1</sup>, P. Bagai<sup>1</sup>, S. Sharma<sup>2</sup>, R. Bhalla<sup>3</sup>, C. Kumar<sup>4</sup>, A. Mishra<sup>1</sup>, A. Ahuja<sup>1</sup></p><p><italic><sup>1</sup>CanKids...Kidscan, CEPAA, Delhi, India; <sup>2</sup>CanKids...Kidscan, Capacity Building & Parent & Survivor Group, Delhi, India; <sup>3</sup>CanKids...Kidscan, CEPAA and Resource Mobilization, Delhi, India; <sup>4</sup>CanKids...Kidscan, CEPAA & KCK, Delhi, India</italic></p><p><bold>Background/Objectives</bold>: No childhood cancer control plan or policy in India. Survival outcomes estimated to be as low as 20‐40%. Awareness about childhood cancer, gold color, gold ribbon and gold glow as symbols was low. A focused advocacy campaign with a brand and to adopt new themes each year was built, to promote Gold color as brand, just as pink is for Breast cancer thereby engaging all stakeholders.</p><p><bold>Design/Methods</bold>: Go Gold India campaign launched in 2015 invoking Childhood Cancer international hash tag “Act Now for Kids with Cancer” with specific theme Taj Goes Gold between February International Childhood Cancer Day (ICCD) and September Childhood Cancer Awareness Month. On ICCD children with cancer decorated Light it up Gold Taj Mahal cut outs in 44 cancer centers lit up by hospital managements. On Nurses and Doctors' Day pediatric oncology professionals pinned with Gold ribbons. On Survivor Day “I Deserve best cancer treatment, care and support” poster and essay competition was spearheaded. Spanning 6 months, survivors pinned Gold Ribbons and ran Pledge campaign online and offline. September saw a 5day 1500km Car Rally in Uttar Pradesh and social mobilization campaign to bring children parents and survivors to Agra for Taj to go Gold. The campaign is followed in Year 2 by Go Gold India–for Warriors and Angels inspired by We are one song and using Yellow wristbands.</p><p><bold>Results</bold>: The Taj went Gold from September 25‐27 adorned with gold ribbons and Light it Up Gold Taj cut outs, first ever Childhood Cancer Exhibition, 1900 children, parents at Taj Mahal and extensive media coverage. 95,000 pledges collected from India and overseas, State Government announced formation of Task Force and WHO India and Central Government Health Ministry pledged support.</p><p><bold>Conclusions</bold>: Sustained and attractive advocacy campaign with strong image and brand needs to be built up year on year to engage stakeholders.</p></sec><sec id="pbc26772-sec-9970"><label>P-583</label><title>Impact of Early Intensive Nutritional Intervention on Malnutrition Status in Pediatric Cancer –Role of Non Governmental Organisation (NGO)</title><p>G. Chinnaswamy<sup>1</sup>, <underline underline-style="single">P. Bahl</underline><sup>2</sup>, J. Chadha<sup>2</sup>, K. Bhanushali<sup>1</sup>, N. Mahakal<sup>2</sup>, S. Jatia<sup>1</sup>, M. Prasad<sup>1</sup>, B. Arora<sup>1</sup>, S. Banavali<sup>1</sup></p><p><italic><sup>1</sup>Tata Memorial Hospital, Department of Pediatric and Medical Oncology, Mumbai, India; <sup>2</sup>Cuddles foundation, Cuddles foundation, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Pre‐existing malnutrition in pediatric cancer patients adversely influences treatment outcomes. Additionally, treatment toxicities has a detrimental effect on the nutritional status. Early and aggressive nutritional intervention is found to improve nutritional status and in turn, overall outcomes. We analysed the impact of early intervention on the nutritional status of children across 6 hospitals in India where the nutritional intervention was supported by an NGO. Cuddles Foundation(CF) is the only organization in India that focuses on providing holistic nutritional intervention to children afflicted with cancer.</p><p><bold>Design/Methods</bold>: Children with newly diagnosed cancer, aged 0‐16 years, and with coexisting severe acute malnutrition(SAM) between Jan’2016 to Dec’2016 were included in the study. Weight(for age), Height(for age), Weight for length, BMI, MUAC and Triceps skin fold thickness(TSFT) were measured and their Z scores/percentiles were calculated at baseline, 1<sup>st</sup> and 3<sup>rd</sup> month of assessment. Nutritional interventions included incorporating Ready to use therapeutic food(RUTF), other Nutritional supplements including micronutrients (Vitamin D, B12, Folate and Calcium if found deficient) and close monitoring by dedicated nutritionists who were recruited by the NGO.</p><p><bold>Results</bold>: 61 newly diagnosed pediatric cancer children with SAM, were enrolled. Mean age of the study group is 3.4 years and M:F‐1:1.2. Average BMI improved from 12.3 to 13.22Kg/m<sup>2</sup> in 4 weeks. Correspondingly the median Weight shifted from 11.35 to 13.4 kg. Over 3 months, 77% showed an improvement in nutritional status with intervention: 31/61(51%) converted to mild malnutrition/normal nutrition and 16/61(26%) improved to moderate malnutrition status while only 14/61(23%) continued to be SAM.</p><p><bold>Conclusions</bold>: Early and aggressive nutritional intervention in cancer children with pre‐existing malnutrition significantly improves the nutritional status. This impacts positively on chemotherapy tolerance and long term outcomes. NGOs (CF) focussed on holistic nutritional support can play an important role in improving outcomes in LMICs where malnutrition is highly prevalent in children with cancer.</p></sec><sec id="pbc26772-sec-9980"><label>P-584</label><title>UNITE2CURE ‐ Accelerating Drug Development</title><p><underline underline-style="single">N. Scobie</underline><sup>1</sup>, H. Delphine<sup>2</sup>, C. Copland<sup>2</sup></p><p><italic><sup>1</sup>Unite2Cure, Zoé4life, Sullens, Switzerland; <sup>2</sup>Unite2Cure, Kick Cancer, Brussels, Belgium</italic></p><p><bold>Background/Objectives</bold>: There is growing recognition across the parent/patient and professional community that promising new drugs for children and teenagers with cancer are not being developed quickly enough. This is a multi‐faceted problem that requires an urgent co‐ordinated pan‐European approach. The problem is not just medical but also economic. Pharmaceutical companies consider the adult population their key customer base. Childhood cancers have been neglected as they are made up of rare illnesses, none of which offer a lucrative market for commercially developed drugs.</p><p><bold>Design/Methods</bold>: There are many groups and charities working for similar aims. We aim to provide a parent‐led platform, that with the Accelerate Platform, will mobilize this support. Under the banner “Unite Against Childhood and Teenage Cancer, we aim to build upon a growing desire for change in order to save more children with cancer and allow others to access better, kinder new drugs. Our approach will be to work supportively and collaboratively with all stakeholders to share ideas and identify solutions. Together we will amplify the voice of children and teenagers with cancer</p><p><bold>Results</bold>: A few basic changes to European law, as well as collaborative funding ideas could transform the situation and harness the major advances that have been made in biological science for the benefit of children</p><p><bold>Conclusions</bold>: The Paediatric Medicines Regulation promotes research into all children's illnesses. However, with regard to cancer in particular, it has not lived up to the promise it held out to provide them with safe and efficient medicines.</p><p>Specific reforms to the PMR would ensure that every time a drug company develops a new treatment for adults, the drug's potential for combating childhood illnesses be evaluated. Alternative funding models also should be explored. This would have a significant impact on the health of young people generally, but, in particular, it would benefit those with cancer.</p></sec><sec id="pbc26772-sec-9990"><label>P-585</label><title>Factors Associated with Abandonment of Pediatric Cancer Treatment in Peru: A Multicenter Cohort Study</title><p><underline underline-style="single">L. Vasquez</underline><sup>1</sup>, R. Diaz<sup>2</sup>, S. Chavez<sup>2</sup>, I. Maza<sup>1</sup>, E. Hernandez<sup>2</sup>, M. Oscanoa<sup>1</sup></p><p><italic><sup>1</sup>Rebagliati National Hospital, Pediatric Oncology, Lima, Peru; <sup>2</sup>National Institute of Neoplastic Diseases, Pediatric Oncology, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Abandonment is a major cause of treatment failure and poor survival in children with cancer of low and middle income countries; although in our country it is not well documented. The aim of this study was to examine the prevalence and associated factors of treatment abandonment in pediatric patients with cancer.</p><p><bold>Design/Methods</bold>: We have analyzed socio‐demographic and clinical data from the two major institutions in Peru in childhood cancer during 2012 to 2014. Definition of treatment abandonment was used from the SIOP (International Society of Paediatric Oncology) PODC (Paediatric Oncology in Developing Countries) Abandonment of Treatment Working Group recommendation.</p><p><bold>Results</bold>: A total of 1135 children diagnosed with malignant solid tumors were retrospectively reviewed and 209 (18.4%) abandoned treatment. Univariate logistic regression analysis showed significant higher abandonment rates in children living in the southern (OR 2.35; p<0.001) and eastern cities of Peru (OR 3.64; p=0.001); prolonged travel time to tertiary center (> 5 hours; OR 2.75, p= 0.002); rural setting (OR 3.44; p<0.001) and lack of parental formal job (OR 4.39; p= 0.001). According to cancer diagnosis, children with retinoblastoma had more abandonment rate (OR 1.79; p= 0.020) compared with other solid tumors. There was a trend of decreasing abandonment rates over time (p=0.004). In multivariate regression analyses, a rural origin and lack of formal parental employment were independently predictive of abandonment.</p><p><bold>Conclusions</bold>: Treatment abandonment prevalence in our country is high and closely related to socio‐demographical factors. Outcome could be substantially improved by strategies that help to prevent abandonment of therapy based on these results.</p></sec><sec id="pbc26772-sec-10000"><label>P-586</label><title>Developing a Tiered‐System of Quality of Care Indicators for Pediatric Oncology Resource‐Limited Settings</title><p><underline underline-style="single">C. Wong</underline><sup>1</sup>, A. Billett<sup>1</sup>, P. Friedrich<sup>2</sup>, L. Lehmann<sup>1</sup>, I. Albanti<sup>1</sup>, L. Morrissey<sup>1</sup>, K. Houlahan<sup>1</sup>, C. Rodriguez‐Galindo<sup>2</sup></p><p><italic><sup>1</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Pediatric Oncology, Boston, USA; <sup>2</sup>St. Jude Children's Research Hospital, Global Pediatric Medicine, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Consensus is lacking on prioritization (collection, monitoring, and benchmarking) of pediatric oncology (PO) quality of care (QoC) indicators in distinct resource settings. Measurement of resource‐specific indicators that shift from illustrating capacity to reflecting performance in cancer care delivery is needed to assess, identify gaps, and improve QoC.</p><p>Objectives: To develop a pilot for consensus on a PO tiered‐system of indicators that measures QoC in low‐ and middle‐income countries.</p><p><bold>Design/Methods</bold>: Systematic and grey literature review generated potential indicators. A multidisciplinary group of experts reached consensus through a modified Delphi process. Indicators were rated on two consecutive rounds using a 5‐point Likert scale survey (1=Strongly Agree; 5=Strongly Disagree) based on importance and feasibility for resource‐limited PO settings. For round 3, participants individually categorized indicators applicable for each one of four resource‐based tiers ranging from basic (Tier‐1) to advanced (Tier‐4), then ranked a pre‐determined number of top (60<sup>th</sup> percentile) indicators for each tier (round 4). Roundtable discussions, review of results, and modification of indicators followed each round. Consensus was reached upon >65% agreement (or median <2) after consecutive rounds.</p><p><bold>Results</bold>: From an initial 107, consensus was reached on 10 top indicators for Tier 1; 28, 33, and 37 for Tiers 2‐4, respectively. Indicators addressed a range of domains including safety, supportive care, treatment abandonment, and long‐term survival. Only four indicators were represented across all tiers relating to the proportion of: patients with documented treatment plan available to all providers, hand‐hygiene compliant providers, patients treated according to standardized treatment plans with monitoring of outcomes, and 5 year survival rates.</p><p><bold>Conclusions</bold>: The pilot led to consensus on PO QoC indicators for resource‐limited settings, but these varied across tiers based on resource availability. Validation of the tiered‐system of indicators with a larger group of experts and development of measurement strategies will follow.</p></sec></sec><sec id="pbc26772-sec-10010"><title>Other</title><sec id="pbc26772-sec-10020"><label>P-587</label><title>The Pediatric Hematology Oncology Bestbits Project: A Journal Review and Virtual Journal Club Initiative</title><p><underline underline-style="single">N. Alexander</underline><sup>1</sup>, J. Brzezinski<sup>1</sup>, N. Waespe<sup>1</sup>, F. Bellavance<sup>2</sup>, A. Punnett<sup>1</sup></p><p><italic><sup>1</sup>Hospital for Sick Children, Pediatric Hematology Oncology, Toronto, Canada; <sup>2</sup>Hospital for Sick Children, Information services, Toronto, Canada</italic></p><p><bold>Background/Objectives</bold>: Scanning the appropriate journals for relevant articles to stay updated and interpreting the impact of new research is challenging in the expanding field of Pediatric Hematology Oncology. Following a pilot Journal Review Initiative, where 20 fellows participated by screening and appraising relevant articles in 27 journals, writing 155 summaries in 5 issues over 1 year, online expansion was proposed to broaden educational opportunities and participation and facilitate interactive discussions.</p><p>We aim to create an open access online interactive learning resource of relevant current literature in Pediatric Hematology Oncology and facilitate practice of journal screening, summarizing and critical appraisal. We hypothesize that participation in “BestBits” initiative will improve journal reading habits, self‐efficacy in screening journals and critically appraising journal articles, and be a convenient way to keep up to date with new literature.</p><p><bold>Design/Methods</bold>: A needs assessment was sent to Pediatric Hematology Oncology fellows and staff across Canada and they were invited to register online to participate in journal review and other learning activities. Following initial design and development of www.bestbits.ca, the first phase of the initiative was launched. A 2‐month schedule for Journal Review was developed: assigned journals are reviewed and relevant articles to read and appraise, selected using a standardized framework. Summaries with interpretation are submitted online after extensive editorial review and journal review is posted online.</p><p><bold>Results</bold>: Online participant surveys, editorial review and website statistics will be used to evaluate participation and provide feedback on learning activities and processes. We will analyze number of hours and articles read, proportion of articles read completely and self‐efficacy in staying updated of the participants.</p><p><bold>Conclusions</bold>: Staying updated with Pediatric Hematology Oncology literature is challenging and creating an open access relevant resource may be useful to practitioners, and promote journal reading and critical appraisal. Further development will involve interactive virtual journal club and self‐assessment educational activities.</p></sec><sec id="pbc26772-sec-10030"><label>P-588</label><title>Development of the First East African Pediatric Hematology Oncology Fellowship Program in Uganda</title><p><underline underline-style="single">E. Ishigami</underline><sup>1</sup>, N. Kagoro<sup>2</sup>, J. Lubega<sup>2</sup>, J. Slone<sup>2</sup>, G. Airewele<sup>2</sup>, P. Mehta<sup>2</sup>, K. Wilson‐Lewis<sup>1</sup>, E. Fruge<sup>2</sup>, R. Kansiime<sup>3</sup></p><p><italic><sup>1</sup>Texas Children's Hospital, Cancer and Hematology Centers, Houston, USA; <sup>2</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>3</sup>Baylor College of Medicine Children's Foundation‐Uganda, Pediatrics, Kampala, Uganda</italic></p><p><bold>Background/Objectives</bold>: An estimated 300,000 children develop cancer annually. With few trained Pediatric Hematology/Oncology (PHO) experts to provide care in sub‐Saharan Africa (SSA), the majority die. To sustainably improve quality of care in SSA, Texas Children's Cancer and Hematology Centers (TXCH), and Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) partnered with the Ministry of Health of the Republic of Uganda and 3 other Ugandan Partners in 2015 to create the East Africa Pediatric Hematology Oncology Training (EAPHOT) fellowship.</p><p><bold>Design/Methods</bold>: The goal of the EAPHOT fellowship is to increase PHO expert numbers in East Africa. The two year curriculum includes didactics and supervised clinical experience. The program is directed by a full‐time TXCH faculty in Uganda complimented by rotating TXCH faculty. The curriculum includes online lectures together with electronic tracking of each fellow's progress, weekly Tumor Boards with TXCH faculty, a bi‐monthly leadership seminar, and access to the Texas Medical Center Library. The fellows can utilize the TXCH global consultation system for immediate help with difficult cases. The second year of fellowship focuses on clinical quality improvement and research.</p><p><bold>Results</bold>: As of March 2017, a total of 8 fellows from Uganda, Tanzania, and Kenya, have enrolled in the PHO fellowship program. The online lecture system has been well received. Fellows have accessed the didactic lectures over 111 times. Fellows spend 4 hours weekly reviewing lectures. Positive evaluations of faculty, lectures, and overall fellowship effectiveness were received. The EAPHOT program model has been adopted by Makerere University College of Health Sciences (Kampala) and Uganda Cancer Institute to develop other sub‐specialty training programs.</p><p><bold>Conclusions</bold>: The program is on track to train and build a critical mass of PHO specialists in the East Africa region and a similar program is planned for Botswana to train pediatric hematologists‐oncologists for the Southern Africa region.</p></sec><sec id="pbc26772-sec-10040"><label>P-589</label><title>Setting Up Strong Core Business Infrastructure to Ensure Sustainability: East Meets West ‐ How to Set Up in Developing Countries, Making Programs Sustainable</title><p><underline underline-style="single">K. Wilson‐Lewis</underline><sup>1</sup>, N. Kagoro<sup>2</sup>, R. Bullock<sup>3</sup>, E. Ishigami<sup>1</sup></p><p><italic><sup>1</sup>Texas Children's Hospital, Pediatrics, Houston, USA; <sup>2</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>3</sup>Texas Children's Hospital, Cancer and Hematology, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: In an effort to improve the outcomes of children with cancer and blood disorders in developing countries, the Texas Children's Cancer and Hematology Centers Global HOPE (Hematology Oncology Pediatric Excellence) program aims to build capacity and strengthen healthcare infrastructure in Sub‐Saharan Africa (SSA). These activities require a significant investment of money, expertise and other resources. Given the level of investment needed, strong business management is critical to the overall success of these efforts.</p><p><bold>Design/Methods</bold>: Methods of business management vary between settings within SSA and those of western partners. Challenges include working in bureaucratic and under‐resourced government healthcare systems. While understanding that differences exist in business practices and that regulations vary, it is necessary to focus on achieving the highest level of practice possible. To that end, the approach has been to understand local practices and regulations, identify the differences and work with local leadership to strengthen practices where needed. Examples of this strategy include facilities planning and maintenance, financial management, monitoring and evaluation systems (M&E), information systems management and general operational management. This has been accomplished by creating and implementing Standard Operating Procedures (SOPs) as a means to clarify process, role, and responsibility and to increase the transparency of business operations.</p><p><bold>Results</bold>: The process of developing SOPs proved helpful in obtaining stakeholder input and support for revised or new processes. Adjustments to existing processes proved challenging but not impossible. To date, outcomes include improved financial reporting and management capabilties, which has increased the confidence of program stakeholders thus, increasing program fundability and sustainability. Additionally, advances in data collection, management and reporting for M&E have been accomplished to add breadth and depth of information for program reporting.</p><p><bold>Conclusions</bold>: Good business practice should be viewed as a requirement of Global Health Programs to ensure program success and sustainability.</p></sec><sec id="pbc26772-sec-10050"><label>P-590</label><title>Challenges in Managing Grants in Global Settings</title><p><underline underline-style="single">E. Ishigami</underline><sup>1</sup>, N. Kagoro<sup>2</sup>, L. Morin<sup>2</sup>, C. Chu<sup>2</sup>, K. Wilson‐Lewis<sup>1</sup></p><p><italic><sup>1</sup>Texas Children's Hospital, Pediatrics, Houston, USA; <sup>2</sup>Baylor College of Medicine, Pediatrics, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: Grant funding plays a significant role in funding global health. As a center that has quite successfully obtained grant funding, the Texas Children's Cancer and Hematology Centers (TXCH) has many years of experience in traditional U.S. based grants management. While this experience has proven helpful to supporting it's rapidly expanding Global HOPE (Hematology‐Oncology Pediatric Excellence) Program, unique challenges have required adapted approaches to grants management in the global setting.</p><p><bold>Design/Methods</bold>: New challenges include the complexity of collaborations across countries, difficulty in long‐distance communication, differences in grants management, finance, cash and procurement processes, pace of regulatory processes, and lack of resources at global sites. These challenges were making it difficult for Principal Investigators to accomplish their projects and spend grant funding as planned. For example, executed sub‐awards from a U.S. institution to a global institution were difficult to obtain and challenging to implement due to reimbursement based cash flow practices. To better manage the portfolio of global grants, the TXCH formed a working group with representation of administrative and research leadership, pre‐ and postaward staff, the PI and other key stakeholders to review new grant opportunities and to monitor the progress of awarded grants.</p><p><bold>Results</bold>: This working team has served to overcome many of the challenges through which were making grant funds difficult to spend. For example, clearer communication with the PI and grants managers has helped to overcome roadblocks with subawards, rebudgets and reporting. Dedicating pre‐ and postaward staff increased their project familiarity, thus improving their response times and increasing team morale. A key realization was the need for increased support to PIs with global projects due to operational challenges they face in a global setting.</p><p><bold>Conclusions</bold>: Strong grants management is vital to the success of global health programs, where more grants management and operational support is needed to meet the unique challenges.</p></sec><sec id="pbc26772-sec-10060"><label>P-591</label><title>Development of the Online Didactic Training Platform for the East African Pediatric Hematology Oncology (PHO) Fellowship Program</title><p><underline underline-style="single">N. Kagoro</underline><sup>1</sup>, E. Ishigami<sup>2</sup>, P. Mehta<sup>1</sup>, J. Slone<sup>1</sup>, J. Lubega<sup>1</sup>, G. Airewele<sup>1</sup>, K. Wilson‐Lewis<sup>2</sup>, E. Fruge<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>2</sup>Texas Children's Hospital, Pediatrics, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: There is a dire lack of specialists in pediatric oncology in Africa. Literature shows that a significant number of African‐born physicians migrate to high‐income countries to obtain specialist clinical training and few return. The East Africa PHO Fellowship was developed in Uganda to build a critical mass of PHO specialists from Uganda and the East Africa region through formal training and accreditation. The goal of the program was to develop a two–year PHO fellowship curriculum for local limited settings at low cost to ensure program sustainability. To address the lack of local PHO expertise and reduce the cost of sending fellows in a U.S. based institution for training, we integrated an online didactic platform into the PHO Fellowship. This online training comprises of web‐based recorded lectures by Texas Children's Cancer and Hematology Centers (TXCH)/ Baylor College of Medicine (BCM) exeperts accessible on Blackboard</p><p><bold>Design/Methods</bold>: A committee with African expertise, comprised of pediatric oncologists, hematologists, and psychosociologists, was created to spearhead the process of formatting, reviewing, and adapting lecture content to local settings. TXCH PHO specialists were invited to create lectures covering the curriculum topics that were then edited, reviewed and approved by the committee. Once approved, PHO specialists voice recorded the lectures which were then uploaded as interactive tools onto Blackboard.</p><p><bold>Results</bold>: Twenty‐six faculty members from TXCH/BCM recorded presentations that were uploaded as part of the curriculum. The fellows were subsequently exposed to numerous PHO specialties. Additionally, by not requiring Houston‐based faculty members to travel to Uganda to present, the program saved an annual expenditure of $260,000 USD.</p><p><bold>Conclusions</bold>: The content of the lectures will be periodically updated to ensure it remains relevant. Furthermore, at the end of the two year fellowship, the fellows will participate in exit surveys in order to attain feedback on their experience with the lectures and course.</p></sec><sec id="pbc26772-sec-10070"><label>P-592</label><title>Localized Ewing's Sarcoma of the Mandible Managed Surgically with Free Fibula Flap Reconstruction in a Toddler</title><p><underline underline-style="single">S. Mishra</underline><sup>1</sup>, R. Arora<sup>2</sup>, S. Dabas<sup>3</sup>, S. Jain<sup>4</sup>, G. Kapoor<sup>4</sup></p><p><italic><sup>1</sup>Department of Pediatric Surgical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India; <sup>2</sup>Department of Plastic and reconstructive surgery, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India; <sup>3</sup>Department of Surgical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India; <sup>4</sup>Department of Pediatric Hematology & Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India</italic></p><p><bold>Background</bold>: Ewing's sarcoma(ES) of head and neck is rare comprising 1‐4% of all cases. Jaw lesions present a distinct surgical challenge due to cosmetic inadequacy and functional impairment. We wish to present this child with ES of mandible successfully managed with resection and free fibular flap reconstruction.</p><p><bold>Design/ Method</bold>: Retrospective review of hospital records</p><p><bold>Results</bold> 2 ½ years‐old‐boy had left jaw swelling for 2 months. Workup confirmed localized ES of left mandible up‐to the midline. After 4 cycles of neo‐adjuvant chemotherapy (VAC/IE), there was partial response. Since radiation posed higher long term complications, parents chose surgery. He underwent segmental resection of left mandible including teeth of left lower jaw up‐to right 1st premolar, preserving the left angle of mandible. Frozen‐section revealed clear margins. Reconstruction was done by plastic and reconstructive surgeons using free fibular flap. Harvested vascularized fibula was remodeled by osteotomies after accurate measurements and calculations, to give the exact shape of excised mandible. Fixation with re‐absorbable screws and plate allowed for growth potential. Vascular anastomosis was performed using operating‐microscope and 9‐0 sutures. Tracheostomy was done to prevent airway obstruction. The 7‐hours surgery did not require blood transfusion. He was electively ventilated for 48 hours and recovered smoothly. Tracheostomy tube was removed on 10th day. The free flap was healthy. Histopathology showed 100% necrosis (Huvos Grade 4) with negative margins, hence radiation was avoided. Cosmetic appearance was excellent. Soft diet was resumed after one month and chemotherapy was restarted. The child is well 5 months after surgery and awaits dental implants.</p><p><bold>Discussion</bold>: Free fibular flap reconstruction for ES of mandible gives an excellent cosmetic and functional result. A thorough literature search revealed that it has been reported in very few children younger than 3 years. Long term follow up through puberty is recommended for any growth discrepancy which may need distraction osteotomy.</p></sec></sec><sec id="pbc26772-sec-10080"><title>Haematology ‐ Acute Lymphoblastic Leukaemia</title><sec id="pbc26772-sec-10090"><label>PO-001</label><title>Pediatric Acute Lymphoblastic Leukaemia: The Journey So Far and the Long Road Ahead</title><p><underline underline-style="single">R. Chennamaneni</underline><sup>1</sup>, S. Bala<sup>1</sup>, S. Gundeti<sup>1</sup>, L. maddali<sup>1</sup></p><p><italic><sup>1</sup>Nizam's Institute Of Medical Sciences, Medical Oncology, Hyderabad, India</italic></p><p><bold>Background/Objectives</bold>: Acute lymphoblastic leukaemia(ALL) is the most common childhood cancer,of which B‐ALL and T‐ALL account for 80% and 20% respectively.With the recent advances in therapy and supportive care,survival rates have improved dramatically,but are still lower in developing countries compared to developed countries.In the present study,we analyzed the outcomes in pediatric ALL at our institute.</p><p><bold>Design/Methods</bold>: This is a single centre,retrospective study.Patients with diagnosis of ALL aged from 0‐21 years,who presented from January 2010 to December 2016 to our institute were evaluated.</p><p><bold>Results</bold>: A total of 240 patients were analyzed.The median age at presentation was 12 years (5months to 21years) with male to female ratio of 2.1:1.The median hemoglobin, leukocyte count, platelet count were 8.2gm/dl(1.2‐16),18000cells/μl(500‐4,40,000),50,000cells/μl(4000‐5,20,000)respectively.B‐ALL and T‐ALL were seen in 154(64%) and 86(36%) of patients respectively. Evaluable cytogenetics were present in 119(50%)of patients,of which 29(24%) had high risk cytogenetics.Treatment protocols used were MCP‐841 and BFM‐95 ALL.Post‐induction complete response,partial response and induction failure were seen in 198(83%),29(12%),13(5%)patients respectively.The baseline characteristics were comparable among B‐ALL and T‐ALL groups except for higher median leukocyte count of 40,650(1600‐4,40,000) in T‐ALL.The 3‐year event‐free survival(EFS) and overall survival(OS) of the entire study population was 52% and 58% respectively.The 3‐year EFS and OS in B‐ALL and T‐ALL were 59%,64% and 45%,49% respectively.On univariate analysis male sex,organomegaly,leukocyte count of >1 lakh and lack of post‐induction response had significant impact on EFS and OS(p=0.006,0.003,0.02,0.003 for EFS respectively and p=0.005,0.01,0.04,0.001 for OS respectively). Age,lymphadenopathy,mediastinal mass or lineage(B‐ALL vs T‐ALL) had no significant impact.High risk cytogenetics had significant impact on EFS but not OS(p=0.04 for EFS).</p><p><bold>Conclusions</bold>: B‐ALL constituted the majority in our study. Male sex,organomegaly,>1 lakh leukocyte count and lack of post‐induction response had significant impact on outcome.3‐year EFS and OS was 52% and 58% which indicates that, we have a long way to go in terms of achieving outcomes equivalent to western published literature.</p></sec><sec id="pbc26772-sec-10100"><label>PO-002</label><title>An Anusual Case of Massive Leukoencephalitis in a Child with an Early Meningeal Relapse of Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">R. Parasole</underline><sup>1</sup>, G. Giagnuolo<sup>1</sup>, A. Varone<sup>2</sup>, F. Petruzziello<sup>1</sup>, D. Cicala<sup>3</sup>, N. Marra<sup>1</sup>, G. Maisto<sup>1</sup>, G. Menna<sup>1</sup></p><p><italic><sup>1</sup>Santobono‐Pausilipon Hospital, Pediatric Hemato‐oncology, Napoli, Italy; <sup>2</sup>Santobono‐Pausilipon Hospital, Department of Neurosciences, Napoli, Italy; <sup>3</sup>Santobono‐Pausilipon Hospital, Paediatric Neuroradiology Unit, Napoli, Italy</italic></p><p><bold>Background/Objectives</bold>: Central nervous system (CNS) is a frequent site of relapse in pediatric Acute Lymphoblastic Leukemia (ALL). Triple intrathecal therapy (TIT) with cytarabine, methotrexate and prednisone is the mainstay therapy of CNS relapse. However, TIT may provoke significant toxicity on CNS. We describe the case of a child with an early isolated CNS relapse of ALL who showed massive leukoencephalopathy after the first TIT.</p><p><bold>Design/Methods</bold>: At therapy discontinuation, during disease restaging, the diagnostic lumbar puncture showed turbid cerebrospinal fluid (CSF) for pleocytosis (8100 cells/uL) and cytospin confirmed the presence of blast B‐cells. The patient showed negative physical and neurological examination and normal blood count. Suddenly, TIT was performed to reduce the abnormal liquoral pleocytosis. To prevent toxicities from tumor lysis syndrome, the patient received hydratation, allopurinol, desamethasone, acetazolamide and seizure prophylaxis with levetiracetam. After few hours, the patient showed hyperthension, skin rash, hallucinations, hypothonia of lower limb, until complete paralisis of all legs. A brain resonance (MRI) showed diffuse hyperintensity of white matter, particularly in subcortical, cerebellar areas, optic chiasm and brainstem in T2‐Flair sequences. This pattern was interpreted as grade IV leukoencephalopathy. The child was transferred to intensive care unit due to respiratory distress that required intubation. A diagnostic lumbar puncture performed during the following days showed CSF negativity.</p><p><bold>Results</bold>: Patient persisted in deep coma for 5 days before restart a spontaneous breathing. After waking up, he showed rapid neurological ameliorations. Systemic chemotherapy with high‐dose MTX and IT ARA‐C was restarted without any additional neurotoxicity. Dosage of interleukin 6 levels on CSF is ongoing.</p><p><bold>Conclusions</bold>: The severity and rapidity of event's onset, associated with quickly CSF remission, suggests that neurotoxicity could be related to cytokine release syndrome due to massive blast lysis, rather than to direct drug damage on CNS. The CSF IL‐6 dosing could clarify the pathogenesis of the event.</p></sec><sec id="pbc26772-sec-10110"><label>PO-003</label><title>Characteristic of Nutrition Status, Dietary Intake, Mother's Knowledge and Practices in Feeding to Children with Cancers at Pediatric Center, Hue Central Hospital, Vietnam</title><p><underline underline-style="single">P.H. Hung</underline><sup>1</sup>, H. Vu Thi<sup>2</sup></p><p><italic><sup>1</sup>Hue Central Hospital, Pediatric Center, Hue, Vietnam; <sup>2</sup>Hue Central Hospital, Pediatric Center, Hue‐ Vietnam, Vietnam</italic></p><p><bold>Background/Objectives</bold>: Adequate nutrition is one of the components of supportive and palliative care, plays an important role in success of childhood cancer treatment. However, this issue has not been paid much attention in Vietnam.</p><p>The purpose of this study was to assess nutrition status, dietary intake of children with cancer, knowledge and practices on children care and how mothers feed the children.</p><p><bold>Design/Methods</bold>: A cross sectional study was conducted in 76 children with cancer aged 6 months ‐15 years. Children was measured their weight and height. Food intake data were taken and mothers were interviewed about feeding knowledge and practices.</p><p><bold>Results</bold>: The results showed that malnutrition accounts for 31,6% (<‐2SD to ‐3SD was 23,7% and <‐3SD to ‐4SD was 7,9 %), under height was 44,8% (<‐2SD to ‐3SD was 29 % and <‐3SD to ‐ 4SD was 15,8 %). The energy consumption was less than 50% of the energy need by age and by disease. Protein energy consumption rate accounts for 10%. No dietary intake of milk was 34,6%, beef 32,6 %, eggs 19.2%.</p><p><bold>Conclusions</bold>: Nutrition is an important part of the health of all children, but it is especially important for children getting cancer treatment. In our center malnutrition and under height in children with cancer in our center were high. Nutritional knowledges and practices on childhood cancer care and the feeding of the mothers were quite poor. In order to improve the situation, providing education about nutrition for the mothers is needed.</p></sec><sec id="pbc26772-sec-10120"><label>PO-004</label><title>Successful Treatment of Acute Biphenotypic Leukemia in Children Low‐Dose Chemotherapy in Uzbekistan</title><p><underline underline-style="single">S. Ibragimova</underline><sup>1</sup></p><p><italic><sup>1</sup>Institute Of Hematology And Blood Transfusion, Children, Tashkent, Uzbekistan</italic></p><p><bold>Background/Objectives</bold>: According to some authors, the optimal therapeutic approach for acute biphenotypic leukemia may include aggressive chemotherapy and stem cell transplantation, but this is not supported by serious research. The paper assessed the effectiveness of chemotherapy protocol ALL‐MB‐2008 with low‐dose methotrexate in the treatment of acute biphenotypic leukemia.</p><p><bold>Design/Methods</bold>: There were 5 patients with biphenotypic acute leukemia. The average age of the patients was 8,4 ± 1,3, the ratio of the gender: 2 males, 3 females. In the immunological study of bone marrow, all patients had a blast cells linearly mixed immunophenotype (B + myelo), on morphological and cytochemical features of blast cells referred to lymphoblasts. An initial data: all patients spleen was less than 4 cm, initial leukocyte count was 30 thousand. One patient had t (9; 22) BCR / ABL p190 and t (9; 22) BCR / ABL p210 PCR, from the 15th day, for induction he received an additional imatinib 300 mg/m<sup>2</sup> daily inside.</p><p><bold>Results</bold>: Of the 300 patients with acute leukemia treated in children's department of the Research Institute of Hematology in Uzbekistan for the period 2014‐2016. 5 patients diagnosed with acute biphenotypic leukemia and treated with ALL‐based induction regimen. Early response to the 15th day of treatment in all patients ascertained. All 5 patients went into clinical remission after induction course. During induction all 5 patients had severe sepsis, bronchopneumonia. On the 36th day, all patients achieved clinical remission. The patients received consolidation chemotherapy according to plan for the intermediate‐risk group with low doses of MTX 30 mg/m<sup>2</sup> intramuscularly weekly, with additional lumbar puncture with three cytotoxic drugs. A median follow‐up of 15.4 months. The 2‐year disease‐free survival and overall survival estimates were 100%.</p><p><bold>Conclusions</bold>: ALL‐based low‐dose chemotherapy regimen has shown high efficacy in a significant reduction in toxicity. The use of this protocol enabled outpatient treatment.</p></sec><sec id="pbc26772-sec-10130"><label>PO-005</label><title>Current Outcomes of Acute Lymphoblastic Leukemia (ALL) Among Children in Gulf Counties (GC); A Systematic Analysis</title><p><underline underline-style="single">Z. Kanakkande Kandy</underline><sup>1</sup></p><p><italic><sup>1</sup>Burjeel Hospital, pediatric hematology and ooncology, Abu Dhabi, United Arab Emirates</italic></p><p><bold>Background/Objectives</bold>: Published literature from GC on ALL in children is scant. This comprehensive review of published literature was conducted to understand the current outcome of childhood ALL in GC.</p><p><bold>Design/Methods</bold>: A search of Medline and EMBASE using keywords leukemia, child, and Gulf Countries was carried out. All studies, which reported outcomes on survival, related to ALL published up to, 2016, are included. The results of the searches were compared and merged. The reference list of all included studies was searched to identify any other eligible studies.</p><p><bold>Results</bold>: The number of studies published is scarce. Of the 8 studies identified, 7 single centre studies and 1 multicentre study from 4 out of 7 GC met the inclusion criteria. There were a total of 2,780 children with ALL (32‐698 children/study). The median age at presentation was 0—4.37 years in majority of the studies. Minimum Residual Disease (MRD) was not used in majority of cases. Treatment consisted of chemotherapy but there was considerable variation in chemotherapy use among different canters. Different chemotherapies were used; most commonly often without (Minimal Residual Disease) MRD based risk stratification. There was only one multicenter study published yet. Median overall survival (OS) was range 72‐86.9% and Event Free Survival (EFS) Range 30.6‐73%. Reported rate of abandonment were limited. Data on long‐term side effects was also very limited.</p><p><bold>Conclusions</bold>: Survival outcomes of ALL in children in GC are encouraging. Lack of publication from many centers makes it difficult to understand current practices and outcome from many centers. We recommend co ordinated multicentre approach in collaboration with western centers in treating and analyzing experiences to address several questions. Role of children cancer registry for entire Gulf Countries and its effective use is highly recommended.</p></sec><sec id="pbc26772-sec-10140"><label>PO-006</label><title>Outcome of Childhood Acute Lumphoblastic Leukemia Over 12 Year: Local Institutional Experience at Northwestern Region of Kingdom of Saudi Arabia, Tabuk</title><p><underline underline-style="single">T. Khattab</underline><sup>1</sup>, M. Alpakra<sup>2</sup>, E. Hanafy<sup>3</sup>, G. Mahmoud<sup>3</sup>, Z. Alzahrani<sup>4</sup>, H. Sawi<sup>4</sup>, N. Ahmed<sup>3</sup>, M. Fawzy<sup>5</sup></p><p><italic><sup>1</sup>King Salman Armed Forces Hospital, Prince Sultan Oncology Center‐ Tabuk, Jeddah‐ 21423, Saudi Arabia; <sup>2</sup>Khamis Masheet Armed Forces Hospital, Oncology, Abha, Saudi Arabia; <sup>3</sup>King Salman Armed Forces Hospital, Oncology, Tabuk, Saudi Arabia; <sup>4</sup>King Salman Armed Forces Hospital, Pediatrics, Tabuk, Saudi Arabia; <sup>5</sup>Children cancer Hospital, Oncology, Tanta, Egypt</italic></p><p><bold>Background/Objectives</bold>: Childhood acute lymphoblastic leukemia ALL cure rates reached 85%. Progress resulted from combination chemotherapy, central nervous system preventive therapy and maintenance chemotherapy. Cytogenetic, immunophenotyping, and early treatment response refine risk categorization. In our center we use Children Cancer Group CCG regimens.</p><p><bold>Objectives</bold>: Find relapse time and site, survival percentage in relapsed cases. Assess our event free survival EFS and overall survival OS and Death causes.</p><p><bold>Design/Methods</bold>: From January 2005 to December 2016 children with ALL are collected. Bone marrow BM immunophenotyping and cytogenetic data are gathered. Cerebrospinal fluid CSF, early treatment response and post‐induction minimal residual disease MRD are collected. Relapse time and site are determined as well as EFS and OS.</p><p><bold>Results</bold>: Sixty‐six patients, male29, age range (1.5‐11) year, median 5 years. Immunophenotyping; 56/66 B‐lineage ALL, 5/66 T‐ALL, 3 unknown, 1 pro‐B and 1 mixed‐lineage. CSF positive 7/66 (11%); cytogenetics; normal 12, hyperdiploidy 4, t(9;22) 2 and one for each MLL, Runx, TEL/AML and trisomy‐21. Early response to therapy available in 22/66; rapid early response 19/22 (86%) and slow early response 3/22 (14%). Positive MRD post‐induction 3/66 and negative 6/66. Chemotherapy was based on CCG regimens; low‐risk (1991, 1891) 31/66 (47%), intermediate‐risk (1961 arm‐C, 1882) 16/66 (24%) and high‐risk (1961 arm‐D) 18/66 (29%). Relapse incidence 17/66 (26%); very early 3/17, 2 combined and 1 isolated BM (2/3 survived). Early relapse; 2 BM, 2 combined, 1 CNS (4/5 survived). Late relapse; 4 BM, 4 combined, 1 CNS (5/9 survived). 11/17 (65%) survived relapsed cases; 4 allogeneic stem cell transplant (SCT), 2 awaiting SCT, 5 cured with second‐line chemotherapy. EFS 44/66 (67%) and OS 56/66 (85%). Death causes; 5 refractory ALL, 3 toxic deaths, 1 secondary neoplasm 5 year off‐therapy (Glioblastoma Multiform) and 1 died in car accident.</p><p><bold>Conclusions</bold>: CCG chemotherapy regimens with applying risk stratification would have favorable outcome.</p></sec><sec id="pbc26772-sec-10150"><label>PO-007</label><title>Chromosome Abnormalities in Childhood Cancer</title><p><underline underline-style="single">K. Lee</underline><sup>1</sup>, J. Kim<sup>1</sup>, J. Seo<sup>1</sup>, E. Choi<sup>2</sup>, J. Kim<sup>1</sup></p><p><italic><sup>1</sup>Kyungpook National University, Pediatrics, Daegu, Republic of Korea; <sup>2</sup>Daegu Catholic University Medical Center, Pediatrics, Daegu, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Chromosome abnormalities have been found in leukemia and solid tumor since Nowell and Hungerford discovered the first in 1960. We reviewed the results of 15,921 cytogenetic studies for 34 years.</p><p>Cytogenetic study had been done with various samples of peripheral blood for clinical diagnosis of chromosomal abnormal patient or reproductive problem, of amniotic fluid or cadaver for the genetic counseling or prenatal diagnosis and of peripheral blood, bone marrow and/or tumor mass for the cancer patient in the Pediatric Cytogenetic Laboratories of Kyungpook National University Hospital, Daegu, Republic of Korea between 1981 and 2014.</p><p><bold>Design/Methods</bold>: The type of cancer was various. In cancer patient the sample s were collected at diagnosis, remission and relapse. No mitogen was applied in cancer cytogenetic study. Trypsin‐Giemsa stain for banding was applied for all chromosome preparation.</p><p>Chromosome study was done in 16,350 cases. The data were analyzed in 15,921 excluding 429 cases of no cell growth or no date. The samples were peripheral blood in 8,323, amniotic fluid and chorionic villi in 1,035, bone marrow (BM) and tissue in 6,563 cases. Annual number of examine was 816 in recent 10 years.</p><p><bold>Results</bold>: Male to female ratio was 1:1.1. The mean age was 23.8 y/o (1 day∼89 y/o).</p><p>Of BM samples for cancer patient, numerical aberrations were found in 217 cases (hypodiploidy; 131, hyperdiploidy; 50, hypotriploidy; 3, hypertriploidy; 5, hypotetraploidy; 5 and hypertetraploidy; 23) and structural abnormalities were found in 1,092 (Philadelphia chromosome; 314, t(8:21), t(15:17), t(1:19), t(7:11), t(8:14); 317 and partial trisomy or monosomy; 461).</p><p>Only 2 Philadelphia chromosomes were found in two childhood CML patient.</p><p><bold>Conclusions</bold>: During cell culture study we realized a certain factors will cause chromosome abnormalities during mitosis, perhaps just before prophase?</p><p>Cytogenetic study for cancer patients is very convenient and very essential tool for the diagnosis, the process of remission and relapse classically since 1960.</p></sec><sec id="pbc26772-sec-10160"><label>PO-008</label><title>Pattern of Acute Leukemia Presentation at a Tertiary Hospital in Nigeria</title><p><underline underline-style="single">V. Nwatah</underline><sup>1</sup>, A. Oyesakin<sup>1</sup>, N. Ukpai<sup>1</sup>, E. David<sup>2</sup>, T. Wakama<sup>2</sup>, O. Oniyangi<sup>1</sup></p><p><italic><sup>1</sup>National Hospital Abuja, Department of Paediatrics, Abuja, Nigeria; <sup>2</sup>National Hospital Abuja, Department of Hematology, Abuja, Nigeria</italic></p><p><bold>Background/Objectives</bold>: Acute leukemia is a common childhood malignancy but its occurrence in low and middle income countries are under‐reported. Its pattern of presentation varies depending on several factors. The objective of this report is to determine the pattern of presentation of acute leukemias in children at a tertiary hospital in Nigeria.</p><p><bold>Design/Methods</bold>: A retrospective cross‐sectional study of children managed for acute leukemia at the Paediatric department in a 5 year period. Of 31 patients, 27 had adequate records which were reviewed. Data collected include patient's demographics, clinical features and treatment outcome.</p><p><bold>Results</bold>: There were 16 males and 11 females, aged 8 months to 16 years (mean 7.45 years ± 4.75 SD). Middle class was the predominant socio‐economic status of caregivers (51.9%). Forty‐eight percent of the patients were referred from tertiary health centre while 40.7% were from secondary health centres. The pattern of clinical features were fever (85.2%), pallor (92.6%) and splenomegaly (51.9%). The specific leukemia type ratio of Acute Myeloid leukemia (AML) to Acute lymphoblastic leukemia (ALL) was 1: 2.9. The parents of three patients took their children away before commencement of treatment, one patient completed treatment and 6 (22.2%) died before completing treatment. Nearly half of the patients were lost to follow up to seek alternative care while 9 (33.3%) of the patients were in remission at last follow up. Lost to follow‐up was found not to be significantly associated with socioeconomic status, age and sex with p‐values of 0.68, 0.43 and 0.56 respectively.</p><p><bold>Conclusions</bold>: Acute lymphoblastic leukemia remain the predominant type of childhood leukemia in our setting. Majority of the patients presented with fever and pallor moreover the default to follow‐up plagued treatment completion.</p></sec><sec id="pbc26772-sec-10170"><label>PO-009</label><title>OPG, RANKL and DKK1 in Childhood Acute Lympoblastic Leukemia</title><p>M. Stratigaki<sup>1</sup>, A. Sfiridaki<sup>2</sup>, E. Athanasopoulos<sup>1</sup>, N. Katzilakis<sup>1</sup>, <underline underline-style="single">E. Stiakaki</underline><sup>1</sup></p><p><italic><sup>1</sup>University of Crete‐ University Hospital of Heraklion, Pediatric Hematology‐Oncology, Heraklion Crete, Greece; <sup>2</sup>Venizeleion General Hospital, Blood Transfusion Center, Heraklion Crete, Greece</italic></p><p><bold>Background/Objectives</bold>: Acute Lymphoblastic Leukemia(ALL) the commonest childhood malignancy, in many cases presents with musculoskeletal manifestations. Bone lessions are also manifested as treatment complications. The pathogenesis of bone disorders in children with ALL has not been clarified thoroughly so far. Recently, the biology of bone metabolism has been studied extensively and new molecules are identified such as osteoprotogerin(OPG), a protein which inhibits the loss of the bone, proteins RANKL/RANK with osteoclastic activity and the molecule Dickkopf (DKK1), a soluble inhibitor of the osteoblastic activity of the Wnt/b‐catenin pathway.</p><p>The study of the OPG, RANKL/RANK and DKK1 system in childhood ALL</p><p><bold>Design/Methods</bold>: Forty patients(24 boys), aged 1‐18 years old(mean age 7 years) with ALL (38 Β‐ lineage) were studied. All patients received treatment according to current ALL protocols and risk stratification group, 33 median and 7 high risk. Three (7,5%) of them relapsed. The serum values of OPG, RANKL and DKK1 were determined at diagnosis and the end of treatment. Statistic analysis was made with the use of t‐test (paired t‐test)</p><p><bold>Results</bold>: A statistically significant decrease of osteoprotogerin values was estimated at the end of treatment compared to the levels at diagnosis. The RANKL and DKK1 values determined increased at the end of treatment compared to diagnosis, without statistical signifigance. Although bone manifestations at diagnosis or during the treatment were documented in 25% of our patients, there was no statistically significant difference in OPG, RANKL and Dkk1 values between children with or without bone manifestations.
<table-wrap id="nlm-table-wrap-4" xml:lang="en" orientation="portrait" position="anchor"><table frame="hsides" rules="groups"><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><thead><tr valign="bottom" style="border-bottom:solid 1px #000000"><th align="left" valign="bottom" rowspan="1" colspan="1"></th><th align="left" valign="bottom" rowspan="1" colspan="1"><bold>Mean value at Diagnosis</bold></th><th align="left" valign="bottom" rowspan="1" colspan="1"><bold>Mean value at the end of treatment</bold></th><th align="left" valign="bottom" rowspan="1" colspan="1"><bold>P value</bold></th><th align="left" valign="bottom" rowspan="1" colspan="1"><bold>SE</bold></th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1"><bold>OPG</bold></td><td align="left" rowspan="1" colspan="1">24,4545</td><td align="left" rowspan="1" colspan="1">14,1973</td><td align="left" rowspan="1" colspan="1">< 0.0001</td><td align="left" rowspan="1" colspan="1">2,24561</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>RANKL</bold></td><td align="left" rowspan="1" colspan="1">804,502</td><td align="left" rowspan="1" colspan="1">876,84</td><td align="left" rowspan="1" colspan="1">0,699218</td><td align="left" rowspan="1" colspan="1">186,533</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>DKK1</bold></td><td align="left" rowspan="1" colspan="1">945,7254</td><td align="left" rowspan="1" colspan="1">1193,28</td><td align="left" rowspan="1" colspan="1">0,17037</td><td align="left" rowspan="1" colspan="1">178,895</td></tr></tbody></table><permissions><copyright-holder>John Wiley & Sons, Ltd.</copyright-holder><license><license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p></license></permissions></table-wrap></p><p><bold>Conclusions</bold>: According our preliminary results, a significant decrease of OPG values estimated between diagnosis and treatment completion.The precise role of OPG, RANKL/RANK and DKK1 in childhood ALL needs further investigation.</p></sec><sec id="pbc26772-sec-10180"><label>PO-010</label><title>Microrna‐155‐5P, Promoted Proliferation and Suppressed Apoptosis by Regulating the FOXO3A Signaling Pathway, Is Associated with Early Relapse in Pediatric Acute Lymphoblastic Leukemia</title><p><underline underline-style="single">Y.L. Tang</underline><sup>1</sup>, L.B. Huang<sup>1</sup>, C. Liang<sup>1</sup>, X.J. Liu<sup>1</sup>, X.Q. Luo<sup>1</sup></p><p><italic><sup>1</sup>The First Affiliated Hospital ‐ Sun Yat‐sen University, Department of Pediatrics, Guangzhou, China</italic></p><p><bold>Background/Objectives</bold>: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Treatment effect in early recurrence of ALL is very bad, so we need to identify miRNAs that can predict risk of early relapse in pediatric patients with ALL.</p><p><bold>Design/Methods</bold>: We used the high‐throughput miRNA‐seq analysis between three diagnostic bone marrow samples and three early relapse bone marrow samples to determine miRNA expression profiles associated with early relapse in ALL. Six miRNAs were selected for further confirmation performed by real time quantitative PCR on thirty‐one diagnostic samples and ten early relapse samples. Apoptosis and proliferation were analyzed using siRNA transfection, MTS assay, western blot and flow cytometry.</p><p><bold>Results</bold>: Our results demonstrated that miR‐155‐5p was up‐regulated in early relapse samples compared with diagnostic samples. miR‐155‐5p promoted cell proliferation and suppressed cell apoptosis by negatively regulating the expression of tumor suppressor‐Forkhead box O3a (FOXO3a) in ALL cells. Remarkably, miR‐155‐5p over‐expression inhibited the expression of FOXO3a and its downstream targets bim and p27kip1. Meanwhile, miR‐155‐5p knockdown induced the expression of FOXO3a and its downstream targets. Furthermore, FOXO3a over‐expression inhibited cell proliferation and induced cell apoptosis by promoting the expression of bim and p27kip1 in ALL cells.</p><p><bold>Conclusions</bold>: These results provide a possible underlying molecular mechanism to explain the association between miR‐155‐5p and early relapse in pediatric ALL, and suggest that approaches to inhibit miR‐155‐5p expression or induce FOXO3a expression may offer promising therapeutic strategies in the ALL early relapse treatment.</p></sec></sec><sec id="pbc26772-sec-10190"><title>Haematology ‐ Myeloid Leukemias, Myelodysplastic and Myeloproliferative Syndromes</title><sec id="pbc26772-sec-10200"><label>PO-011</label><title>Down Syndrome Associated Acute Leukemia of Children in Georgia: 10‐Year Follow‐Up</title><p><underline underline-style="single">M. Khvedelidze</underline><sup>1</sup>, A. Shengelaia<sup>1</sup>, T. Javakhadze<sup>1</sup></p><p><italic><sup>1</sup>Children Central Hospital, Hematology/Oncology, Tbilisi, Georgia</italic></p><p><bold>Background/Objectives</bold>: Children with Down syndrome (DS) have a 10 to 15‐fold higher risk of developing B‐cell acute lymphoblastic leukemia (DS‐ALL) and acute myeloid leukemia (DS‐AML). Despite higher treatment related toxicities, risk‐based therapy for Down syndrome related childhood acute leukemia has been widely appreciated across many clinical trials.</p><p><bold>Design/Methods</bold>: Clinical records of 7 children with Down syndrome associated acute leukemia, admitted over the last 10 years were retrospectively analyzed. The patients were treated at M. Iashvili Children's Central Hospital, department of hematology/oncology,‐ the only facility in Georgia providing care for children with hematological malignancies.</p><p><bold>Results</bold>: 7 children (6 Males and 1 Female) with Down syndrome have been admitted since the January of 2005. Median age of the patients was 27 months (range: 18‐32 months), three of them were diagnosed DS‐AML and four presented with DS‐ALL.</p><p>Considering an overall number of 390 new cases of acute childhood leukemia (ALL‐307 and AML‐83 cases) admitted at the hospital since 2005, Down syndrome associated acute leukemia accounted for approximately 1.8% of all cases. Despite widely appreciated higher risk of developing acute megakaryocytic leukemia (AML‐M7) in children with Down syndrome, none of the analyzed DS‐AML cases showed AML‐M7 morphology or phenotype. All DS‐ALL patients were diagnosed as Common ALL.</p><p>DS‐AML patients were treated with AML‐BFM‐2004 and DS‐ALL cases with ALL‐IC‐BFM 2004 protocol. All DS‐ALL patients had good treatment response and have been staying disease free. One of the DS‐AML patients experienced an induction failure and another developed bone marrow relapse after 135 days of induction, both patients died of the disease.</p><p><bold>Conclusions</bold>: The 10‐year <italic>incidence</italic> of Down syndrome associated acute leukemia of childhood in Georgia is comparable to reported rates from other countries, although according to our data, the cases of DS‐ALL outnumbered DS‐AML patients and we also observed a trend of higher event free survival of DS‐ALL patients comparing to DS‐AML.</p></sec><sec id="pbc26772-sec-10210"><label>PO-012</label><title>Acute Myeloid Leukemia: Correlation of Cytogenetics and Outcome in a Tertiary Care Pediatric Centre</title><p><underline underline-style="single">M. Naseer</underline><sup>1</sup>, P. Ankit<sup>1</sup>, K. Purva<sup>1</sup>, C. Shraddha<sup>1</sup>, K. VP<sup>1</sup>, M. Sangeeta<sup>1</sup>, S. Archana<sup>1</sup>, D. Mukesh<sup>1</sup>, S. Nitin<sup>1</sup>, A. Bharat<sup>1</sup></p><p><italic><sup>1</sup>Bai Jerbai Wadia Hospital for Children, Department of Pediatric Hemato‐Oncology, Mumbai, India</italic></p><p><bold>Background/Objectives</bold>: Acute leukemia constitutes most common childhood cancers worldwide and in India. Over the past 20 years, the outcome of Acute Myeloid Leukemia (AML) in children has improved substantially. There is limited data on childhood AML in India.</p><p><bold>Design/Methods</bold>: Retrospective analysis of 42 patients with AML from Jan 2012 till March 2017 was done. Demographic data collected, Cytogenetics obtained for risk stratification (WHO classification). Induction (7+3 & 5+2) followed high dose cytarabine (3 cycles) as consolidation followed by 1 year of maintenance with 6TG and Cytarabine. Remission and relapse rates calculated with respect to risk stratification. Follow up data analyzed.</p><p><bold>Results</bold>: 76% of the patients belonged to 1‐10 years with Male: Female ratio of 2:1. Study included 35 patients of AML and 7 of APML. Of the 32 patients treated, 3 denied treatment. Post induction remission was seen in 56% with failure in 44%. Post induction remission rates (MRD <0.1%) were 38%, 33% and 27% respectively and failure rates of 7%, 64% and 28% in low, intermediate and high risk patients. None of Low risk patients relapsed whereas 25% and 28% of patients relapsed in intermediate and high risk respectively. Of the 6 who completed treatment 3 year overall survival was 50% (rest 3 relapsed). Of the 32 treated patients 6 (18%) had post induction death due to sepsis (90%), bleeding manifestation (6%) and other causes (4%) (Hyperleukocytosis).The low survival rate is due to low socioeconomic strata, poor supportive care, and non availability of bone marrow transplantation facility.</p><p><bold>Conclusions</bold>: Low risk group has good remission rates with none relapsing as yet with high percentage of relapse in intermediate and high risk group. To improve overall survival in intermediate and high risk patients, risk based chemotherapy, optimization of supportive care and affordable transplant facility is mandatory even in low resource set up.</p></sec><sec id="pbc26772-sec-10220"><label>PO-013</label><title>Childhood Noonan Syndrome with FLT3‐ITD‐Positive Acute Myeloid Leukemia – A Case Report</title><p><underline underline-style="single">T. Sarashina</underline><sup>1,2</sup>, H. Goto<sup>2</sup>, N. Miyagawa<sup>2</sup>, T. Yokosuka<sup>2</sup>, K. Fukuda<sup>2</sup>, F. Iwasaki<sup>2</sup>, S. Hamanoue<sup>2</sup>, M. Shiomi<sup>2</sup>, S. Goto<sup>2</sup>, H. Azuma<sup>1</sup></p><p><italic><sup>1</sup>Asahikawa Medical University, Pediatrics, Asahikawa, Japan; <sup>2</sup>Kanagawa Children's Medical Center, Division of Hemato‐oncology/Regenerative Medicine, Yokohama, Japan</italic></p><p><bold>Background/Objectives</bold>: Noonan syndrome (NS) is a RASopathy characterized by facial dysmorphy, developmental disorder, short stature, and a wide spectrum of heart defects. Hematologic disorders such as myeloproliferative disease or acute lymphoid leukemia have been reported in patients with NS. In non‐syndromic patients, somatic <italic>PTPN11</italic> mutations may be detected in juvenile myelomonocytic leukemia (JMML), pediatric common acute lymphoid leukemia, pediatric acute monocytic leukemia (FAB M‐5).</p><p><bold>Design/Methods</bold>: Case presentation: Here, we present a clinical and molecular characterization of a childhood NS patients with FMS‐like tyrosine kinase3‐ internal tandem duplication (<italic>FLT3‐ITD</italic>)‐positive acute myeloid leukemia (AML). The patient was a 12‐year‐old male who presented with swollen and bleeding gums and enlarged hepatomegaly, no splenomegaly. The complete blood count revealed thrombocytopenia and leukocytosis. Bone marrow aspiration consisted of 83.4% monoblasts, which were stained with nonspecific esterase and no peroxidase, and he was diagnosed with AML (FAB‐M5a). Moreover, genetic testing revealed a <italic>FLT3‐ITD</italic>‐positive mutation. From a clinical characteristic such as short stature and distinctive facial feature, <italic>PTPN11</italic> mutation was detected by genetic testing, and Noonan syndrome was diagnosed. He received remission induction therapy. After short term of remission, AML relapsed during maintenance therapy. He underwent stem cell transplantation (SCT) and died of progressive disease. Comprehensive mutation analysis of an 88‐gene panel was performed using targeted next‐generation sequencing in leukemic cells at the onset.</p><p><bold>Results</bold>: In our case, <italic>MLL</italic> partial tandem duplication, <italic>FLT3‐ITD, RUNX1</italic> mutation were identified in the analysis.</p><p><bold>Conclusions</bold>: <italic>FLT3‐ITD</italic>‐positive AML with NS is an extremely rare case and we discuss our patient with NS and the results of genetic analysis in leukemic cells.</p></sec></sec><sec id="pbc26772-sec-10230"><title>Haematology ‐ Lymphomas</title><sec id="pbc26772-sec-10240"><label>PO-014</label><title>Childhood Non‐Hodgkin Lymphomas in the West and the Southwest Regions of Algeria from January, 2000 Till December, 2009</title><p>M. Rouaida<sup>1</sup>, L. D<sup>2</sup>, <underline underline-style="single">B. Ahmed</underline><sup>3</sup>, B. N<sup>4</sup>, K. L.A<sup>5</sup>, B. M<sup>6</sup>, T. Hadj<sup>7</sup>, T. Mahmoud<sup>8</sup></p><p><italic><sup>1</sup>E H S Emir Abdelkader, Hematology/Oncology, Oran, Algeria; <sup>2</sup>Service de biostatistique‐ faculté de médecine d'Oran, Biostatistique, Oran, Albania; <sup>3</sup>Clinique Medicale Infantile Sainte Therese, Hematology/Oncology, Annaba, Algeria; <sup>4</sup>Service de biostatistique‐ faculté de médecine d'Oran, Biostatistique, Oran, Algeria; <sup>5</sup>E.H S premier Novembre, Hemato‐Oncology, Oran, Algeria; <sup>6</sup>CHU Oran, Biostatistique, Oran, Algeria; <sup>7</sup>C H U Oran, Hematology, Oran, Algeria; <sup>8</sup>C H U Oran, Hemato‐Oncology, Oran, Algeria</italic></p><p><bold>Background / Objectives: Summary</bold> The non‐Hodgkin lymphomas (NHL) occupied the first place of cancersin childhood during year 2003, with a <bold>16.7 % fr</bold>equency according to statistics given by the Register of cancers of Algiers.</p><p>The objective of our study is to describe the epidemiological, clinical and histological profiles of paediatric NHLin the Western and the Southwest regions of Algeria during decade 2000 to 2009.</p><p><bold>Design/Methods</bold>: it is an observational study from the files of patients less than 16 years old, hospitalised in the Emir AbdelkaderCentre (CEA) for the diagnosis of NHL.</p><p>LMNH was defined according to clinical, cytological and/or histological criteria of the WHO.</p><p>Registration and analysis of data were performed on software SPSS version 20.</p><p><bold>Results</bold>: 213 children were registered as LMNH over ten years.</p><p>A peak of incidence of NHLwas observed between 2 ‐ 8 years. NHL are rare before the age of 2 years. The abdominal sitewas the most frequent with a 47 % rate. Unusual sites of the disease were observed in 11 % of patients. Stade III was predominant in all sites of our series. Lymphoblastichistological type was the most frequent with a 45 % rate, followed by Burkitt type (30 %) and type T (17 %).</p><p><bold>Conclusions</bold>: NHLare frequent in children. They are clinically different from adult NHL because of theextranodal disease. For these pathologies, early diagnosis remains a priority in themanagement.</p></sec><sec id="pbc26772-sec-10250"><label>PO-015</label><title>PET/TC Utility in the Assessment of the Response to Treatment in Pediatric Lymphomas</title><p><underline underline-style="single">R. Lopez‐Almaraz</underline><sup>1</sup>, A. Echebarría Barona<sup>1</sup>, U. Gonzalez Camacho<sup>1</sup>, J.M. De Pedro Olabarri<sup>1</sup>, M. Garcia‐Ariza<sup>1</sup>, R. Adan Pedroso<sup>1</sup>, T. Rodríguez Inchausti‐<sup>2</sup>, I. Astigarraga Aguirre<sup>1</sup></p><p><italic><sup>1</sup>Hospital Universitario Cruces, Pediatric Hematology and Oncology Unit, Cruces‐ Bilbao, Spain; <sup>2</sup>Hospital Universitario Cruces, Nuclear Medicine Service, Cruces‐ Bilbao, Spain</italic></p><p><bold>Background/Objectives</bold>: Evaluate the response to chemotherapy (Ch) in the 18F‐FDG‐PET/CT of pediatric patients with Hodgkin's Lymphoma (HL) and Non‐Hodgkin's Lymphoma (NHL) to decide the correct therapeutic attitude.</p><p><bold>Design/Methods</bold>: Retrospective observational study of pediatric HL and NHL diagnosed in a tertiary hospital in the last 9 years (January 2008‐January 2017).</p><p><bold>Results</bold>: We reviewed 26 patients, 54% were HL (10.5years and 65%male), 46% were NHL; of which 67% were Burkitt's Lymphoma (6.25years and 67%male, another 25% T Lymphoblastic Lymphoma(mean 5.75years and 50%male and the rest were anaplastic large cell lymphoma (8%). Within the HL,30% were lymphocytic predominance; Half IA stages that were resolved exclusively with surgery and the remainder, IIA stages requiring Ch without radiotherapy (RT); All presented complete morpho‐metabolic response in PET/CT. The remaining 10 patients(70%) were of the classical subtype: 9 patients (stages IA,IIA,IIIA and IV) required only Ch since some presented partial morphological response and all complete metabolic in PET/CT. A single patient with stage IV also required RT for partial morpho‐metabolic response. 100%of patients are currently in complete remission (RC). Among the Burkitt L, 63% (2 III‐AR, 1 IV‐AR, 1 III‐RI and 1 I‐BR) required an increase in the risk group for presenting a partial morpho‐metabolic response (one case confirmed by biopsy) 75% currently in CR, one in treatment and one deceased. The remaining three did not require group increase by complete morpho‐metabolic response after Ch induction. Within patients with Lymphoblastic Lymphoma and anaplastic are all in CR; But only one PET/CT scan was used to evaluate the response</p><p><bold>Conclusions</bold>: The use of PET/CT is very established in the case of HL when making decisions regarding the therapeutic attitude. Nevertheless it needs more studies in NHL. It seems reasonable that in the presence of a partial metabolic response to induction in In NHL, should lead to an increase in the risk group.</p></sec><sec id="pbc26772-sec-10260"><label>PO-016</label><title>Primary Bone Lymphomas: Report of 10 Cases from a Single Center</title><p><underline underline-style="single">N. Kurucu</underline><sup>1</sup>, C. Akyüz<sup>1</sup>, I. Bajin<sup>1</sup>, B. Aydın<sup>1</sup>, A. Üner<sup>2</sup>, A. Varan<sup>1</sup>, B. Yalcin<sup>1</sup>, M. Buyukpamukcu<sup>1</sup>, T. Kutluk<sup>1</sup></p><p><italic><sup>1</sup>Hacettepe University Faculty of Medicine, Department of Pedatric Oncology, ANKARA, Turkey; <sup>2</sup>Hacettepe University Faculty of Medicine, Department of Pathology, ANKARA, Turkey</italic></p><p><bold>Background/Objectives</bold>: Primary bone lymphomas (PBL) constitute less than 5% of all extra‐nodal non‐Hodgkin lymphomas (NHL). The objective of this study was to report our institutional experience with bone lymphomas over a 35‐year period.</p><p><bold>Design/Methods</bold>: From 1980 to 2016, 1412 children with NHL were admitted to the Pediatric Oncology Department of Hacettepe University. Of these, ten children with primary bone lymphoma (except for fascial bone and cranium) were evaluated retrospectively.</p><p><bold>Results</bold>: There were six males and four females with a median age of 84 months. Most common complaints were pain and swelling. Median duration of symptoms was 2 months. Most common tumor location was femur and tibia. Two patients had localized lymph node involvement and two had polyosseous disease. Histopathological subtypes were precursor T cell lymphoma in three patients, anaplastic large cell lymphoma in one, precursor B cell lymphoma in one and unclassified in five. Patients were treated with various chemotherapeutic regimens according to histopathological subtype. Three patients received radiotherapy. Recurrence was observed in four patients within a median 17.5 months; three of which lost the follow‐up and one died with infection. Two patients died from disease progression, three died from treatment‐related complications. Six patients (60%) are alive and disease free at a median of 172 (42‐322) months. Overall and event free survival rates were 77% and 48%. Polyosseous disease had shorter overall survival rates than monoosseous types (85% vs 66.7% p:0.68).</p><p><bold>Conclusions</bold>: Although secondary involvement of bones in lymphoma is not uncommon, lymphomas originating from bone are rare. Most cases are seen in the fifth‐sixth decade. Primary bone lymphoma constitutes 0.7% of our NHL cases. Lymph node involvement and polyosseous disease has worse prognosis in adults. Multicenter studies with more cases are necessary to determine prognostic factors in childhood bone lymphomas.</p></sec><sec id="pbc26772-sec-10270"><label>PO-017</label><title>We Have Cases Withprimary Gastrointestinal Lymphoma Complicated with Intussusception, The Clinical Data were Retrospectively and Analyzed</title><p><underline underline-style="single">C. Zhang</underline><sup>1</sup></p><p><italic><sup>1</sup>Zhengzhou Children's Hospital, Surgical pediatric oncology, ZhengZhou, China</italic></p><p><bold>Background/Objectives</bold>: To summarize the features of children with primary gastrointestinal lymphoma complicated with intussusception.</p><p><bold>Design/Methods</bold>: Patients records in Children′s Hospital of Zhengzhou were retrieved for cases whose initial diagnosis was intussusception and discharge diagnosis included lymphoma.Clinical data of 11 patients with primary gastrointestinal lymphoma complicated with intussusception with extensive follow‐up, treated in our department between January 2012 and December 2016, were retrospectively and analyzed.</p><p><bold>Results</bold>: All 11 patients with PGIL presented as intussusception initially, age from 1.6 to 10 (10 cases>3), while intussusception appeared repeatedly in 5 cases (3 cases>3). All 11 patients received surgical treatment,among them,abnormal lumps were found at intussusceptum in 9 cases,local intestinal wall were thicken and rigid. In 1 case, there was a suspicious focal necrosis around the rigid wall.Local resection was performed successfully for each case without postoperative complication of intestinal obstruction, anastomotic leakage or stricture.Pathological examination revealed 6 cases of diffuse large B‐cell lymphoma and 5 of Burkitt′s lymphoma. 1 cases was classified to be tumor stage Ι, the remaining 10 cases to be stage Ⅱ.10 cases were treated with chemotherapy, the other 1 given up treatment, and died 13 months after operation.During a median follow‐up period of 25 months, tumor recurrence had not been found in these 10 cases.</p><p><bold>Conclusions</bold>: For children with recurrent intussusception or episode at atypical age, PGIL should be concerned.Abnormal mass on intestinal wall, or intestinal wall stiffness such as leather, or mesenteric mass should be resected for Pathological examination. Early postoperative chemotherapy can provide children with PGIL a good prognosis.</p></sec></sec><sec id="pbc26772-sec-10280"><title>Haematology ‐ Stem Cell Transplantation (Haematological Diseases/Technique and Supportive Care)</title><sec id="pbc26772-sec-10290"><label>PO-018</label><title>A Case of Congenital Dyserthropoietic Anemia Successfully Treated with Haploidentical Hematopoietic Stem Cell Transplantation</title><p><underline underline-style="single">M. Al‐Hameed</underline><sup>1</sup>, V. Balasa<sup>2</sup>, S. Bahrani<sup>3</sup>, H. Al‐Hamid<sup>4</sup>, J. Rosenthal<sup>1</sup></p><p><italic><sup>1</sup>City of Hope Comprehensive Cancer Center, Pediatrics Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Duarte‐ CA, USA; <sup>2</sup>Valley Children's Hospital, Pediatric Hematology/Oncology, Madera‐ CA, USA; <sup>3</sup>City of Hope/ Alpha Clinic, Hematology/Oncology ‐ T cells therapeutics, Duarte‐ CA, USA; <sup>4</sup>Providence Hospital and Medical Center, Internal Medicine, Southfield‐ MI, USA</italic></p><p><bold>Background/Objectives</bold>: Congenital dyserythropoietic anemia (CDA) is a group of rare anemia disorders in which there is bone marrow dyserythropoiesis and secondary hemochromatosis. CDA is classified into three major types (I, II, III) based on bone marrow morphology, genetic mutations and inheritance pattern. Allogenic hematopoietic stem cell transplantation (HSCT) is the only cure for CDA and most reported cases used HLA‐identical sibling or matched unrelated donors.</p><p><bold>Design/Methods</bold>: Case report.</p><p><bold>Results</bold>: We report an 8 year‐old male with CDA requiring monthly blood transfusion and deferasirox who was referred to our center for HSCT evaluation. Due to lack of HLA‐identical sibling or matched unrelated donor, the decision was made to proceed with haploidentical HSCT from his father. The non‐myeloablative conditioning regimen consisted of Antithymocyte globulin, Busulfan, and Fludarabine. Post‐transplant cyclophosphamide (ptCY) following uneventful infusion of mobilized hematopoietic stem cells, and tacrolimus with mycophenolate‐mofetil were used for prevention of graft‐vs‐host disease (GVHD). Myeloid and platelet engraftment were recorded on day +16 and day +78, respectively. The patient tolerated the treatment well with minimal adverse effects. Evaluation of bone marrow on day +111 showed normo‐cellular marrow(60%) with mild erythrocytic hyperplasia and adequate granulopoiesis. During the treatment course, he experienced only few episodes of infections, mild GI‐GVHD, and mild skin‐GVHD that were all resolved. One year post‐HSCT, the peripheral count revealed; WBC(4.2k/μL), hemoglobin(11.2g/dL), hematocrit(27.3%) and platelets(143,000/μL). The patient condition remained stable and he remains transfusion free. He resumed his normal childhood and is happily attending school.</p><p><bold>Conclusions</bold>: CDA is a rare disorder with paucity of data regarding its management. HSCT is the only cure available today. Our experience showed that haploidentical donors are good alternatives when HLA‐matched sibling or matched unrelated donors are unavailable. The advancement in the non‐myeloablative conditioning regimen with the use of ptCY, suggests that haploidentical HSCT could be an option for CDA treatment in the future.</p></sec><sec id="pbc26772-sec-10300"><label>PO-019</label><title>Haploidentical Stem Cell Transplantation with Post‐Transplant Cyclophosphamide for Pediatric Relapsed/Refractory Solid Tumours: A Feasible Direction</title><p><underline underline-style="single">S. Kohli</underline><sup>1</sup>, S. NIVARGI<sup>2</sup>, D. THAKKAR<sup>2</sup>, N. RASTOGI<sup>2</sup>, R. MISRA<sup>2</sup>, S. YADAV<sup>2</sup></p><p><italic><sup>1</sup>Medanta, PHO/BMT, Gurgaon, India; <sup>2</sup>Medanta, Pho/Bmt, Gurugram, India</italic></p><p><bold>Background/Objectives</bold>: Haploidentical stem cell transplantation (SCT) with T‐cell depleted grafts have been reported in few patients with neuroblastoma whereas T cell replete grafts and post‐transplant Cyclophosphamide (PTCy) has rarely been reported for treatment of relapsed/refractory solid tumours, and needs to be evaluated in v/o unavailability of donors and cost issues in developing countries assocociated with T cell depleted grafts.We evaluated 6 such patients with refractory solid tumours.</p><p><bold>Design/Methods</bold>: Six patients with refractory solid tumours were evaluated prospectively. Of these 4 patients had neuroblastoma ‐ stage 3 to 4 disease post relapse. Fifth patient of Ewing's sarcoma had CNS and skeletal relapse with bone marrow involvement. Sixth patient with retinoblastoma had hepatic and skeletal relapse. All patients were in complete remission before SCT except two with neuroblastoma who had partial remission. All patients with neuroblastoma received MIBG with Bortezomib based chemotherapy before transplant. Conditioning: All patients received Fludarabine(Flu) and cyclophosphamide(Cy) and total body irradiation (TBI) except one patient with neuroblastoma who received melphalan with Flu/Cy. All Patients received PTCy as part of post‐transplant GVHD prophylaxis.</p><p><bold>Results</bold>: Post SCT one patient with neuroblastoma died due to veno‐occlusive disease and the other died due to progressive CNS disease. The third patient was in complete remission with grade 1 chronic liver GVHD on treatment and is now 14 months post‐transplant. Fourth patient of neuroblastoma relapsed 3 months post‐transplant and was on palliative chemotherapy with WRIST protocol and is now 1 year post transplant. The patient with Ewing's sarcoma was in complete remission and is now day + 200 post HSCT with chronic GVHD of the skin on treatment. Sixth patient with retinoblastoma has a short followup and had neutrophil engraftment on Day + 13.</p><p><bold>Conclusions</bold>: Haploidentical SCT with PTCy seems feasible and efficacious for treatment of refractory solid tumours and needs further evaluation for long term outcomes.</p></sec><sec id="pbc26772-sec-10310"><label>PO-020</label><title>Successful Haploidentical T Cell Replete Peripheral Blood Stem Cell Haematopoietic Stem Cell Transplantation in a Young Girl with Diamond Blackfan Anemia</title><p><underline underline-style="single">M. Ramzan</underline><sup>1</sup>, S. Katewa<sup>1</sup></p><p><italic><sup>1</sup>Manipal Hospital, Pediatric Hematology Oncology & BMT, Jaipur, India</italic></p><p><bold>Background/Objectives</bold>: Diamond‐Blackfan anemia (DBA) is a rare congenital hypoplastic anemia that usually presents in infancy and childhood. Only curative therapy for DBA is haematopoietic stem cell transplantation (HSCT). Most published cases have used matched related and unrelated donor HSCT with myeloablative conditioning regimens.</p><p><bold>Design/Methods</bold>: Haploidentical HSCT in DBA is scarcely mentioned in literature. We report a 5 years old girl who diagnosed with DBA at the age of 6 months. She was steroid refractory and on chronic transfusion therapy.</p><p><bold>Results</bold>: In view for non‐availability of suitable donor, underwent 5/10 haploidentical mismatch related T cell replete PBSC HSCT from ABO compatible father utilizing a myeloablative conditioning regimen including intravenous busulfan (total dose of 520 mg/m<sup>2</sup>), fludarabine (total dose of 175mg/m<sup>2</sup>), thiotepa (10mg/kg) and rabbit ATG (4.5 mg/kg). She was also treated for class I and II HLA antibody (mean fluorescence index of 20000 each) followed by one cycle of fludarabine (total dose of 180mg/m<sup>2</sup>) and dexamethasone prior to HSCT to prevent rejection. Repeat HLA antibody titers were not done. Post transplant cyclophosphamide on day+3 and +4 with tacrolimus and mycophenolate mofetil were used as GVHD prophylaxis. Total CD34+ stem cell dose was 27 x 10<sup>6</sup>/kg of recipient. Her neutrophil engrafted on day+ 15. She had full donor chimerism post HSCT on day+30, +60, +200 and +365. On day+78 she had steroid refractory grade III acute gut GVHD which was non responsive to adequate doses of etanercept, mesenchymal stem cells, basiliximab and infliximab, but eventually it responded to equine ATG and oral methotrexate. Her immunosuppression was weaned off very slowly. At 12 months of follow up she had full donor chimerism with hemoglobin of 15.2g/dl, reticulocytes of 1% and almost complete immune reconstitution of all hematopoietic stem cells.</p><p><bold>Conclusions</bold>: Haploidentical HSCT represents an effective option for cure in patients with DBA.</p></sec></sec><sec id="pbc26772-sec-10320"><title>Solid Non Brain Tumours ‐ Neuroblastoma</title><sec id="pbc26772-sec-10330"><label>PO-021</label><title>Burden of Neuroblastoma in Developing Countries: The Children's Hospital Lahore Pakistan Experience</title><p><underline underline-style="single">A. Ahmad</underline><sup>1</sup>, N. Uddin<sup>1</sup>, F.S. Khan<sup>1</sup></p><p><italic><sup>1</sup>The Children's Hospital and the Institute of Child Health Lahore, Paediatric Haematology/Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: The Oncology Department Of The Children's Hospital Lahore is a 60 bedded unit providing treatment to over 1000 new childhood cancer cases each year and over 300 admissions per month with bed occupancy rate around 200%.The aim of this retrospective study was to analyze the spectrum of Neuroblastoma and burden of high risk malignancy on the public sector tertiary center with lack of MIBG scan, N‐Myc amplification and stem cell transplantation services.</p><p><bold>Design/Methods</bold>: Prospective review of 70 patients with Neuroblastoma enrolled from June 2015 to December 2016 was done. Data regarding their age, sex, type, staging and clinical features, bone and bone marrow involvement, course of therapy and outcome after making diagnosis on tissue biopsy.</p><p><bold>Results</bold>: Total 70 patients with age ranging from< 1 to 9 years (Median age of 3 yrs) were included. M: F Ratio was 1.8:1, 49/70 70% of cases non‐infantile and 21/70 30% with infantile type. 15/70 (22%) had stage III at presentation while 55/70 (78%) was of stage IV. 33/70 (47%) had mainly abdominal mass as the main presenting complaint, 5/70 (7%) as paraplegia, 5/70 as nasal polyp, neck and mediastinal involvement, 2/70 (3%) as bony masses and proptosis 25/70 (36%) as multiple presentations. 52/70(74%) had to travel more than 100KM to reach the primary treatment center. 37/70(53%)% had bone involvement at presentation and 49/70(70%) had bone marrow involvement. 28/70(40%) had successfully completed the chemotherapy, 13/70(19%) abandoned treatment, 17/70 (24%) expired due to progressive disease and infections, 7/70(10%) were put on palliative Rx at presentation 5/70(7%) on chemotherapy.</p><p><bold>Conclusions</bold>: <italic>In resource</italic> limited settings<bold>,</bold> Neuroblastoma stage IV is a challenging malignancy to deal with. There is intense need of increased capacity building to diagnose and treat them early and implementation of effective infection control measures with better survival options in these patients.</p></sec><sec id="pbc26772-sec-10340"><label>PO-022</label><title>Therapeutic Plasma Exchange for a Case of Refractory Opsoclonus Myoclonus Ataxia Syndrome</title><p><underline underline-style="single">J. Greensher</underline><sup>1</sup>, J. Louie<sup>1,2</sup>, J. Fish<sup>1,3</sup></p><p><italic><sup>1</sup>Northwell Health, Hofstra Northwell School of Medicine, Hempstead, USA; <sup>2</sup>Long Island Jewish Medical Center, Department of Pathology ‐ Transfusion Medicine, New Hyde Park, USA; <sup>3</sup>Cohen Children's Medical Center, Division of Pediatric Hematology Oncology and Stem Cell Transplantation, New Hyde Park, USA</italic></p><p><bold>Background/Objectives</bold>: Opsoclonus myoclonus ataxia syndrome (OMAS) is an immune‐mediated phenomenon affecting ∼3% of neuroblastoma cases. OMAS has a chronic, relapsing‐remitting course causing significant long‐term morbidity. Therapeutic plasma exchange (TPE) effectively treats other immune‐mediated neurologic disorders. We present a case of paraneoplastic OMAS that was refractory to all common treatments, but resolved after TPE.</p><p><bold>Design/Methods</bold>: This is a case report of a 14‐month‐old boy who achieved complete remission of otherwise refractory OMAS after TPE, and a 2<sup>nd</sup> remission after undergoing TPE for a relapse ∼3 years later.</p><p><bold>Results</bold>: A14‐month‐old boy presenting with 6 weeks of chaotic eye movements, jerking of the extremities, diminishing truncal support, trembling, loss of motor milestones, and a mass of the celiac axis was diagnosed with intermediate‐risk neuroblastoma with paraneoplastic OMAS. Two cycles of chemotherapy, including carboplatin, etoposide, doxorubicin, and cyclophosphamide, resulted in complete cancer remission, while the OMAS persisted. Over ∼4 years, oral prednisone, high‐dose pulse dexamethasone, monthly intravenous immunoglobulin (IVIG), 3 courses of rituximab, a 2<sup>nd</sup> course of cyclophosphamide, ∼2.5 years of adrenocorticotropic hormone, and several months of mycophenolate mofetil were trialed without resolution of symptoms. Ultimately, the patient achieved rapid remission with initiation of TPE, rituximab, and monthly IVIG. Following remission, he continued monthly tapering TPE, receiving 14 treatments in total. After over 3 years without relapse he re‐presented with OMAS following a viral illness, with no evidence of neuroblastoma recurrence. Within 1 month of restarting treatment with TPE, oral prednisolone, IVIG, and rituximab, the patient again achieved remission. He maintained an OMAS score of 0 after a course of 6 TPE treatments without tapering and after weaning off of oral steroids.</p><p><bold>Conclusions</bold>: TPE prefaced complete remission of OMAS for a patient with highly refractory disease, initially, and again after relapse. This important proof‐of‐principle case demonstrates the potential efficacy of TPE in neuroblastoma‐associated OMAS.</p></sec><sec id="pbc26772-sec-10350"><label>PO-023</label><title>Treatment of High‐Risk Neuroblastoma</title><p>A. Hizhnikov<sup>1</sup>, <underline underline-style="single">A. Kazancev</underline><sup>1</sup>, P. Kerimov<sup>1</sup>, R. Pimenov<sup>1</sup></p><p><italic><sup>1</sup>Blokhin Cancer Research Center, Department of thoracoabdominal childrens oncology surgery Institute of Pediatric Oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: To improve the results of treatment of patients with high‐risk neuroblastoma.</p><p><bold>Design/Methods</bold>: 32 patients with high‐risk neuroblastoma received treatment from the DOG Research Institute from 2009 to 2016. The median follow‐up time was 19.8 months. The study included 21 (65.6%) boys and 11 (34.4%) girls. The age of the patients ranged from 1.7 to 15 years, the average age was 4.6 ± 3.3 years. Patients were divided into 2 groups depending on the regimens of chemotherapy.he programmed treatment included induction HT, surgical treatment, high‐dose CT, radiation therapy and biotherapy with retinoic acids. Four patients from group I who did not receive a complete response or a good partial response at the end of the phase of induction chemotherapy received systemic radiotherapy 131I‐MIBG.</p><p><bold>Results</bold>: The effectiveness of induction chemotherapy in the I group was 94.7%, in the II group ‐ 84.6%. Bone marrow cleansing, with induction chemotherapy, was significantly more frequent in group I after 1 course, in 71.5% of patients. All patients in the I group had bone marrow sanation, 2 (15.4%) patients in the II group of bone marrow sanation were not reached. The two‐year OS of patients with stage 4 in group I was 65.6 ± 14.0%, in group II, 43.1 ± 14.7%. The two‐year EFS in the I group was 33.4 ± 14.5%, in the II group ‐ 23.1 ± 11.7%. We found that systemic radiotherapy significantly correlated with the absence of progression or relapse of the disease. Radical surgery does not affect the prognosis of the disease.</p><p><bold>Conclusions</bold>: Induction HT with topotecan, used in group I showed a higher direct efficacy, OS and EFS in group I were higher. Patients who, at the end of the induction phase, have an active residual tumor tissue determined to perform systemic radiotherapy with 131I‐MIBG.</p></sec><sec id="pbc26772-sec-10360"><label>PO-024</label><title>Dokuz Eylul University Treatment Experience of Neuroblastoma</title><p><underline underline-style="single">D. Ince</underline><sup>1</sup>, D. Kizmazoglu<sup>1</sup>, R.E. Cecen<sup>1</sup>, M. Erdem<sup>1</sup>, S. Aktas<sup>2</sup>, E. Serinan<sup>2</sup>, A. Demiral<sup>3</sup>, R. Cetingoz<sup>3</sup>, E. Ozer<sup>4</sup>, H. Guleryuz<sup>5</sup>, M. Olguner<sup>6</sup>, K. Mutafoglu<sup>1</sup>, and N. Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University Institute of Oncology, Dept. of Pediatric Oncology, Izmir, Turkey; <sup>2</sup>Dokuz Eylul University Institute of Oncology, Dept. of Basic Oncology, Izmir, Turkey; <sup>3</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiation Oncology, Izmir, Turkey; <sup>4</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Pathology, Izmir, Turkey; <sup>5</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiodiagnostics, Izmir, Turkey; <sup>6</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Pediatric Surgery, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: To evaluate clinical characteristics and outcome of the Turkish Pediatric Oncology Group (TPOG) Neuroblastoma treatment protocol for our patients with neuroblastoma between 2000‐2017.</p><p><bold>Design/Methods</bold>: There were 89 patients with neuroblastoma, 60 of them were eligible. MYCN, 1p, 11q, 17q status were investigated. The INSS staging, COG risk stratification systems were used. TPOG‐NB‐2003/2009 protocols were used. Low RG; stage1 only surgery, stage2 surgery plus 3courses chemotherapy, stage4S 4courses chemotherapy. Intermediate RG; extra 2‐4courses chemotherapy were given. Maintanance therapy, 13‐cis‐RA were given for 10 weeks. High RG, 4‐6courses conventional CT or high dose CT+ ASCT. Maintenance therapy, 13cis‐RA were used for 6 months.</p><p><bold>Results: LRG‐(n:12)</bold>: Nine stage‐1, one stage‐2, two stage‐4S patients. One 4S‐patient died. Median follow‐up time: 55mos, 5‐/10‐years OS and EFS rates were 92%. <bold>IRG‐(n:23)</bold>: CR achieved by primary surgery+CT in two stage‐2 cases. CR achieved in three stage‐4S patients by CT+delayed surgery. Incomplete primary surgery was performed in two of 18 stage‐3&4 patients; 6CR, 9PR achieved by CT+surgery, delayed surgery was performed in four. In IRG Induction (CT+Surgery) response was 95% CR+PR. RT was performed to primary tumor in 5 patients and for metastasis in one. Median follow up time 26mos (2mos‐12yrs), 5‐/10‐yrs EFS 90%, OS 95%. <bold>HRG‐(n:25)</bold>: Incomplet primary surgery was performed in 5 patients. Induction (CT+Surgery) response was 92% CR+PR. Delayed surgery was performed in 20‐patients (11‐complete). Radiotherapy was performed to primary tumor in 18‐patients. 5‐/10‐yrs EFS was 30%. Nine patients had refractory disease, six had systemic relapse. Median relapse time was 27mos (9‐58mos). Median follow up time 46mos (4mos‐14.5yrs), 5‐/10‐yrs OS were 58% and 31%, respectively. Two patients died related to ASCT, and 10 died with progression.</p><p><bold>Conclusions</bold>: Neuroblastoma treatment was standartized by TPOG‐NB‐protocols. Stage, MYCN‐amplification, risk groups, primary tumor site were found significantly related to survival rates. Survival rates were acceptable and consistent with the literature.</p></sec><sec id="pbc26772-sec-10370"><label>PO-025</label><title>Treatment of Relapse Neuroblastoma: Dokuz Eylul University Experience</title><p><underline underline-style="single">D. Ince</underline><sup>1</sup>, M. Erdem<sup>1</sup>, R.E. Cecen<sup>1</sup>, D. Kizmazoglu<sup>1</sup>, E. Ozer<sup>2</sup>, A. Demiral<sup>3</sup>, R. Cetingoz<sup>3</sup>, S. Aktas<sup>4</sup>, H. Guleryuz<sup>5</sup>, M. Olguner<sup>6</sup>, K. Mutafoglu<sup>1</sup>, and N.Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University Institute of Oncology, Dept. of Pediatric Oncology, Izmir, Turkey; <sup>2</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Pathology, Izmir, Turkey; <sup>3</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiation Oncology, Izmir, Turkey; <sup>4</sup>Dokuz Eylul University Institute of Oncology, Dept. of Basic Oncology, Izmir, Turkey; <sup>5</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiaodiagnostics, Izmir, Turkey; <sup>6</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Pediatric Surgery, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: To evaluate clinical characteristics and response to treatment of patients with relapse/refractory neuroblastoma.</p><p><bold>Design/Methods</bold>: Medical records of 21 patients with relapse/refractory neuroblastoma after treatment with TPOG‐NB 2003/2009 protocols were evaluated retrospectively. The clinical characteristics, relapse types and treatments were analized.</p><p><bold>Results</bold>: Median age at relapse was 3.5yrs (6mos‐11.5yrs), M/F:3.2. One patient was in LowRG stage‐4S. In HighRG stage‐3&4 patients (n:20), MYCN amplified in 6/17 patients (35%). 17q aberation was detected in 3 of MYCN(‐) cases, del 1p was detected in one case. Shimada was unfavourable in 15 patients. Tumor localization: surrenal (n:14), paraspinal (n:3), midline (n:3). Metastasis sites: bone (85%), bone marrow (70%), lymph node (45%), lung (15%), CNS (%10). There were 9 patients with refractory disease, 10 patients with systemic relapse, one patient with primary relapse. Median relapse time was 25mos (30‐64mos). Median progression time of refractory patients was 8mos (4‐39mos). Average 3 courses (1‐8 courses) TCV (Topotecan, Cyclophosspamide, Vincristine) were given to 11 patients. Three courses ICE were given to 5 patients. Topotecan, temozolamide, metronomic treatment were given to one patient. High dose chemotharapy+ASCT were performed to total 11 patients (seven received TCV, 3 received ICE). Remission was not achieved in nine patients despite HDCT+ASCT, and TCV, ICE, metronomic therapy, RIST protocol, temozolomide were given to these cases. Remaining two patients died. In four refractory cases without ASCT history received TCV, ICE, vinorelbine+temozolamide treatments. Also TCV, ICE, RIST protocol or metronomic oral cyclophospamide/etoposide were given as 3th line relapse treatment. Median OS for relapse patients was 41m (6m‐8yrs); 12mos‐OS 48%, 18mos‐OS 27%. Nine patients were followed more than 4 years.</p><p><bold>Conclusions</bold>: Patients with relapse neuroblastoma had advanced stage disease, unfavourable histology, and MYCN amplification (35%). Progression free survival times prolonged up to 8 years. Relapse/refractory neuroblastoma behave as chronic disease with different, multiple treatment strategies.</p></sec><sec id="pbc26772-sec-10380"><label>PO-026</label><title>Treatment of Non High Risk Neuroblastoma Patients Following Siopel Protocol in Vietnam from 2013 to 2015</title><p><underline underline-style="single">Q. Vu</underline><sup>1</sup>, N. Nguyen<sup>2</sup>, L. Bui<sup>2</sup>, H. Pham<sup>3</sup>, C. Le<sup>4</sup>, N. Le<sup>4</sup>, T. Hoang<sup>5</sup>, N. Ngo<sup>1</sup>, H. Nguyen<sup>1</sup>, L. Phung<sup>6</sup>, V. Nguyen<sup>7</sup>, H. Le<sup>8</sup></p><p><italic><sup>1</sup>Vietnam Children's Hospital, Humans Genetics Department, Hanoi, Vietnam; <sup>2</sup>Vietnam Children's Hospital, Oncology Department, Hanoi, Vietnam; <sup>3</sup>Vietnam Children's Hospital, Surgery Department, Hanoi, Vietnam; <sup>4</sup>Vietnam Children's Hospital, Radiology Department, Hanoi, Vietnam; <sup>5</sup>Vietnam Children's Hospital, Pathology Department, Hanoi, Vietnam; <sup>6</sup>Vinmec International Hospital, Oncology Department, Hanoi, Vietnam; <sup>7</sup>Hanoi University of Sciences‐ Hanoi National University, Genetics Department, Hanoi, Vietnam; <sup>8</sup>Vietnam Children's Hospital, Emergency Department, Hanoi, Vietnam</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma is the most popular pediatric solid tumor in the first year. The treatment is based on the risk stratification. In Vietnam, we now focus in treatment for non‐high risk patients. So we study in neuroblastoma patients in 3 years (2013‐2015) for evaluation our results of treatment following the SIOPEL protocol.</p><p><bold>Design/Methods</bold>: The patients is classified in non‐high risk group using the INRG classification and treated following the SIOPEL protocol. We followed up the patient each 6 months after treatment to collect the information.</p><p><bold>Results</bold>: There are 61 non‐high risk patients in 3 years, in which 54/61 patients are treated by the SIOPEL protocol. The ratio of complete or partial response in our study at the end of protocol and at the end of study is 61,11% and 80%, respectively. The very low and low risk patients have the complete response. There are 3 aggressive patients in intermediate group. The spontaneous regression is found in 3 patients (1 Ms and 2 L2 stage). The 2 years EFS is 87,88%.</p><p><bold>Conclusions</bold>: The SIOPEL protocol for non‐high risk neuroblastoma patient is adaptive, and give the good result for treatment on Vietnamese patients.</p></sec><sec id="pbc26772-sec-10390"><label>PO-027</label><title>Clinical Effects of High Risk Neuroblastoma with Chromosome 1P36 Deletion Post Autologous Stem Cell Transplant</title><p><underline underline-style="single">D. Zhang</underline><sup>1</sup>, B. Wang<sup>1</sup>, Z. Yue<sup>1</sup>, W. Zhao<sup>1</sup>, G. Zhu<sup>1</sup>, X. Wang<sup>1</sup>, S. Li<sup>1</sup>, M. Jin<sup>1</sup>, M. Qin<sup>1</sup>, X. Ma<sup>1</sup></p><p><italic><sup>1</sup>Beijing Children's Hospital Affiliated to Capital Medical University, Hematology Oncology Center, Beijing, China</italic></p><p><bold>Background/Objectives</bold>: By describing the clinical features of post autologous stem cell transplant high risk Neuroblastoma (HR‐NB) patients with 1p36 deletion and their clinical outcomes, the goal was to make further progress in better survival rate and life quality.</p><p><bold>Design/Methods</bold>: A retrospective study of all HR‐NB patients with 1p36 deletion, who attended the pediatric hematology oncology centre from April 2014 to April 2016 and received systematic treatment and follow‐up care, was performed.</p><p><bold>Results</bold>: A total of 11 HR‐NB patients with 1p36 deletion, all INSS‐IV, were included in the study,4 were male and 7 female. The average age was 43 months. There were 11 cases with bone marrow metastasis and 10 cases with multiple bone metastasis. N‐myc gene amplification was detected in 4 patients.11 patients were treated with 4‐5 courses of chemotherapy before the operation. The amount of reinfused stem cells was 2.62∼10.68*106/L, and the median follow‐up time was 14.9 months (9‐32 months). All the 7 patients in stable state were in the maintenance treatment of retinoic acid. Three cases recurrent tumor progression in 3, 5 and 5 months after the reinfusion respectively. The other one occurred bone marrow recurrence and intracranial metastasis 3 months after retinoic acid chemotherapy completed.</p><p><bold>Conclusions</bold>: HR‐NB patients with 1p36 deletion had a high risk of developing bone marrow and bone metastases, and 1/3 of them were associated with N‐myc gene amplification. Autologous stem cell transplantation is a safe and effective therapeutic method. However, in 3‐6 months after reinfusion and during retinoic acid maintenance therapy, tumor progression may happen and lead to poor prognosis, suggesting the strength of systemic treatment of these patients is not quiet enough. Therefore, close clinical monitoring was needed after stem cell transfusion. Intensification chemotherapy in 3 months interval, a second dose of autologous stem cell transplantation may be the primary means of prevention disease progression.</p></sec><sec id="pbc26772-sec-10400"><label>PO-028</label><title>A Single‐Center Study on the Clinical Efficacy and Progression of Neuroblastoma in Pediatric Patients</title><p><underline underline-style="single">Y. Zhang</underline><sup>1</sup>, D. Huang<sup>1</sup>, W. Zhang<sup>1</sup></p><p><italic><sup>1</sup>beijing tongren hospital ‐ capital medical university, pediatric, Beijing, China</italic></p><p><bold>Background/Objectives</bold>: Study on the clinical outcome of NB associated with different risk factors by analyzing the clinical data of 147 NB patients collected in the past nine years at Beijing Tongren Hospital.</p><p><bold>Design/Methods</bold>: 147 patients of NB collected from January 2006 to January March 2015 and treated with induction and consolidation treatment.The average following‐up time was 32.15±21.05 months. We used SPSS 20.0 software for analyzinged the clinical data using SPSS 20.0 software for studying on the relationship between outcome of NB and different risk factors..</p><p><bold>Results</bold>: In 147 cases, 97 patients were male (65.266%), and 50 patients were female (34.8%). The average age of the patients was (3.76±2.83) years old.The OS of 147 NB patients was 54.4% (80/147). 67 Patients of NB were dead. The medium survival time of patients of NB was 48.0 months.The medium survival time of 117 patients of HR NB was 41.1 m, and the 1 year‐, 2 year‐, 3year‐, 4 year‐ and 5 year OS of them was 69%,54%,45%,29%, and 16%. The medium survival time of 30 patients of IR NB was 60 m, and the 1 year‐, 2 year‐, 3year‐, 4 year‐ and 5 year OS of them was 92%,86%,86%,86%, and 86%.73 patients of recurrence NB as followed up. Only 3 patients (3/73) of IR group of NB appeared recurrence (<italic>P</italic>=0.001). The 4 year OS of 70 patients (70/117) of HR NB with relapse was only 23%.</p><p><bold>Conclusions</bold>: Relapse was and older age were main risk factors in NB, no matter what group. The prognosis of IR NB was very good, but the prognosis of HR NB was poor. Therefore, we would like to resolve these problems for better prognosis we should diagnosis early and reduce relapse using reasonable diagnosis and treatment technology for improving the survival outcome of NB, special HR group patients.(improve the survival outcome?).</p></sec></sec><sec id="pbc26772-sec-10410"><title>Solid Non Brain Tumours ‐ Renal Tumours</title><sec id="pbc26772-sec-10420"><label>PO-029</label><title>A Rare Cause of Renal Mass in the Childhood: Malignant Solitary Fibrous Tumor</title><p><underline underline-style="single">G. Ersoy</underline><sup>1</sup>, D. Tuğcu<sup>2</sup>, B. Koç<sup>1</sup>, C. Bayram<sup>1</sup>, I. Odaman Al<sup>1</sup>, F. Akici<sup>1</sup>, A. Ayçiçek<sup>1</sup>, G.N. Ozdemir<sup>1</sup></p><p><italic><sup>1</sup>Kanuni Sultan Suleyman Training and Research Hospital ‐, Pediatric Hematology Oncology, Istanbul, Turkey; <sup>2</sup>Istanbul University School of Medicine, Pediatric Hematology Oncology Department, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Solitary fibrous tumors (SFT) are very rare, mostly benign neoplasms and originate from mesenchymal spindle cells. SFT rarely originate from kidney.</p><p><bold>Design/Methods</bold>: Here we desciribe a case of malignant, renal origin SFT with four local recurrences and metastases.</p><p><bold>Results</bold>: A 12 year old male patient admitted to our clinic with hematuria. Investigations revealed an abdominal mass of 40×42 mm and radical nephrotomy was planned. Pathological diagnosis of the lesion was renal SFT the tumor was defined as malignant. As the tumor was totally resected, monthly follow‐up was planned for the patient. One year later, ultrasound revealed a recurrent mass lesion at the primary tumor side. It was excised totally and pathological diagnosis was same as the primary tumor. After surgery, radiotherapy to tumor site and salvage chemotherapy with ifosfamide, cisplatin and etoposide were applied. No residual or recurrent mass were found at the end of the therapy. However 3 months later, a 1 cm noduler contrast enhanced mass lesion near L1 vertebra was recorded at magnetic resonance imaging (MRI). The lesion was surgically removed and diagnosed as the primary tumor. An alternative chemotherapy protocol was applied after operation. Monthly follow‐up was continued however 3 months after recurrent masses at renal and pelvic region were found. At surgery, 2 lesions with the sizes of 19x15x8 cm and 5,5 cm were found and resected. An alternative chemotherapy regimen was used again. The patient was up on bevacisumab for treatment.</p><p><bold>Conclusions</bold>: There are 49 renal SFTs described at the literature up to time and 7 are malignant. This tumour is mostly seen in adulthood, only 2 patients are younger than 18 years old (4 and 18) and both of them have benign tumors. This case is the youngest patient described in literature with malignant solitary fibrous tumour.</p></sec><sec id="pbc26772-sec-10430"><label>PO-030</label><title>The First Local High‐Dose Chemotherapy Administration Experience in a Metastatic Wilms Tumor Pediatric Patient with Pleura and Lungs Involvement</title><p><underline underline-style="single">E. Levchenko</underline><sup>1</sup>, E. Gumbatova<sup>2</sup>, O. Mamontov<sup>1</sup>, S. Rosengard<sup>3</sup></p><p><italic><sup>1</sup>Petrov Research Institute of Oncology, Thoracic surgery, Saint‐Petersburg‐ Pesochniy, Russia; <sup>2</sup>Petrov Research Institute of Oncology, Paediatric Oncology, Saint‐Petersburg‐ Pesochniy, Russia; <sup>3</sup>Petrov Research Institute of Oncology, Anesthesiology, Saint‐Petersburg‐ Pesochniy, Russia</italic></p><p><bold>Background/Objectives</bold>: Our aim is to report the first clinical case of successful chemoperfusion of lungs and pleural cavity in a child with Wilms tumor.</p><p><bold>Design/Methods</bold>: In March 2014 a right kidney mass lesion was found. Tumor resection with right nephroureterectomy was performed in a local clinic. The patients received subsequent chemotherapy for stage III, blastemal type nephroblastoma according to SIOP 2003 protocol. In May 2015, a routine check‐up revealed an early relapse with multiple lung metastases. Abroad 4 chemotherapy cycles with subsequent 15 Gy whole‐lung irradiation and high‐dose chemotherapy with autologous hemopoietic stem cell transplantation were performed. In May 2016 a chest CT scan revealed the second early relapse with lungs involvement.</p><p>In June 2016 a left thoracotomy was performed. An intraoperative revision revealed two metastases in the lower lobe and an additional subpleural lesion 3 mm in diameter. After wedge resection of the lower lobe of the left lung the further revision yielded another centrally located lesion about 10 mm in diameter in the 6<sup>th</sup> segment. An anatomic resection of the segment was performed. Another three nodular lesions 3 to 4 mm in diameter were found on the parietal pleura of the diaphragm. After the partial pleurectomy the intraoperative morphology results indicated metastatic pleural involvement by nephroblastoma. Therfore, the lung was disconnected from circulation, blood vessels were cannulated, and 30‐minute normothermic lung perfusion with 500 mcg of dactinomycin [1.6 mcg/cm<sup>3</sup> × 310 cm<sup>3</sup>(350 ‐ SVI)] was performed. Due to the parietal pleura involvement found there followed an additional 60‐minutes hyperthermic pleural perfusion with 150 mg of cisplatin.</p><p><bold>Results</bold>: The postoperative recovery was uneventful. The CT scan shows no signs of lungs involvement.</p><p><bold>Conclusions</bold>: The case described illustrated the feasibility and safety of local lung and pleura chemoperfusion in a heavily pretreated chemoresistant pediatric cancer patient.</p></sec><sec id="pbc26772-sec-10440"><label>PO-031</label><title>Non‐Wilms' Malignant Masses of Kidney: Experience of Few Patients with Improved Outcome</title><p><underline underline-style="single">B. kumar</underline><sup>1</sup>, V. upadhyaya<sup>1</sup>, R.N. rao<sup>2</sup>, S. kumar<sup>3</sup></p><p><italic><sup>1</sup>Sanjay Gandhi Post Graduate Institute of Medical Sciences‐ Lucknow‐ UP‐ India, Paediatric Surgical Superspeciality, Lucknow, India; <sup>2</sup>Sanjay Gandhi Post Graduate Institute of Medical Sciences‐ Lucknow‐ UP‐ India, Pathology, Lucknow, India; <sup>3</sup>Sanjay Gandhi Post Graduate Institute of Medical Sciences‐ Lucknow‐ UP‐ India, Radiodiagnosis, Lucknow, India</italic></p><p><bold>Background/Objectives</bold>: Wilms' tumour accounts for almost 85% while other rare renal tumours including stromal tumours constitute only 15% of all paediatric renal masses. Differentiation is important for better outcome as each tumour has different chemotherapy protocol. Clear cell sarcoma, Rhabdoid tumour and Ewing`s / PNET tumour of kidney are rare tumours, considered as UNFAVORABLE tumorus due to its aggressive nature and late presentation.</p><p>Our aim is to present the characteristics, disease course, management and final outcome with these rare renal tumours in few patients which showed relatively better outcome.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed the electronic hospital, operation theatre and follow‐up records of all patients having non‐Wilms' renal malignant masses between July 2012 to July 2016; managed at our centre. Details of patients were evaluated including demography, clinical presentations, investigations, intra‐operative grading, pathology, management, final outcome and follow‐up. Last follow‐up was January 2017. Clinical examinations, ultrasonography, X‐rays and CT/PET‐scans were tools of follow‐up.</p><p><bold>Results</bold>: From July, 2012 to July, 2016, six patients with non‐Wilms' renal tumours were managed. Final diagnosis were clear cell sarcoma in 3 patients, rhabdoid tumour in 2 patients and Ewing's/PNET tumour in 1 patient. Almost all patients presented in stage II/III and received neo‐adjuvant chemotherapy followed by surgery and chemo/radiotherapy. One patient with clear cell sarcoma could not be operated; showed partial response to chemotherapy and died due to chemotherapy related toxicity. All 5 patients are under follow‐up without recurrence. Follow‐up period ranged from 6 – 48 months.</p><p><bold>Conclusions</bold>: The clinical characteristics of these rare renal tumours are similar to that of Wilms' tumour and preoperative diagnosis is almost impossible without histopathology/immunohistochemistry, even with modern imaging techniques. Some of these tumours progress rapidly and may result in fatal outcome. Early diagnosis and multimodal interventions in form of surgery/chem./radiotherapy are essential for better outcome.</p></sec></sec><sec id="pbc26772-sec-10450"><title>Solid Non Brain Tumours ‐ Bone Tumours</title><sec id="pbc26772-sec-10460"><label>PO-032</label><title>Ewing's Sarcoma 10‐Year Experience at the National Medical Center 20 De Noviembre ISSSTE. A Third Level Hospital in a Low Income Country</title><p><underline underline-style="single">E. Baños</underline><sup>1</sup>, F. Arreguin<sup>1</sup>, B. Almazan<sup>1</sup>, A. Benito<sup>1</sup>, J. Robles<sup>1</sup></p><p><italic><sup>1</sup>National Medical Center 20 de Noviembre ISSSTE, Pediatric Oncology, Mexico City, Mexico</italic></p><p><bold>Background/Objectives</bold>: Ewing sarcoma occur more frequently in the second decade of life and comprise about 4% of pediatric tumors. With current protocols, survival for localized disease is around 60% and in metastatic disease is 25%.</p><p><bold>Design/Methods</bold>: A descriptive, longitudinal, observational study that included 20 patients´files with Ewing's Sarcoma at the National Medical Center “20 de Noviembre” ISSSTE in a period from January 2006 to December 2016.</p><p><bold>Results</bold>: Male predominance was observed (1.8:1) ; mean age of presentation was 9.9 years with a minimum and maximum age of 1 and 16 years. Of the total cases 8 (40%) were osseous and 12 (60%) were extraosseous; 9 cases were located and 11 metastasic cases, representing 45% and 55% respectively. The duration of onset of symptoms at diagnosis varied from 1 to 24 months with an average of 3.5 months. The primary sites of bone disease were lower extremities and lower limbs. The primary sites of extraosseous disease were Head and Thoracic Wall. The duration of follow‐up varied from 1 month and 125 months with an average of 32.3 months; Overall survival was 85%; For patients with localized disease, overall survival was 88.9% and for metastatic disease 91%.</p><p><bold>Conclusions</bold>: A predominance was observed in the male gender, mean age of presentation of 9.9 years said results differ from that reported in other studies. Likewise, a predominance of extraosseous localization was observed, and overall survival was higher than that observed in other studies.</p></sec><sec id="pbc26772-sec-10470"><label>PO-033</label><title>Clinical Presentation, Management and Outcomes of Primary Ewing Sarcoma of the Spine in Childhood‐ A Case Series</title><p><underline underline-style="single">B. Dubashi</underline><sup>1</sup>, S. Kayal<sup>1</sup>, A. Mukherji<sup>2</sup></p><p><italic><sup>1</sup>Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER, Medical Oncology, Puducherry, India; <sup>2</sup>Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER, Radiotherapy, Puducherry, India</italic></p><p><bold>Background/Objectives</bold>: Spine usually accounts for 6% of the Primary sites in Ewing Sarcoma. They usually present with malignant spinal cord compression necessitating early workup and treatment. Local therapy is challenging. We are presenting a short‐case series of the clinical presentation, management and outcomes of primary Ewing sarcoma of the spine in children.</p><p><bold>Design/Methods</bold>: The case records of 45 children during the period 2013‐ 2016 with a diagnosis of Bone sarcoma presenting to the department of Medical Oncology in a regional cancer centre were screened for primary spinal Ewing Sarcoma. Clinical manifestations, treatment details including chemotherapy, surgery and radiotherapy and survival outcomes were noted.</p><p><bold>Results</bold>: Seven children with primary spinal Ewing Sarcoma were identified during the study period. The median age was 10 years (2‐18) with M:F ratio of 3:4. Five children presented with Para‐paresis of which two patients developed a flaccid paraplegia during the work up. Primary site of presentation included Cervical (n=3), Cervical and Thoracic (n=1), Dorso‐lumbar (n=1) and Lumbosacral (n=2). Two patients had metastasis to the bones at presentation. Three patients underwent laminectomy with excision of the mass. All patients received radiotherapy. Non metastatic patients were treated with VAC/IE protocol while patients with metastasis were treated with VAC protocol. On the date of analysis, 4 patients had progressive disease during the treatment and succumbed to illness, 2 patients completed treatment and are alive and free of disease with no neurological deficit. One patient is undergoing chemotherapy.</p><p><bold>Conclusions</bold>: Primary Spinal Ewing sarcoma are rare tumours requiring a multimodality treatment with surgery, chemotherapy and radiotherapy. They can present with Oncologic emergency. They have a poor outcome to therapy in terms of response and survival.</p></sec><sec id="pbc26772-sec-10480"><label>PO-034</label><title>Outcome of Ewing Sarcoma in Children, Twenty Years Experience from a Single Center in Turkey</title><p><underline underline-style="single">N. Eker</underline><sup>1</sup>, B. Yılmaz<sup>1</sup>, G. Tokuc<sup>1</sup>, E. Senay<sup>1</sup>, B. Berk<sup>1</sup>, O. Dogru<sup>1</sup></p><p><italic><sup>1</sup>Marmara University, Pediatric Hematology and Oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Ewing sarcoma (ES) is the second common primary bone malignancy in pediatric patients. Usually, these tumors occur in bone but sometimes they can olsa orginate in soft tissue. These tumors are agressive and treatment involves multidurgs chemotherapy, radiotherapy and surgery. The aim of this study was to determine outcomes of Ewing sarcoma in pediatric patients who was treated in our instution.</p><p><bold>Design/Methods</bold>: This is a retrospective study of 75 pediatric patients with Ewing Sarcoma treated in between 1996 to 2016.</p><p><bold>Results</bold>: During a 20‐year period, 75 patients were identified with Ewing Sarcoma in hospital database and their records were analyzed retrospectively. Of the 75 patients, 45 (60%) were males, 30 (40%) were females. The mean age was 10 years (ranging from 1year to 17 years). All of the patients had received the same chemotherapy protocol at presentation. This protocol involved ifosfamide, etoposide, vincristine, doxorubicine, cyclophosphamide and actinomycin. After 3 cycles of chemotherapy, surgery had been performed for most of the patients. Radiotherapy had been performed for the patients who had more than 10% viable cells after pathological examinations. For these patients, chemotherapy had been changed and continued during and after radiotherapy. The second chemotherapy protocol invoved vincristine, cyclophosphamide and topotecan. At the presentation, 22 (29 %) patients had metastatic disease. During the follow up 16 (23 %) patients had relapsed. The 5‐year event free survival and overall survival were 46 % and 58,5 %. Metastatic disease at presentation was the significant factor on overall survival.</p><p><bold>Conclusions</bold>: The management of a child or adolescent with Ewing sarcoma is best carried out in a specialized center under the care of a multidisciplinary team, in order to obtain the best outcome for the patient. Early diagnosis is very important because metastatic disease at presentation reduces the overall survival.</p></sec><sec id="pbc26772-sec-10490"><label>PO-035</label><title>Expression of TUBB3 and RRM1 Proteins as Markers of Drug Resistance to Gemcitabine / Docetaxel Chemotherapy in Childhood Osteosarcoma</title><p>A. Levashov<sup>1</sup>, <underline underline-style="single">E. Senzhapova</underline><sup>1</sup>, D. Khochenkov<sup>2</sup></p><p><italic><sup>1</sup>Pediatric Hematology and Oncology Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Pediatric Hematology and Oncology, Moscow, Russia; <sup>2</sup>Experimental Diagnostic and Treatment of Tumor Institution FSBI «N.N. Blokhin Russian Cancer Research Center», Experimental Diagnostic and Treatment of Tumor, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The treatment results of refractory childhood osteosarcoma are not satisfactory. According to the data of different pilot trials progression‐free survival curves dramatically tend to zero with a median follow‐up in 6‐10 months. Role of the TUBB3 and RRM1 proteins expression as markers of drug resistance to gemcitabine / docetaxel chemotherapy in childhood osteosarcoma is unknown.</p><p><bold>Design/Methods</bold>: The aim of this study was to estimate TUBB3 and RRM1 proteins expression in biopsy specimens and tumor tissue samples with poor response (grade I and II of tumor cells necrosis rate) after neoadjuvant chemotherapy and surgery of the primary site.</p><p>TUBB3 and RRM1 proteins expression was assessed by immunohistochemical method using anti‐RRM1 polyclonal (Protein Tech) and anti‐TUBB3 monoclonal (clone TU‐20, Santa Cruz) antibodies. TUBB3 positive specimen was defined as weak (+), moderate (++), strong (+++) colouring of the tumor nuclei with number of positive tumor cells above 10 percents. RRM1 positive specimen was defined as moderate (++), strong (+++) colouring of the tumor nuclei and cytoplasm with number of positive tumor cells above 25 percents. All patients were treated according to therapy like – EURAMOS1.</p><p><bold>Results</bold>: TUBB3 positive sample was revealed in 8 out of 14 (57.1%) biopsy specimens, in 3 out of 20 (15%) postoperative specimens. RRM1 positive sample was revealed in 10 out of 14 (71.4%) biopsy specimens, in 9 out of 20 (45%) postoperative specimens. TUBB3 positive, RRM1 positive sample was revealed in 5 out of 14 (37.5%) biopsy specimens, in 2 out of 20 (15%) postoperative specimens. There was not determined any significant correlation between expression of these markers and metastatic status of patients.</p><p><bold>Conclusions</bold>: These data suggest that optimal time of using gemcitabine / docetaxel could be adjuvant chemotherapy.</p></sec><sec id="pbc26772-sec-10500"><label>PO-036</label><title>The Best Strategy as the First Line Treatment Through Pediatric Iranian Population with Osteosarcoma; A Retrospective Matched Cohort Study</title><p><underline underline-style="single">M. Faranoush</underline><sup>1</sup>, A. Mehrvar<sup>1</sup>, M. Tashvighi<sup>1</sup>, A.A. Hedayati Asl<sup>1</sup>, M.A. Ehsani<sup>2</sup>, N. Mehrvar<sup>3</sup>, M. Alebouyeh<sup>1</sup></p><p><italic><sup>1</sup>MAHAK Pediatric Cancer Treatment and Research Center, Oncology, Tehran, Iran; <sup>2</sup>Tehran University of Medical Sciences, Bahrami Hospital, Tehran, Iran; <sup>3</sup>Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran</italic></p><p><bold>Background/Objectives</bold>: One of the utmost important challenges in Iranian health system is pediatric malignancies. Osteosarcoma, the common primary bone tumor, has a low survival rate in Iran. We designed this study to choose the best strategy for chemotherapy. Our goal is improving the survival rate of these patients.</p><p><bold>Design/Methods</bold>: This study conducted as a retrospective analytical cohort matched project. The randomized samples implied children less than 15 years old with approved pathological report of osteosarcoma. Patients with matched inclusion criteria categorized into two groups who administered by high dose methotrexate (HD MTX) and individuals with non‐HD MTX. The failure events and survival rate of these groups were estimated by SPSS software version 22.</p><p><bold>Results</bold>: Fourty one eligible patients (non HD MTX (n=21) and HD MTX (n=20) groups) with the mean age of 11.5±0.48 years were evaluated. 65.2% of patients with HD MTX and 34.8% of non‐HD MTX group had conferred relapse and metastasis. The median time of events was one and nine months through patients with HD MTX and non HD MTX groups respectively. The 5‐year survival rate of patients with HD MTX and non‐HD MTX was 18.4% versus 43.5%. Also the median time of disease free survival rate was more in non HD MTX patients (11.5 months versus one month).</p><p><bold>Conclusions</bold>: Findings revealed that survival rate and delaying in failure events were more in patients who administered by non HD MTX. As this study designed on the Iranian pediatric patients, the authors suggest on using non‐HD MTX regiment for Iran pediatric osteosarcoma patients.</p><p><bold>Acknowledgement</bold>: The authors thank staffs of medical documentation unit and research department at MPCTRC for their services and thank the orthopedic surgeons and radiotherapy unit for providing assistance with the clinical procedures.</p></sec><sec id="pbc26772-sec-10510"><label>PO-037</label><title>Survival of Patients with Childhood Osteosarcoma; A Single Center Experience</title><p>R.E. Senay<sup>1</sup>, B. Yilmaz<sup>1</sup>, N. Eker<sup>1</sup>, <underline underline-style="single">A.G. Tokuc</underline><sup>1</sup>, O. Dogru<sup>1</sup>, B. Berk<sup>1</sup></p><p><italic><sup>1</sup>Marmara University Medical Faculty, Paediatric haematology oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: This study presents clinical outcome and midterm follow up of patients with childhood osteosarcoma with <90 % necrosis rate according to the presence of metastasis during initial diagnosis</p><p><bold>Design/Methods</bold>: Retrospective analysis of a prospectively collected single center database were evaluated. Thirty one patients with the diagnosis of osteosarcoma were enrolled between December 1995 and February 2017. Demographic variables, necrosis degree, rate of recurrence, rate of remission and survival were analyzed according to the presence of metastasis during the initial diagnosis</p><p><bold>Results</bold>: Patents age ranged between 5‐19 years during The initial diagnosis, 17 (54.8%) of them were female and,14 (45.2%) of them were male. The mean follow‐up period ranged between 4‐133 months ( with an average of 41,13 ± 35 months). There were metastases in 5 cases (16,1%) and local invasion in 1 case (3,2%) during the initial diagnosis. Chemotherapy and surgical therapy was performed for each patient. The rate of necrosis ranged from 5% to 100% and it was 90% in 20 (64.5) patients. During the follow up period; recurrence was observed in 10 (32.3%) cases, mortality was observed in 9 (29%) and complete remission was detected in 22 (71%) of the cases. The five‐years overall survival rate was 80.6% and mean survival time was 104.23 ± 10.27 months (95% CI: 84.11‐124.36). There was no statistically significant difference in survival between groups those include presence of metastasis at the time of diagnosis and <90% necrosis in follow‐up and nonmetastatic at the time of diagnosis and <90% necrosis in follow‐up (p>0,05).</p><p><bold>Conclusions</bold>: These data shows 80% survival rate in midterm follow up. There has been no difference demonstrated in survival according to the presence of metastasis during the initial diagnosis.</p></sec></sec><sec id="pbc26772-sec-10520"><title>Solid Non Brain Tumours ‐ Soft Tissue Sarcomas</title><sec id="pbc26772-sec-10530"><label>PO-038</label><title>Transnasal Endoscopic Surgery in Complex Treatment of Esthesioneuroblastoma in Children</title><p>D. Buletov<sup>1</sup>, <underline underline-style="single">O. Merkulov</underline><sup>2</sup>, T. Gorbunova<sup>2</sup>, V. Polyakov<sup>2</sup></p><p><italic><sup>1</sup>Russian Cancer Research Center N.N. Blokhin, head and neck tumors, Moscow, Russia; <sup>2</sup>Russian Cancer Research Center N.N. Blokhin, head and neck department, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Esthesioneuroblastoma is a rare malignant tumor. The efficacy of transnasal endoscopic removal of the tumor in the treatment of adult patients ENB is not in doubt. However, the possibility of this type of surgical treatment of ENB in children has not been studied sufficiently.</p><p><bold>Design/Methods</bold>: From 2003 to 2016 the study included 11 patients. Mean patient age at diagnosis ‐ 9 years. Staging according to the TNM‐classification. Stage I was determined at 2, III ‐ y 1, IV ‐ in 8 cases. Intracranial spread has been observed in 4 cases. 8 patients had got chemotherapy and radiation therapy. Chemotherapy was included from 6 to 10 courses: Vincristine 1 mg/m<sup>2</sup> to 1 and Day 8, cyclophosphamide 500 mg/m<sup>2</sup> to 1 and Day 8, doxorubicin 20 mg/m<sup>2</sup> of 2 and 4 day carboplatin 360 mg/m<sup>2</sup> of 1 day. Chemotherapy was administered in neoadjuvant regime 5 patients. Radiation therapy was performed in 8 patients in the 1.8 ‐ 2.4/day. At the primary tumor RT 50.4 Gy was performed in 5 patients and further irradiated lymph nodes 40 Gy in 3. Complex therapy, including surgical treatment, carried out in 7 patients. Transnasal removal of the tumor was performed in 6 patients, of whom one of them to remove the tumor transnasal access was conducted twice, a second operation was performed for recurrent disease.</p><p><bold>Results</bold>: Currently, 6 patients (54.5%) lived from 3 months to 13 years. One patient withdrew from the study immediately after diagnosis. Died of tumor progression ‐ 4 (36.4%).</p><p><bold>Conclusions</bold>: Based on our data shows the effectiveness of integrated treatment of common stages of ENB in children. In all cases of transnasal endoscopic removal of the tumor reached radicalism. The promise of this type of treatment requires further study and definition of clear criteria for inclusion in the scheme and therapy protocols ENB children.</p></sec><sec id="pbc26772-sec-10540"><label>PO-039</label><title>Transnasal Endoscopic Surgery in Complex Treatment of Soft Tissue Sarcomas in Children</title><p><underline underline-style="single">D. Buletov</underline><sup>1</sup>, O. Merkulov<sup>2</sup>, V. Polyakov<sup>2</sup>, T. Gorbunova<sup>2</sup></p><p><italic><sup>1</sup>Russian Cancer Research Center N.N. Blokhin, head and neck tumors, Moscow, Russia; <sup>2</sup>Russian Cancer Research Center N.N. Blokhin, head and neck department, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Currently, the method of transnasal endoscopic surgery (TEC) is becoming increasingly popular in the treatment of nasal cavity, skull base and paramenegial localization. This work is the first experience of TEC in children with Malignant tumors in Russia</p><p><bold>Design/Methods</bold>: From 2015 to 2017 25 transnazal surgical operations were performed in 24 patients. 14 female patients, 10 male patients. In 16 cases, one‐stage tumor removal was performed, in 9 cases cytoreductive tumor resection (biopsy) was performed.The youngest patient at the time of the operation was 36 days. The oldest patient ‐ 17 years and 1 month.The histological composition of the neoplasms was different: rhabdomyosarcomas, gliomas, Burkitt's lymphomas, angoimas, and others. 23 patients are alive at the moment, 1 patient died 3 months after the end of special treatment for estezioneeroblastoma</p><p><bold>Results</bold>: 23 patients are alive at the moment, 1 patient died 3 months after the end of special treatment for estezioneeroblastoma. Surgical complications: intraoperative ‐ cavernous sinus lesions ‐ 2. There were no complications in the postoperative period</p><p><bold>Conclusions</bold>: Endonasal surgery with the help of modern endoscopy techniques plays an important role both in the formulation of the diagnosis, and in the subsequent treatment and detection of relapses. In the modern world it is a method of choosing for treatment benign neoplasm, but also malignant neoplasms of the nasal cavity, the base of the skull and paramenengial localization. It is important to note that with the use of these modern technologies in patients of different ages, we have achieved the main goals of endoscopic interventions: complete visual control of performed manipulations; safety; preservation of the mucosa and anatomical structure; Minimal traumatism for the patient (absence of skin incisions); Easy tolerability in adults and children; The possibility to do without a long period of rehabilitation in the postoperative period.</p></sec><sec id="pbc26772-sec-10550"><label>PO-040</label><title>Treatment of Head and Neck Malignant Rhabdoid Tumors with Combined Intensive Chemotherapy and 125I Particle Implantation: Report of 2 Cases Follow‐Up for Over 2.5 Years</title><p><underline underline-style="single">C. Duan</underline><sup>1</sup>, M. Jin<sup>1</sup>, X. Ma<sup>1</sup>, D. Zhang<sup>1</sup>, W. Zhao<sup>1</sup>, Q. Zhao<sup>1</sup>, X. Wang<sup>1</sup></p><p><italic><sup>1</sup>Beijing Children's Hospital, heamatology/oncology, Beijing, China</italic></p><p><bold>Background/Objectives</bold>: Malignant rhabdoid tumors(MRT) is a rare, highly aggressive pediatric malignancy that primarily develops during infancy and early childhood. Despite the existing standard of intensive multimodal therapy, the prognosis of patients with MRT is still dismal. To add to the current knowledge, here we report 2 cases of MRT in the head and neck region treated with anthracycline and platinum‐based chemotherapy and brachytherapy.</p><p><bold>Design/Methods</bold>: The clinical records of 2 patients with head and neck MRT treated in Beijing Children's Hospital between Oct 2011 and May 2014 were retrospectively studied.</p><p><bold>Results</bold>: The medical records of two boys, onset age of 1.2y and 4.5y respectively were studied. One patient with primary tumor site at the right neck, another patient with the primary tumor site at the left neck, and metastasis to the right nasopharynx and multiple facial bones. The primary tumors size were 8*8cm and 6*6 cm respectively, were all stage III, and were all unresectable. Immunohistochemical results showed that the INI‐1 were all negative. They were treated with chemotherapy after biopsies were done.</p><p>The chemotherapy protocol was as follows: vincristine, cyclophosphamide, doxorubicin (VDCPM1) at weeks 1,7,13,19,25, and cyclophosphamide, carboplatin, etoposide (CPM5+CE) at weeks 4,10,16,22,28. <sup>125</sup>I particle implantations were done after 5 and 6 cycles of chemotherapy respectively. The evaluation showed very good partial remission of the tumor after the treatment completed. Both patients had IV grade neutropenia, I‐II degree anemiaand thrombocytopenia.Both patients suffered from grade 1‐2 skin reaction after seed implantation, manifested as erythema or mild edema of the local skin, which can be improved within 1‐2 weeks. Now the follow‐up time were 64 month and 34 month respectively, and the two patients remained stable.</p><p><bold>Conclusions</bold>: Anthracycline and platinum‐based intensive chemotherapy combined with <sup>125</sup>I particle implantation may be a promising treatment option for extra‐renal, extra‐cranial MRT without distant metastasis.</p></sec><sec id="pbc26772-sec-10560"><label>PO-041</label><title>Outcome of Bone and Soft Tissue Sarcomas in Children at a Tertiary Care Center in Pakistan</title><p><underline underline-style="single">Z. Fadoo</underline><sup>1</sup>, S. Resham<sup>1</sup>, N. Mushtaq<sup>1</sup>, A.R. Rizvi<sup>2</sup>, S. altaf<sup>1</sup></p><p><italic><sup>1</sup>Aga Khan University, oncology, karachi, Pakistan; <sup>2</sup>Aga Khan university, Pediatrics and Child Health, Karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: There is paucity of data regarding demographic characteristics and outcomes of bone and soft tissue sarcomas from the developing world including Pakistan. We analyzed the clinical features, and outcome of children with bone and soft tissue sarcomas treated over last 10 years at Aga Khan University Hospital.</p><p><bold>Design/Methods</bold>: Records of patients treated from January 2005 to December 2015 at Aga Khan University Hospital, histologically confirmed diagnosis of bone and soft tissue sarcomas were reviewed. Kaplan‐Meier curves were created to assess overall survival (OS) and event free survival (EFS) with relapse and death as outcome.</p><p><bold>Results</bold>: Forty three patients were eligible. 27(62.7%) were bone tumors with 13(48.1%) osteosarcoma, and 14(51.8%) ewings sarcoma. There were 16(37.2%) soft tissue sarcomas with 12(75%) rhabdomyosarcoma along with fibrosarcoma & synovial sarcoma (12%) each respectively.</p><p>There were 11/43(25.5%) patients with metastatic disease, 4 osteosarcomas, 4 ewings and 3 rhabdomyosarcoma respectively. The median age for bone sarcoma was 12 years while soft tissue sarcoma was 6 years. Distal Femur was the most involved site ‐ 10/27 (37%) in bone tumors and parameningeal 4/12 (33%) was the most common site in rhabdomyosarcoma.</p><p>There were 6/43 (13.9%) patients who received minimal to no therapy. There were 10/43 (23%) relapses on therapy. The estimated 5‐year EFS was 43.4% (95%CI: 9.8%‐73.9%) and OS at 5 years was 54.7% (95%CI: 23.9%‐77.6%).</p><p><bold>Conclusions</bold>: Outcomes of sarcomas in the developing world are poor due to multiple factors. Delayed presentation, poor tolerance of therapy, poor nutritional status at baseline, abandonment of therapy and lack of easy access to medical care due to financial constraints are some of the major factors responsible.</p></sec><sec id="pbc26772-sec-10570"><label>PO-042</label><title>Treatment Results in Pediatric Head and Neck Rhabdomyosarcomas: A Single Center Experience</title><p>K. Mutafoglu<sup>1</sup>, <underline underline-style="single">D. İnce</underline><sup>1</sup>, D. Kizmazoglu<sup>1</sup>, Y. Olgun<sup>2</sup>, M. Erdem<sup>1</sup>, A. Demiral<sup>3</sup>, R. Cetingoz<sup>3</sup>, H. Guleryuz<sup>4</sup>, E. Ozer<sup>5</sup>, T. Erdag<sup>2</sup>, and N.Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University Institute of Oncology, Dept. of Pediatric Oncology, Izmir, Turkey; <sup>2</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Otorhinolaryngology, Izmir, Turkey; <sup>3</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiation Oncology, Izmir, Turkey; <sup>4</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiodiagnostics, Izmir, Turkey; <sup>5</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Pathology, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: To evaluate head and neck localized rhabdomyosarcomas in our center.</p><p><bold>Design/Methods</bold>: Medical records of 32 patients with head and neck localized RMS between 1988‐2016, analyzed retrospectively.</p><p><bold>Results</bold>: The median age of diagnosis was 6.5yrs (18 mos‐17 yrs),M/F:1.0. Localization of tumors were as follows; parameningeal: 19, orbit:7, cheek:1, scalp:2, tongue:1,hard palate:1. According to IRS, TNM stage distribution: stage I (n:15), stage II(n:4), stage III(n:10), stage IV(n:3). Clinical grouping: CG‐1: 3% (n:1), CG‐2: 6% (n:2), CG‐3: 82% (n:26), CG‐4: 9% (n:3). The primary surgery was performed for three patients. All other patients received chemotherapy as the initial treatment. IRS based treatment regimens were used in 24 patients, COG ARST0431 protocol was used for other 8 patients. RTwas given to all the primary sites except two who were lost to follow up. Total resection with secondary surgery was performed for one patient with cheek primary because of chemo and radio‐resistant tumor. The median follow‐up time was 33 mos (2 mos‐17 yrs). Four patients were lost to follow up at 8<sup>th</sup> month with disease (n:3) and at 37<sup>th</sup> month without disease (n:1). 3‐yrsOS rate was 76%, 5and10yrs OS rates were 71%. 3yrsEFS rate was 63%, and 5, 10yrsEFS rates were 58%. Totally 7 patients died with progressive disease at median 26 months (10‐49 mos). Two patients died with refractory and progressive disease at 10 months. Nine patients relapsed. Median relapse time was 19mos (6‐40 mos). Three patients with relapsed disease are alive and relapse treatment is going on. A treatment resistant patient is alive after second line surgery with NED. Five patients with relapsed disease died with progression despite anticancer treatment.</p><p><bold>Conclusions</bold>: Fourty percent of patients had advanced stage disease, 91% of patients were in clinical group 3‐4, local control was problem. Overall and event free survival rates were acceptable.</p></sec><sec id="pbc26772-sec-10580"><label>PO-043</label><title>Successful Treatment of Tandem High‐Dose Chemotherapy with Allogeneic Stem Cell Transplantation in Advanced Ewing Sarcoma</title><p><underline underline-style="single">T. Miyamura</underline><sup>1</sup>, Y. Hashii<sup>1</sup>, H. Yoshida<sup>1</sup>, N. Naka<sup>2</sup>, K. Hamada<sup>2</sup>, S. Takenaka<sup>2</sup>, F. Isohashi<sup>3</sup>, H. Minagawa<sup>1</sup>, N. Nakagawa<sup>1</sup>, T. Fujiwara<sup>1</sup>, K. Ozono<sup>1</sup></p><p><italic><sup>1</sup>Osaka University Graduate School of Medicine, Pediatrics, Osaka, Japan; <sup>2</sup>Osaka University Graduate School of Medicine, Orthopedic surgery, Osaka, Japan; <sup>3</sup>Osaka University Graduate School of Medicine, Radiology, Osaka, Japan</italic></p><p><bold>Background/Objectives</bold>: Ewing sarcoma (ES) is a rare malignancy of bone and soft tissue. The prognosis of advanced metastatic ES remains very poor and treatment strategy has not been established. We report two cases of advanced ES treated by tandem high‐dose chemotherapy with allogeneic stem cell transplantation (SCT). They survived without disease for more than 4 years, therefore it may be an effective treatment strategy for advanced ES.</p><p><bold>Design/Methods</bold>: Patient 1 was a 15‐year‐old girl with ES originating in right ilium with multiple lung metastases. Patient 2 was an 11‐year‐old girl with ES originating in left ilium with multiple lung metastases. They received multi‐drug chemotherapy and radiation therapy to the primary legion. We then performed first high‐dose chemotherapy (VP16/CBDCA/CY) with autologous stem cell transplantation (SCT). They underwent surgical resection of primary lesion after hematological recovery. Their treatment response were good, and they achieved complete response. After that, we performed second high‐dose chemotherapy (CY/LPAM) with allogeneic SCT. The donor of patient 1 was HLA‐matched sibling, and severe adverse event including GVHD was not detected. The donor of patient 2 was HLA 2 loci mismatched mother (KIR ligand mismatch). Moderate engraftment syndrome was occurred although severe GVHD was not detected.</p><p><bold>Results</bold>: Patients 1 and 2 survived without disease for 70 months and 54 months, respectively.</p><p><bold>Conclusions</bold>: We reported two cases of advanced ES treated with multi‐drug chemotherapy and local radiation therapy, plus tandem high‐dose chemotherapy with autologous and allogeneic stem cell rescue. They survived without disease progression for more than 4 years. It was reported that ES can express tumor antigens which can be recognized by T cells, making allogeneic SCT an effective option. Intensive high‐dose tandem chemotherapy with alkylating agents and allogeneic tumor immunotherapy could be an effective treatment strategy for advanced ES.</p></sec></sec><sec id="pbc26772-sec-10590"><title>Solid Non Brain Tumours ‐ Retinoblastoma</title><sec id="pbc26772-sec-10600"><label>PO-044</label><title>Evaluation of Retinoblastoma Patients Undergoing Enucleation in the Backdrop of IIRB and AJCC TNM Classification; Clinical Features and 5 Year Outcome Analysis</title><p><underline underline-style="single">A. alkofide</underline><sup>1</sup>, H. Katan<sup>2</sup>, M. Ayas<sup>1</sup>, A. Ali<sup>1</sup>, I. AlFawaz<sup>1</sup>, S.K. Siddiqui Khawar<sup>1</sup>, G. Barria<sup>1</sup>, M. Foudaneel<sup>3</sup>, A.S. Alhmouz<sup>1</sup>, S. AlMesfer<sup>2</sup>, Y. Khafagh<sup>4</sup></p><p><italic><sup>1</sup>King Faisal Specialist Hopsital & Research Center, Pediatric Hematology Oncology, riyadh, Saudi Arabia; <sup>2</sup>King Khaled Eye Specialist Hopsital, Opthalmology, Riyadh, Saudi Arabia; <sup>3</sup>AlFaisal University, Medcial College, Riyadh, Saudi Arabia; <sup>4</sup>King Faisal Specialist Hopsital & Research Center, Oncology Center, riyadh, Saudi Arabia</italic></p><p><bold>Background/Objectives</bold>: To determine the clinical profile and outcome of patients with Retinoblastoma (Rb) who underwent unilateral or bilateral enucleation in the backdrop of International intraocular retinoblastoma classification (ABC Classification) and TNM Staging System.</p><p><bold>Design/Methods</bold>: Medical charts of 58 pediatric (Age≤14 years) patients with retinoblastoma who underwent enucleation, treated at King Faisal Specialist Hospital and Research Centre (KFSHRC), and King Khaled Eye Specialist Hospital Riyadh, Saudi Arabia from 2012‐2016 were reviewed</p><p><bold>Results</bold>: Among the cohort, 51.7% (30) were female. Median age at diagnosis was 20.5 months (3‐97.8). Retinoblastoma was unilateral in 51.7% (30), bilateral in 44.8% (26) and trilateral in 3.4(2) patients. One (1.7%) had metastatic disease at presentation. 61 enucleations were performed in 58 patients. International Classification for Intraocular Retinoblastoma was carried out for all eyes. 43 (70.5%) were in Group E, 11(18%) Group D, 3(4.9%) Group C and A each, followed by 1 (1.6%) in Group B. All patients underwent chemotherapy as chemoreduction and/or chemoprevention. 52 (85.2%) received chemoreduction and, 5 (8.2%) chemoprevention and 4 (6.6%) chemoreduction and chemoprevention. 4(6.9%) patients received thermotherapy, 1(1.7%) cryotherapy and 1(1.7%) trans‐pupillary intravenous carboplatin. Information on TNM classification and IIRB was available on 46 patients. 9 (19.5%) of our T1, T2a patients were classified as Stage D or Stage E. Post‐enucleation 17.2% (10) of our patients received External Beam Orbital Radiotherapy (EBORT). Of 44 evaluable cases, 93.2% (41) were in CR, 4.5(2) had stable disease and remaining 2.3% (1) progressive disease. With 3 (5.2%) mortalities (2 with bilateral, 1 with unilateral tumor), probability of five year overall survival for the whole cohort was 93% (0.930±0.040); 94.5% (0.945±0.038) for Group E and 80% (0.800±0.179) for Group D.</p><p><bold>Conclusions</bold>: The IIRB is essential in making decision about enucleation however, TNM Classification plays a pivotal role in deciding on post‐enucleation treatment for RB patients to avoid over treatment.</p></sec><sec id="pbc26772-sec-10610"><label>PO-045</label><title>Are Bone Marrow Examination and Lumbar Puncture Necessary in the Initial Evaluation of Retinoblastoma?</title><p><underline underline-style="single">K.T. D</underline><sup>1</sup>, M.Y. Chan<sup>1</sup>, S.Y. Soh<sup>1</sup>, A.M. Tan<sup>1</sup>, C.M.J. Lam<sup>1</sup>, B.L. Quah<sup>1</sup></p><p><italic><sup>1</sup>KK Women's and Children's hospital, Paediatric Haematology and Oncology, Singapore, Singapore</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma is the commonest primary intraocular malignancy of childhood. Bone marrow examination and lumbar puncture for cerebrospinal fluid (CSF) cytology are done together with EUA as initial metastatic work up for all patients with retinoblastoma in our institution. However, this is not routinely practiced in some centres.</p><p>This retrospective study aims to determine the prevalence of metastasis at diagnosis and to evaluate the value of these investigations in patients with retinoblastoma treated in KK Women's and Children's Hospital, Singapore (KKH).</p><p><bold>Design/Methods</bold>: The study was approved by Singhealth Centralized Institutional Review Board. Retrospective analysis of patients with retinoblastoma from May 1997 to March 2017 was performed.</p><p><bold>Results</bold>: Seventy‐eight patients were included; 38 (48.7%) boys, 40 (51.3%) girls. Forty‐five (57.7%) had unilateral disease, 32 (41%) bilateral disease and 1 (1.3%) trilateral disease. Median age at presentation was 25 months (range 1 to 107 months) for unilateral disease and 13 months (range 3 to 24 months) for bilateral disease. Two (2.6%) patients had positive family history. Four (5.1%) patients had metastatic disease at presentation to KKH. One had CSF (Cut optic nerve showed involvement) and one had bone marrow involvement (Blood count was abnormal) at diagnosis. One had initial treatment overseas and presented to KKH with metastatic relapse in bone marrow, CSF, liver and bone. The 4<sup>th</sup> patient had suprasellar extension on MRI but no CSF positivity. Costs for bone marrow and lumbar puncture tests were SGD 2500 to 3000 (USD 1785 to 2142).</p><p><bold>Conclusions</bold>: The prevalence of metastasis at diagnosis is very low at our institution. The patients with metastasis can be picked up by other means like clinical examination, blood counts, MRI and histology of optic nerve involvement. It is not necessary to investigate all patients with retinoblastoma, thus saving substantial financial and time costs for our patients and institution.</p></sec><sec id="pbc26772-sec-10620"><label>PO-046</label><title>Clinicoradiologic Features of Retinoblastoma at National Institute of Child Health Karachi, Pakistan</title><p><underline underline-style="single">U. Imam</underline><sup>1</sup>, F. Ali<sup>1</sup></p><p><italic><sup>1</sup>Child Aid Association‐national Institute Of Child Health, Pediatric Oncology, Karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Retinoblastoma is a primary intra ocular neoplasm of childhood which is presented at a very young age with leukocoria. This study aims to determine the clinico radiological features of retinoblastoma over a period of nine years from 2007 to 2015 using existing hospital record sheets.</p><p><bold>Design/Methods</bold>: A record of 176 children with retinoblastoma derived from hospital sheets treated at Pediatric Oncology department of National Institute of Child Health, Karachi from January 2007 to December 2015 using specially designed Performa after informed consent from parents.</p><p><bold>Results</bold>: Out of 176 patients with Retinoblastoma, 99 (56%) were male and 77 (44%) were females, age range was 2‐ 120 months, average (mean ± S.D.) age was 42 ± 21.1 months. 50% clinically presented with orbital proptosis. 69.8% of children were referred from outside Karachi. Bilateral disease was significantly high in children below 2 years of age (31.6%) as compared to children above 2 years (11.5%) P< 0.05. Family history of Retinoblastoma was negative in all children with bilateral tumors. There was a mean time lag of 11.8 months between appearance of first symptom and consultation with the Oncologist. 24.4% patients were referred with tumor recurrence after primary enucleation and its frequency was high in children above 5 years of age [10 (52.6%) out of 19 children] as compared to patients below 5 years [33 (21.0%) out of 157 children] (p<0.01).56 patients (32 %) had metastatic disease and CNS involvement was noticed in 39 patients.</p><p><bold>Conclusions</bold>: High frequency of advanced stage disease suggests late referrals to the treatment facility and a significant percentage of children were registered with tumor recurrence, these findings reflect lack of multidisciplinary approach in patient management. Therefore, integrated efforts are needed to create awareness among masses and healthcare personnel for early referrals and uniformity in patient evaluation and management.</p></sec><sec id="pbc26772-sec-10630"><label>PO-047</label><title>Effective Parameters at Diagnosis and Relation of Clinical Stage of the Disease in Children with Retinoblastoma</title><p><underline underline-style="single">E. Unal Cabi</underline><sup>1</sup>, D. Kavlak Akar<sup>1</sup>, N. Tacyildiz<sup>1</sup>, H. Dincaslan<sup>1</sup>, K. Gunduz<sup>2</sup>, G. Yavuz<sup>1</sup></p><p><italic><sup>1</sup>Ankara Üniversity Faculty of Medicine, Pediatric Hematology‐Oncology, Ankara, Turkey; <sup>2</sup>Ankara Üniversity Faculty of Medicine, Ophthalmology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: RB cases are diagnosed in advanced intraocular stages and with orbital /metastatic disease in Turkey.We aimed to determine the duration of diagnosis & the parameters that affect this period, with the relation to clinical stage.</p><p><bold>Design/Methods</bold>: We enrolled 100 RB patients. The data obtained through a survey of the families. Patients' files were reviewed for the clinical stage, exact date of diagnosis, starting date of treatment, which can not be obtained from the family. In the questionnaire addressed to the parents; the parameters that could be effective during the clinical diagnosis & stage were questioned. The duration between detection of first symptom and diagnosis were evaluated with dividing into parts such as patient related delayed diagnosis, delayed diagnosis due to the doctor and delayed treatment.</p><p><bold>Results</bold>: The age of diagnosis 21day‐5 years, with median 11mos. Common finding was leucocoria in 59% & strabismus in 32% of patients. Family related delay of diagnosis was 2‐450 days. median 9 days, doctor related 0 ‐416 days, median 5,5 days. The total diagnosis delay range 3‐640 days median of 42.5days. The eyes were Group E 44%, Group D 16.5%,19% Group C, 13% Group B 7,5%Group A. 64% of patients underwent enucleation in group E & the delay in diagnosis was longer than the other groups. In the families with low SES patient‐related diagnosis delay was higher than patient‐related diagnosis delay in families with high SES Familial RB retinoblastoma patients were diagnosed at an earlier stage,3%,71%,23% and 3% of the patients were diagnosed by first,second, third, fourth ophthalmologist, respectively.</p><p><bold>Conclusions</bold>: In our study, the delay time of RB diagnosis was shorter than some studies. However, more than half of our patients were diagnosed at advanced intraocular stages. We think that the most important and effective parameters in delayed diagnosis are insufficient awareness of families and especially healthcare workers.</p></sec></sec><sec id="pbc26772-sec-10640"><title>Solid Non Brain Tumours ‐ Liver Tumours</title><sec id="pbc26772-sec-10650"><label>PO-048</label><title>Localized Focal Nodular Hyperplasia of Liver in Children, 9 Cases, 5 Years Experiences</title><p><underline underline-style="single">W. han</underline><sup>1</sup></p><p><italic><sup>1</sup>Beijing Children's Hospital, Department of Surgical Oncology, Bei Jing, China</italic></p><p><bold>Background/Objectives</bold>: To evaluate the clinical diagnosis and treatment of focal nodular hyperplasia(FNH) in children of liver.</p><p><bold>Design/Methods</bold>: 9 cases of focal nodular hyperplasia of liver confirmed by operation and pathology in our hospital from 2006 to 2012 were investigated retrospectively.</p><p><bold>Results</bold>: The age of onset ranged from 1‐11 years old. Primary clinical manifestation: 3 cases for fever, 1 case for vomiting, 1 case for abnormal liver function, 1 case for abdominal distension, 2 cases for abdominal pain, 1 case for intussusception, 1 case for tumor family history (lung cancer). All lesions were found by imaging.3 cases of alpha‐fetoprotein (AFP) measuring mildly elevated, 6 cases were normal, 1 case of β‐HCG increased, 8 cases were normal. Hepatitis B virus infection of 1 patient was positive. Pathological performance of 9 cases were typical, all patients underwent gross surgical resection, no complications and death postoperatively as well as perioperatively. AFP decreased to normal after surgery in 3 cases, the other two cases were not investigated. Liver function abnormality ameliorated after surgery. 5‐10 year follow‐up, all patients survived with event free.</p><p><bold>Conclusions</bold>: The genetic predisposition of FNH is not obvious. The disease can lead to abnormal liver function and AFP. The misdiagnosis is common although not fatal. Surgical resection is important for treatment also for ruling out the other malignancy of liver.</p></sec><sec id="pbc26772-sec-10660"><label>PO-049</label><title>Living‐Related Transplantation of a Liver in Children with Hepatoblastoma</title><p>A. Ijovskyi<sup>1</sup>, O. Kotenko<sup>2</sup>, G. Klymnyuk<sup>3</sup>, <underline underline-style="single">O. Belokon</underline><sup>4</sup>, M. Grigorian<sup>2</sup>, M. Stezhka<sup>3</sup>, A. Popov<sup>2</sup>, A. Gusev<sup>2</sup>, A. Grinenko<sup>2</sup>, D. Fedorov<sup>2</sup>, A. Korshak<sup>2</sup></p><p><italic><sup>1</sup>National Cancer Institute MPH of Ukraine, Pediatric Oncology, Kiev, Ukraine; <sup>2</sup>National Institute of Surgery and Transplantology named after O.O. Shalymov, Liver Transplantation, Kiev, Ukraine; <sup>3</sup>National Cancer Institute, Department of Pediatric Oncology, Kiev, Ukraine; <sup>4</sup>National Cancer Institute, Pediatric Oncology, Kiev, Ukraine</italic></p><p><bold>Background/Objectives</bold>: Malignant liver tumors make 1 – 2% of a number of all tumors of the child age, with yearly incidence of 1,5 cases per million of children aged up to 15 years.</p><p><bold>Design/Methods</bold>: At the posthoc analysis as of from 2008 to 2014 in Ukraine at the stage of surgical treatment of hepatoblastomas in children 7 living‐related transplantations of a liver were performed, among them: orthotopic transplantation of the lateral section of a liver from the live relative donor (mother) was executed to five patients at the stage of surgical treatment, to one patient ‐ hepatectomy, total pancreatectomy, gastroduodenectomy, splenectomy, extended lymphadenectomy, esophagojejunostomy, mesocaval shunting, orthotopic transplantation of the left lateral section of the liver from the live relative donor (mother) with cava portal transposition, and the transplantation concerning recurrence of hepatoblastoma after left‐sided expanded hepatectomy was executed to one patient.</p><p>Average age of children to whom the living‐related transplantation of a liver was carried out made 2,7 years. Chemotherapy according to the clinical protocol SIOPEL 3 was carried out to all patients, group of high risk.</p><p><bold>Results</bold>: The average time of the execution of the operation made 14,5 hours. In the postoperative period biloma of the resective surface of the graft developed in 1 patient, it was removed by way of ultrasound‐controlled puncture. Complete remission of the disease was recorded in all 7 patients to whom living‐related transplantation of the liver was executed. The five‐year survival rate of patients with hepatoblastoma to whom transplantation of the liver was executed makes 100%, the five‐year survival of the graft made 100%.</p><p><bold>Conclusions</bold>: Executing the living‐related transplantation of a liver in children with hepatoblastoma of a liver is a difficult stage of multimodality therapy demanding considerable material and technical support and it allows to achieve good remote results statistically authentically.</p></sec></sec><sec id="pbc26772-sec-10670"><title>Solid Non Brain Tumours ‐ Germ Cell Tumours</title><sec id="pbc26772-sec-10680"><label>PO-050</label><title>CCHE Experience in High Risk Malignant Extracranial Pediatric Germ Cell Tumors</title><p><underline underline-style="single">O. Arafah</underline><sup>1,2</sup>, S. Ahmad<sup>1,2</sup>, G. Taha<sup>3</sup>, N. elkinaai<sup>5</sup>, M. Elwakeel<sup>6</sup>, W. Rashed<sup>7</sup>, M. essam<sup>8</sup>, D. Elgalaly<sup>8</sup></p><p><italic><sup>1</sup>National Cancer Institute. Cairo University, Pediatric Oncology, Cairo, Egypt; <sup>2</sup>57357 Hospital. Cairo, Pediatric Oncology, Cairo, Egypt; <sup>3</sup>57357 Hospital. Cairo, Pediatric Oncology, Cairo, Egypt; <sup>4</sup>57357 Hospital. Cairo, Surgical Oncology, Cairo, Egypt; <sup>5</sup>57357 Hospital. Cairo, Pathology, Cairo, Egypt; <sup>6</sup>57357 Hospital. Cairo, Radiodiagnosis, Cairo, Egypt; <sup>7</sup>57357 Hospital. Cairo, Clinical Trial Unit, Cairo, Egypt; <sup>8</sup>57357 Hospital. Cairo, Clinical Research, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Suboptimal outcomes remain for several groups of patients with malignant extracranial germ cell tumors (MGCTs), including patients with extragonadal tumors, advanced and metastatic diseases. Future studies should be directed toward intensifying therapy for those poor risk groups with long term follow up for late effects.</p><p><bold>Design/Methods</bold>: High risk patients with MGCTs treated at CCHE were retrospectively analysed for epidemiological and survival outcomes. They were treated according to the protocol adopted from AGCT01P1 for high risk from July 2007 till end of December 2015. All patients were followed up until June 2016.</p><p><bold>Results</bold>: 75 out of 122 eligible patients with MGCTs were high risk. Mean age was 4.8 years with male to female ratio 1:4. Extragonadal tumors were 56 cases (42 females and 14 males), versus 19 ovarian cases. Sacrococcygeal sites predominates in females while mediastinal followed by sacrococcygeal sites predominates in males. Main histological types in extragonadal cases were Yolk sac tumor followed by Mixed GCT and Germinoma. Main histological types in ovarian cases were Dysgerminoma followed by Yolk sac tumor and Mixed GCT. In Extragonadal sites, Five years OS were 77.8 % and 62.8 % for stage III and IV respectively while Five years EFS were 74.3 % and 67.8 % for stage III and IV respectively. In ovarian cases, Five years OS and EFS were 100% for stage III and 33.3% for stage IV. No significant P value in five years OS and EFS between those below 11 years of age and above.</p><p><bold>Conclusions</bold>: Poor outcome for high risk (MGCTs) necessitates more intensified therapy especially for metastatic tumors. Improved risk stratification systems, novel approaches and more efficient salvage protocols are needed to improve the outcome of those poor risk patients.</p></sec><sec id="pbc26772-sec-10690"><label>PO-051</label><title>Primary Retroperitoneal/Abdominal Germ Cell Tumour in Children: Challenges in Management</title><p><underline underline-style="single">B. kumar</underline><sup>1</sup>, V.D. upadhyaya<sup>1</sup>, S. kumar<sup>2</sup>, R.N. rao<sup>3</sup></p><p><italic><sup>1</sup>Sanjay Gandhi Post Graduate Institute of Medical Sciences, Paediatric Surgical Superspeciality, Lucknow, India; <sup>2</sup>Sanjay Gandhi Post Graduate Institute of Medical Sciences, Radiodiagnosis, Lucknow, India; <sup>3</sup>Sanjay Gandhi Post Graduate Institute of Medical Sciences, Pathology, Lucknow, India</italic></p><p><bold>Background/Objectives</bold>: Primary extra‐gonadal germ cell tumours are rare and account for only 1 – 4% of all germ cell tumours. Prognosis is usually excellent after complete excision but peri‐operative management is a distinct challenge. Aim of this study is to present peri‐operative problems and morbidity associated with management of these tumours.</p><p><bold>Design/Methods</bold>: We retrospectively evaluated the patients having non‐renal retroperitoneal/abdominal masses from July, 2012 to July, 2016 at our centre from hospital records with diagnosis of germ cell tumour. Details of patients were reviewed including demography, clinical presentations, investigations, peri‐operative problems, pathology, management, final outcome and follow‐up.</p><p><bold>Results</bold>: From July, 2012 to July, 2016, 11 patients with retroperitoneal/abdominal germ cell tumour were managed. Diagnoses were yolk sac tumour (YST) in 3 patients and teratoma in 8 patients. 4 patients were female and age ranged from 2.5 months to 6 years (median age 14 months). 2 patients had respiratory problems while 3 had sub acute bowel obstructions at the time of presentation. Patients with YSTs and 2 patients with immature teratoma received chemotherapy. Almost complete excision performed in all patients. Peri‐operative problems include excessive bleeding (2), excision of part of adjacent organ (2), hypothermia and respiratory problems and chemo related toxicity (1). Adhesive bowel obstructions occurred in 5 patients with in 3 month of post surgery in which 4 required re‐explorations and adhesiolysis. 2 patients were died while 2 were lost in follow‐up. Rest patients are under follow‐up without recurrence. Follow‐up period ranged from 6 – 45 months.</p><p><bold>Conclusions</bold>: The management of retroperitoneal/abdominal germ cell tumour (GCT) is challenge. Various surgical difficulties and morbidity associated with resection of these tumours depends on clinical presentation, size and site of tumour and age of patient.</p></sec><sec id="pbc26772-sec-10700"><label>PO-052</label><title>Twenty Years' Experience in the Management of Childhood Germ Cell Tumors</title><p>R.E. Senay<sup>1</sup>, O. Dogru<sup>1</sup>, <underline underline-style="single">A.G. Tokuc</underline><sup>1</sup>, N. Eker<sup>1</sup>, B. Yilmaz<sup>1</sup>, B. Berk<sup>1</sup></p><p><italic><sup>1</sup>Marmara University Medical Faculty, Paediatric Oncology, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Germ cell tumors (GCT) account for 2‐3% of childhood tumors. It is most commonly seen under 3 years and over 12 years old. GCTs are most commonly localized in the gonads. We have examined our patients who diagnosed and treated with GCT at our center retrospectively.</p><p><bold>Design/Methods</bold>: Sixty two children and adolescence who were diagnosed and treated with GCT at our center between 1996 and 2016 analyzed retrospectively.</p><p><bold>Results</bold>: The patients age ranged between 5 days to 17 years. Thirty‐five of patients were girls (57%) and 27 were boys (43%). The most common tumor localization with 29(47%) patients was gonads. Sixteen patients (25,8%) had metastatic disease at presentation. The most common histologic subtype was mature teratoma with 14 (22%) patients and 14 patients (22%) with yolk sac tumor. Alpha‐fetoprotein (AFP) was elevated in 29 (46%) of cases whereas beta‐human chorionic gonadotropin (β‐hCG) was elevated in only 4 (4%) of cases. Twenty‐two cases (35%) were treated with total surgical resection and they didn't receive chemotherapy. Six patients (10%) received radiotherapy in addition to surgery and chemotherapy. Thirty‐three patients (53,3 %) received BEP (bleomycin, etoposide, cisplatin) as a first line chemotherapy. During the follow up 6 (10 %) patients had relapsed. Five years overall survival rate of our patients was 95%, retrospectively.</p><p><bold>Conclusions</bold>: Germ cell tumors have favorable outcome in children. These tumors can be cured with surgical resection followed by cisplatin‐based chemotherapy and radiotherapy for selected patients. As a result of our own data analysis, it has been found that our survival rates are similar to current literature data.</p></sec></sec><sec id="pbc26772-sec-10710"><title>Solid Non Brain Tumours ‐ Rare Tumours</title><sec id="pbc26772-sec-10720"><label>PO-053</label><title>Intracranial Inflammatory Myofibroblastic Tumor: Efficacy of Crizotinib</title><p>F. Chambon<sup>1</sup>, S. Bohrer<sup>1</sup>, J.L. Michel<sup>2</sup>, A. Chamouine<sup>3</sup>, M. Jehanne<sup>1</sup>, <underline underline-style="single">Y. Reguerre</underline><sup>1</sup></p><p><italic><sup>1</sup>CHU Félix Guyon, Pediatric Hematology‐Oncology, Saint Denis De La Reunion, Reunion; <sup>2</sup>Chu Félix Guyon, Pediatric Surgery, Saint Denis De La Reunion, Reunion; <sup>3</sup>CH Mayotte, Pediatric Department, Mamoudzou, Mayotte</italic></p><p><bold>Background/Objectives</bold>: Inflammatory myofibroblastic tumors (IMT) are rare tumors in children and young adults, considered to be intermediate malignancies and rarely metastasizing. About 50% of IMT present an anaplastic lymphoma kinase (ALK) rearrangement. We report the case of a 15‐year‐old girl, who developed a lung tumor and brain metastasis with a limited ALK amplification, who was treated with crizotinib.</p><p><bold>Design/Methods</bold>: In December 2015, the patient arrived in Mayotte hospital for cough and hemoptysis for one year. She also had 2 seizures after her arrival. Radiological thoracic explorations showed a 9cm tumor in the left inferior lobe and brain MRI showed five gadolinium‐enhancing brain lesions, especially one of 6.5cm in the frontal lobe. Microscopic partial brain tumor resection was performed. The pulmonary tumor was completely removed by lobectomy. Both pathological exams showed an IMT negative for ROS1 but over‐expressing ALK with a rearranged form in 12 to 15% of cells. Steroids (2mg/kg) alone during 2 weeks and then chemotherapy (Methotrexate/Vinblastine) were introduced but did not improve neurological lesions. Crizotinib was initiated as compassionate at a dose of 250mg twice daily.</p><p><bold>Results</bold>: Crizotinib is a chemical inhibitor of ALK and mesenchymal‐epithelial transition, but it also inhibits ROS1‐rearranged tyrosine kinase receptors. It has been shown to be effective in non–small‐cell lung carcinoma and has also been tested successfully in other ALK‐driven tumors, notably large‐cell anaplastic lymphoma and certain paediatric cancers. Previous reports suggested that crizotinib cannot cross the blood‐brain barrier and may be unable to control CNS IMT. In this case, complete remission on brain metastasis was achieved after 6 weeks of crizotinib despite multiple brain localizations and low ALK positive tumor cells rate. No recurrence of thoracic nor brain lesion was observed after a year.</p><p><bold>Conclusions</bold>: This case suggests that ALK‐targeted therapy by crizotinib may strengthen current strategies against IMTs, even in CNS tumors.</p></sec><sec id="pbc26772-sec-10730"><label>PO-054</label><title>Treatment of Kaposiform Hemangioendothelioma with Kasabach‐Merritt Phenomenon by Corticosteroids and Vincristine: Experience of the Children's Hospital 1, Ho Chi Minh, Vietnam</title><p><underline underline-style="single">T. Nguyen</underline><sup>1</sup>, A. Phan<sup>1</sup></p><p><italic><sup>1</sup>Children's Hospital 1, Hematology‐Oncology, Ho Chi Minh, Vietnam</italic></p><p><bold>Background/Objectives</bold>: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with over 70% of cases associated with Kasabach‐Merritt phenomenon (KMP), a life‐threatening constellation of thrombocytopenia, coagulopathy and purpura. We reported the results of corticosteroids and vincristine in the management of KHE with KMP.</p><p><bold>Design/Methods</bold>: We retrospectively analyzed the medical records of patients with KHE and KMP who were treated with corticosteroids and vincristine at Children's Hospital 1, Ho Chi Minh, Vietnam from January 2013 to December 2015.</p><p><bold>Results</bold>: Six cases, median age 3 months (1‐16 months) with a male:female ratio of 1:1 were treated by corticosteroids and vincristine. All patients had large KHE developing from the lumbar region (33.3%), extremities (33.3%), face (16.7%) and retroperitoneum (16.7%). Clinical manifestation included anemia and purpura (100%), gastrointestinal bleeding (16.7%), infection and ulceration at the hemangioendothelioma (16.7%) and acute respiratory distress due to the presence of tumoral compression (33.3%). At diagnosis, the median platelet count and fibrinogen levels was 10.5x10<sup>9</sup>/L (4‐17x10<sup>9</sup>/L) and 0.8 g/L (0.6‐0.9 g/L) respectively. The duration of corticosteroid therapy was 23±6 weeks. Vincristine was given intravenously at 0.05 mg/kg per dose weekly for four times, followed by monthly for six times. Only one out of 6 patients with partial response had to use vincristine for 9 months. The rates of complete, partial and no response were 50% (3/6 cases), 33.3% (2/6 cases) and 16.7% (1/6 cases) respectively with a median follow‐up of 15 months. The platelet counts normalized after 3.6 ±1.2 weeks. Fibrinogen levels returned to normal after 3.3±0.8 weeks. Reduction in size of the tumor by 50% was achieved after 4.2±0.5 weeks, and by 80% after 27.2±8.9 weeks. The recurrence rate of KMP was 33.3% (2/6 cases). Vincristine had mild and transient side effects compared to corticosteroids.</p><p><bold>Conclusions</bold>: First‐line therapy with corticosteroids and vincristine is one of the options for unresectable KHE with KMP.</p></sec></sec><sec id="pbc26772-sec-10740"><title>Solid Non Brain Tumours ‐ Histiocytosis</title><sec id="pbc26772-sec-10750"><label>PO-055</label><title>A Case of Juvenile Xanthogranuloma Involving Bone Marrow During Treatment of A Pre‐B Acute Lymphoblatic Leukemia</title><p><underline underline-style="single">J.E. Park</underline><sup>1</sup>, O.K. Noh<sup>2</sup></p><p><italic><sup>1</sup>Ajou University School of Medicine, Pediatrics, Suwon, Republic of Korea; <sup>2</sup>Ajou University School of Medicine, Radiation Onvology, Suwon, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Juvenile xanthogranuloma (JXG) is a rare benign disorder which is one of the diseases classified as non‐Langerhans cell histiocytosis, whose etiology and pathogenesis is still unclear. JXG is generally characterized by solitary or multiple cutaneous nodules which resolve spontaneously over a few years. However, it is uncommonly possible to present extra‐cutaneous disorder and progress symptomatic systemic disorder through involving multiple organs.</p><p><bold>Design/Methods</bold>: We review the chart a case of systemic JXG involving bone marrow, multiple bone and skin during treatment of acute lymphoblastic leukemia.</p><p><bold>Results</bold>: The adolescent patient suffered unexplained prolonged fever, scalp pain, hip joint pain, and right knee joint pain for 2 weeks during treatment in the course of interim maintenance chemotherapy. According to the pathologic findings of bone marrow, there is no evidence of leukemia relapse but finding diffuse infiltration of histiocytes with several Touton‐type giant cells; positive for CD68, negative for CD1a, S‐100 protein. Bone and skin biopsies confirmed the same findings. Symptoms have been resolved since maintenance chemotherapy which included vincristine, dexamethasone, 6‐mercaptopurine and methotrexate. Bone marrow involvement of JXG is very rare and has been reported to occur only less than 1 year of age, but this case is reported in 16‐years‐old boy during acute lymphoblastic leukemia treatment.</p><p><bold>Conclusions</bold>: We experienced a systemic JXG involving bone marrow, multiple bone and skin during treatment of acute lymphoblastic leukemia.</p></sec></sec><sec id="pbc26772-sec-10760"><title>Brain Tumours</title><sec id="pbc26772-sec-10770"><label>PO-056</label><title>Tumors of the Central Nervous System in the First Year of Life. One Single Institution Experience</title><p><underline underline-style="single">M. Garcia‐Ariza</underline><sup>1</sup>, A. Echebarria Barona<sup>1</sup>, R. Lopez‐Almaraz<sup>1</sup>, R. Adan Pedroso<sup>1</sup>, N. Bilbao Salcines<sup>1</sup>, A. Ricondo De Diego<sup>1</sup>, I. Ojinaga Niño<sup>1</sup>, L. Galbarriatu Gutierrez<sup>2</sup>, E. Ruiz de Gopegui Ruiz<sup>2</sup>, O. Aurtenetxe Saez<sup>3</sup>, I. Martin Guerrero<sup>3</sup>, L. Zaldumbide Dueñas<sup>4</sup>, A. Navajas<sup>1</sup>, I. Astigarraga Aguirre<sup>1</sup></p><p><italic><sup>1</sup>Hospital Universitario Cruces, Pediatric Hematology and Oncology Unit, Cruces‐ Bilbao, Spain; <sup>2</sup>Hospital Universitario Cruces, Neurosurgery Unit, Cruces‐ Bilbao, Spain; <sup>3</sup>Hospital Universitario Cruces, Biocruces Health Research Institute, Cruces‐ Bilbao, Spain; <sup>4</sup>Hospital Universitario Cruces, Pathological Anatomy Unit, Cruces‐ Bilbao, Spain</italic></p><p><bold>Background/Objectives</bold>: Central nervous system (CNS) tumors in the first year of life are a very specific pediatric brain tumor group, with difficulties in the diagnosis and treatment. They associate a worse prognosis and more sequelae compared to older children. We reviewed our series and experience.</p><p><bold>Design/Methods</bold>: A retrospective study of infants under one year of life diagnosed with CNS tumors from 2001 to 2016. Clinical, histological, treatment and sequelae data were collected.</p><p><bold>Results</bold>: Fourteen infants were identified. Males were 57%. Median age at diagnosis was 6 months (range 0‐10). Most were supratentorial and without dissemination (93% in both cases). No CSF was positive. Astrocytic tumors represented the largest group of tumors (50%), most of them were low grade glioma (71%). Embryonal, neural, choroid plexus and melanocytic tumors were 22%, 14%, 7% and 7% respectively. No ependymal tumor was reported. Therapies included surgery 93% (partial resection 43%, biopsy 29%, and complete resection 21%), chemotherapy 43% and high‐dose chemotherapy (HDCH) 7%. No radiation therapy was administered in any case. Survival was 57% with a median follow up of 30 months. Among the survivors, the most frequent sequelae were neurological (75%) and ophthalmological (62.5%). Only in one case there was no sequel.</p><p><bold>Conclusions</bold>: In our review, survival in infants diagnosed with CNS tumors in the first year of life was 57%, and significant sequelae were observed. Localized supratentorial masses without dissemination was the most common presentation but neurosurgical procedures achieved complete resection in only 21%. Radiotherapy was avoided. Management of CNS tumors at this age is more complicated. The role of HDCH remains to be defined.</p></sec><sec id="pbc26772-sec-10780"><label>PO-057</label><title>Diffuse Leptomeningeal Glioneuronal Tumour: A Case Report</title><p><underline underline-style="single">S. Guram</underline><sup>1</sup>, J. Suththanantha<sup>1</sup>, B. Messahel<sup>1</sup>, K. Allinson<sup>2</sup></p><p><italic><sup>1</sup>Addenbrookes Hospital, Department of Paediatric Oncology, Cambridge, United Kingdom; <sup>2</sup>Addenbrookes Hospital, Department of Pathology, Cambridge, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Diffuse leptomeningeal glioneuronal tumor (DL‐GNT) is a rare brain tumor with a distinct molecular profile and aggressive biological behavior. These lesions often present with insidious onset and can progress rapidly leading to death with a median survival reported as 22 months. The natural history of this rare entity is not fully understood.</p><p><bold>Design/Methods</bold>: We describe a rare case of DL‐GNT diagnosed on post mortem. A 23 month old boy presented with weight loss and vomiting. A MRI of the head and spine demonstrated extensive leptomeningeal spread in the spinal and intracranial compartments, suggestive of a neoplastic process. A leptomeningeal biopsy revealed a low grade primary glial lesion. There were no operative options and he was therefore commenced on treatment on the SIOP LGG2 Study. However he demonstrated progressive disease in spite of chemotherapy both radiologically and clinically with loss of speech and seizures. He later developed hydrocephalus and a ventriculo‐peritoneal shunt was inserted. He deteriorated and passed away at the age of 4 years.</p><p><bold>Results</bold>: The macroscopic, histological and molecular findings were characteristic of diffuse leptomeningeal gioneuronal tumour.</p><p>Immunohistochemically, the tumour cells expressed S100 and synaptophysin. They were negative for CD34, NeuN, GFAP and mutant IDH‐1. The MIB‐1 proliferation index was less than 1%. Interphase fluorescent in situ hybridisation (iFISH) showed a concurrent BRAF‐KIAA1549 gene fusion and loss of 1p36.</p><p><bold>Conclusions</bold>: This case demonstrates the need for biological markers to be integrated with clinic‐pathological markers in order for both diagnostic and prognostic risk stratification.</p></sec><sec id="pbc26772-sec-10790"><label>PO-058</label><title>Retrospective Analysis of Our Patients with Pons Glioma</title><p><underline underline-style="single">D. İNCE</underline><sup>1</sup>, D. Kizmazoglu<sup>1</sup>, M. Erdem<sup>1</sup>, A. Demiral<sup>2</sup>, R. Cetingoz<sup>2</sup>, H. Guleryuz<sup>3</sup>, K. Mutafoglu<sup>1</sup>, and N. Olgun<sup>1</sup></p><p><italic><sup>1</sup>Dokuz Eylul University Institute of Oncology, Dept. of Pediatric Oncology, Izmir, Turkey; <sup>2</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiation Oncology, Izmir, Turkey; <sup>3</sup>Dokuz Eylul University Faculty of Medicine, Dept. of Radiodiagnostics, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: To evaluate characteristics and treatment responses of with diffuse pons glioma in our center</p><p><bold>Design/Methods</bold>: Medical files of patients with malignant CNS tumors between 1987‐2017 were analyzed retrospectively. There were 23 patients with pons glioma. Three of them went to another center, one of them diagnosed as demyelinizan disease and other one as encephelatic lesion laterly. These 5 patients excluded and 18 patients found evaluable.</p><p><bold>Results</bold>: The median age at diagnosis was 7 yrs (2.6‐18yrs), M/F:1.25. Age distrubution: <5 yrs 4 patients, 5‐10 yrs 8 patients, 10‐18 yrs 6 patients. The most frequent complaints: cranial nerve paralysis (61%), visial impairment (56%), headache (44%), power loss (44%) and speech disorder (%33).</p><p>Surgery was performed to extrinsic component of mass in 3 patients. Sixteen patients received radiotherapy. Two patients died before RT, on 2th week and sixth month. RT total doses varied between 50‐60 Gy. Thirteen patients were received chemotherapy, four patients died before chemo, an one patient is still receiving RT. Chemotherapy protocoles were changed over the years: MOPP (Mechlorethamine, vincristine, prednisone, procarbazine) in 3 patients, NOPP (Nitrosourea, vincristine, prednisone, procarbazine) in 2 patients, ICE (Ifosfamide, carboplatin, cisplatin) in five patients, oral cyclophosphamide in one patient, temozolamide in one patient and bevacizumab in one patient. Median progression free survival rate was 6mos (2weeks ‐18mos). Progression free survival rate for 6mos was 82%, for one year was 22%, for 18mos was 0%. Median dead time was 9.5mos (2 weeks‐2yrs). One year, 18mos, and two years overall survival rates were 52%, 39% and 13% respectively.</p><p><bold>Conclusions</bold>: Diffuse pons glioma is a group of tumor in which the helplessness experienced in treatment. Despite radiotherapy and chemotherapy, patients are still dying. The progression free and overall survival rates of patients were similar to literature. But we need new therapy agents which will improve the progression free survival rates.</p></sec><sec id="pbc26772-sec-10800"><label>PO-059</label><title>Into Cancer‐Free World with the Use of Mitotic Crossing Over Inhibitors</title><p><underline underline-style="single">P. Ivanovski</underline><sup>1</sup>, L. Garavelli<sup>2</sup>, I. Ivanovski<sup>2</sup>, A. Ivanovski<sup>3</sup></p><p><italic><sup>1</sup>Children's University Hospital, General Pediatrics, Belgrade, Serbia; <sup>2</sup>Arcispedale Santa Maria Nuova‐IRCCS‐ Reggio Emilia‐ Italy., Clinical Genetics Unit‐ Department of Obstetrics and Pediatrics‐, Reggio Emilia, Italy; <sup>3</sup>University of Belgrade, Chemical Faculty, Belgrade, Serbia</italic></p><p><bold>Background/Objectives</bold>: Achivment of new SIOP mission: No Child Shoud Contract Cancer.</p><p><bold>Design/Methods</bold>: A comprehensive reading of papers on cancer epidemiology and pathogenesis, and creating an own theory for cancer prevention.</p><p><bold>Results</bold>: There are no literature data about neoplasms which originate from terminally differentiated cells (TDCs) such as Purkinje neurons, Betz neurons, and alpha motoneurons. This indicates that carcinogenesis cannot occur in cells not having mitotic potential, and consequently there is no mitotic crossing over (MCO) and no loss of heterozygosity (LOH), a mechanism responsible for the disabling of tumor suppressor genes. All known cancers so far, have been derived from cells possessing mitotic activity. Cancer is just a “privilege” of these cells. Larger body cell burden, longer life, means more mitoses, more MCO, more LOH and greater chances for cancer development.</p><p><bold>Li–Fraumeni syndrome</bold>(LFS) is a rare, autosomal dominant, hereditary disorder that pre‐disposes carriers to cancer development, because of <bold><italic>germline heterozygous</italic></bold> TP53 mutation. This mutation is present in all body cells, including TDCs. Classical and most frequent LFS malignancies are sarcomas, cancers of the breast, brain (especially glioblastomas), adrenocortical carcinoma, leukemias and lymphomas. Despite exaggerated predisposition for cancer development, no cancer originating from TDCs has been seen in LFS persons, so far. In all malignant cells of all tumors in LFS, <italic>homozygous TP53 mutation (LOH at TP53)</italic> is present, which is generated by MCO events during mitoses of the cells.</p><p><bold>Conclusions</bold>: Experiments on TP53+/− mice (an animal LFS model) must be done, protecting the mice with MCO inhibitors (rad51, rad52, rad53 inhibitors, commercially available). If these experiments result in cancer prevention, then the scientists must search for MCO inhibitor which would be orally supplemented to all humans during the life. Presently, the drug of choice is Acidum Acetylsalicylicum. Before its use as cancer chemoprevention, the molecule must be modified, to be eliminated its hemorrhagic side effects.</p></sec><sec id="pbc26772-sec-10810"><label>PO-060</label><title>Treatment Results of Who Grade III Ependymomas at EGE University Hospital</title><p>A. Sahin<sup>1</sup>, <underline underline-style="single">M. Kantar</underline><sup>1</sup>, H. Hekimci Ozdemir<sup>1</sup>, K. Serra<sup>2</sup>, S. Aksoylar<sup>1</sup>, N. Cetingul<sup>1</sup>, Y. Anacak<sup>2</sup>, T. Turhan<sup>3</sup></p><p><italic><sup>1</sup>Ege University School of Medicine, Pediatrics‐ Pediatric Oncology Division, Izmir, Turkey; <sup>2</sup>Ege University School of Medicine, Radiation Oncology, Izmir, Turkey; <sup>3</sup>Ege University School of Medicine, Pediatric Neurosurgery, Izmir, Turkey</italic></p><p><bold>Background/Objectives</bold>: Prognosis of grade III ependymoma changed over the years, and requires multi‐institutional approach. In this analysis we aimed to analyze demographic features and treatment results of anaplastic ependymoma at our institution.</p><p><bold>Design/Methods</bold>: Thirteen patients aged mean 78 months (30‐192) were diagnosed to have WHO grade III ependymoma after surgery. There were 7 female, 6 male. Tumor location was infratentorial and spinal in 11 patients (85%) and supratentorial in 2 patients.</p><p><bold>Results</bold>: In treatment, 10 patients were amenable to gross‐total resection while, 3 underwent subtotal resection. Nine out of 13 patients were given CS radiation therapy (54 Gy primary, 36 Gy spinal), three cranial radiation only, and one primary spinal irradiation.</p><p>As chemotherapy regimen, except two patients treated with vincristine, procarbazine and prednisolone, other patients were treated according to the POG posterior fossa study (cisplatinum plus etoposide for 3 cycles, cyclofosfamide plus vincristine for 8 cycles). Seven patients were also given intratecal methotrexate weekly for leptomeningeal involvement.</p><p>Mean duration of follow‐up is 114 months (5‐312). During this period three patients recurred and died of disease. In survival analysis, 5‐year EFS rate is 70.5%, and OS rate is %70.5.</p><p><bold>Conclusions</bold>: Grade III ependymomas are difficult group of tumors. Surgery followed by radiation are the standard treatment type. In analysis, resection type or tumor site were not significantly related with prognosis.</p></sec><sec id="pbc26772-sec-10820"><label>PO-061</label><title>Ependymomas in Children: A Retrospective Analysis of 22 Cases</title><p><underline underline-style="single">C. Karadeniz</underline><sup>1</sup>, A. Okur<sup>1</sup>, F.G. Pinarli<sup>1</sup>, A. Borcek<sup>2</sup>, A. Poyraz<sup>3</sup>, H. Bora<sup>4</sup></p><p><italic><sup>1</sup>Gazi University School of Medicine, Pediatric Oncology, Ankara, Turkey; <sup>2</sup>Gazi University School of Medicine, Pediatric Neurosurgery, Ankara, Turkey; <sup>3</sup>Gazi University School of Medicine, Pathology, Ankara, Turkey; <sup>4</sup>Gazi University School of Medicine, Radiation Oncology, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: To evaluate the clinical characteristics and long‐term outcome of pediatric patients with ependymoma.</p><p><bold>Design/Methods</bold>: A total of 22 patients (13 boys and 9 girls) with newly diagnosed ependymoma between 1993 and 2016 were retrospectively evaluated. An analysis of the demographic, histological and clinical data including the treatment modalities, follow‐up and survival analyses were made. Histopathological examination was evaluated according to World Health Organization (WHO) classification and tumors are classified as low‐grade (WHO Grade I‐II), and high‐grade (WHO Grade III) ependymomas.</p><p><bold>Results</bold>: The median age at the time of diagnosis was 8.7 years. The median follow‐up time was 17.5 months (range: 1‐236 months). The most common site of ependymomas was posterior fossa region (68.2%). Primary tumor localization were spinal cord in 3 patients. There were thirteen and nine patients with WHO Grade II and III histology, respectively. Two patients had evidence of spinal metastatic disease at diagnosis. Treatment consisted of surgery, radiotherapy, and chemotherapy. Gross total resection and subtotal resection were achieved in 11 (50.0%) and 10 (45.5%) cases, respectively. Radiotherapy was administered to 17 patients and 8 patients received also chemotherapy. The most frequently used regimens were platinum‐based. Three patients experienced tumor progression/relapse. Ten patients were alive without disease. Ten year overall and event free survival rates of all patients were %71 and %42, respectively. There were no statistically significant differences in overall and evet‐free survivals of the patients when compared according to subgroups consisting of grade (II vs III), gross total and less than gross total surgery, and with or without adjuvant chemotherapy (p>0.05).</p><p><bold>Conclusions</bold>: Ependymomas are locally invasive tumors with occasional spinal metastases. Despite multimodality treatment including surgery, radiotherapy and chemotherapy, the event‐free survival rates are not satisfactory. The role of the chemotherapy for ependymomas needs to be defined in larger series and clinical trials.</p></sec><sec id="pbc26772-sec-10830"><label>PO-062</label><title>Pediatric Intracranial Germ Cell Tumors: A Single Institutional Experience</title><p><underline underline-style="single">C. Khaiman</underline><sup>1</sup>, S.L. Laohasurayothin<sup>1</sup>, K. Chiangthong<sup>1</sup>, P. Techavichit<sup>1</sup>, D. Sosothikul<sup>1</sup>, P. Seksarn<sup>1</sup>, S. Shuangshoti<sup>2</sup></p><p><italic><sup>1</sup>King Chulalongkorn Memorial Hospital, Division of Pediatric Hematology and Oncology‐ Department of Pediatrics, Bangkok, Thailand; <sup>2</sup>Chulalongkorn University, Department of Pathology‐ Faculty of Medicine, Bangkok, Thailand</italic></p><p><bold>Background / Objectives: Background</bold>: Intracranial germ cell tumors (IGCTs) are considered rare with highly curable neoplasms. The incidence of IGCTs in Eastern Asia is high as compared to western countries.</p><p><bold>Objectives</bold>: To study clinical characteristics and outcomes of children with IGCTs.</p><p><bold>Design/Methods</bold>: A retrospective review in patients diagnosed with IGCTs at Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016.</p><p><bold>Results</bold>: Eighteen patients were diagnosed with IGCTs (11 males and 7 females). Age ranged from 5 to 14 years (median 10.5 years). Presenting symptoms were consisted of hydrocephalus (9 patients), weakness (2 patients), diabetes insipidus (2 patients), visual disturbances (3 patients) and increase intracranial pressure (2 patients). Histopathological diagnosis was germinoma in ten patients (55.6%), yolk sac tumor in 2 patients (11.1%) and mixed germ cells in 5 patients (27.8%).</p><p>Elevated markers were revealed in approximately 25% of patients. Tumor sites were pineal gland (7 patients), suprasellar (5 patients) thalamic and cerebellar (1 patient each) while the rests were multifocal. Four patients had leptomeningeal involvement. Treatment included total removal in three, partial removal in four while the rest underwent biopsy. Adjuvant chemotherapy was given in all patients. Radiotherapy was given in 16 patients and craniospinal radiation (CSI) was given in leptomeningeal metastasis. With the median follow up of 26 months, five patients experienced relapse, four of them died of disease. Overall survival is 88.9% in germinomatous IGCT and 37% in non‐germinomatous IGCTs.</p><p><bold>Conclusions</bold>: Treatment outcomes of germinomatous IGCTs are favourable while the outcomes of leptomeningeal metastasis and non<italic>‐</italic>germinomatous IGCTs are poor. Innovation of therapy should be developed to improve outcomes.</p></sec><sec id="pbc26772-sec-10840"><label>PO-063</label><title>Evaluation of Acute Toxicities and Treatment Outcomes for Pediatric Medulloblastoma Patients Treated with Craniospinal Irradiation (CSI)</title><p><underline underline-style="single">T. Mehmood</underline><sup>1</sup></p><p><italic><sup>1</sup>Shaukat Khanum Memorial Cancer Hospital and Research Centre, Radiation Oncology, Lahore, Pakistan</italic></p><p><bold>Background/Objectives</bold>: We retrospectively report the acute toxicities and outcomes of pediatric medulloblastoma patients treated with CSI using cranial and spinal posterior‐anterior photon at our institution.</p><p><bold>Design/Methods</bold>: From September 2011 to August 2013, 19 patients were treated. Standard‐risk patients received 23.4 Gy (RBE) CSI and tumor bed boost to 54 Gy (RBE); high‐risk (HR) 36Gy (RBE) and 55.8 Gy (RBE), respectively (2 with spine boosts of 5.4Gy (RBE) and 12.6 Gy (RBE)). All patients received concurrent weekly vincristine. 3 HR patients received additional daily carboplatin. Toxicities were documented according to CTCAEv4.</p><p><bold>Results</bold>: Median age was 10.3 years (range 3.7‐17.4). 11 were female, 14 were standard‐risk. At baseline, mean neuropsychological abilities across a broad range of performance based measures and parent reported functioning were in the average range (Wechsler IQ Mean=101.86, SD=13.18, Range 76‐115). Most toxicities were grade 1‐2 (G1‐2). The only G3+ toxicities were: nausea/vomiting (G3, n=3), anorexia (G3, n=9, max weight loss G2), decreased hemoglobin (G3, n=3), leukopenia (G3, n=3; G4, n=1) and thrombocytopenia (G3, n=1). The patient with G4 leukopenia also had G3 thrombocytopenia; she had high‐risk medulloblastoma, treated with spine boost, vincristine and carboplatin. G3+ bone marrow toxicity occurred in 4/5 HR patients and all patients receiving carboplatin. Hepatic and renal toxicities were mild. Of 8 patients with available audiograms, at median 11.3 months from end of RT (range 6.6‐26.6), 5 had mild‐moderate hearing loss, 3 had none. Of 8 patients for whom detailed post‐radiotherapy imaging was available, none had radiation necrosis. Follow‐up data were available for 16 patients. At median follow up of 13.8 months (range 3.8‐24.5), 14 are alive without disease, 1 is alive with cerebellar and thecal sac recurrences, and 1 is alive with ventricular recurrence.</p><p><bold>Conclusions</bold>: The CSI technique is safe and well‐tolerated. The observed GI, bone marrow, hepatic, and renal toxicities depend on chemotherapy regimen.</p></sec><sec id="pbc26772-sec-10850"><label>PO-064</label><title>Clinical‐Epidemiological Characteristics of Central Nervous System Germ Cell Tumors in Children and Adolescents at the Edgardo Rebagliati Martins National Hospital During the Period 1998‐2016</title><p><underline underline-style="single">G.G. paredes</underline><sup>1</sup>, E. Guzman<sup>1</sup></p><p><italic><sup>1</sup>Rebagliati Hospital, Oncology Pediatric, Lima, Peru</italic></p><p><bold>Background/Objectives</bold>: Brain germinal tumors are infrequents but good prognosis by multimodal treatment.</p><p><bold>Design/Methods</bold>: Descriptive, retrospective study of brain germinal tumor under 18 years.</p><p><bold>Results</bold>: Population of 3,263 cases oncologics, 447 patients with brain tumors where nine were brain germ cell tumors during the last 18 years. Mean age 8.2 years, five boys and four girls, male:female sex ratio 1:2. Race: indian 55.5%, white 44.4%. Clinic: headache and vomiting 100%, diplopia 77.7%, polyuria 66.6%, ptosis and seizures 11.1%. Four suprasellar region, three sellar region, one bifocal and one infrasellar. Two‐thirds had diabetes insipidus requiring vasopressin, 44.4% had hormone deficiencies requiring corticosteroids and thyroid hormone, one t presented low growth hormone. At diagnosis, five patients underwent radical sub‐total resection (55.5%), three patients underwent a biopsy only and one patient underwent a gross total resection. Histopathology: germinoma in seven patients (77.7%) and non‐ germinomatous in two cases (both immature teratomas); no patients demonstrated chromosomal deletions or translocations. Serum alpha‐fetoprotein was elevated in one of seven cases of germinomas and elevated HCGβ in the two cases of immature teratoma. The first case was an eight years old boy diagnosed in 1998 who received radiotherapy alone after surgery and relapse‐death six months later. Since 1999, chemotherapy has been administered complementary to surgery and radiotherapy with four courses of carboplatin‐etoposide, alternated with ifosfamide‐etoposide. At the time of this report, seven patients (77.7%) are alive and in remission of disease, with an overall survival of 730 months and a median survival of 81.1 months</p><p><bold>Conclusions</bold>: Germinal tumors of the CNS are uncommon in Peru as opposed to germinal gonadal tumors. Brain germinal tumors are more frequent in boys, with the suprasellar localization and the germinoma subtype being the most frequent. Chemotherapy complementary to surgery and radiotherapy demonstrates a good response and avoids the need for a second surgery with high survival</p></sec><sec id="pbc26772-sec-10860"><label>PO-065</label><title>Ectopic Meningioma of the Frontal Bone in a 14‐Years‐Old Boy Followed by a Frontal Subdural Meningioma ‐ Case Report</title><p><underline underline-style="single">K. Zakrzewski</underline><sup>1</sup>, E. Nowosławska<sup>1</sup>, W. Grajkowska<sup>2</sup>, P.P. Liberski<sup>3</sup>, M. Zakrzewska<sup>3</sup></p><p><italic><sup>1</sup>Polish Mother's Memorial Hospital ‐ Research Institute, Department of Neurosuregry, Łódź, Poland; <sup>2</sup>The Children's Memorial Health Institute, Department of Pathology, Warsaw, Poland; <sup>3</sup>Medical University of Łódź, Department of Molecular Pathology and Neuropathology, Łódź, Poland</italic></p><p><bold>Background/Objectives</bold>: Intracranial meningiomas are relatively rare tumors in children accounting for less than 5% of all primary brain tumors, part of them affecting patients with genetically‐dependent phakomatoses or children post CNS irradiation. Ectopic meningiomas of the skull bone are extremely rare entity in a pediatric population.</p><p><bold>Design/Methods</bold>: We describe here the case of a 14‐years‐old boy presented with a 6‐months history of a slow‐growing solid mass of the right frontal bone. CT examination revealed tumor, 60 x 80 mm in diameter, located within the right frontal bone with destruction of its normal layers and visibly marked spiculated periosteal reaction. MRI examination confirmed right frontal bone tumor, 72 x 70 x 19 mm in diameter, slightly compressing adjacent brain structures. After contrast administration there was a small homogenous enhancement of the tumor with marked fragmentary enhancement of adjacent dura suggesting possible infiltration. No other intracranial abnormalities were noted.</p><p><bold>Results</bold>: The bone tumor was resected totally with subsequent cranioplasty, no infiltration of the dura was observed. In histological examination transitional meningioma (WHO grade I) was diagnosed. In the series of following MRI examinations slowly growing subdural, extracerebral mass in the same region was noted, One year after the iniltial surgery, the patient was operated on again. Subdural meningioma attached to the inner wall of the dura, was resected with the subsequent duraplasty. Histological examination revealed transitional meningioma (WHO grade I) identical as tumors located within the bone. Two‐years postoperative follow‐up was uneventful, with no tumor recurrence on MRI examinations.</p><p><bold>Conclusions</bold>: Ectopic meningioma of childhood may present as a separate tumor of the skull, without macroscopically visible crossing and destroying the dura. However it may be followed by a second, subdural extracereballar tumor of the same histological pattern.</p></sec></sec><sec id="pbc26772-sec-10870"><title>Treatment and Care ‐ Surgery (IPSO)</title><sec id="pbc26772-sec-10880"><label>PO-066</label><title>Sacrococcygeal Tumors in Patients with and without Anorectal Malformations: A Single Institution Comparative Study</title><p>C. Reck<sup>1</sup>, <underline underline-style="single">A. Vilanova Sanchez</underline><sup>1</sup>, T. Maloof<sup>1</sup>, L. Weaver<sup>1</sup>, J. Stanek<sup>2</sup>, M.A. Levitt<sup>3</sup>, R.J. Wood<sup>3</sup>, J.H. Aldrink<sup>4</sup></p><p><italic><sup>1</sup>Nationwide Children's Hospital, Pediatric Surgery‐ Center for Colorectal and Pelvic Reconstruction, Columbus, USA; <sup>2</sup>Nationwide Children's Hospital, Biostatistics‐ Hematology/Oncology/Bone Marrow Transplantation, Columbus, USA; <sup>3</sup>Nationwide Children's Hospital‐ The Ohio State University College of Medicine, Pediatric Surgery‐ Center for Colorectal and Pelvic Reconstruction, Columbus, USA; <sup>4</sup>Nationwide Children's Hospital‐ The Ohio State University College of Medicine, Pediatric Surgery, Columbus, USA</italic></p><p><bold>Background/Objectives</bold>: Despite variability at presentation, sacrococcygeal tumors (SCT) in patients with and without anorectal malformations (ARM) appear histologically similar. The purpose of this study was to identify differences in oncologic outcomes between these two groups.</p><p><bold>Design/Methods</bold>: A retrospective review was performed utilizing our institutional cancer database and colorectal/pelvic reconstruction database for patients with sacrococcygeal or presacral masses between 1990‐2017. Data captured included age at surgical resection, Altman classification, histopathology, recurrence, and follow‐up.</p><p><bold>Results</bold>: Forty‐five patients comprised our cohort, 12 had ARM. Median age at resection was older with ARM (15 months; range 2 days to 17.7 years) than without ARM (<1 month; range 1 day to 6.9 years) (p=0.05). All patients with ARM had Altman type 4 tumors, and histopathology included mature teratoma (8), yolk sac tumor (1), lipoma (1), and unknown (2). Altman classification for patients without ARM included type 1 (9), type 2 (9), type 3 (1), type 4 (7), and unknown (7). Histopathology for patients with SCT without ARM included mature teratoma (20), immature teratoma (7), malignant teratoma/germ cell tumor (4), ganglioneuroma (1), and unknown (1). Altman classification was statistically different between the groups (p<0.0001). There were 7 recurrences, 3 with ARM (25%) at a median time of 3.6 years, and 4 without ARM (12%) at a median time of 1.8 years. Recurrences were not statistically different between the two groups (p=0.36). Three of the recurrences were due to failure of coccyx resection (2 in the ARM group). 5 ‐year event free survival was 64.3% (95% CI: 15.1% ‐ 90.2%) in the ARM group and 86.9% (95% CI: 64.3% ‐ 95.6%) in the no‐ARM group.</p><p><bold>Conclusions</bold>: Presacral masses in patients with ARM are resected at a later age, are more likely to have higher Altman classification, and have a high rate of recurrence without complete removal of coccyx at initial operation.</p></sec><sec id="pbc26772-sec-10890"><label>PO-067</label><title>Caval Replacement in Pediatric Surgical Oncology: Evidences from 3 Cases</title><p><underline underline-style="single">C. Grimaldi</underline><sup>1</sup>, A. Bertocchini<sup>1</sup>, A. Crocoli<sup>1</sup>, A. Castellano<sup>2</sup>, A. Serra<sup>2</sup>, L. Monti<sup>3</sup>, A. Inserra<sup>1</sup></p><p><italic><sup>1</sup>Bambino Gesù Children's Hospital ‐ IRCCS, Surgery, Rome, Italy; <sup>2</sup>Bambino Gesù Children's Hospital ‐ IRCCS, Oncohematology, Rome, Italy; <sup>3</sup>Bambino Gesù Children's Hospital ‐ IRCCS, Radiology, Rome, Italy</italic></p><p><bold>Background/Objectives</bold>: Caval encasement from retroperitoneal tumors is a rare complication in pediatric malignancies. Data about extensive tumor resections with simultaneous caval replacement in adults are scant. Furthermore, only few reports exist on in the pediatric population. In adults, indications to this challenging surgery are mainly oncological (absent or inadequate response to chemotherapy) or clinical (treatment of symptoms of caval obstruction: renal failure, lower limb edema). In children, this procedure is still considered a salvage treatment without clearly extablished indications.</p><p><bold>Design/Methods</bold>: Data were retrospectively collected from our Institution Cancer Data Base from January 2009 to February 2017.</p><p><bold>Results</bold>: Three patients (2 adrenal neuroblastomas, 1 renal cell carcinoma) underwent tumor resection and inferior vena cava (IVC) replacement. One patient with neuroblastoma underwent a auto transplantation of the kidney. One patient is alive a disease free 37 months after surgery. Two patients died of recurrence of the disease 26 and 21 months after surgery, respectively. In one patient the conduit is patent at follow up (37 months), while in 2 patients thrombosis of the conduit was demonstrated at short term after surgery, at 30 and 45 days respectively. In none of those patients signs of caval obstruction after thrombosis of the conduit were experienced. In all patients the anastomosed renal veins were patent at last follow up.</p><p><bold>Conclusions</bold>: This is a small but interesting series, however it's limited to pediatric patients and has a long follow‐up. Major vascular reconstructions are possible with experienced surgeons tailoring reconstructive techniques to the anatomy and extension of the lesions with low mobility and good long‐term function.</p></sec><sec id="pbc26772-sec-10900"><label>PO-068</label><title>Systemic Response Evaluated by Curie Score is not Correlated to the Complexity and Outcome of Primary Tumor Resection in High‐Risk Neuroblastoma</title><p><underline underline-style="single">T. Hishiki</underline><sup>1</sup>, Y. Kanamori<sup>2</sup>, A. Fujino<sup>2</sup>, T. Watanabe<sup>2</sup>, K. Tahara<sup>2</sup>, M. Ohno<sup>2</sup>, T. Takezoe<sup>2</sup>, C. Kiyotani<sup>3</sup>, Y. Shioda<sup>3</sup>, D. Tomizawa<sup>3</sup>, M. Kato<sup>3</sup>, K. Terashima<sup>3</sup>, T. Osumi<sup>3</sup>, O. Miyazaki<sup>4</sup>, M. Kitamura<sup>4</sup>, K. Matsumoto<sup>3</sup></p><p><italic><sup>1</sup>National Center for Child Health and Development, Surgical Oncology, Tokyo, Japan; <sup>2</sup>National Center for Child Health and Development, Pediatric Surgery, Tokyo, Japan; <sup>3</sup>National Center for Child Health and Development, Children's Cancer Center, Tokyo, Japan; <sup>4</sup>National Center for Child Health and Development, Radiology, Tokyo, Japan</italic></p><p><bold>Background/Objectives</bold>: The role of surgical resection in the treatment of high‐risk neuroblastoma has been a matter of debate. Some postulated the advantage of aggressive surgery, indicating that complete tumor resection leads to a better prognosis. However, this is questioned with the speculation that tumors responding better to chemotherapy are likely to be removed easily compared to chemoresistant tumors. We conducted a retrospective review of our institutional experience to eliminate the correlation between response to induction chemotherapy and surgical resectability</p><p><bold>Design/Methods</bold>: Medical records of 27 patients with metastatic neuroblastoma who underwent definitive surgery at our institute from 2002 to 2014 were reviewed. Systemic response to induction chemotherapy was evaluated using the Curie score (CS), a 123I‐MIBG scintigraphy‐based quantitative parameter for metastatic diseases. Surgical outcome of cases with one or more CS at the end of induction chemotherapy were compared to those whose CS were eradicated.</p><p><bold>Results</bold>: Twenty‐three cases had tumors of abdominal origin and four had mediastinal tumors. We used IDRF, which is a measure to predict safe resection of low‐ and intermediate‐ risk neuroblastoma, to evaluate the predicted complexity of definitive surgery. Clearance of IDRF by induction chemotherapy did not correlate to the clearance of CS. As a result of surgery, >90% resection was obtained in 22 cases, while five cases resulted in <90% resection. There were no statistical correlation between CS and extent of resection. The presence of CS was a significant predictor of lower overall survival, whereas the extent of surgery did not affect the overall and event‐free survival.</p><p><bold>Conclusions</bold>: Our study suggests that a good response to induction chemotherapy evaluated by Curie score does not guarantee an easier, complete resection of the primary tumor. There are tumors that are easy to remove in poor responders, and vice versa. Precise evaluation using a larger cohort is warranted to verify this finding.</p></sec><sec id="pbc26772-sec-10910"><label>PO-069</label><title>Analysis of Surgery for Pediatric Solid Tumors after Centralization of Care in the Netherlands</title><p><underline underline-style="single">M. Jans</underline><sup>1</sup>, S. Terwisscha van Scheltinga<sup>1</sup>, C. van de Ven<sup>1</sup>, H. Heij<sup>1</sup>, J. Wilde<sup>2</sup>, G. Tytgat<sup>3</sup>, M. Wijnen<sup>1</sup></p><p><italic><sup>1</sup>Prinsess Máxima Center, Pediatric Surgery, Utrecht, The Netherlands; <sup>2</sup>Hôpitaux universitaires de Genève, Pediatric Surgery, Genève, Switzerland; <sup>3</sup>Prinsess Máxima Center, Pediatric Oncology, Utrecht, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: Since 2015 all surgical care for pediatric solid tumors in The Netherlands has been centralized at the Princess Máxima Center for Pediatric Oncology in Utrecht. The aim of this study is to evaluate surgical complications and mortality for both neuroblastoma (NBL) and Wilms tumors (WT) since the start of centralization.</p><p><bold>Design/Methods</bold>: A prospective observational cohort study was conducted including all children diagnosed and treated for either neuroblastoma or WT between 2015‐2017 at the Princess Máxima Center. Surgery related complications and mortality were documented. Outcome was compared with our pre‐centralization cohort of pediatric solid tumors between 1998‐2014.</p><p><bold>Results</bold>: [1] Primary tumor resection for NBL was performed in 33 children. Peroperative complication rate was 27% (vs. 42%). Short‐term postoperative complication rate was 42% (vs. 43%). Postoperative PICU support due to complications was necessary for 3% (vs. 5%). Secondary surgery for complications was performed in 6% (vs. 8%). No surgery related mortality occurred (vs. 2%).</p><p>[2] Surgery for WT was performed in 61 children. Peroperative complication rate was 6% (vs. 4%). No tumor rupture occured (vs. 2%). Short‐term postoperative complication rate was 26% (vs. 19%). No postoperative PICU support for surgical complications was necessary (vs. 2%). Secondary surgery for complications was performed in 8% (vs. 6%). No surgery related mortality occurred (vs. 0%).</p><p><bold>Conclusions</bold>: A series of surgery related complications and mortality in children treated for neuroblastoma and Wilms tumors since the start of centralized pediatric oncological care in The Netherlands is analyzed. Peroperative complication rate for neuroblastoma has clearly improved since the start of centralized care. Percentage of surgery related adverse events for Wilms tumors is similar.</p></sec><sec id="pbc26772-sec-10920"><label>PO-070</label><title>Our Experience with Staged Nephron Sparing Surgery in Synchronous Bilateral Wilms Tumour</title><p><underline underline-style="single">Z. Jenovari</underline><sup>1</sup>, Z. Karady<sup>2</sup>, E. Varga<sup>2</sup>, M. Csoka<sup>2</sup>, T. Budi<sup>2</sup></p><p><italic><sup>1</sup>Semmelweis University, 2nd. Department of Pediatrics, Budapest, Hungary; <sup>2</sup>Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary</italic></p><p><bold>Background/Objectives</bold>: In bilateral Wilms tumour the primer nephrectomy on the more affected side and nephron sparing surgery on the other side was accepted method, but follow up studies proved the worsening of kidney function. There are no evidences yet regarding the optimal way to preserve the maximal renal tissue and to provide sufficient oncological treatment.</p><p><bold>Design/Methods</bold>: We retrospectively analysed the data of patients treated in our unit with synchronous bilateral Wilms tumour in the last 10 years.</p><p><bold>Results</bold>: 5 patients were found; all were infants at the first admission (av. 5 month). Male/female ratio: 1/4. None had pulmonary metastasis, or lymph node enlargement.</p><p>2 patients underwent primer surgery, the first patient bilateral enucleation, the other unilateral nephrectomy. After chemotherapy both patient underwent further operation, the first patient unilateral nephrectomy; the other wedge resection of the contralateral tumour. Both patients had postoperative chemotherapy, and both have worsening kidney function on the follow up.</p><p>3 patients underwent staged nephron‐sparing surgery started on the less affected side after preoperative chemotherapy. The timing of the operation was determined by regular MRI or US. None of these patients underwent biopsy. The histology (taken at the operation) was favorable in 2, unfavorable in one case. The 2<sup>nd</sup> stage contralateral nephron‐sparing surgery attempted after further chemo cycles, the timing was determined by radiology, and also followed by chemotherapy. None of the patients got radiotherapy. All but one patient is tumour free, all has both side significant renal tissue, and all has normal kidney function. One tumour recurrence occurred; nephron‐sparing surgery was done.</p><p>The mean follow up is 4 years (8 months‐8 years)</p><p><bold>Conclusions</bold>: The preoperative chemotherapy may decrease the rate of nephrectomy. The staged nephron sparing surgery carried out after preoperative chemotherapy, with interval and postoperative chemotherapy seems safe and effective way to preserve the maximal amount of renal tissue.</p></sec><sec id="pbc26772-sec-10930"><label>PO-071</label><title>Outcome of Bilateral Wilms Tumor: Experience from a Single Tertiary Care Centre from India</title><p><underline underline-style="single">B. Jindal</underline><sup>1</sup>, K. Sambandan<sup>1</sup>, K.K. Govindaranjan<sup>1</sup>, B.K. Naredi<sup>1</sup></p><p><italic><sup>1</sup>JIPMER, Department of Pediatric Surgery, Pondicherry, India</italic></p><p><bold>Background/Objectives</bold>: Approximately 5‐7% of children with Wilms tumor present with bilateral disease. Bilateral WT are usually associated with the presence of nephrogenic rests, congenital malformations and predisposing syndromes. The major challenge in bilateral disease is to achieve a cure and at the same time to preserve sufficient functional renal tissue for normal growth and development. Renal failure is major contributor (12%) of morbidity and mortality. We planned to review the cases of bilateral WT treated at our institute, and factors contributing to their morbidity and mortality.</p><p><bold>Design/Methods</bold>: Retrospective review of case records of bilateral WT treated at our hospital, from year 2009 to 2016 and their outcome.</p><p><bold>Results</bold>: Total of 6 cases of bilateral WT were operated over the last 7 years. Of these six cases. Five were synchronous and one had metachronous bilateral WT; two had syndromic association, one each with Denysh Drash Syndrome and WAGR syndrome, of which one had additional associated horse shoe kidney anomaly. Two underwent sequential partial nephrectomy for synchronous bilateral WT, two had simultaneous nephrectomy and tumorectomy, and one with horse shoe kidney with bilateral WT underwent left nephrectomy and partial nephrectomy on other side. Of these six patients, three expired, two lost to follow up and only one is doing well at 2.5 year follow up.</p><p><bold>Conclusions</bold>: Renal failure is a major contributor of morbidity/mortality in bilateral WT and the incidence is high in developing countries due to late presentation. The associated glomerulopathy with Denysh Drash syndrome and WAGR syndrome in which condition the incidence of renal failure increases to 50% and 90% respectively. Nephron sparing surgery (NSS) should be the aim to prevent renal insufficiency, rather than achieving a negative surgical margin which can be dealt with radiotherapy. Sequential nephrectomy or simultaneous NSS still a debatable point which cannot be conferred from this small study.</p></sec><sec id="pbc26772-sec-10940"><label>PO-072</label><title>Peripherally Inserted Central Catheters by Pediatric Surgeons for Children with Cancer: Initial Experience from a Developing Country</title><p><underline underline-style="single">W.E. Oliveira Júnior</underline><sup>1</sup>, F.F. Gonçalves<sup>1</sup>, V. Kremer<sup>1</sup>, R.C. Ribeiro<sup>1</sup></p><p><italic><sup>1</sup>Barretos Childrens Cancer Hospital, Pediatric Surgery Department, Barretos, Brazil</italic></p><p><bold>Background/Objectives</bold>: A long‐term venous access is essential in children when treating malignant diseases. Peripherally inserted central catheters (PICCs) have been shown to be a valuable alternative to traditional devices providing central access for this patients. PICCs have been used for many years in developed countries, but there are few studies focused on pediatric oncology patients in developing countries. The purpose of this study was to evaluate our initial experience with PICCs specially with regard to feasibility, catheter life, complications and reason for removal in children with cancer in a developing country pediatric hospital.</p><p><bold>Design/Methods</bold>: A retrospective analysis of all pediatric oncology patients who underwent PICC line insertion by the pediatric surgery team at our institution from March 2016 to March 2017 were enrolled in the study. Demographic features, primary diagnosis, catheter days, reason for removal and complications were reviewed.</p><p><bold>Results</bold>: Forty‐six PICCs were inserted into 40 children during the 12‐month period. Median catheter life was 40 days, ranging from 2 to 287 days, with a total of 3046 catheter days. Complication rate of 6.23 per catheter days was recorded. The common reasons for catheter removal were suspected infection, occlusion, dislodgement, and breakage with rates of 3.28, 2.29, 0.98, and 0.32 per 1,000 catheter days, respectively. When compared to solid tumors, hematological malignancies had a higher median catheter permanence (46 vs. 35 catheter‐days), and Lymphomas showed the highest median with 84 catheter‐days.</p><p><bold>Conclusions</bold>: PICC lines are feasible and provides reliable long‐term intranegativenous access in children suffering from malignancies. Although better care and proper dressings are important to minimize premature removals and suspected infection. Education for both parents and nursing team and guidelines are needed to improve complication rates.</p></sec><sec id="pbc26772-sec-10950"><label>PO-073</label><title>Tumour Biopsies ‐ Reaching the Core</title><p><underline underline-style="single">J. Burns</underline><sup>1</sup>, D. Wanaguru<sup>1</sup>, I. Nicklaus‐Wollenteit<sup>2</sup>, S. McGuirk<sup>3</sup>, D. Hobin<sup>4</sup>, S. Arul<sup>1</sup>, M. Pachl<sup>1</sup></p><p><italic><sup>1</sup>Birmingham Children's Hospital, Department of Paediatric Surgery and Urology, Birmingham, United Kingdom; <sup>2</sup>Birmingham Children's Hospital, Department of Histopathology, Birmingham, United Kingdom; <sup>3</sup>Birmingham Children's Hospital, Department of Interventional Radiology, Birmingham, United Kingdom; <sup>4</sup>Birmingham Children's Hospital, Department of Medical Oncology, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Percutaneous renal tumour biopsies are crucial in planning neoadjuvant chemotherapy and the timing of surgical resection in the UK. The number of cores taken is operator dependant and can result in inadequate tissue for diagnosis or tumour rupture with consequent upstaging.</p><p>This study attempts to define the minimum number of cores required for diagnosis and to document the incidence of tumour rupture in relation to number of core samples taken.</p><p><bold>Design/Methods</bold>: Biopsy technique was by the ultrasound guided percutaneous method in all cases and using the coaxial technique.</p><p>This was a retrospective review of prospectively collected data. All percutaneous trucut renal tumour biopsies taken between February 2002 and September 2016 were included in the analysis. Those with inadequate data about the number of cores taken were excluded.</p><p>Data on demographics, diagnosis, diagnostic adequacy and number of cores were collected. Details of whether immunohistochemistry, genetics and tissue typing had been performed on the biopsy tissue were also collected.</p><p><bold>Results</bold>: Renal units biopsied N=103; M:F 55:48</p><p>Diagnosis included Wilms tumour in 90 cases and other tumours in 13 (Mesoblastic nephroma (2); Primitive Neuroectodermal Tumour (3); Rhabdomyosarcoma (1); Nephroblastomatosis (2); oxalosis (1); normal (1); Neuroblastoma (1); Rhabdoid (1); Desmoplastic SRCT (1)</p><p>Median number of cores (range) was 4 (1‐10). There were 6 non‐diagnostic biopsies which had a median (range) number of cores 3 (1‐6)</p><p>There was one tumour rupture following a biopsy and this patient had 7 cores taken.</p><p>The lowest number of core biopsies with 100% diagnostic accuracy was 3 and the lowest number able to give diagnosis, immunohistochemistry and genetics was 1 core.</p><p><bold>Conclusions</bold>: Three good cores are the minimum number required for diagnosis and this should be subjective and operator dependent. One single good core contains enough tissue for diagnosis, immunohistochemistry and genetics.</p><p>Further investigation for other tumour sites is ongoing.</p></sec><sec id="pbc26772-sec-10960"><label>PO-074</label><title>Possibilities of Endosurgery in Diagnosis of Tumor Diseases of of Thoracic and Abdominal Localization at Children</title><p><underline underline-style="single">D. Rybakova</underline><sup>1</sup></p><p><italic><sup>1</sup>Federal State Budgetary Institution “Russian Cancer Research Center. NN Blokhin ”of the Ministry of Health of Russia, Children oncology, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: Diagnostic endosurgery is successfully approved in adult oncology and there are data on use of this method in children oncology in foreign literature.</p><p><bold>Design/Methods</bold>: to define possibilities of endosurgery in diagnosis of tumor of thoracic and abdominal localization at children</p><p><bold>Results</bold>: From 2007 to 2012 with the diagnostic purpose it is carried out the 160th operation at 153 children, from which 63 laparoscopic and 44 thoracoscopic biopsies. Except diagnostic biopsies it was executed 53 thoracoscopic resections of lungs at 51 children for the purpose of diagnostics of progressing of a disease, confirmation of metastatic defeat or inflammatory process that made 33% of all diagnostic operations. The age of patients varied from 2 months to 19 years. And children about one year there were 9,8%. Duration the thoracoscopic and laparoscopic biopsies made from 20 minutes to 260 minutes, on average 59 minutes. Blood loss during diagnostic operations averaged 78,3 ml. Intraoperative complications are in 5 cases, and postoperative in – 8. After the endosurgery operations at 59,3% of patients special treatment was carried out, 7,4% had a repeated operation, but already in radical volume and in 33,3% were written out on continuation treatment in a residence or in profile establishment.The average time of the beginning of special treatment made 4 days.</p><p><bold>Conclusions</bold>: Advantages of use of endosurgery in children's oncology are: early terms of the beginning of special treatment, small injury, the minimum blood loss, low number of postoperative complications, early activation of the patient and reduction of terms staying in a hospital, good cosmetic effect. Performance the endosurgery of operations at children with malignant tumors it is possible aged from several weeks, thus the oncological principles of performance of surgery aren't broken, and also the age of the child isn't the limiting factor for performance the endosurgery of operations.</p></sec><sec id="pbc26772-sec-10970"><label>PO-075</label><title>Severe Combined Immunodeficiency (SCID) Mimicking as a Neuroblastoma Stage MS (NB‐MS)</title><p><underline underline-style="single">C. Sánchez‐Montenegro</underline><sup>1</sup>, A. Lizano‐Contreras<sup>1</sup>, S. Vega‐Salas<sup>1</sup>, M. Sánchez‐Salazar<sup>2</sup>, M. Delgado‐Avendaño<sup>2</sup>, Y. Gamboa‐Chaves<sup>2</sup>, J.C. Barrantes‐Zamora<sup>3</sup>, G. Ivankovich‐Escoto<sup>4</sup>, D. Matus‐Obregón<sup>4</sup>, G. Lazo‐Páez<sup>4</sup>, B. Valverde‐Rojas<sup>5</sup></p><p><italic><sup>1</sup>Hospital Nacional de Niños “Dr.Carlos Sáenz Herrera”, Pediatric Surgical Oncology‐ Oncology Service‐ Department of Hematology‐Oncology, San José, Costa Rica; <sup>2</sup>Hospital Nacional de Niños “Dr.Carlos Sáenz Herrera”, Pediatric Medical Oncology‐ Oncology Service‐ Department of Hematology‐Oncology, San José, Costa Rica; <sup>3</sup>Hospital Nacional de Niños “Dr.Carlos Sáenz Herrera”, Pediatric Surgical Oncology & Pediatric Medical Oncology‐ Oncology Service‐ Department of Hematology‐Oncology, San José, Costa Rica; <sup>4</sup>Hospital Nacional de Niños “Dr.Carlos Sáenz Herrera”, Department of Pediatric Immunology and Rheumatology, San José, Costa Rica; <sup>5</sup>Hospital Nacional de Niños “Dr.Carlos Sáenz Herrera“, Flow Cytometry Service‐ Laboratory of Specialized Studies and Research, San José, Costa Rica</italic></p><p><bold>Background/Objectives</bold>: Neuroblastoma MS has specific characteristics including presence ≤18 months of age and metastases to liver, skin, or bone marrow. The aim is present a case were a primary immunodeficiency was the etiology for the clinical findings in a child suspected of Neuroblastoma MS (NB‐MS).</p><p><bold>Design/Methods</bold>: Retrospective analysis of the medical record of a patient admitted in the National Children's Hospital (Costa Rica), which was first examined by the Oncology Service and subsequently diagnosed/treated by the Pediatric Immunology and Rheumatology Department (SIRP).</p><p><bold>Results</bold>: A 4‐months‐old female, with 2 previous admissions due to bronchiolitis and oxygen dependence, consulted for irritability, fever, and diarrhea. The mother mentioned 15 days of evolution of skin nodules. On physical examination hepatomegaly and subcutaneous nodules were documented. Abdominal ultrasound documented a solid nodule in the right adrenal gland, hepatomegaly with multiple disseminated solid nodular lesions. Upon clinical suspicion of NB‐MS, biopsy of a subcutaneous nodule and bone marrow aspirate/biopsy were performed. Skin biopsy did not report malignancy but cultured <italic>Nocardia farcinica</italic>. Bone marrow aspirate reported absence CD4/CD8 lymphocytes, and therefore assessment of the SIRP was requested. Review of previous blood counts showed persistent lymphopenia (<200/μl). Patient required hospitalization (Intensive Care Unit) for infections treatment: subcutaneous nodule/tracheobronchial aspirate with <italic>Nocardia farcinica</italic>, septicemia due to <italic>Granulicatela adiacens</italic>, tracheobronchial aspirate with <italic>Candida albicans</italic> and BCGitis. Peripheral blood lymphocyte subsets count was compatible with Severe Combined Immunodeficiency (SCID) T‐ B‐ NK+. Follow‐up abdominal ultrasound showed multiple hepatic non‐vascularized calcified nodules and a right adrenal gland´s nodule partially organized with microcalcifications. The patient received a bone marrow transplant from her HLA identical mother, 3 months after diagnosis.</p><p><bold>Conclusions</bold>: The blood count should be assessed for all neonatal/infant masses, to rule out leukopenia (Immunodeficiencies) before thinking about malignancy. Not all the classic features of NB‐MS should be classified as neoplastic origin without ruling out other pathologies.</p></sec></sec><sec id="pbc26772-sec-10980"><title>Treatment and Care ‐ New Drugs/Experimental Therapeutics</title><sec id="pbc26772-sec-10990"><label>PO-076</label><title>Early Evaluation of Precision Medicine Efficiency for Swedish Children and Adolescents with Cancer</title><p><underline underline-style="single">C. Rinaldo</underline><sup>1</sup>, J. Vigholm<sup>1</sup>, H. Haapa Hybinette<sup>1</sup>, Y. Copeland Wahlo<sup>1</sup>, P. Kogner<sup>1</sup>, M. Heyman<sup>1</sup>, C. Petersen<sup>1</sup>, A. Harila Saari<sup>1</sup>, I. Øra<sup>1</sup></p><p><italic><sup>1</sup>Karolinska University Hospital, Pediatric oncology, Stockholm, Sweden</italic></p><p><bold>Background/Objectives</bold>: Today approximately 20% of pediatric cancer patients will experience treatment failure and die of disease. Huge efforts from academics and pharmaceutics have resulted in many potential compounds to be clinically tested. ITCC – Innovative Therapies for Childhood Cancer is the umbrella organization for experimental clinical trials in Europe and currently 51 centers participate.</p><p>AIMS:To enable all Swedish pediatric patients with relapse or refractory cancer to be included into early phase clinical trials of precision medicine against their disease with the long term aims to increase survival rates and quality of life for children and adolescents with cancer.</p><p><bold>Design/Methods</bold>: The innovative clinical trial unit at the Pediatric Oncology unit at Karolinska University Hospital in Stockholm was accredited as an ITCC center in January 2016. Two senior consultants and two experienced pediatric oncology research nurses were appointed, all 50% for the time being. The need for additional research nurses and administrative staff is a priority for 2017.</p><p><bold>Results</bold>: The Working Plan is largely defined including designation of the organization structure, requirement of human resources, facilities, financial requirements, and education of the staff. The administrative work of a yearly opening of 3–4 clinical trials with approvals to the competent authorities and ethical board is finalized. 17 first patients have been enrolled in the INFORM study. Financial support has increased with the help of Barncancerfonden, Entrepreneurs of good and others (additional applications are pending).</p><p><bold>Conclusions</bold>: Initiation and management of a Phase I/II clinical trial unit for pediatric cancer patients in Sweden is of utmost significance. To be part of the future development of pediatric cancer treatment will stimulate clinicians and researchers to plan and conduct their own experimental trial questions. The unit is of important educational benefit for young health care staff during their specialization prior to pediatric cancer positions.</p></sec></sec><sec id="pbc26772-sec-11000"><title>Treatment and Care ‐ Supportive Care</title><sec id="pbc26772-sec-11010"><label>PO-077</label><title>Venous Thromboembolism in Children with Cancer</title><p>Y. Aguilar de la Red<sup>1</sup>, B. Ponce Salas<sup>1</sup>, <underline underline-style="single">C. Mara Fernandez</underline><sup>1</sup>, J. Huerta Aragonés<sup>1</sup>, E. Cela de Julian<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Oncohematology Section., Pediatric. Gregorio Marañón General University Hospital, Madrid, Spain</italic></p><p><bold>Background/Objectives</bold>: Cancer may be considered as a hypercoagulable state and therefore, venous thromboembolism is a frequent complication in adulthood. Even though it is also frequent in pediatric oncology patients, risk factors and prophilaxis/treatment are not so well described.</p><p><bold>Design/Methods</bold>: We analysed 12 patients (0‐16 years old) from 2011‐2017, who presented a thrombosis or venous thromboembolism (VTE) during cancer treatment or the follow up.</p><p><bold>Results</bold>: 12 patients were studied, 8 were female (66.6%). Median age at diagnosis of cancer was 7.2 years old (DS 5.02). Median time from cancer diagnosis to VTE was 8.13 months(DS 11.6). Symptoms were only present in 16.7% of them. Underlying malignancies were: 8 solid tumours (66,6%)(Wilms tumour the most frequent, ‐37,5%‐), 4 acute leukemias(33,3%) ‐3 lymphoblastic, 1 acute promyelocytic leukemia(APL)‐. The most common risk factor was the presence of a central venous catheter(CVC) (75%)‐8 patients‐ (41,7% Port‐a‐cath), hospitalization in 25% ‐4‐, recent surgery in 16% ‐2‐, recent treatment with corticosteroids (33%)‐4‐, with asparaginase (16 %)‐2‐, mechanical ventilation (16%)‐2‐. 7 of 10 patients (70%) were non‐0 blood group. Only 8patients had inherited thrombophilic factors studied, only 2 had any of them. Obesity and sepsis were not risk factors for VTE in our study.</p><p>5 patients (41,7%) received specific treatment for the VTE, all of them with enoxaparin at VTE diagnosis. On 3 of them therapy was substituted afterwards by acenocumarol. The duration of therapy in 2 patients(16.7%) was longer than specific malignancy treatment.</p><p>Regarding results, 6(50%) of the VTE were completely resolved, 1 patient died during APL induction treatment.</p><p><bold>Conclusions</bold>: Children with cancer are at risk to develop secondary VTE. In our small study, most common risk factors described were having a CVC placed, and solid tumour versus haematologic malignancy. There is still much to be learned about risk factors and the need of specific guidelines for treatment and prophylaxis.</p></sec><sec id="pbc26772-sec-11020"><label>PO-078</label><title>Dietary Management of Chylothorax Secondary to Mediastinal Lymphadenopathy in a Patient with Leukaemia</title><p>M.J. Crowley<sup>1</sup>, D.I. Sinha<sup>2</sup>, D.M. Caswell<sup>3</sup>, <underline underline-style="single">C. Barton</underline><sup>1</sup></p><p><italic><sup>1</sup>Alder Hey Children's Hospital NHS Foundation Trust, Department of Paediatric Oncology, Liverpool, United Kingdom; <sup>2</sup>Alder Hey Children's Hospital NHS Foundation Trust, Department of Paediatric Respiratory Medicine, Liverpool, United Kingdom; <sup>3</sup>Alder Hey Children's Hospital NHS Foundation Trust, Department of Paediatric Haematology, Liverpool, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: We report the case of a teenage patient newly diagnosed with T cell acute lymphoblastic leukaemia, presenting with chylous pleural effusions secondary to significant mediastinal lymphadenopathy. We describe our experience in the management of the condition, and a review of current literature.</p><p><bold>Design/Methods</bold>: As the patient continued to receive chemotherapy to treat his leukaemia, a conservative medical approach was taken, with intensive dietetic input to institute a minimal fat diet, incorporating an exchange system. The major dietetic challenge was providing sufficient calorie and protein intake, requiring fat free nutritional supplements (e.g. paediasure plus juice) which the patient found unpalatable. Subsequently, supplemental parenteral nutrition was commenced. As his clinical condition improved, fat content of the diet was gradually increased. Parenteral nutrition was stopped and medium chain triglyceride supplements were added, with relaxation of dietary restrictions based on clinical assessment.</p><p><bold>Results</bold>: Eventually, the chylothorax fully resolved both clinically and radiologically, through conservative management alone. The patient struggled significantly with dietary restriction, requiring significant nutritional counselling and adaptation of his diet to aid compliance.</p><p><bold>Conclusions</bold>: There are no best practice guidelines for the management of chylothorax. A single systematic review from 2015 identifies a lack of consensus in management options, with the strongest evidence coming from case reports, which are highly heterogeneous, and lacking in clinical detail. This case report provides greater detail on the crucial role of dietetic support in managing chyle leak, lacking in previous reports. Further research is needed to generate robust clinical guidance.</p></sec><sec id="pbc26772-sec-11030"><label>PO-079</label><title>The Management of Fever in Children with Cancer in the North of Scotland</title><p>T. Lawes<sup>1</sup>, <underline underline-style="single">J. Calley</underline><sup>1</sup>, L. Adam<sup>1</sup>, N. Abdelrazig<sup>1</sup>, H. Bishop<sup>1</sup>, N. Ahmad<sup>1</sup></p><p><italic><sup>1</sup>Royal Aberdeen Children's Hospital, Department of Paediatric Oncology, Aberdeen, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Outcomes in children with cancer continue to improve but febrile neutropenia remains a major cause of mortality. Early recognition and treatment‐ particularly rapid antibiotic administration‐ improves outcomes, whilst appropriate de‐escalation of care can allow safe discharge. Standards of care have been proposed by both the National Institute for Health and Care Excellence (NICE) and the Managed Service Network (MSN) for Children & Young People with Cancer in Scotland. Our aim was to audit the management of fever in paediatric oncology patients presenting to the tertiary centre in the North of Scotland and implement a quality improvement (QI) intervention to support care delivery.</p><p><bold>Design/Methods</bold>: A retrospective criterion‐based sample of the first 50 episodes of fever retrieved from case notes of paediatric oncology patients treated in the years 2013‐2015 was analysed for performance against key standards in clinical assessment, early intervention, and escalation/de‐escalation decisions.</p><p><bold>Results</bold>: The management of 52 episodes from 13 patients were analysed of which 28 were febrile neutropenia and 24 febrile non‐neutropenia. Within the target time of 60 minutes 89% of patients were assessed by a doctor, 69% of blood cultures were performed and 64% of empirical antibiotics were administered. Those with a paediatric early warning score ≥ 2 were seen earlier, and were more likely to receive antibiotics within the target time (100% vs. 55%, <italic>P=</italic> 0.013). There was 98% adherence to local empirical antibiotic policy. 61% and 93% of patients were de‐escalated appropriately at 24 and 48‐96 hours respectively.</p><p><bold>Conclusions</bold>: Clinical assessment and intervention within the first 60 minutes was identified as our key target area for QI. A febrile neutropenia management proforma has been developed. This is being implemented as part of a wider QI project alongside updates to family information, reinforcement of emergency care standards by multi‐disciplinary team scenario‐based training, and implementation of a programme of regular audit.</p></sec><sec id="pbc26772-sec-11040"><label>PO-080</label><title>Parental Decision Making and Quality of Life in Children with Cancer</title><p><underline underline-style="single">M.H. Chen</underline><sup>1</sup>, L.H. Huang‐<sup>2</sup>, W.Y. Hu<sup>2</sup>, Y.L. Lee<sup>2</sup>, K.P. Yao<sup>3</sup>, Y.C. Chang<sup>4</sup></p><p><italic><sup>1</sup>Tzu Chi University of Science and Technology, nursing, Hualien, Taiwan R.O.C.; <sup>2</sup>National Taiwan University, nursing, Taipei, Taiwan R.O.C.; <sup>3</sup>National Taiwan University, psychology, Taipei, Taiwan R.O.C.; <sup>4</sup>Tamkang University, Mathematicis, Taipei, Taiwan R.O.C</italic>.</p><p><bold>Background/Objectives</bold>: This study purpose to explore the family‘s parental treatment decision making and quality of life of having a child diagnosed with cancer in the hospital.</p><p><bold>Design/Methods</bold>: The institutional review board at the hospital approved all study procedures. Research design using a Indepth interviews and focus group discussions approach in was parents of children diagnosed with cancer in the hospital.Using a participant observation study approach for data collection and themes were uncovered from each interview data set and rigorous methods to data analysis. Record the data with the process recording in interview and participant observation. Data analysis by authors and parent.</p><p><bold>Results</bold>: The cancer treatment decisions made by the parents while their hospitalized children are being treated for cancer mainly include choosing the appropriate hospitals and treatment process. There are fourth themes of the quality of life:</p><p>(1)Physiologically: Their sleep is disturbed due to the treatments of the children; They are more prone to feeling tired or catching a cold.(2) Psychologically: They are concerned about (a) the side effects of the treatments on the children, and (b) the children's emotional changes under the invasive treatments; Feeling guilty when the other children in the family are being neglected; Feeling difficult reconciling the demands of work and caring for the sick children.(3) The changes in everyday lives: The diets are mainly composed of self‐grown food; Timely isolations in the home environments; Living in one's tribe.(4) Using the support system: The mutual support among husbands, wives, siblings, and paramedical staff.</p><p><bold>Conclusions</bold>: It was expected that findings of the study could provide family members and paramedical staff be the positive force supporting the healing of children.</p></sec><sec id="pbc26772-sec-11050"><label>PO-081</label><title>Correlation Between Neck Circumference and ARM Muscle Area in Children and Adolescents with Malignant Neoplasms</title><p>R.L. Ferretti<sup>1</sup>, <underline underline-style="single">P.S. Maia‐Lemos</underline><sup>1</sup>, K.J.T. Guedes<sup>1</sup>, E.M.M. Caran<sup>1</sup></p><p><italic><sup>1</sup>Pediatric Oncology Institute ‐ IOP/GRAACC/UNIFESP, Pediatric, Sao Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Malnutrition in children and adolescents with malignant neoplasms may be underestimated in the diagnosis of the disease when considering only the Body Mass Index. Anthropometric measures are able to detect early malnutrition. Neck circumference (NC) is a simple, inexpensive, and easily applicable measure in clinical practice. Arm Muscular Area (AMA) is recognized in the literature as a good indicator of muscle mass depletion. The main objective of this study is to verify if there is a correlation between the measurement of NC AMA.</p><p><bold>Design/Methods</bold>: A cross‐sectional study that evaluated children and adolescents between 0 and 20 years of age with malignant neoplasms at a Specialized Pediatric Oncology Institute from October 2015 to June 2016. The measurements of NC were evaluated and, for AMA calculation, arm circumference and skinfold triceps, all performed by trained evaluators, following anthropometric techniques standardized by the literature. The chi‐square test was performed to verify the association between inadequacy of AMA and the sexes, with significance level p <0.05. The correlation between NC and AMA was performed through the Pearson correlation.</p><p><bold>Results</bold>: Among 647 patients, 42,66% (276) were females. The mean age for females was 8.65 (± 5.78) and for males was 9.07 (± 6.08). The correlation between NC and AMA was linear positive and strong (r=0.80), with a higher correlation coefficient for males than for females (r=0.84 vs r=0.74). There was a significant difference between the sexes and inadequacy of AMA (p=0.01).</p><p><bold>Conclusions</bold>: It was concluded that there is a strong correlation between NC and AMA, with a higher outcome for males. In addition, NC is a simple measure, easy to apply and very useful in clinical practice.</p></sec><sec id="pbc26772-sec-11060"><label>PO-082</label><title>Emplacement of Single‐Lumen Subcutaneous Port by Angio‐Radiology Service: Our Experience in the Last Ten Years</title><p><underline underline-style="single">A. De Lucio</underline><sup>1</sup>, M. gonzalez<sup>1</sup></p><p><italic><sup>1</sup>yes, Hematology‐Oncology Department, Sta. Cruz de Tenerife, Spain</italic></p><p><bold>Background/Objectives</bold>: Emplacement of single‐lumen subcutaneous port (SSQP) in pediatric patients is a daily routine. In last years, it has also been used not only in oncologic patients but also in children with chronic diseases with little complications.</p><p><bold>Design/Methods</bold>: Medical records of pediatric patients (≤15 years of age) who underwent SSQP at our Hospital between 2005 and 2015 by Angio‐radiology Service. Variables analyzed included gender, age at diseases’ diagnostic, disease, time between diagnosis and collocation, absolute neutrophils and platelets count before procedure, vein used and complications in those years.</p><p><bold>Results</bold>: A total of 121 SSQPs placed in 105 patients (65 males and 40 females). Eighty four cases were malignant diseases (80%) and 21 no malignant (20%). Acute lymphoblastic/myeloblastic leukemia and lymphoma were the most common diagnosis (40%). Median age at diagnosis was 5.8 years (1m‐14.8 years).Time between diagnostic and collocation was 11.2 days in malignant cases (excluding two cerebral tumors and an opsoclonus syndrome). In the other group, it was 12.3 months.</p><p>Right internal jugular vein was used as the first location in all the cases. Median absolute neutrophil count before procedure was 6147/mm3 (range 0–181,000) while median platelet was 261,384/mm3 (range 9,000‐835,000). Median weight was 27 Kilogram (range 4‐77.5).</p><p>A total of 34 patients (32.3%) had some complication: 16 catheter malfunction (81.2% solved with urokinase), 20 local positive blood cultures, 6 with hematoma or skin infection, 2 broken system and 1 hemotorax. During first month, there were 13 patients with any complication (5 within first week, 2 of them during procedure).</p><p>New SSQP was placed in 13 patients for different causes (56.2% infections, 25% catheter broken/malfunction and 12.5% relapse after years).</p><p><bold>Conclusions</bold>: We conclude that SSQP is useful and safe in all pediatric patients with a low risk of complications. Their early collocation does not carry additional complications in comparison with other Services.</p></sec><sec id="pbc26772-sec-11070"><label>PO-083</label><title>Assessment of the Use of Parenteral Nutritional in Intensive and Semi Intensive Therapy Units Pediatric Oncology</title><p><underline underline-style="single">B.C. Elias</underline><sup>1</sup>, P. dos Santos Maia Lemos<sup>2</sup>, N. Dorascenzi Magri Teles<sup>1</sup></p><p><italic><sup>1</sup>Instituto de Oncologia Pediatrica, Nutrition, São Paulo, Brazil; <sup>2</sup>Instituto de Oncologia Pediátrica, Nutrition, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: Parenteral nutritional (PN) consists in provide the macro and micronutrients directly into the circulatory system for patients who are unable to receive enteral nutritional therapy (ENT). Considering that patients under cancer treatment undergo intensive treatments that compromise nutritional status, PN is an alternative to meet the patient's current needs. The present study had the goal to evaluate the use of PN in intensive care units (ICU) and pediatric oncology special care units (SCU).</p><p><bold>Design/Methods</bold>: Retrospective observational study performed at a pediatric oncology institute, which included patients aged 0 to 18 years old, hospitalized in the ICU and SCU for more than 24 hours using PN.</p><p><bold>Results</bold>: In a sample of 565 hospitalizations, 3,5% of patients had indication of PN. The main clinical diagnoses were tumors of the Central Nervous System (40%) and Osteosarcomas (15%). The main indication for PN was to the diagnosis of Typhlitis (35%). According the Body Mass Index, 60% had malnutrition and 40% eutrophy. Using the Arm Circumference, 30% were below adequate. The fasting time until the beginning of the PN ranged from 2 to 16 days. Hydroelectrolytic disorders, hemodynamic instability and scheduling of exams were the main reasons for prolonged fasting until early onset of PN.</p><p><bold>Conclusions</bold>: In cases where the enteral route is contraindicated, PN may provide better control of complex disease states, but studies analyzing its practice in pediatric oncology patients are scarce, indicating that more studies are needed.</p></sec><sec id="pbc26772-sec-11080"><label>PO-084</label><title>Use of Apheresis Platelet Concentrates: One Center Experience</title><p><underline underline-style="single">Z. salcioglu</underline><sup>1</sup>, G. Ersoy<sup>1</sup>, K. sanli<sup>2</sup>, G. Aydogan<sup>1</sup>, F. Akici<sup>1</sup>, E. Uysalol<sup>1</sup>, B. Koc<sup>1</sup>, E. Yılmaz<sup>1</sup>, C. Bayram<sup>1</sup>, A. Ayçiçek<sup>1</sup>, G.N. Ozdemir<sup>1</sup></p><p><italic><sup>1</sup>Kanuni Sultan Suleyman Training and Research Hospital ‐, Pediatric Hematology Oncology, Istanbul, Turkey; <sup>2</sup>Kanuni Sultan Suleyman Training and Research Hospital ‐, Blood Bank Department, Istanbul, Turkey</italic></p><p><bold>Background/Objectives</bold>: Thrombocytopenia is a commonly encountered problem for patients who are treated with chemotherapeutic agents. These patients are transfused by random donor platelets (RDPs) or apheresis derived platelets (ADPs) for bleeding or prophylaxis</p><p><bold>Design/Methods</bold>: This study is continued between 01 January 2012 and 30 April 2014 to assess indications to use ADPs instead of RDPs, in pediatric hematology and oncology clinic. Patients’ data are collected retrospectively from blood bank records and patients’ registry of our hospital database.</p><p><bold>Results</bold>: ADPs are reserved for 56 patients whose age between 1 to 16 years old. ALL is the most common patient group (36 patients:64,3 %), followed by the AML (12 patients:21,4 %), Wilms’ tumor (3 patients), Glanzmann thrombasthenia (2 patients), non‐Hodgkin Lymphoma (2 patients), neuroblastoma (1 patient) respectively. ADPs ordered per patient are 1 to 20 (med:6,6±4,1). ADPs are prepared as two bags mostly in form of 4+4 (92,1%), followed by 6+6 (4,5%) and 8+8 (2,2%) forms respectively. Apheresis thrombocyte was used mostly for prophylaxis no:265 (74,6%) and no:90 (25,4%) for bleeding. No mortality from bleeding is observed during study period. Platelet counts before transfusion were between 1000‐86000/mm<sup>3</sup> (med: 26.000/mm³). 30 complete unit ADPs (8,4%) and 12 one bag ADPS are disposed due to expired date of use.</p><p><bold>Conclusions</bold>: Preparation of ADP from single donor is an expensive procedure. Usage of upcoming expiration dated thrombocyte concentrates must be monitored closely by blood bank. As a result it is understood that our clinic need to revise the indications of thrombocyte concentrates use and need to focus on education about thrombocyte concentrate use.</p></sec><sec id="pbc26772-sec-11090"><label>PO-085</label><title>Assessing Nurses’ Knowledge and Skills on Identification and Management of Cytotoxic Induced Extravasation in Oncology Day Care in a Tertiary Care Hospital‐ Via Clinical Audit</title><p><underline underline-style="single">A. Feroz</underline><sup>1</sup></p><p><italic><sup>1</sup>Aga Khan University Hospital, Ibne Zohar Daycare Oncology, Karachi, Pakistan</italic></p><p><bold>Background/Objectives</bold>: Incidences of extravasations are being monitored as a key quality indicator in oncology areas, however to work more towards precision, a need for assessment of knowledge and hands on capacity of nurses in identifying and early managing of cytotoxic extravasation was identified.</p><p><bold>Design/Methods</bold>: Clinical Audit was the identified strategy for assessment, with the help of existing best practice institutional guideline, checklist was being developed; piloted on oncology nurses not working in day care oncology, and validity was gained. A clinical audit was performed from 15th July, 2016 to 5th August, 2016, in which initially observation was made on nurses’ assessment of 48 cytotoxic administration follow‐up patients. In second phase staffs were being asked to demonstrate management of extravasation in simulated based setting.</p><p><bold>Results</bold>: Around 82% of patients were being assessed for condition of last cannulated site, however only 3% of discoloration of IV sites were identified and being notified to physicians on floor. On hands on management of extravasation only 70% of nurses were able to aspirate residual cytotoxics from skin and 30% were comfortable in injecting hydrocortisone at extravsated site.</p><p><bold>Conclusions</bold>: A strong need for hands on training for extravasation assessment and management is being identified for oncology nurses. Video based and simulated based learning can be taken as a strategy for training of oncology nurses on rare occurring situations like extravasation.</p></sec><sec id="pbc26772-sec-11100"><label>PO-086</label><title>An Assessment of Central Line Associated Blood Stream Infections (CLABSI) in Southern Vietnam</title><p><underline underline-style="single">R. Huynh</underline><sup>1</sup>, V.S. Nguyen<sup>1</sup>, C. Assanasen<sup>2</sup></p><p><italic><sup>1</sup>UTHSCSA, Long School of Medicine, San Antonio‐ Texas, USA; <sup>2</sup>UTHSCSA, Pediatric Hematology/Oncology, San Antonio‐ Texas, USA</italic></p><p><bold>Background/Objectives</bold>: Though Vietnam has become one of the top 10 fastest growing economies globally, as an LMIC it still needs improvement in pediatric oncology care. Survival rates as low as 5% have been reported in Vietnam in 2008, and although it has risen beyond this point, the rates remain well below that of their Western developed counterparts. This low survival rate has been attributed to differences in chemotherapy treatments as well as inexperience with supportive care preventative measures such as central line associated blood stream infection (CLABSI) monitoring.</p><p><bold>Design/Methods</bold>: Medical directors at three institutions in Ho Chi Minh City Vietnam (City Children's Hospital, Children's Hospital #2, and Children's Hospital #1) were surveyed to determine how central line infections were identified and monitored in their pediatric hematology/oncology patient populations. Questions included whether the director was familiar with the recent ASPIC guidelines for the prevention of CLABSIs, monitoring policies, and current estimates. Education of staff using a train‐the‐trainer approach was implemented with the development of infrastructure and policies to monitor rates long term. Staff members surveyed also provide insight into gaps in care.</p><p><bold>Results</bold>: Though limited by many resources, two surveyed institutions reported the majority of their pediatric oncology patients used central lines regularly. One hospital had not yet begun caring for pediatric oncology patients. All three, however, did not have current policies or procedures in place for CLABSI monitoring. Estimated infection rates reported varied widely ranging from 10‐30%. Hospital directors have viewed initial responses to supportive care training positively. Direct observation revealed inconsistencies and unanticipated problems, such as ineffective occlusive dressing adhesive within the humid environment.</p><p><bold>Conclusions</bold>: There are no reports on the CLABSI rates in pediatric cancer hospitals within southern Vietnam. Our report represents the initiation and commitment toward this quality improvement effort. As improvement takes place over time, further details will be provided.</p></sec><sec id="pbc26772-sec-11110"><label>PO-087</label><title>Hospital Construction or Person‐to‐Person Transmission is the Source of Pneumocystis Jiroveci Pneumonia Outbreaks in Pediatric Acute Leukemia Under Prophylaxis?</title><p><underline underline-style="single">K.S. Lee</underline><sup>1</sup>, D.E. Roh<sup>1</sup>, H.R. Suh<sup>1</sup>, S.Y. Min<sup>1</sup>, T.K. Jo<sup>1</sup>, J.K. Suh<sup>1</sup>, J.Y. KIM<sup>1</sup></p><p><italic><sup>1</sup>Kyungpook National University Hospital, Department of Pediatrics, Daegu, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: After the era of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis, PCP is decreasing and rare. However, there are limited reports about transmission and disease courses of PCP in pediatric immunocompromised patients under TMP/SMX prophylaxis. Recently a cluster of PCP was reported in a hospital construction setting, we investigated this study to assess the risk factors of PCP outbreaks.</p><p><bold>Design/Methods</bold>: We retrospectively reviewed the medical records of pediatric patients who were diagnosed with hematologic malignancies and solid tumor and received chemotherapy at Kyungpook National University Children's hospital between October 2014 and March 2017. Among the patient diagnosed pneumonia during chemotherapy, medical records of patients who did not respond to empirical antibiotics therapy for community acquired pneumonia or hospital acquired pneumonia were reviewed. Clinical characteristics were reviewed.</p><p><bold>Results</bold>: From October 2014 to March 2017, four patients who received chemotherapy and TMP/SMX prophylaxis were diagnosed as proven or suspected PCP. All cases occurred within 3 months period from August to December 2016 under the hospital construction. The duration of each episode overlapped in time suggesting the possibility of person‐to‐person transmission. They were on chemotherapy with acute lymphoblastic leukemia, one on consolidation and the other three on maintenance chemotherapy. Three PCP patients during maintenance chemotherapy were clinically improved after TMP/SMX treatment and adjuvant corticosteroid therapy. The PCP patient during consolidation chemotherapy expired due to progressive acute respiratory distress syndrome and pneumothorax while receiving mechanical ventilator support. Two patients showed <italic>Pneumocystis carinii</italic> PCR positive and the other two patients showed negative results.</p><p><bold>Conclusions</bold>: The cluster of PCP is significant in terms of air borne and person‐to‐person transmission of <italic>pneumocystis</italic> in a hospital construction setting. Considering the high morbidity and mortality of PCP, respiratory isolation of suspected patients and construction environmental reservoirs control are also important in addition to accurate diagnosis and early treatment.</p></sec><sec id="pbc26772-sec-11120"><label>PO-088</label><title>Sibling Support for Children Who have been Treated for a Cancer: A Collaborative Approach</title><p><underline underline-style="single">N. Kisby</underline><sup>1</sup>, N. Shaw<sup>2</sup>, T. West<sup>2</sup></p><p><italic><sup>1</sup>Candlelighters, Family Support, Leeds, United Kingdom; <sup>2</sup>Leeds Teaching Hospitals Trust, Oncology Outreach Team, Leeds, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Candlelighters has been providing support for families affected by childhood cancer for over 40 years. As part of this support, specific sibling groups for children affected by childhood cancer have been developed. These groups are supported by wider members of the Multidisciplinary team. The overall aim in undertaking work directly with siblings, is that every brother and sister has the opportunity to receive support within an environment in which they feel safe and comfortable. Siblings are often viewed as the ‘forgotten’ group and their needs can be overlooked. As siblings try to come to terms with the severity of their brother or sister's illness this may give rise to a number of conflicting emotions.</p><p><bold>Design/Methods</bold>: The Candlelighters groups offer them the time and opportunity to be with other siblings who are in the same situation as themselves. It also gives them the opportunity to be the focus (even for just a few hours) and opportunity just to be themselves.</p><p>The groups provide the chance to talk with some of the professionals who are directly involved with the care of their families enabling them to ask questions which they may feel uncomfortable asking their families for fear of upsetting them. Most importantly it is about providing a space for the siblings to have time out and to have fun. The groups are held once per month alternating between children going through treatment and bereaved siblings. Three times per year, the groups come together for a trip. The monthly groups are held at Candlelighters (The Square).</p><p><bold>Results</bold>: “Candlelighters are fun and help me forget stuff going on at home”,</p><p>“Candlelighters help people make more friends” and</p><p>“At Candlelighters you can always say your feelings”.</p><p><bold>Conclusions</bold>: As the feedback in our results states the sibling groups provide much needed support for all siblings affected by childhood cancer.</p></sec><sec id="pbc26772-sec-11130"><label>PO-089</label><title>Breakthrough Disseminated Invasive Fusariosis Fungal Infection in a Patient with Acute Myeloid Leukemia Under Micafungin Prophylaxis, Case Report</title><p><underline underline-style="single">Y. Madney</underline><sup>1,2</sup>, S. Samir<sup>2</sup>, S. Mahmoud<sup>2</sup>, A. Salama<sup>3</sup>, M. Gaber<sup>4</sup>, K. Alsheshtawi<sup>5</sup>, L. Shalaby<sup>2</sup></p><p><italic><sup>1</sup>National cancer institute ‐ Cairo university ‐EGYPT, pediatric oncology, CAIRO, Egypt; <sup>2</sup>Children cancer hospital 57357‐ EGYPT, Pediatric oncology, Cairo, Egypt; <sup>3</sup>children cancer hospital 57357‐ Egypt, clinical pathology, Cairo, Egypt; <sup>4</sup>children cancer hospital 57357‐ Egypt, clinical microbiology, Cairo, Egypt; <sup>5</sup>children cancer hospital 57357‐ Egypt, clinical research, Cairo, Egypt</italic></p><p><bold>Background/Objectives</bold>: Invasive fusariosis, though rare, may cause disseminated infections in patients with hematological malignancies and in hematopoietic stem cell transplant recipients. The mortality attributable to Fusarium infections in immunocompromised patients ranges from 50% to 70%</p><p><bold>Design/Methods</bold>: We report a case of acute myeloid leukemia, male patient, 7 years old admitted in our hospital (Children Cancer Hospital Egypt 57357). Patient started induction chemotherapy with micafungin prophylaxis from d1 chemotherapy according to our policy. At day 20 induction patient had multiple skin lesion started as erythematous raised papules, indurated and painful with a central area of necrosis as well as target lesions and perforated nasal septum. Patient was shifted to broader spectrum liposomal amphotericin B.</p><p><bold>Results</bold>: Fusarium was isolated from Blood culture, fungal screening was done including CT Chest, sinuses and abdomen showing non specific bilateral pulmonary infiltration and sinusitis. Fundus examination was free. Biopsy taken from skin lesion showed fungal hyphae that are septated with branching and associated with round bulbous ends consistent with fusarium infection. Clinical improvement with healing and ulceration of skin lesion with resolution of pulmonary infiltration after recovery from neutropenia. Bone marrow aspirate done to assess response to treatment showed complete remission. Patient discharged on voriconazole after achieving therapeutic level. Reassessment before 2<sup>nd</sup> cycle chemotherapy showed clinical and radiological improvement, patient kept on voriconazole as secondary prophylaxis.</p><p><bold>Conclusions</bold>: Fusariosis though rare it should be suspected and covered with appropriate antifungal in presence of suspected cutaneous lesions in immunocompromised patients. Due to the lack of clinical trials and the critical role of immune reconstitution in the outcome of fusariosis, the optimal treatment strategy for patients with severe Fusarium infection remains unclear. Reversal of immunosuppression is recommended whenever possible.</p></sec><sec id="pbc26772-sec-11140"><label>PO-090</label><title>Enteral Feeding with Gastrostomy in Pediartic Oncology Patients: Complications and Limits</title><p>L. Genere<sup>1</sup>, <underline underline-style="single">P. Marec Berard</underline><sup>1</sup></p><p><italic><sup>1</sup>Institut d'hématologie et d'oncologie pediatrique IHOP, Centre Léon Berard, Lyon, France</italic></p><p><bold>Background/Objectives</bold>: Nutritional state is a major prognostic factor in pediatric oncology. Enteral feeding by gastrostomy is increasingly used to prevent and treat malnutrition in this population. The main objective of our study is to describe immediate and late complications arising after a gastrostomy placement procedure.</p><p><bold>Design/Methods</bold>: We performed a retrospective monocentric observational study of children treated between 2012 and 2016 in a pediatric oncology center and who benefited from a placement of button gastrostomy during oncological treatment.</p><p><bold>Results</bold>: thirty three patients (17 male, 16 female), mean age 10.3 years, have benefited from a button gastrostomy placement. Fourteen were malnourished at the time of diagnosis (42%), and 27 at the time of gastrostomy insertion (81%), – on average 10.7 months later. Percutaneous radiologic placement was used in 66% of cases. Prophylactic antibiotics were prescribed for 22 patients (66.7%). Enteral feeding started on average 1.7 days after procedure. The mean delay from insertion to removal was 21.3 months. We report 46 side effects (1 arising in the first 15 days and 45 later) consisting in leaks (34.4%), infection requiring general (31.2%) or local (9.4%) antibiotic treatment, vomiting (23.3%), granulation tissue formation (21.2%), bedsore(6.2%), and accidental removal (15.2%). At the time of button removal 33 % of patients were still undernourished.</p><p><bold>Conclusions</bold>: Gastrostomy feeding in chronic pediatric diseases is well described. In pediatric oncology, its benefit is not clearly demonstrated and responsible for numerous late complications which could disturb oncological treatment plan. Some of these complications could be avoided by an earlier nutritional evaluation and support.</p></sec><sec id="pbc26772-sec-11150"><label>PO-091</label><title>Exploring Nurses’ Understanding of Chemotherapy‐Induced Nausea and Vomiting in Paediatric Cancer Patients: A Quantitative Study</title><p><underline underline-style="single">E. Neumann</underline><sup>1</sup></p><p><italic><sup>1</sup>Birmignham Children's Hospital NHS Foundation Trust, Haematology/Oncology, Birmingham, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Background: Chemotherapy remains the first‐line treatment for many paediatric cancer conditions but research by Wood <italic>et al</italic>. (2015) found chemotherapy‐induced nausea and vomiting (CINV) to be the most documented distressing side‐effect of childhood cancer treatment. Research among the adult population found cancer nurses’ played an integral role in the management of CINV but their knowledge and understanding was lacking. There was no comparable data available within the paediatric field.</p><p>Aim: To explore and understand nurses’ knowledge of CINV and identify future learning needs, ultimately improving patient care through improved knowledge of symptoms by staff.</p><p><bold>Design/Methods</bold>: Method: This quantitative study adapted a previously used questionnaire to explore nurses’ understanding of CINV, working in a Principle Treatment Centre (PTC) and three, Level 3 Paediatric Oncology Shared Care Units (POSCU's) within the United Kingdom. A purposive sampling technique was utilised with a paper‐based questionnaire targeting the population of all registered nurses working at these four sites (n=143). Results were analysed using descriptive and inferential statistics to demonstrate nurses’ overall understanding and knowledge of CINV in relation to paediatric cancer.</p><p><bold>Results</bold>: Results Response rate was 51%. An overall knowledge gap existed amongst nurses at all research sites and no significant differences in the knowledge level between PTC and POSCU nurses was observed. Nurses had no awareness of the available assessment tools for CINV.</p><p><bold>Conclusions</bold>: Conclusions Nurses’ knowledge on these distressing symptoms needs to be increased in order to improve patient care and experience. The most popular choices for receiving further education were face: face and online modules while self‐directed learning featured as the least popular choice among all participants. There was a significant gap in knowledge regarding available assessment tools, therefore knowledge should be increased on this subject.</p></sec><sec id="pbc26772-sec-11160"><label>PO-092</label><title>Current Status and Challenges of Support for Pediatric Cancer Patients’ Siblings ‐ An Analysis of Ward Managers’ Free Descriptions ‐</title><p><underline underline-style="single">J. Nonaka</underline><sup>1</sup>, M. Yonayama<sup>1</sup>, S. Oka<sup>1</sup>, M. Yamazaki<sup>1</sup>, M. Uchida<sup>2</sup></p><p><italic><sup>1</sup>kanagawa University of Human Services Faculty of Health & Social Work School of, nursing, Yokosuka, Japan; <sup>2</sup>Nagano College of Nursing, Nursing, Nagano, Japan</italic></p><p><bold>Background/Objectives</bold>: A questionnaire survey was conducted on support for the siblings of children with diseases or disabilities, involving ward managers, and their free descriptions were analyzed to clarify the current status and challenges of such support.</p><p><bold>Design/Methods</bold>: subjects:Seventy ward managers supporting the siblings of children hospitalized in pediatrics throughout Japan.Data collection method and procedure: Questionnaires were distributed in envelopes to facilities which previously consented to cooperate with the study.</p><p>Analytical method: The contents of the collected descriptions were analyzed and grouped based on semantic similarities and differences to create categories. The approval of the research ethics committee of the researchers’ facility was previously obtained.</p><p><bold>Results</bold>: Respondents’ backgrounds: Among the 70 ward managers of hospitals specializing in pediatrics throughout Japan, 36 of 10 facilities responded.</p><p> supporting end‐stage pediatric patients’ siblings ; supporting siblings not allowed to enter wards> ; supporting discharge to home ; making environmental and temporal arrangements for siblings and families to stay together ; holding events for siblings ; providing explanations to siblings.</p> <p> making environmental and systematic arrangements for siblings and families to stay together ; organizing systems to take care for siblings ; developing human resources ; and performing nursing care for families. As for the status of sibling support, the respondents noted the following issues: insufficient manpower ; the risk of infection ; individualized approaches ; alternative equipment use.</p> <p><bold>Conclusions</bold>: The ward managers made environmental, temporal, and systematic arrangements, such as coordinating visits, and gave considerations with awareness. It was also noted that they carefully considered appropriate methods to support end‐stage patients’ siblings, as such support was difficult, and required sufficient consideration, highlighting the necessity of establishing systems for ward managers to provide sibling and family support.</p></sec><sec id="pbc26772-sec-11170"><label>PO-093</label><title>Factors Affecting Fatigue in Pediatric Oncology Patients</title><p><underline underline-style="single">A.M. Platschek</underline><sup>1</sup>, V. Abeln<sup>1</sup>, B. Hero<sup>2</sup>, T. Simon<sup>2</sup>, H.K. Strüder<sup>1</sup></p><p><italic><sup>1</sup>German Sport University Cologne, Institute of Movement and Neurosciences, Cologne, Germany; <sup>2</sup>University of Cologne, Department of Pediatric Oncology and Hematology‐ Children's Hospital, Cologne, Germany</italic></p><p><bold>Background/Objectives</bold>: Cancer‐related fatigue is one of the most frequent and severe symptoms experienced by pediatric oncology patients during treatment. Fatigue is multidimensional, with the most distressing symptoms affecting quality of life. There is uncertainty regarding the predictive power of physical activity prior to disease relative to other factors on fatigue outcome in pediatric cancer patients.</p><p><bold>Design/Methods</bold>: In eleven pediatric cancer patients (6 female; mean age=11.82±2.44 years) PedsQL Multidimensional Fatigue Scale questionnaire was completed during cancer therapy. Types of cancer present in this study were leukemia (n=3), lymphoma (n=5), sarcoma (n=2) and neuroblastoma (n=1). The standard treatment for the pediatric patients was adjuvant chemotherapy according to national protocols. Daily activity level before disease was retrospectively interrogated with 24 hours division self‐report (active time, sleeping, sitting, lying awake in bed) at the beginning of treatment. Pearson correlations and Students t‐test were used to analyze the data (α=0.05).</p><p><bold>Results</bold>: Mean time between start of cancer therapy and fatigue questionnaire was 147.55±64.46 days. Mean activity level before disease was 5.64±2.11 hours per day and ranged between 2.00 and 8.00 hours. Patients with higher activity level before disease show a significant higher fatigue score during cancer therapy (r=0.715, P=0.013), higher scores indicate lower fatigue. However, age (r=‐0.356, P=0.283) and gender (r=0.584, P=0.059) had a less severe impact on fatigue outcome.</p><p><bold>Conclusions</bold>: Activity status before disease seems to be a more powerful predictor of fatigue among pediatric oncology patients than other factors like gender or age. These findings emphasize the importance of physical activity in lessening side effects in cancer therapy.</p></sec><sec id="pbc26772-sec-11180"><label>PO-094</label><title>N‐Acetylcysteine as a Secondary Prophylaxis for Ifosfamide Induced Renal Tubulopathy in Children with Solid Tumors: Case Series</title><p>M. Rojas Vasquez<sup>1</sup>, <underline underline-style="single">M. Diachinsky</underline><sup>1</sup>, M. Romaniuk<sup>2</sup>, S. Mckillop<sup>2</sup></p><p><italic><sup>1</sup>Stollery Children's Hospital, Pediatric Hematology Oncology, Edmtonon, Canada; <sup>2</sup>Stollery Children's Hospital, Pediatric Hematology Oncology, Edmonton, Canada</italic></p><p><bold>Background/Objectives</bold>: Ifosfamide (IFO) is a commonly used chemotherapy agent in pediatric solid tumors. A known side effect of IFO is renal tubulopathy (RT). There is limited data suggesting that N‐acetylcysteine (NAC) can prevent nephropathy induced by IFO. We aim to report a cohort of children with RT secondary to IFO successfully treated with NAC.</p><p><bold>Design/Methods</bold>: Case series of children with solid tumors between the ages of 0 – 17 years and RT secondary to IFO treated with NAC.</p><p><bold>Results</bold>: Two patients fulfilled the criteria. Patients received NAC intravenously post IFO as follow: 150mg/kg hours 5‐6, 50mg/kg hours 6‐10 and 100mg/Kg hours 10‐24.</p><p>Patient one had Relapsed Rhabdomyosarcoma and received IFO 2400 mg/m2/day with Etoposide 100mg/m2/day on days 1,2 and 3 and Carboplatin 635mg/m2 on day 3 that was extended for eight courses. Patient two had Osteosarcoma previously treated with high‐dose methotrexate, cisplatin and doxorubicin for ten weeks and subsequently required oral replacement with magnesium. She then received two courses of IFO 2800mg/m2/day and Etoposide (100mg/m2/day) for five days. Both patients received pre‐, post‐hydration and Mesna as per institutional guidelines.</p><p>Patient one developed RT after course 5 and patient two after course 1. Both had significant hypophosphatemia, hypomagnesemia, hypokalemia, hyponatremia and acidosis requiring intravenous replacement of sodium chloride, potassium phosphate and magnesium followed by two weeks of oral replacement. Patient one received NAC on courses 6, 7 and 8 and patient two on course 2. After first course of NAC, both patients developed mild hypophosphatemia, hypomagnesemia and acidosis with other electrolytes normal requiring few days of oral potassium, phosphate and magnesium. Patient one did not required electrolytes replacement after courses 7 and 8.</p><p><bold>Conclusions</bold>: We report two patients with solid tumors with RT secondary to IFO who responded to treatment with NAC when given concomitantly with IFO. Prospective studies are required to further confirm this therapeutic approach</p></sec><sec id="pbc26772-sec-11190"><label>PO-095</label><title>Intestinal Mucor Infection in a Patient with Non‐Hodgkin's Lymphoma During Induction Chemotherapy</title><p>A. Erbay<sup>1</sup>, F. Sarialioglu<sup>1</sup>, <underline underline-style="single">N. Yazici</underline><sup>1</sup>, S. Ezer<sup>2</sup>, B. Hasbay<sup>3</sup></p><p><italic><sup>1</sup>Baskent University, Department Of Pediatric Oncology‐Hematology, Adana, Turkey; <sup>2</sup>Baskent University, Department Of Pediatric Surgery, Adana, Turkey; <sup>3</sup>Baskent University, Department Of Pathology, Adana, Turkey</italic></p><p><bold>Background/Objectives</bold>: Intestinal mucor mycosis is a very rare and frequently a fatal condition in immuno‐compromised patients.</p><p><bold>Design/Methods</bold>: An 8 year‐old male was diagnosed as stage III NHL in another hospital. Before admission to our center, after first course of chemotherapy he had experienced a tumor lysis and posterior reversible ensefalopathy syndrome (PRESS). We detected a low creatinin clearence, panhypogammaglobulinemia, B type lymphopenia and partial response of lymphoma. Immunosupression type could not be adressed if it was primary or secondary. Intravenous Immunoglobulin (IVIG) was administered and B block of BFM regimen was started. Febrile neutropenia was occured early. Meropenem, teicoplanin and fluconazol were given as emprical treatment. Amikacin was added for resistant fever. In 5th day of antibiotics, he had abdominal cramps and vomiting. There were fluid levels in plain X‐ray. Nasogastric decompression, metronidazol and caspofungin were started. After 3 days of conservative management for cytological improvement, laparotomy was made. In jejunal and ileal segments there were necrosis and perforations. Ileostomy and segmentary jejunal resection were made. After 2 days, a second surgery was made with resection of ileum with necrosis. Specimen showed mucor mycosis. Liposomal amfoterisin B was started.</p><p><bold>Results</bold>: After the completion of treatment for febrile neutropenia, a course of vinkristin, doxorubicin, cyclophosphamide and etoposide was given. A third surgery was done for abcess after 40 days of the second surgery. Mucor mycosis was again displayed in specimen.Amphotericin B was continued for 125 days. We switched to posaconazole because of kidney functions. Chemotherapy could not be continued due to fungal infection and nephrotoxicity. Weekly rituximab was adminestered for 4 courses. The patient is still under follow‐up with in remission for 14 months for primary disease.</p><p><bold>Conclusions</bold>: This patient was presented because of rare and highly lethal fungal infection during induction treatment of Burkitt's lymphoma. He was treated with surgical resections and antifungal treatment.</p></sec></sec><sec id="pbc26772-sec-11200"><title>Treatment and Care ‐ Palliative Care</title><sec id="pbc26772-sec-11210"><label>PO-096</label><title>Palliative Care for Children Case Study at Taso Uganda</title><p><underline underline-style="single">S. Nandaula</underline><sup>1</sup></p><p><italic><sup>1</sup>Uganda Cancer Institute, Palliative care and research, Kampala, Uganda</italic></p><p><bold>Background/Objectives</bold>: Many people live and die of pain in Uganda. A study was done to describe family, and leaders from different communities on the impact of each community based service delivery and interventions. The major objective was to see that all childern are cared for with diginity especially when diagnosed with a terminal illness</p><p><bold>Design/Methods</bold>: Different modules were used in Uganda and there after rapid evaluation fields techniques in each community was done, getting data from three sources: observations of clinical and the encounters, interviews with informants and the local healthy leaders not forgetting data collections and statistics</p><p><bold>Results</bold>: We interviewed 33patients with a terminal illness, 27 caregivers, 36staff, 25client representatives and 29community leaders. In each site, Antivirals were used effectively. Children valued being treated with dignity and respect without discrimination. Being supported at home reduced physical, emotional and financial burden of traveling to and care at health facilities. Practical support and instruction in feeding and bathing patients facilitated a good death at home with all the information given.</p><p>In each community mobile phones enabled access to clinical and social support work Client representatives and community leaders reported that caring for the HIV/AIDS children especially in poor communities was stressful, but also rewarding, with resilience forced by having good treatment therapies.</p><p><bold>Conclusions</bold>: This programme was new and it was reported to be successful because they integrated symptom control with practical physical care, education and spiritual care for these children. Holistic pediatric palliative care can be delivered effectively in the face of community leaders and integrated in public health approach.</p></sec></sec><sec id="pbc26772-sec-11220"><title>Treatment and Care ‐ Psychosocial (PPO)</title><sec id="pbc26772-sec-11230"><label>PO-097</label><title>Breaking the Barrier of Childhood Cancer Treatment Abandonment: The Case of Ghana</title><p><underline underline-style="single">A. Sarpong</underline><sup>1</sup></p><p><italic><sup>1</sup>Korle Bu Teaching Hospital, Department of Child Health, Accra, Ghana</italic></p><p><bold>Background/Objectives</bold>: High Treatment abandonment rates is a major contributor to treatment failure in developing countries. In 2010, 62% of children receiving treatment for cancer abandoned treatment in Ghana. In the same year, an International Twinning project commenced. There has been a continuous decline in the number of children that interrupted treatment between 2010 and 2016. This paper assesses the factors motivating parents to continue with treatment, despite daunting constraints; and the contributions of the Twinning Project towards the progress made.</p><p><bold>Design/Methods</bold>: Key project activities include training (workshops and internships), treatment sponsorship, psychosocial support and setting up of data registers. Analysis of data from two facility‐based registers established a consistent decline in treatment abandonment from 2010 to 2016. With the aid of questionnaire, 42% of the parents were randomly selected and interviewed face‐to‐face, between January and December 2016. STATA (version 12) was used for the data analysis and descriptive statistics employed for the results presentation.</p><p><bold>Results</bold>: A total of 285 children were presented for cancer treatment at the two centres in 2016. Participants in the study were 120 parents (80% females, 20% males). Majority (31%) said treatment sponsorship was the key enabling condition helping them continue with treatment. Psychosocial support (peer counselling‐18% and nurse‐guardian counselling‐17%) were the most important factors that urged parents on. Other factors of motivation were financial support from extended family and other sources (8%), believe in God‐(7%), and love for the child‐(6%).</p><p><bold>Conclusions</bold>: Psychosocial support and treatment sponsorship combined were cited by two‐thirds (66%) of respondents as most important factors contributing to the lowering of treatment abandonment rates. International Twinning partnership with activities that include training, psychosocial support and treatment sponsorship hold the potential to lowering treatment abandonment rates in developing countries. Advocacy for sustainable treatment funding by governments is important if treatment abandonment could be eliminated in developing countries.</p></sec><sec id="pbc26772-sec-11240"><label>PO-098</label><title>Setting An Agenda for Advocacy, Research, and Care of Siblings of Children with Cancer</title><p><underline underline-style="single">M. Alderfer</underline><sup>1</sup>, M. Goldish on behalf of SPARCCC & Summit participants<sup>2</sup></p><p><italic><sup>1</sup>Alfred I duPont Hospital for Children, Center for Healthcare Delivery Science, Wilmington, USA; <sup>2</sup>Sibling Partnership for Advocacy‐ Research and Care in Childhood Cancer, USA</italic></p><p><bold>Background/Objectives</bold>: The purpose of this presentation is to describe the process and outcome of the Sibling Research Summit, a 1.5 day invitation‐only gathering of researchers, clinicians, advocates, community‐partners and siblings of children with cancer focused upon setting an agenda for advocacy, research, and care of siblings of children with cancer.</p><p><bold>Design/Methods</bold>: In November 2016, the Sibling Partnership for Advocacy, Research and Care in Childhood Cancer (SPARCCC) hosted a Sibling Research Summit in Philadelphia, with financial support from Alex's Lemonade Stand Foundation (ALSF). After introductory remarks from members of SPARCCC and ALSF, the panel of adolescent and young adult siblings told their stories of how cancer impacted them and their families. The researchers, clinicians, and advocates then introduced themselves and their work. Recent systematic reviews of the sibling literature were presented and the group set out to identify priorities for moving advocacy, research and care of siblings of children with cancer forward.</p><p><bold>Results</bold>: Four priority areas were identified and discussed: 1) Identifying and measuring the “ultimate costs” of childhood cancer on siblings (i.e., psychosocial development, achievement, financial); 2) Screening siblings of children with cancer for unmet needs and adjustment difficulties and providing appropriate levels of care (e.g., education, monitoring, intervention); 3) Developing evidence‐based interventions and empirically evaluating new and existing community‐based interventions for siblings (e.g., oncology camps, SuperSibs); and, 4) Advancing education and awareness within families, communities (e.g., schools) and the healthcare system regarding psychosocial issues faced by siblings in families of children with cancer and influencing healthcare policy (i.e., including siblings in family‐centered care).</p><p><bold>Conclusions</bold>: Progress is being made in understanding and addressing the psychosocial needs of siblings of children with cancer, however, coordinated international collaborations of key stakeholders are needed to propel these efforts forward.</p><p>We acknowledge the generous support of ALSF and CIGNA and whole‐heartedly thank all Sibling Research Summit participants.</p></sec><sec id="pbc26772-sec-11250"><label>PO-099</label><title>Exploring Family and Staff Educational Needs at Major Referral Pediatric Oncology Hospitals: A Qualitative Study in EL Salvador, Guatemala and Mexico</title><p><underline underline-style="single">E. Atwood</underline><sup>1</sup>, F. Antillon<sup>2</sup>, S. Fuentes Alabi<sup>3</sup>, L. Vega‐Vega<sup>4</sup>, I. Albanti<sup>5</sup></p><p><italic><sup>1</sup>Harvard T.H. Chan School of Public Health, Global Health & Population, Boston, USA; <sup>2</sup>Unidad Nacional de Oncologia Pediatrica, Pediatric Oncology, Guatemala City, Guatemala; <sup>3</sup>Benjamin Bloom National Children's Hospital, Centro Medico Ayudame a Vivir, San Salvador, El Salvador; <sup>4</sup>Hospital Infantil Teleton de Oncologia, Pediatric Oncology, Queretaro, Mexico; <sup>5</sup>Dana Farber/Boston Children's Cancer and Blood Disorders Center, Global Health Institute, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Best practices for identifying and matching the informational needs of parents at the time of their child's diagnosis with cancer are currently unknown, and research in low‐ and middle‐income countries is even more limited. There is also little guidance about how to deliver information to parents and in what setting. Aspects to consider when developing the information include the socioeconomic level of parents, cultural or language barriers, and the availability of qualified personnel or resources to create educational materials. This study assessed how families receive information and explored further needs regarding the most important topics and the desired method of communication.</p><p><bold>Design/Methods</bold>: A qualitative study was designed and over 50 in‐person interviews were conducted in English and Spanish using a structured guide. Key informants included parents, physicians, nurses, psychosocial staff, administrative and foundation leadership, volunteers, communication and government professionals. The study sites included Unidad Oncología Pediátrica in Guatemala, Benjamin Bloom Hospital in El Salvador, and Hospital Infantil Teletón de Oncología in Mexico. NVivo was used for thematic analysis.</p><p><bold>Results</bold>: Across all sites, the most common questions were: Why my child? What is cancer? How do I discuss this with my other children? The educational needs included explaining the origin of cancer and addressing perceptions of guilt and myths about cancer, how to care for the child at home and adherence to treatment. The preferred communication medium was an audiovisual tool such as a video, with internet and radio as secondary options.</p><p><bold>Conclusions</bold>: This study demonstrates that educational needs of parents differ despite geographic proximity and shared language. Developing an educational program in resource‐limited settings can be challenging, but it is crucial to maintain family participation. This study can be used as a guide for other programs wanting to develop educational materials. Further research could evaluate the effectiveness of the information in educating parents.</p></sec><sec id="pbc26772-sec-11260"><label>PO-100</label><title>The Effect of Sexual Health on Body Image and Self Esteem Among Adolescents and Young Adults with Cancer</title><p><underline underline-style="single">Y. Ben‐Gal</underline><sup>1</sup></p><p><italic><sup>1</sup>Schneider Children's Medical Center of Israel, Pediatric Hematology‐oncology, Petach‐Tikva, Israel</italic></p><p><bold>Background/Objectives</bold>: During adolescence hormonal, physical and mental changes occur. These changes effect body image, self esteem and sexual health,and are more complex in teenager cancer patients. The disease and therapies, effect negatively on their body image and self esteem.</p><p>Objectives ‐ identify the variables affecting self esteem, body image and sexuality among teenagers cancer patients</p><p><bold>Design/Methods</bold>: During 4 years, data was collected via interviews with 26 adolescent cancer patients that treated in the Department of Pediatric Hematology Oncology of SCMCI.</p><p><bold>Results</bold>: Fourteen adolescent boys and 12 girls participated. Average age was 16.46 years, Female adolescent possessed a lower self‐image and body image than their male counterparts (p < 0.0025). A decrease was found in body image among male adolescents who underwent fertility preservation procedure, (3.1) compared to those who had not (3.6) (p < 0.001). Female teenagers with GnRH antagonist treatment reported a significantly higher self‐image and body image compared to those not treated (p < 0.014).</p><p>Adolescents who engaged in their sexuality prior to their illness experienced a decrease in self‐image and body image.</p><p>Pearson test showed positive correlation (0.67) (p < 0.00) between body image and self‐image, and negative correlation (‐0.57) (p < 0.001) between body image and side effects.</p><p>Regression analysis of demographic data and sexually related variants found higher satisfaction with body image (p < 0.00), intimate behavior prior to illness (p < 0.001) and parental marital status (married) are predictive of higher self‐esteem during treatment.</p><p><bold>Conclusions</bold>: Self‐esteem and body image are negatively affected by side‐effects of cancer treatment. As the perception of the side effects by the teenagers is greater, there is a decrease in body‐image and self‐esteem. There is a need for a comprehensive preparation prior to fertility preservation procedures and medical treatment with explanations and emotional support for adolescents. Preparing such an intervention, further study on the effect of fertility preserving procedures on body‐image and self‐esteem are needed.</p></sec><sec id="pbc26772-sec-11270"><label>PO-101</label><title>Health Related Quality of Life During Treatment in Adolescents Aged 12‐18 Years with Cancer</title><p><underline underline-style="single">M. Bult‐Mulder</underline><sup>1</sup>, S. Sasja<sup>1,2,3</sup>, K. Van Bindsbergen<sup>1</sup>, H. de Ridder‐Sluiter<sup>1</sup>, V. Chris<sup>4</sup>, V.L. Raphaela<sup>5</sup>, M. Hans<sup>2</sup>, V.N. Max<sup>1</sup>, G. Martha<sup>1,2</sup></p><p><italic><sup>1</sup>Prinsess Máxima Center, Psychosocial Research & Healthcare Innovation, Utrecht, The Netherlands; <sup>2</sup>Emma Children's Hospital‐ AMC, Pediatric Oncology, Amsterdam, The Netherlands; <sup>3</sup>St. Jude Children's Research Hospital, Psychology, Memphis, USA; <sup>4</sup>Amalia Children's Hospital‐ Radboud University Medical Center, Medical Psychology, Nijmegen, The Netherlands; <sup>5</sup>VU Medical Center, Pediatric Hematology/Oncology, Amsterdam, The Netherlands</italic></p><p><bold>Background/Objectives</bold>: A cancer diagnosis influences health related quality of life (HRQOL). The objectives for this study are: 1) to describe the HRQOL of adolescents aged 12‐18 years in active treatment for cancer and compare them to their healthy peers, 2 ) to get insight in the oncology specific HRQOL during treatment.</p><p><bold>Design/Methods</bold>: HRQOL was measured using the PedsQL (Pediatric Quality of Life Inventory) 4.0. Mean scale scores were compared between adolescents with cancer (<italic>N</italic>=73, <italic>Mage=</italic>14.71, <italic>SD</italic>=1.85) and a healthy reference group (<italic>N=</italic>268, <italic>Mage=</italic>14.23, <italic>SD</italic>=1.51) using MANOVA analysis. To measure Cancer‐specific HRQOL, the PedsQL Cancer Module 3.0 was used. Scores were dichotomized as absence of problems (‘never‐almost never’) and prevalence of problems (‘sometimes‐ often, almost often). Percentages were calculated to determine the proportion of adolescents reporting problems on the PedsQL Cancer module 3.0.</p><p><bold>Results</bold>: Adolescents under active cancer treatment reported significantly lower physical (M<sup>cancer</sup> 57.11, M<sup>control</sup> 85.58), emotional (M<sup>cancer</sup>72.05, M<sup>control</sup>76.36), social (M<sup>cancer</sup> 78.56, M<sup>control</sup>88.84), school (M<sup>cancer</sup>57.67,M<sup>control</sup>75.47), psychosocial (M<sup>cancer</sup>69.43, M<sup>control</sup>80.22), and total HRQOL scores (M<sup>cancer</sup>65.14, M<sup>control</sup>82.09), all <italic>p</italic>s<.05, effect sizes were small to large (ɳ2= .10 to .44). Prevalence of cancer specific HRQOL problems was highest for items on pain (hurt in joint or muscle, 42.9%), nausea (nausea during treatment 47.1%, food doesn't taste good 54.3%, nausea when smelling food 61.4%), worry (about relapse 45.7%, about side effects 52,9%), cognitive (problems paying attention 47.1%) and physical appearance (not looking good 47.1%) domains.</p><p><bold>Conclusions</bold>: Lower HRQOL and Cancer specific problems are experienced on both physical and psychosocial domains. Monitoring of HRQOL is of utmost importance to adequately support adolescents. Interventions should focus on physical aspects of relieving pain and nausea but also on information about treatment to decrease worrying, help with schoolwork and support for dealing with body image.</p></sec><sec id="pbc26772-sec-11280"><label>PO-102</label><title>Preliminary Feasibility and Acceptability of Light Therapy to Increase Energy in Adolescents and Young Adults Newly Diagnosed with Solid Tumors</title><p><underline underline-style="single">V. Crabtree</underline><sup>1</sup>, H. Zhang<sup>2</sup>, J. Brigden<sup>1</sup>, L.A. Christy<sup>1</sup>, M. Wilson<sup>3</sup>, A. Pappo<sup>4</sup></p><p><italic><sup>1</sup>St Jude Children's Research Hospital, Psychology, Memphis, USA; <sup>2</sup>St Jude Children's Research Hospital, Biostatistics, Memphis, USA; <sup>3</sup>University of Tennessee Health Science Center, Ophthalmology, Memphis, USA; <sup>4</sup>St Jude Children's Research Hospital, Oncology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Fatigue is one of the most consistent, distressing symptoms reported by pediatric oncology patients. Bright white light has been shown to prevent increases in fatigue in adult breast cancer patients and reduce fatigue in adult cancer survivors. However, no definitive intervention to reduce fatigue has been developed for pediatric oncology patients. The current study was designed to estimate the feasibility and acceptability of bright white light as an intervention to decrease fatigue in adolescents/young adults (AYA) who are newly diagnosed and receiving treatment for solid tumors, including lymphoma.</p><p><bold>Design/Methods</bold>: Twenty‐nine AYA (ages 12‐22) diagnosed with a solid malignancy, including lymphoma, in the past 30 days who have begun cancer‐directed therapy have been approached to participate. Participants were randomized to receive dim red light (DRL, n = 12) or bright white light (BWL, n = 11) for 30 minutes upon awakening daily for eight weeks. Side effects are assessed weekly via modified Systematic Assessment for Treatment Emergent Effects (SAFTEE).</p><p><bold>Results</bold>: Feasibility of the intervention was a priori defined as at least 65% of participants consenting to participate. At preliminary data check, 79.3% of approached participants (n=23) consented, demonstrating initial evidence of feasibility. To determine acceptability, a stopping rule was developed to evaluate side effects of extreme headache or eye strain after the first 15 participants completed intervention. Preliminary findings demonstrate that no DRL patients reported extreme headaches or eye strain. One BWL patient reported extreme blurred vision during week 2, and no BWL patients reported extreme headache.</p><p><bold>Conclusions</bold>: Preliminary findings of this feasibility and acceptability trial of bright white light to reduce fatigue in AYA newly diagnosed with solid tumors demonstrate that use of light therapy is both feasible and acceptable. Measures of fatigue, mood, and adherence continue to be collected and should provide additional information regarding potential efficacy of this promising intervention.</p></sec><sec id="pbc26772-sec-11290"><label>PO-103</label><title>Managing Your Health: Development of a Self‐Management Skills Intervention to Overcome Barriers to Transition Readiness Among Adolescent and Young Adult (AYA) Cancer Survivors</title><p><underline underline-style="single">A. Viola</underline><sup>1</sup>, M. Masterson<sup>2</sup>, D. Carey<sup>2</sup>, S. Stephens<sup>2</sup>, S. Manne<sup>1</sup>, K. Devine<sup>1</sup></p><p><italic><sup>1</sup>Rutgers‐ Cancer Institute of New Jersey, Medicine/Population Science, New Brunswick, USA; <sup>2</sup>Rutgers‐ Cancer Institute of New Jersey, Medicine, New Brunswick, USA</italic></p><p><bold>Background/Objectives</bold>: Childhood cancer survivors are a growing population who are at risk for adverse late effects from treatment. Survivors require lifelong “risk‐based” follow‐up care; however, less than 1 in 5 survivors obtain the necessary care. Many survivors are lost to follow‐up in the transition from pediatric to adult follow‐up care, partially due to low “transition readiness” or having the skills, motivation, and resources to make the transition. Few interventions have been developed to improve transition readiness among adolescents and young adults (AYAs) with cancer. This study aimed to identify the content of the self‐management intervention for AYA survivors.</p><p><bold>Design/Methods</bold>: Initial interviews with 19 AYA survivors of pediatric cancer identified barriers and facilitators to risk‐based care. Next, we conducted interviews with 5 AYA survivors (ages 18‐25, 3 female), 1 parent and 3 medical providers to identify essential components of a self‐management intervention. Informed by these interviews and the Social‐Ecological Model of Readiness to Transition, the basic content of the intervention was developed. Three AYA survivors gave feedback on intervention modules. Thematic content analysis by two independent raters was used to identify targets for the intervention.</p><p><bold>Results</bold>: The major themes for the self‐management modules included: understanding treatment and the survivorship care plan, the logistics of managing health care and insurance, negotiating family involvement in care, dealing with emotions, and staying healthy in the context of life transitions. Initial feedback from the AYA survivors indicated that the content was relevant, but should include interactive elements (narrated presentations, videos, tailored feedback) to make the intervention more engaging.</p><p><bold>Conclusions</bold>: Incorporating AYA survivors, parents, and providers in the design phase has been essential to content development for the self‐management program. We are currently refining the content to be used in a randomized controlled trial with AYA childhood cancer survivors.</p></sec><sec id="pbc26772-sec-11300"><label>PO-104</label><title>Psychological Challenges Faced When Fighting Childhood Cancer During Wartime in Syria</title><p><underline underline-style="single">O. Fawaz</underline><sup>1</sup>, A. F PATENAUDE<sup>2</sup></p><p><italic><sup>1</sup>al bairouni university hospital for cancer, pediatric department, damascus, Syria; <sup>2</sup>Dana‐Farber Cancer Institute, Center for Cancer Genetics and Prevention, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Childhood cancer is a challenge for the child, his/her parents and medical care providers in limited resource countries. When war conditions and violence are present, treatment is much harder, physically and emotionally for all involved.</p><p><bold>Design/Methods</bold>: From observations and discussions with colleagues, patients and parents during the 7 years in which much of Syria has experienced war, we report on ways in which occurrence of war and associated hardships adds multiple burdens and challenges, threatening the psychological equilibrium and coping efforts of patients, parents and providers. Observations occurred at the Department of Pediatric Oncology at Al Bairouni Hospital in Damascus, one of 3 Syrian hospitals offering specialized pediatric cancer treatment</p><p><bold>Results</bold>: Disempowerment was the major psychological burden. Fear, anxiety and loss of hope were also difficult. Psychological challenges faced when treating cancer during wartime include: changing the life priority of the child and his/her family, lack of medication availability and increased costs, difficulties and dangers of transport of patients to and from the hospital location, and the heavy, resulting psychological impacts on patient, parents and medical care providers. Exposure to war and worry about the safety of near and distant family members affects medical care providers’ attention, availability and energy as well.</p><p><bold>Conclusions</bold>: Childhood cancer is a complicated problem in Syria. Unsafe hospital locations and difficulties of transport during wartime and other problems create challenge in childhood cancer management and increase the psychological burdens facing patients, their families and health care providers.</p></sec><sec id="pbc26772-sec-11310"><label>PO-105</label><title>A Service Evaluation Comparing the Need for Psychology Input Between Paediatric Neuro‐Oncology Patients and Paediatric Oncology Patients Within the Leeds Teaching Hospitals Trust Between 2005‐2009</title><p><underline underline-style="single">S. Haley</underline><sup>1</sup>, E. Hirst<sup>1</sup>, S. Wilkins<sup>2</sup>, K. Shimmon<sup>2</sup>, R. Donaldson<sup>2</sup></p><p><italic><sup>1</sup>University of Leeds, School of Medicine, LEEDS, United Kingdom; <sup>2</sup>Leeds Teaching Hospitals Trust, Paediaric Oncology, Leeds, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: Children with brain cancer are known to be more likely to suffer from suicidal ideation and depression than their other oncology counterparts. We hypothesised the need for psychological input would be higher in paediatric neuro‐oncology patients compared to other paediatric oncology patients. We aimed to assess the need for psychological services within the paediatric oncology department and alter services to meet demand.</p><p><bold>Design/Methods</bold>: Patient data were collated from the database within the paediatric oncology department at LTHT from a five year period. We collected information on the patients’ age at diagnosis, gender, tumour type and treatment received, including number of psychology referrals made and reasons for referral. Treatments types and combinations were coded for interpretation.</p><p><bold>Results</bold>: Data was collected for 556 patients, and of these, 102 were referred to clinical psychology services within LTHT. Nearly 45% of the neuro‐oncology patients were referred to psychology compared to 12% in the other oncology group. There were no significant differences for gender or age. The most common treatment for a significant majority(?) of referrals was chemotherapy only – potentially due to long hospital stays and the disruption to daily life.</p><p><bold>Conclusions</bold>: The results are consistent with existing research strengthening further the argument for targeted specialised psychological support in this group. Clinical implications for the service are discussed.</p></sec><sec id="pbc26772-sec-11320"><label>PO-106</label><title>Survivorship Identity in Childhood Cancer Survivors and their Parents: Results from Project Reach</title><p><underline underline-style="single">C. Hungr</underline><sup>1</sup>, L.B. Kenney<sup>1</sup>, C.J. Recklitis<sup>1</sup></p><p><italic><sup>1</sup>Dana Farber Cancer Institute, Pediatric Oncology, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Health implications of “Survivor” and “Victim” identity have been described in adult cancer survivors, but little is known about identity in childhood cancer survivors (CCS). This study investigated CCS and their parents’ views on the child's survivorship identity, and the association of identity with the child's functioning.</p><p><bold>Design/Methods</bold>: Fifty‐nine CCS (34% female, Mean age=16.7) from a prospective cohort study rated their identification with “Survivor” and “Victim” identity on a five‐point scale, perceived impact of cancer on their identity, and frequency of thought about their cancer. Parents completed parallel ratings on perception of their child's identity, impact of cancer on their child, and frequency of their own thoughts about their child's cancer. Identity terms were dichotomized into high and low (cutoff ≥3). Current functioning was assessed by the PedsQL.</p><p><bold>Results</bold>: Overall, few CCS (3.5%) or parents (5.2%) endorsed “Victim” identity, while a majority of CCS (78%) and parents (86%) endorsed “Survivor” identity. PedsQL scores were not associated with parent or child ratings of either identity. Within parent‐child dyads, a significant number of parents (16/59) thought about the cancer more frequently than their child did (Kappa=0.19). Also, dyads disagreed significantly on endorsement of “Survivor” identity, where 19 of 59 dyads gave discrepant ratings (K=‐0.09). Of these 19, 12 resulted from parents endorsing their child as “Survivor” while their child did not. Dyads agreed significantly on the impact cancer had on child's identity (K=0.24).</p><p><bold>Conclusions</bold>: Few CCS or parents identify with the term “Victim,” though they commonly identify with the term “Survivor.” Although parent‐child dyads agreed on the impact cancer had on CCS identity, parents overall thought about the cancer more frequently, and were more likely than their child to see their CCS as a “Survivor.” Notably, CCS identity was not related to quality‐of‐life. Future study could explore long‐term functional implications of survivorship identity.</p></sec><sec id="pbc26772-sec-11330"><label>PO-107</label><title>Putting Ayas in a Room Together: Launching an Adolescent and Young Adult Oncology Council</title><p><underline underline-style="single">R. Johnson</underline><sup>1</sup>, B. Pflugeisen<sup>2</sup>, P. Patterson<sup>3</sup>, C.F. Macpherson<sup>2</sup>, B. Ray<sup>2</sup>, J. Rebecca<sup>2</sup></p><p><italic><sup>1</sup>Mary Bridge Children's Hospital/MultiCare Health System, Pediatric Hematology/Oncology, Tacoma, USA; <sup>2</sup>Mary Bridge Children's Hospital/MultiCare Health System, MultiCare Institute for Research and Innovation, Tacoma, USA; <sup>3</sup>CanTeen Australia, CanTeen Australia, Sydney‐ NSW, Australia</italic></p><p><bold>Background/Objectives</bold>: Facilities and programs targeting adolescents and young adults (AYAs; aged 15‐39) are now emerging within community cancer centers in the United States. We describe the formation and first meeting of a community AYA stakeholder council and report the discussion themes and priorities of this group.</p><p><bold>Design/Methods</bold>: We created a stakeholder council to identify the healthcare needs and preferences of AYAs treated at community cancer centers. The group, which included nine patients/survivors, two parents, one spouse, one sibling, two researchers, and an AYA‐focused child life specialist, convened at a one‐day workshop moderated by CanTeen Australia. Participants shared and compared their healthcare experiences and identified unmet needs. Workshop notes were analyzed using inductive content analysis to identify themes. The group also prioritized topics for future discussion and action.</p><p><bold>Results</bold>: The experiences of AYAs treated at community centers varied widely, but the majority reported satisfaction with their cancer treatment experience. Experience, identity, expression, and advocacy were the major themes of discussion.</p><p>The group was enthusiastic about sharing stories and advocating for others. They identified topics for future discussion by identifying and ranking the greatest healthcare‐related needs of AYAs at community medical centers. Peer connection was identified as the most pressing need, followed by government advocacy to improve programming and financial support, complementary medicine, research & clinical trials, staff education, choice & voice in decision‐making, fertility, survivorship, and mental health services.</p><p><bold>Conclusions</bold>: Most AYAs reported positive treatment experiences at community medical centers. They desire more peer connection, financial support and empowerment in healthcare decision‐making.</p></sec><sec id="pbc26772-sec-11340"><label>PO-108</label><title>Development of the First Psychosocial Oncology Program in Armenia</title><p><underline underline-style="single">A. Kamalyan</underline><sup>1</sup>, Y. Asribabayan<sup>1</sup>, J. Fernandez<sup>2</sup>, B. Delaney<sup>2</sup>, I. Albanti<sup>3</sup>, L. Lehmann<sup>4</sup>, L. Sargsyan<sup>1</sup>, A. Avagyan<sup>1</sup>, L. Safaryan<sup>1</sup>, G. Tamamyan<sup>1</sup></p><p><italic><sup>1</sup>Muratsan Hospital Complex of Yerevan State Medical University, Clinic of Chemotherapy, Yerevan, Armenia; <sup>2</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Department of Psychosocial Oncology and Palliative Care, Boston, USA; <sup>3</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Global Health Initiative, Boston, USA; <sup>4</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Pediatric Stem Cell Transplant Center, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: Historically in Armenia, cancer has been viewed exclusively as a medical issue and there were no comprehensive psychosocial services offered to patients. In an effort to integrate psychologic care into multidisciplinary cancer care we developed a psychosocial oncology program. The aim was to provide support to pediatric and adult cancer patients and their families beginning at the time of diagnosis and continuing throughout the course of treatment.</p><p>Thus, in March 2016 at the Clinic of Chemotherapy of Muratsan Hospital Complex of Yerevan State Medical University, with the support of Dana‐Farber/Boston Children's Cancer and Blood Disorders Center Global Health Initiative (DF/BC GHI) and City of Smile Foundation, the first psychosocial oncology program in Armenia was established. The program is staffed by two psychologists (part‐time).</p><p><bold>Design/Methods</bold>: Program development has included the review and analysis of examples of psycho‐oncology delivery of care in high, low– and middle‐income countries (LMIC), design of a psychosocial model of care, creation of a needs assessment tool and format for clinical progress notes, translation of psycho‐educational materials for patients, families, providers, and development of mechanisms for involving volunteers into the service. These activities and others have been carried out in ongoing consultation with the specialists of DF/BC GHI.</p><p><bold>Results</bold>: As a result of the program development the following services are now available to patients and families: psychosocial assessment, individual psychotherapy for patients and their families, group counselling for children and parents, bereavement support, psychoeducation, organized sociocultural activities. During the first year 22 children and their parents (100% of pediatric patients, 176 discrete visits) and 58 adult patients and their relatives (48% of adult patients, 194 visits) received psychosocial support.</p><p><bold>Conclusions</bold>: Psychosocial programs for oncology patients can be successfully implemented in LMIC. Our program can serve as a model for other cancer delivery programs in Armenia and can be replicated in other LMIC.</p></sec><sec id="pbc26772-sec-11350"><label>PO-109</label><title>The Struggle of Families Who Experienced Childhood Cancer and Great East Japan Earthquake Disaster</title><p><underline underline-style="single">K. Kamibeppu</underline><sup>1</sup>, K. Kurihara<sup>1</sup>, M. Ikeda<sup>1,2</sup>, I. Sato<sup>1</sup>, T. Soejima<sup>1</sup>, R. Kikuchi<sup>1,3</sup>, S. Suzuki<sup>1</sup>, Y. Nagoya<sup>4</sup>, Y. Yamane<sup>4</sup>, M. Takahashi<sup>4</sup>, H. Hayasaka<sup>4</sup>, R. Tsuda<sup>4</sup>, M. Imaizumi<sup>5</sup>, A. Sato<sup>5</sup>, H. Shiwaku<sup>6</sup>, Y. Suzuki<sup>6</sup>, Y. Inoue<sup>6</sup>, Y. Sasahara<sup>6</sup>, T. Rikiishi<sup>6</sup></p><p><italic><sup>1</sup>The Universty of Tokyo, Department of Family Nursing‐ Graduate School of Medicine, Tokyo, Japan; <sup>2</sup>Tokyo Women's Medical University, School of Nursing, Tokyo, Japan; <sup>3</sup>Osaka University, Division of Health Sciences‐ Graduate School of Medicine, Osaka, Japan; <sup>4</sup>Miyagi Children's Hospital, Nursing Department, Miyagi, Japan; <sup>5</sup>Miyagi Children's Hospital, Department of Hematology/Oncology, Miyagi, Japan; <sup>6</sup>Tohoku University, Graduate School of Medicine, Miyagi, Japan</italic></p><p><bold>Background/Objectives</bold>: To clarify the struggle of families who experienced two big trauma such as childhood cancer and the Great East Japan Earthquake Disaster.</p><p><bold>Design/Methods</bold>: This study is a part of an ongoing longitudinal study started in April 2015. We conducted a semi‐structured interview every 6 months for 3 years for 7 families who experienced childhood cancer and the earthquake. We analyzed the first interviews of the families by content analysis.</p><p><bold>Results</bold>: The children were diagnosed as ALL, AML, or neuroblastoma etc. at the age of 0 to 15. Four families have experienced the disease before the disaster. At the beginning of the hospitalization, almost all the children missed families and schoolmates. Some mothers suppressed their fear for the prognosis, and faced their children's disease optimistically. Fathers tended to give priority to work, but fathers' emotional support encouraged mothers. If parents needed the other family members’ assistance (i.e. healthy siblings’ or grandparents’), they shared the diagnosis with them. Some sibling somatized psychological distress during prolonged hospitalization, when no one played mother's role at home. The impacts of the disaster varied according to causes (earthquake, tsunami, or radioactive contamination) and degree of the damages they received. Some families had increased cohesiveness through facing the disease, and overcame the disaster. In the opposite direction, some families gained strength by overcoming the disaster, and struggled with the disease constructively. A survivor in their young adulthood reaffirmed that happiness means living a normal life.</p><p><bold>Conclusions</bold>: Although the families had experienced two big trauma, they were able to struggle with the second one in mighty heart in the case families had increased cohesiveness by the first one. We will analyze their longitudinal narratives to clarify challenges, because there might be long‐run bio‐psycho‐social effects of both trauma on the families.</p></sec><sec id="pbc26772-sec-11360"><label>PO-110</label><title>Distress and Biopsychosocial Needs of Brazilian Adolescent and Young Adults Patients with Cancer</title><p><underline underline-style="single">M.F.M. Manhaes</underline><sup>1</sup>, C.D. Bergerot<sup>1</sup></p><p><italic><sup>1</sup>Universidade Federal de São Paulo, Departament of clinical and experimental oncology, São Paulo, Brazil</italic></p><p><bold>Background/Objectives</bold>: A cancer diagnosis can negatively affect the biopsychosocial functioning of adolescents and young adults (AYA).This study aims to describe levels of, and relationships between, distress and biopsychosocial unmet needs in a sample of Brazilian AYA patients with cancer.</p><p><bold>Design/Methods</bold>: A study was conducted among 122 AYA patients with cancer aged 18 to 35 years, treated at a Brazilian public hospital. They were assessed using the Distress Thermometer, the Hospital Anxiety and Depression Scale and the Functional Assessment of Cancer Therapy ‐ General. Descriptive statistics were obtained for all measures, item‐level frequencies were examined to identify common unmet needs and relationships between distress and unmet needs were explored.</p><p><bold>Results</bold>: AYA patients were mostly were male (50.8%), single (54.1%), white (52.5%), diagnosed with, central nervous system (31.1%), hematologic (23%) or genitourinary (15.6%) cancers, at an advanced disease stage (41.8%). AYA reported greater distress (50%), being commonly related to practical (60.7%), emotional (73.8%) and physical (86.1%) problems. Financial (32%), worry (56.6%), nervousness (50%), sadness (31.1%), pain (47.5%), fatigue (39.3%), memory concentration (35.2%), and sleep (32%)were the highest scored. However, 25.4% reported clinical symptoms of anxiety and 9.8% of depression. AYA patients reported poor levels of quality of life that is at 50th percentile of the US norm. Distress, symptoms of anxiety/depression and quality of life were significantly associated with biopsychosocial problems reported (p<.001). Higher levels of distress was predicted by symptoms of anxiety (B=0.2; p<.001), depression (B=0.2; p<.001), emotional (B=0.8; p<.001) and physical (B=0.3; p<.01) problems.</p><p><bold>Conclusions</bold>: Brazilian AYA patients reported high levels and numbers of unmet needs and substantial distress. Strong associations were found between increased distress and more unmet needs. Findings suggest the need for psychosocial intervention for Brazilian cancer patients that target helping them cope with biopsychosocial distress. Further, this preliminary data highlight opportunities to re‐orientate services to better meet AYA needs.</p></sec><sec id="pbc26772-sec-11370"><label>PO-111</label><title>Reflective Practice and Leadership in Global Pediatric Hematology/Oncology</title><p><underline underline-style="single">P. Mehta</underline><sup>1</sup>, J. Slone<sup>1</sup>, K. Chinyundo<sup>1</sup>, E. Ishigami<sup>2</sup>, P. Wasswa<sup>1</sup>, A. Anderson<sup>1</sup>, D. Niremberg<sup>1</sup>, M. Noli<sup>1</sup>, S. Kahan<sup>1</sup>, J. Lubega<sup>1</sup>, G. Airewele<sup>1</sup>, E. Fruge<sup>1</sup></p><p><italic><sup>1</sup>Baylor College of Medicine, Pediatrics, Houston, USA; <sup>2</sup>Texas Children's Hospital, Cancer and Hematology Centers, Houston, USA</italic></p><p><bold>Background/Objectives</bold>: TXCH Global HOPE operates projects in sub‐Saharan Africa (SSA). Placement in leadership positions in such settings can present significant challenges beyond the scope of pre‐service orientation. We have expanded our evidence‐based Reflective Practice & Leadership Seminar (RP&L) methods to provide ongoing leadership education for team members in SSA and fellows in the East African Pediatric Hematology‐Oncology Fellowship Program.</p><p><bold>Design/Methods</bold>: One hour teleconference seminars are routinely conducted with faculty, staff and fellows in 4 sites in Sub‐Saharan Africa. Seminar participants present current challenges and seasoned faculty guide the discussion through a disciplined, step‐wise analysis including a “diagnosis” of the situation and a plan for strategic action – the leadership dimension of a health care professional's role.</p><p><bold>Results</bold>: Topics covered in the seminar included the challenges of introducing a new sub‐specialty into a country, bringing new staff members onto a team, negotiating care delivered by an ancillary in‐country service, petitioning for resources within the context of a larger local organization, negotiating for the change of medical personnel provided through a separate institution, and negotiating change within an external institution that directly affects program function. Self‐report post‐seminar questionnaires indicated participants strongly agreed (5 on 1‐5 scale) with the following statements: the seminar improved their ability to 1) analyze complicated clinical service situations 2) navigate inter‐institutional politics, and 3) effectively build cross‐service relationships to improve patient care.</p><p><bold>Conclusions</bold>: This Global Leadership Seminar has demonstrated success in helping our SSA staff and trainees improve leadership capacity and negotiate change effectively.</p></sec><sec id="pbc26772-sec-11380"><label>PO-112</label><title>Health‐Related Quality of Life in Mothers with Children with Cancer: A Systematic Review</title><p><underline underline-style="single">C. Nicolaou</underline><sup>1</sup></p><p><italic><sup>1</sup>Cyprus University of Technology, Nursing, Limassol, Cyprus</italic></p><p><bold>Background/Objectives</bold>: Studies among parents of children with cancer have focused on anxiety, depression, or post‐traumatic stress, and less so on overall measures, such as Health‐Related Quality of Life (HRQoL).</p><p><bold>Design/Methods</bold>: Literature review in Scopus and Cinahl with terms: mothers OR carers etc AND child* OR adolesc* etc AND cancer or oncolog* etc AND quality of life OR HRQoL etc, in 65 combinations. Selection criteria: mothers (or predominately in mixed samples), children aged<18 in active treatment (no palliative), quantitative, some measure of quality of life, comparative (e.g. population norms, or control group) or correlational, or baseline in interventions, English language, prior 2016.</p><p><bold>Results</bold>: Of 237 studies reviewed in full‐text among 2184, 10 fulfilled all criteria: 6 mothers only, 4 mixed with separate results for mothers, and additional 10 with sample of predominately mothers. With the exception of a series of studies from Canada (N>400), most studies had small sample sizes (N<150). European studies originated from limited number of settings. There were single‐sample correlational studies (e.g. coping, anxiety, depression, sleep quality), internal comparisons (e.g. single‐ vs two‐parent families, time since diagnosis, or same group longitudinal, etc) or external (i.e. mothers of healthy children, or other diagnosis, or population norms). SF‐36 was commonly used. In studies with external comparison, quality of life was significantly reduced amongst mothers (or parents) of children with cancer. Despite cross‐national heterogeneity, in studies that the SF‐36 commonly effect sizes were in the range of 0.5‐1 SD for mental health and ∼0.5 SD for physical health dimension.</p><p><bold>Conclusions</bold>: Physical health as well as mental health aspects of the quality of life appear affected in this vulnerable group, highlighting the need to monitor and incorporate QoL as an outcome measure in assessing the effectiveness of psychosocial intervention programs.The main message is: The Quality of life is compromised in mothers of children with cancer.</p></sec><sec id="pbc26772-sec-11390"><label>PO-113</label><title>Integrating Young Adult Feedback into the Cross‐Cultural Adaptation of an Advance Care Planning Guide for Brazilian Youth Living with Cancer</title><p><underline underline-style="single">M. N. F. Arruda‐Colli</underline><sup>1,2</sup>, M. A. Santos<sup>1</sup>, S. Z. Bedoya<sup>2</sup>, É. A. Oliveira‐Cardoso<sup>1</sup>, L. Wiener<sup>2</sup></p><p><italic><sup>1</sup>University of Sao Paulo, Faculty of Philosophy‐ Sciences‐ and Letters at Ribeirao Preto, Ribeirao Preto, Brazil; <sup>2</sup>National Cancer Institute, Pediatric Oncology Branch, Bethesda, USA</italic></p><p><bold>Background/Objectives</bold>: Given the importance of having culturally appropriate tools to initiate advance care planning conversations with young adults, a cross‐cultural adaptation of <italic>Voicing My CHOiCES<sup>TM</sup></italic> (VMC) in Brazil is underway.</p><p><bold>Design/Methods</bold>: VMC was translated to Portuguese by 2 bilingual translators. A synthesis version was defined and submitted for semantic validation by experts. Patients aged 18‐39 undergoing cancer treatment were then invited to evaluate the modified version in terms of clarity, cultural and age appropriateness, helpfulness and stressfulness. The revised version was back‐translated to English by 2 bilingual translators and discussed with VMC's authors to refine the final Portuguese version. Quantitative data were analyzed by descriptive analysis, while qualitative data were evaluated by thematic content analysis.</p><p><bold>Results</bold>: Nine experts and 15 patients were enrolled. Overall, experts evaluated the tool as “totally adequate” or “adequate” in regards to document structure, relevance of topics covered and adequacy of use across settings with the target‐population. Suggestions for adaptation focused on cultural, legal and linguistic aspects. The document was revised and then introduced to patients. Over 80% of the patients considered all topics covered to be age and culturally appropriate. Similarly, over 80% of the participants found all the topics to be “very helpful” or “helpful” except for the section that addresses funeral planning, which only 53% described as “helpful” and endorsed as being “very stressful”. Patients’ feedback focused on cultural aspects and how to incorporate the tool into the treatment trajectory.</p><p><bold>Conclusions</bold>: Obtaining the target‐population feedback during the semantic validation was essential to ensure appropriate linguistic and cultural adaptations. Further study with the adapted version of VMC in Portuguese will be implemented to evaluate the tool's feasibility and to identify potential burdens and benefits of its use.</p><p><bold>Acknowledgement</bold>: This study is supported by grant #2016/15269‐3, Sao Paulo Research Foundation (FAPESP) and in part by the NIH Intramural Research Program.</p></sec><sec id="pbc26772-sec-11400"><label>PO-114</label><title>A Mixed‐Method Study Conducted in Parents and Professionals to Improve the Concept and Tools of a Psychosocial Intervention to Support Parents in Pediatric Oncology</title><p><underline underline-style="single">D. Ogez</underline><sup>1</sup>, C.J. Bourque<sup>1</sup>, K. Péloquin<sup>2</sup>, R. Ribeiro<sup>2</sup>, D. Curnier<sup>3</sup>, V. Marcil<sup>4</sup>, D. Sinnett<sup>1</sup>, S. Sultan<sup>2</sup></p><p><italic><sup>1</sup>CHU Sainte‐Justine, Research center, Montreal, Canada; <sup>2</sup>Université de Montréal, Psychology, Montreal, Canada; <sup>3</sup>Université de Montréal, Kinesiology, Montreal, Canada; <sup>4</sup>Université de Montréal, Dietetic, Montreal, Canada</italic></p><p><bold>Background/Objectives</bold>: Only two manualized intervention programs have been effective to reduce parental distress when the child is being treated for cancer: Bright Ideas and SCCIP. These programs bear some limitations related to dissemination, focus on the individual vs the family, etc., which we wanted to deal with in a new integrative program, taking the best of what is currently available. The aim of this preliminary study was to refine the design of an integrative program “Regain control together” a 6‐session face‐to‐face intervention to support parents.</p><p><bold>Design/Methods</bold>: This sequential mixed‐method study called for two steps: (1) parents were invited to an information session on the intervention project and completed a questionnaire on objectives, procedure, manuals and tools; (2) after the descriptive analysis of the questionnaire responses, areas for improvement were discussed in a focus group of parents. The process was repeated with professionals. Descriptive analyses of questionnaire responses and a computerized thematic analysis (NVIVO) allowed for organizing different categories of recommendations for program refinement.</p><p><bold>Results</bold>: Six parents and six professionals participated in the study. The results showed the strengths of the program: pertinence for solving problem practical approach and couple intervention. The main areas of improvement were the accessibility of the language for the manuals and the adaptation of the program to different cultures. We discuss the program, recommendations of participants and changes made accordingly. A final version available for a formal Phase II pilot‐test is available and its core features will be presented.</p><p><bold>Conclusions</bold>: This study illustrates that it is necessary to include parents and final users in the elaboration of such intervention programs. The final version will now be available for gradual implementation and testing (feasibility, acceptability, and effects).</p></sec><sec id="pbc26772-sec-11410"><label>PO-115</label><title>Anxiety, Depression, Burn Out and Post Traumatic Stress Disorders in Children with Cancer and Their Mothers</title><p><underline underline-style="single">A. Okur</underline><sup>1</sup>, E.O. Ozmen<sup>1</sup>, E. Güney<sup>2</sup>, F.G. Pinarli<sup>1</sup>, E.G. Saripinar<sup>2</sup>, C. Karadeniz<sup>1</sup></p><p><italic><sup>1</sup>Gazi University, Pediatric Oncology, Ankara, Turkey; <sup>2</sup>Gazi University, Pediatric Psychiatry, Ankara, Turkey</italic></p><p><bold>Background/Objectives</bold>: The aim of this prospective study is to investigate the prevalence of anxiety, depression, burnout and posttraumatic stress disorder in pediatric oncology patients and their mothers.</p><p><bold>Design/Methods</bold>: Children and adolescents (n=60) aged 8‐18 years who were actively treated or followed‐up in remission at Gazi University Pediatric Oncology Department and their mothers were recruited as the study group. The control group for anxiety, depression and burnout (n=30) consisted of children without chronic disease who were admitted to General Pediatric Clinic as outpatients and their mothers. Self‐report questionnaires measuring anxiety and depression were administered to the children and mothers. Post‐traumatic stress disorder (PTSD) scale for children and mothers were performed as face‐to‐face surveys in the presence of the clinician. The control group for PTSD (n=15) consisted of children and their mothers who experiered a serious traumatic event such as traffic accident, earthquake and close relative's death.</p><p><bold>Results</bold>: There was no significant difference with regard to anxiety, depression and burn out in terms of any scale score between children in remission and children under treatment. The mothers of children under treatment were significantly more traumatized and more anxious than those of children in remission. However there was no significant difference in burnout symptoms between mothers of children under treatment and mothers of children in remission. Children with cancer were more depressed and worried than control groups. Mothers of healthy children were significantly less depressed and anxious than mothers of children under treatment and in remission. We found that there were significantly more PTSD symptoms in patients both under treatment and in remission children and mothers of patients than the PTSD control group.</p><p><bold>Conclusions</bold>: These findings suggest that pediatric cancer is a significant stressor for both children and their mothers. Clinicians should be aware of psychiatric symptoms of children who underwent such a life‐threatening condition.</p></sec><sec id="pbc26772-sec-11420"><label>PO-116</label><title>Quality of Life in Survivors of Bone Tumours at Hospital Infantil De Mexico</title><p>M.A. Palomo Colli<sup>1</sup>, J.Z. Lugo Juárez<sup>1</sup>, L.E. Juárez Villegas<sup>1</sup>, J. Mier Cabrera<sup>2</sup>, J.F. Gaytan Morales<sup>1</sup>, <underline underline-style="single">M.</underline><underline underline-style="single">Mier</underline><underline underline-style="single">Cabrera</underline><sup>3</sup>, L. Barcenas Bobadilla<sup>4</sup>, S. Sadowinski Pine<sup>5</sup></p><p><italic><sup>1</sup>Hospital Infantil de México Federico Gómez, Oncology, México, Mexico; <sup>2</sup>Instituto Nacional de Perinatologia “Isidro Espinoza de los Reyes”, Subdireccion investigacion en intervenciones comunitarias, México, Mexico; <sup>3</sup>Hospital Regional Alta Especialidad Ixtapaluca, Pediatrics, Ixtapaluca, Mexico; <sup>4</sup>Hospital Infantil de México Federico Gómez, Nursing, México, Mexico; <sup>5</sup>Hospital Infantil de México Federico Gómez, Pathology, México, Mexico</italic></p><p><bold>Background/Objectives</bold>: Patients with bone tumours (BT) undergo extensive and aggressive chemotherapy treatment and surgery, which can have significant acute and long‐term effects on patients. Considering the high survival rates of childhood cancer, physical and psychosocial long‐term effects, as well as assessment of health‐related quality of life (HRQoL), are becoming new focus of clinical research. Patients with these diagnoses are at high risk of poor HRQoL compared to other childhood cancer survivors.</p><p>Assesment the Quality of life in survivors childhood with BT.</p><p><bold>Design/Methods</bold>: Descriptive and observational study conducted at Hospital Infantil de Mexico “Federico Gómez”. Eligible study participants were enrolled between August 2015 and July 2016. Participants completed a self‐administered questionnaire (KIDSCREEN‐52). The instrument measures ten dimensions: physical well‐being, psychological well‐being, moods and emotions, self‐perception, autonomy, parent relations and home life, social support and peers, school environment, social acceptance (Bullying), and financial resources. Test items are rated on a 100‐point Likert‐type scale. High scores indicate good quality of life</p><p><bold>Results</bold>: Thirteen BT survivors between 8 and 18 years old, who were followed at least one year after complete treatment, participated in this study. Twelve patients with osteosarcoma and one with Ewing Sarcoma. Seven were male. Four (30%) had metastasis at diagnosis. Seven (53.8%) had undergone amputation KIDSCREEN‐52 scores were 64 points for physical well‐being, 75 for psychological, 76 for autonomy, 79 for school environment and social support and 95 for social acceptance.</p><p><bold>Conclusions</bold>: Although many BT survivors report excellent functional and HRQoL outcomes, a significant number report long‐term disability and impairments. Further follow‐up of this cohort, including reassessment to observe changes in scores and perceived disability over time, is clearly warranted. We hope this study will help provide patients and families with needed information about anticipated long‐term outcomes and how to maximize function and RHQoL</p></sec><sec id="pbc26772-sec-11430"><label>PO-117</label><title>School Performance of Childhood Cancer Survivors in Korea: A Multi‐Institutional Study on Behalf of Korean Society of Pediatric Hematology and Oncology (KSPHO)</title><p><underline underline-style="single">M. Park</underline><sup>1</sup>, J.M. Lee<sup>2</sup>, H.J. Park<sup>3</sup>, H.Y. Ju<sup>3</sup>, B.K. Park<sup>3</sup>, J.Y. Kim<sup>4</sup>, S.K. Park<sup>5</sup>, Y.H. Lee<sup>6</sup>, Y.J. Shim<sup>7</sup>, H.S. Kim<sup>7</sup>, J.A. Lee<sup>8</sup>, Y.J. Lim<sup>9</sup>, H.W. Cheuh<sup>10</sup>, J.K. Park<sup>11</sup>, M.J. Lee<sup>12</sup>, S.K. Kim<sup>13</sup>, H.S. Choi<sup>14</sup>, H.J. Kang<sup>15</sup>, K.D. Park<sup>15</sup>, H.Y. Shin<sup>15</sup></p><p><italic><sup>1</sup>Chungbuk National University College of Medicine, Pediatrics, Cheongju, Republic of Korea; <sup>2</sup>Yeungnam University College of Medicine, Pediatrics, Daegu, Republic of Korea; <sup>3</sup>National Cancer Center, Pediatric Oncology, Goyang, Republic of Korea; <sup>4</sup>Kyungpook National University School of Medicine, Pediatrics, Daegu, Republic of Korea; <sup>5</sup>Ulsan University Hospital‐ University of Ulsan College of Medicine, Pediatrics, Ulsan, Republic of Korea; <sup>6</sup>Hanyang University College of Medicine, Pediatrics, Seoul, Republic of Korea; <sup>7</sup>Keimyung University College of Medicine, Pediatrics, Daegu, Republic of Korea; <sup>8</sup>Korea Cancer Center Hospital, Pediatrics, Seoul, Republic of Korea; <sup>9</sup>Chungnam National University College of Medicine, Pediatrics, Daejon, Republic of Korea; <sup>10</sup>Dong‐A University College of Medicine, Pediatrics, Busan, Republic of Korea; <sup>11</sup>Inje University Busan Paik Hospital, Pediatrics, Busan, Republic of Korea; <sup>12</sup>Dankook University College of Medicine, Pediatrics, Cheonan, Republic of Korea; <sup>13</sup>Inha University College of Medicine, Pediatrics, Incheon, Republic of Korea; <sup>14</sup>Seoul National University Bundang Hospital, Pediatrics, Seongnam, Republic of Korea; <sup>15</sup>Cancer Research Institute‐ Seoul National University College of Medicine, Pediatrics, Seoul, Republic of Korea</italic></p><p><bold>Background/Objectives</bold>: Successful return to school after cancer diagnosis is important to facilitate the child's normal learning and attainment of academic skills. Absenteeism in vulnerable cancer survivors might exacerbate treatment‐related learning challenges. In this study, we addressed the issue of peer relationship, school attendance and academic achievement.</p><p><bold>Design/Methods</bold>: Between July 2015 and December 2016, 15 institutions in Korea participated in this study on behalf of Korean Society of Pediatric Hematology and Oncology (KSPHO). We studied 241 children treated for cancer who, at the time of study, were older than 9 years. The self‐reported paper‐and‐pencil questionnaire was used in this study.</p><p><bold>Results</bold>: Approximately 21% of the survivors suffered from lack of friends. Bullying was reported by 29.4% of survivors. There was no difference in experiencing bullying according to disease categories. However, survivors who returned to primary school reported higher incidence of bullying compared to survivors who returned to middle or high school (22.9%, 10.6% and 6.1%, <italic>p</italic>=0.03). The percentage of children who missed classes more than 4 days in a month was higher in survivors with brain tumor than those with other tumors (52.6% vs. 31.8%, <italic>p</italic>=0.04). Survivors reported that they missed school due to physical illness or fatigue (58.0%), medical care (19.0%), and parents’ concern (19.0%). Approximately 41% of children reported learning difficulty, mainly due to the difficulty in understanding the materials (58.0%) or concentration in classes (28.7%). Children who received hospital school support during cancer treatment repeated less often than children who did not (8.3% vs. 17.2%, <italic>p</italic>=0.05). The school marks in Korean language (p=0.03), English (p=0.04), and physical education (p=0.04) was worse for the children with brain tumors than for the children with other tumors.</p><p><bold>Conclusions</bold>: This study demonstrated that survivors of cancers require special care and attention when they return to school. Those treated for brain tumor remain particularly vulnerable.</p></sec><sec id="pbc26772-sec-11440"><label>PO-118</label><title>An Examination of Barriers to Care and Illness Uncertainty in Parents of Children Newly Diagnosed with Cancer</title><p><underline underline-style="single">M. Perez</underline><sup>1</sup>, C. Sharkey<sup>1</sup>, D. Bakula<sup>1</sup>, A. Mullins<sup>1</sup>, S. Mayes<sup>2</sup>, R. McNall‐Knapp<sup>2</sup>, L. Mullins<sup>1</sup></p><p><italic><sup>1</sup>Oklahoma State University, Psychology, Stillwater, USA; <sup>2</sup>University of Oklahoma Health Sciences Center, Pediatric Hematology Oncology, Oklahoma City, USA</italic></p><p><bold>Background/Objectives</bold>: A subset of caregivers of children newly diagnosed with cancer are at risk for psychological distress. Both parental illness uncertainty (IU) and barriers to care have been linked to parental distress. Our previous research indicates that IU may mediate the relationship between barriers to care and distress. To further evaluate the pathways by which barriers to care may impact IU, the present study assessed the relationships between distinct barriers to care (i.e., pragmatics, skills, expectations, marginalization, knowledge/beliefs) and specific components of IU (i.e., ambiguity, lack of clarity, lack of information).</p><p><bold>Design/Methods</bold>: Caregivers (<italic>N</italic>=52) of children newly diagnosed with cancer (<italic>M<sub>Days</sub></italic>=91.1, <italic>SD<sub>Days</sub></italic>=52.3) were recruited at a Midwest medical center, and completed the Barriers to Care Questionnaire (BCQ) and the Parent Perception of Uncertainty Scale (PPUS) as part of a larger study on parental adaptation to the pediatric cancer diagnosis.</p><p><bold>Results</bold>: <italic>Expectations</italic> significantly predicted <italic>ambiguity</italic> (<italic>p</italic>=0.003), <italic>lack of clarity</italic> (<italic>p</italic><0.001), and <italic>lack of information</italic> (<italic>p</italic>=0.002). <italic>Marginalization</italic> significantly predicted <italic>ambiguity</italic> (<italic>p</italic>=0.006), <italic>lack of clarity</italic> (<italic>p</italic>=0.001), and <italic>lack of information</italic> (<italic>p</italic>=0.012). <italic>Skills</italic> significantly predicted <italic>ambiguity</italic> (<italic>p</italic>=0.013) and <italic>lack of information</italic> (<italic>p</italic>=0.010). <italic>Knowledge/beliefs</italic> significantly predicted <italic>ambiguity</italic> (<italic>p</italic>=0.043) and <italic>lack of clarity</italic> (<italic>p</italic>=0.041). <italic>Pragmatics</italic> significantly predicted <italic>ambiguity</italic> (<italic>p</italic>=0.036).</p><p><bold>Conclusions</bold>: Caregivers who perceived low quality of care or personalized the negative experiences of their child's care experienced higher ambiguity and deficits in clarity and information concerning the illness. Parents who reported lower confidence in ability to manage their child's medical care, experienced ambiguity and lack of information regarding illness and treatment. Lastly, parents who disagreed with medical professionals about care reported increased ambiguity and lack of clarity. The results suggest that parents perceiving care as being of low quality or parents disagreeing with medical treatments are experiencing higher IU. Improvements in communication and relationships between caregivers and the clinical team may reduce barriers and IU, and potentially attenuate distress.</p></sec><sec id="pbc26772-sec-11450"><label>PO-119</label><title>Treatment Intensity and Health‐Related Quality of Life in Pediatric Cancer Survivors: The Role of Psychosocial Family Functioning</title><p>N. Racine<sup>1</sup>, B. Russell<sup>2</sup>, M. Khu<sup>3</sup>, K. Reynolds<sup>4</sup>, G. Guilcher<sup>3</sup>, <underline underline-style="single">F. Schulte</underline><sup>5</sup></p><p><italic><sup>1</sup>University of Calgary, Psychology, Calgary, Canada; <sup>2</sup>Alberta Children's Hospital, Hematology‐ Oncology‐ and Transplant Program, Calgayar, Canada; <sup>3</sup>Alberta Children's Hospital, Hematology‐ Oncology‐ and Transplant Program, Calgary, Canada; <sup>4</sup>Alberta Children's Hospital, Long Term Survivor Clinic, Calgary, Canada; <sup>5</sup>Alberta Children's Hospital, Hematology‐ Oncology‐ Transplant Program, Calgary, Canada</italic></p><p><bold>Background/Objectives</bold>: With increased survival of children treated for pediatric cancer, attention has turned to their long‐term health and well‐being. The aim of the current study was to examine treatment intensity as a risk factor for poor HRQL (Health‐Related Quality of Life) in pediatric cancer survivors. It was hypothesized that higher treatment intensity would be associated with lower HRQL. However, it was also hypothesized that family psychosocial functioning (including family cohesion, social support, and availability of resources) would buffer survivors from the deleterious consequences of high treatment intensities.</p><p><bold>Design/Methods</bold>: Fifty‐two pediatric cancer survivors (mean age=11.92 yrs, Range= 6‐17 yrs) and their parents were recruited during routine follow‐up appointments at a hospital‐based long‐term survivor clinic and completed questionnaires addressing HRQL (PedsQL 4.0) and family psychosocial risk (PAT 2.0). Intensity of treatment was determined via a standardized tool (Intensity of Treatment Rating Scale) and was independently rated by two health care providers.</p><p><bold>Results</bold>: Multiple regression analyses revealed that after controlling for age, sex, and parent psychological distress, treatment intensity (<italic>b=</italic> ‐.23, <italic>p</italic> = .04) and psychosocial family risk (<italic>b=</italic> ‐.61, <italic>p</italic><.001) negatively predicted parent‐proxy reported HRQL. Psychosocial family risk moderated the association between parent psychological distress and child HRQL (<italic>b=</italic> ‐.64, <italic>p</italic>=.04).</p><p><bold>Conclusions</bold>: Higher levels of treatment intensity for cancer put children at risk for poor HRQL, which in turn has implications for long‐term social and mental health outcomes. In the current study, a resiliency effect was observed, where children with a history of high levels of treatment intensity were buffered from experiencing poor quality of life if they had low psychosocial family risk.</p></sec><sec id="pbc26772-sec-11460"><label>PO-120</label><title>Decision‐Making in Pediatric Oncology: Needs, Preferences and Experiences of Families</title><p><underline underline-style="single">E.G. Robertson</underline><sup>1,2</sup>, J. Fardell<sup>1,2</sup>, R. Cohn<sup>1,2,3</sup>, C. Wakefield<sup>1,2</sup></p><p><italic><sup>1</sup>Sydney Children's Hospital, Behavioural Sciences Unit‐ Kids Cancer Centre, Randwick, Australia</italic></p><p><italic><sup>2</sup>UNSW Medicine‐ The University of New South Wales, Discipline of Paediatrics‐ School of Women's and Children's Health, Randwick, Australia; <sup>3</sup>Sydney Children's Hospital, Kids Cancer Centre, Randwick, Australia</italic></p><p><bold>Background/Objectives</bold>: Families of children diagnosed with cancer are faced with difficult treatment decisions, including radiation therapy, fertility preservation, and enrolling in research studies. Many patients and parents find it difficult to understand the rationale and implications of treatment options. They may also be at risk of experiencing decisional anxiety and conflict, uncertainty, and distress. We aimed to qualitatively explore the decision‐making process of parents and young people when faced with a treatment decision, as well as any information needs and preferences.</p><p><bold>Design/Methods</bold>: We conducted semi‐structured interviews with recently diagnosed adolescents and parents. Interviews were audio recorded, transcribed verbatim and analysed via content analysis using NVivo. To date, 3 adolescents (mean age=14y) and 8 parents (mean age of child=8y) have completed the interview. The study is still recruiting; anticipated study close is Mar‐17.</p><p><bold>Results</bold>: To date, 3 adolescents (mean age=14y) and 8 parents (mean age of child=8y) have completed the interview. Early findings suggest families often engage in parent‐driven or parent‐child shared decision‐making, with the relationship with their clinician a major influence in the decision process. Parents tend not to include their child in major decisions (e.g. clinical trial enrolment) due to the age of their child, however acknowledge the importance for children to be involved in day‐to‐day decisions (e.g. pain relief). Some parents express dissatisfaction with their level of decisional‐involvement. Barriers to involvement include feeling distressed and overwhelmed with information.</p><p><bold>Conclusions</bold>: Decision‐making in pediatric oncology is complex. Families require clearer information provided in multiple modalities, more guidance to engage in shared decision‐making, and more emotional support throughout the decision process. These findings have contributed to the development of Delta – an online decision‐aid supporting families deciding whether to enrol in a pediatric oncology clinical trial.</p></sec><sec id="pbc26772-sec-11470"><label>PO-121</label><title>Returning Research Results Caregivers’ Reactions Following Computerized Cognitive Training Among Childhood Cancer Survivors</title><p><underline underline-style="single">S. Scott</underline><sup>1</sup>, J. Ashford<sup>1</sup>, K. Clark<sup>1</sup>, K. Martin‐Elbahesh<sup>1</sup>, H. Conklin<sup>1</sup></p><p><italic><sup>1</sup>St. Jude Children's Research Hospital, Psychology, Memphis, USA</italic></p><p><bold>Background/Objectives</bold>: Few researchers routinely disseminate results following participation in a study; however, there is increasing acknowledgment that benefits of returning results far outweigh potential risks. Some researchers endorse returning research results as another component of ethical research. Among a pediatric population, specifically, it is important to determine the preference in which families would like to receive research results and guidelines for developing a clear summary of results. The current study explores the practice of returning results to families of childhood cancer survivors following participation in a computerized cognitive training program using Children's Oncology Group (COG) guidelines.</p><p><bold>Design/Methods</bold>: In a previous study, survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT; N = 68) with identified cognitive deficits were randomly assigned to participate in a computerized cognitive intervention or assigned to a wait‐list. Following conclusion of the previous study, participants’ families were contacted by postal letter, phone call, and/or patient approach and provided with a summary of results from the computerized cognitive training study and a survey gauging their interpretation of the summary, reaction to the results, and preference regarding the return of results.</p><p><bold>Results</bold>: Forty‐three participants returned the survey and caregivers indicated they perceived the results as important (93.0%), helpful (93.0%), relevant to their child (90.7%), and easy to understand (97.7%). The results provided in the summary were mostly interpreted in a positive manner, with many endorsing satisfaction (83.8%) and/or relief (41.9%). Further, many caregivers preferred receiving research results through postal letter (88.4%) or email (46.5%).</p><p><bold>Conclusions</bold>: In summary, the benefits of returning research results regarding the effects of computerized training on childhood cancer survivors far outweigh the perceived risks. The practice of regularly returning research results can directly benefit families when making future healthcare‐related decisions, in addition to disseminating accurate, nuanced research results.</p></sec><sec id="pbc26772-sec-11480"><label>PO-122</label><title>Long Term Positive and Negative Psychological Late Effects for Parents of Childhood Cancer Survivors: An Updated Systematic Review</title><p><underline underline-style="single">K. Shimmon</underline><sup>1</sup>, B. Phillips<sup>2</sup>, P. Siddell<sup>1</sup></p><p><italic><sup>1</sup>leeds teaching hospitals, Paediatric Psychology, leeds, United Kingdom; <sup>2</sup>University of York, Centre for Reviews and Dissemination, York, United Kingdom</italic></p><p><bold>Background/Objectives</bold>: The long term psychological effects of childhood cancer upon parents has been studied extensively, yet uncertainty remains about the degree and nature of any positive or negative psychological sequelae. This paper updates and expands upon a review assessing the literature published between 1988 and 2010 on the positive and negative long term psychological late effects for parents of childhood cancer survivors (CCS) reported at least five years after the child's diagnosis and/or two years after the end of the child's treatment.</p><p><bold>Design/Methods</bold>: Standard systematic review methods were employed. Two independent reviewers conducted searches in the databases CINAHL, EMBASE, PsychINFO and PubMed, performing quality appraisal using the QUALSYST tool and extracting data. Ninety‐one possible papers were reviewed, 19 assessed in full‐text and 10 added, with a total of 25 finally included. Synthesis of the data was undertaken using a narrative framework, as heterogeneity of the underlying data collection precluded quantitative meta‐analysis.</p><p><bold>Results</bold>: A total of 10 new studies including 880 parents were added. Overall, the majority of studies report no differences in levels of psychological distress for parents of survivors compared to norms, with a small subset reporting elevated levels of Post Traumatic Stress Symptoms (PTSS). Two additional studies found lower PTSS and/or higher Post Traumatic Growth (PG). Factors associated with negative long term late effects included: more avoidant coping styles, age of parent, caregiver strain and conflictive family functioning.</p><p><bold>Conclusions</bold>: There is little evidence to suggest that having a child with cancer results in general with increased levels of psychological distress for parents in the long term; some opportunities for personal growth may be experienced, but for others the events trigger PTSS. The clinical implications of these findings argue for awareness and specific referrals when required.</p></sec><sec id="pbc26772-sec-11490"><label>PO-123</label><title>Depressive Symptomathology in 100 AYA Cancer Survivors: A Significant Predictive Model</title><p><underline underline-style="single">M. Tremolada</underline><sup>1</sup>, S. Bonichini<sup>1</sup>, G. Scarzello<sup>2</sup>, G. Basso<sup>3</sup>, M. Pillon<sup>3</sup></p><p><italic><sup>1</sup>University of Psychology, Department of development and social psychology, PADOVA, Italy; <sup>2</sup>Istituto Oncologico Veneto, Pediatric Radiotherapy Unit, Padua, Italy; <sup>3</sup>University Hospital of Padua, Department of Child and Woman's Health‐ Oncology Hematology Division, Padua, Italy</italic></p><p><bold>Background/Objectives</bold>: Due to advances in chemotherapy and supportive care in the last years, the number of childhood cancer survivors has fortunately increased. Unfortunately, they could self‐report several negative psycho‐social effects linked to the cancer treatment. A few studies adopted a mixed‐method approach crossing narrative data with those coming from self‐report questionnaires to identify the possible significant predictors of psychopathologic symptoms in their quality of daily life and in their relationships’ characteristics. The aim of this study is to assess quality of daily life, family and social relationships in pediatric cancer survivors, adopting the mixed method to identify the possible psycho‐social factors impacting on their depressive symptomatology.</p><p><bold>Design/Methods</bold>: Participants consists in 100 north‐east Italian AYA cancer survivors, mean age at diagnosis of 9.26 years (SD=4.29), 51 treated for haematologic disease and 49 for solid tumours, off‐therapy from a mean of 8.19 years (SD=2.62). The Ecocultural Family Interview (Tremolada et al., 2013). new version AYA cancer survivors ‐ took place in the DH of the Onco‐hematology clinic during their medical controls. This interview resulted psychometrically reliable and solid with the extraction of 12 good internal consistence general dimensions from 102 items. Self‐report questionnaires measuring feelings and emotions (CCSS) and the Brief Cope were administered as well.</p><p><bold>Results</bold>: A hierarchical regression analysis showed that depressive symptoms (R<sup>2</sup> = 0.36; F = 7.14 p = 0.0001) were predicted by Age at diagnosis (beta = ‐0.41; p = 0.03), by Relationships with parents (beta = ‐0.22; p = 0.01) and by Self‐blame coping strategy (beta = 0.41; p = 0.0001). Medical and sociodemographic variables didn't impact significantly.</p><p><bold>Conclusions</bold>: A good relationship with parents and older age at the diagnosis were identified as protective factors for depressive symptomatology, while self‐blame coping strategy represented a risk factor. These empirical data should lead to focused interventions.</p></sec><sec id="pbc26772-sec-11500"><label>PO-124</label><title>Child and Family Perspectives of Pediatric Hematopoietic Stem Cell Transplant: A Retrospective Pilot Study</title><p><underline underline-style="single">C. West</underline><sup>1</sup>, D. Dusome<sup>2</sup>, L. Rallison<sup>3</sup>, J. Winsor<sup>1</sup></p><p><italic><sup>1</sup>University of Manitoba, College of Nursing, Winnipeg, Canada; <sup>2</sup>Brandon University, Faculty of Health Studies, Winnipeg, Canada; <sup>3</sup>University of Calgary, Faculty of Nursing, Calgary, Canada</italic></p><p><bold>Background/Objectives</bold>: Pediatric hematopoietic stem cell transplant (HSCT) is a highly intensive treatment. Children and family members experience significant illness distress, including anxiety, depression, and post‐traumatic stress symptoms. The distress of family members plays a pivotal role in the level of distress experienced by ill children during HSCT. The key limitation of existing research is the “family” has primarily been studied from the perspective of individual family members, not the family unit. This study used a family systems‐expressive arts framework to identify the main factors that influence the family transition through HSCT, as well as specific family needs and outcomes.</p><p><bold>Design/Methods</bold>: A retrospective pilot study was conducted using constructivist grounded theory. Fifteen family members (9 parents/primary caregivers, 3 recipients, 3 siblings) from six families participated in two qualitative interviews. During the second interview, participants drew an image of how they experienced HSCT treatment. The researchers guided family members through a “dialoguing with images” process: each family member asked the image questions, and then answered those questions as if they were the image.</p><p><bold>Results</bold>: An inductively derived theory of the family transition through HSCT was developed:the pre‐HSCT trajectory, including the relationship dynamics within the family and those with the health care team, were powerful modulators of this transition. A highly tenuous process of family fragmentation occurred during hospitalization. Experiences of trauma occurred, particularly for ‘parent caregivers’ who lived in the transplant room 24 hours/day, sustaining the ill child. During hospitalization, family members experienced one of two dominant patterns of interaction with health care professionals: expression‐support (5 families) or conflict‐withdrawal (1 family). Following discharge, families struggled to reintegrate, holding unvoiced experiences of trauma, which differed for each family member.</p><p><bold>Conclusions</bold>: We identified a crucial need for targeted family systems‐expressive arts intervention during the transition into HSCT and post‐hospitalization. Acknowledgments: Children's Hospital Research Institute of Manitoba Operating Grant.</p></sec><sec id="pbc26772-sec-11510"><label>PO-125</label><title>Validating the Patient‐Reported Outcomes Measurement Information System (PROMIS‐25) to Measure Health‐Related Quality of Life in Pediatric Lymphoma Patients in Malawi</title><p><underline underline-style="single">K. Westmoreland</underline><sup>1,2</sup>, T. van der Gronde<sup>3</sup>, A. Amuquandoh<sup>3</sup>, S. Itimu<sup>3</sup>, A. Salima<sup>3</sup>, C. Stanley<sup>3</sup>, M. Chikasema<sup>3</sup>, P. Ward<sup>3</sup>, S. Gopal<sup>4,5,6</sup>, B. Reeve<sup>7</sup></p><p><italic><sup>1</sup>UNC Project‐Malawi, Pediatric Hematology Oncology, Lilongwe, Malawi; <sup>2</sup>University of North Carolina, Pediatric Hematology Oncology, Chapel Hill, USA; <sup>3</sup>UNC Project‐Malawi, Oncology, Lilongwe, Malawi; <sup>4</sup>UNC Project‐Malawi, Cancer Program Director, Lilongwe, Malawi; <sup>5</sup>University of Malawi School of Medicine, Oncology and Infectious Disease, Lilongwe, Malawi; <sup>6</sup>University of North Carolina, Oncology and Infectious Disease, Chapel Hill, USA; <sup>7</sup>University of North Carolina, Health Policy and Management, Chapel Hill, USA</italic></p><p><bold>Background/Objectives</bold>: Measuring health‐related quality of life (HRQoL) among cancer patients is important to comprehensively and holistically assess outcomes. Internationally validated tools to measure patient‐reported HRQoL are available, but efforts to translate and culturally validate such tools in sub‐Saharan Africa (SSA) have been scarce.</p><p><bold>Design/Methods</bold>: The Patient‐Reported Outcomes Measurement Information System 25‐item short form (PROMIS‐25) assesses six HRQoL domains: mobility, anxiety, depression, fatigue, peer relationships, and pain interference by asking four questions per domain. A single‐item pain intensity question is also included. The PROMIS‐25 instrument was translated into Chichewa: two forward independent translations, reconciliation, back translation, three independent reviews, finalization, and harmonization. Cultural validation was conducted through five semi‐structured cognitive interviews. Baseline questionnaires were collected for children enrolled in an ongoing prospective lymphoma cohort at Kamuzu Central Hospital in Lilongwe. Psychometric validity was assessed using Spearman's correlation among items within and across domains, Cronbach's alpha for internal consistency reliability within each domain, and t‐test for known group validity.</p><p><bold>Results</bold>: The interviews discovered that the translation of being able to walk ‘one block’ was not culturally applicable; therefore, this item was changed to ‘the length of one soccer pitch’. Thirty‐two lymphoma patients completed the PROMISE‐25 questionnaire. Items within each domain were more correlated than with items outside the domain supporting structural validity. Reliability of each scale was satisfactory (range alpha= 0.68‐0.91). Children with a hemoglobin <9.0 g/dL had worse fatigue HRQoL than those with hemoglobin ≥9.0 g/dL (<italic>p</italic>=0.048). Children with a Lansky performance status (LPS) ≤70 had a worse mobility HRQoL than those with LPS >70 (<italic>p</italic>=0.002).</p><p><bold>Conclusions</bold>: Translation and cultural validation of the PROMIS‐25 into Chichewa for Malawi was successful. As pediatric cancer care and research programs expand in SSA, it will be vital to incorporate assessment of HRQoL using self‐reported instruments validated within the local context.</p></sec><sec id="pbc26772-sec-11520"><label>PO-126</label><title>Educational Interventions with Pediatric Sibling Hematopoietic Stem Cell Donors to Increase Knowledge of Donation and Reduce Anxiety: A Pilot Study</title><p><underline underline-style="single">L. Wiener</underline><sup>1</sup></p><p><italic><sup>1</sup>NCI, Pediatric Oncology Branch, Bethesda, USA</italic></p><p><bold>Background/Objectives</bold>: Siblings are most often selected as a donor match for patients with malignant and nonmalignant hematologic diseases. Research on preparing siblings donors for stem cell donation is limited. Current data suggests that sibling donors are at risk for depression, anxiety, withdrawal, behavioral problems, and lowered self‐esteem. Even after donation procedures are explained, siblings have been found to have difficulty understanding the information and to experience anxiety. No prospective studies examining educational tools and transplant knowledge in sibling stem cell donors are currently available.</p><p><bold>Design/Methods</bold>: A study was designed to assess donor comprehension of donation procedures and to compare knowledge and anxiety prior to and post educational interventions. Participants include siblings of pediatric patients, ages 10‐26. Assessment of baseline knowledge and state anxiety is obtained before and after the consent/assent meeting with the medical team. Donors are then stratified into 2 groups by age. Donors’ ages 10 to 15 play an adapted version of <italic>ShopTalk</italic> and donors’ ages 16 to 25 are provided a workbook designed for sibling stem cell donors. Knowledge and anxiety is reassessed 24 hours following the intervention and again 1 month later.</p><p><bold>Results</bold>: 16 sibling donors enrolled, 7 completed all time points. Knowledge about how stem cells can help a cancer patient was very good at baseline. Areas lacking include how stem cells are collected and possible complications post donation and transplant. A trend for increased knowledge and reduced anxiety has been found post intervention. Enrollment is ongoing.</p><p><bold>Conclusions</bold>: Preliminary results suggest that education that provides information via a game or workbook increases knowledge and may reduce anxiety in sibling donors. Providing detailed information about donation and discussion of procedures should be tailed to the individual learning style and supplemented with additional visual information.</p></sec><sec id="pbc26772-sec-11530"><label>PO-127</label><title>Advantages, Challenges and Opportunities in Working with Participatory Visual Approaches in Qualitative Research Involving Children and Youth in the Context of Cancer Research</title><p><underline underline-style="single">R. Woodgate</underline><sup>1</sup>, P. Tennent<sup>1</sup>, M. Zurba<sup>1</sup></p><p><italic><sup>1</sup>University of Manitoba, Rady Faculty of Health Sciences‐ College of Nursing, Winnipeg, Canada</italic></p><p><bold>Background/Objectives</bold>: Since the mid‐1990s, participatory visual approaches in qualitative research have grown in popularity. Such creative approaches work towards facilitating the authentic expression of the complex realities of people engaged in research, as well as the more affective connections between people, their environments and life situations. The purpose of this presentation is to describe the use of participatory visual approaches including the advantages, challenges and opportunities in research that seeks to advance our understanding of children and youth's perspectives of cancer and cancer prevention.</p><p><bold>Design/Methods</bold>: The advantages, challenges and opportunities in working with participatory visual approaches including drawing and photovoice in qualitative research are gleaned from the literature and research conducted by the first author.</p><p><bold>Results</bold>: Participatory visual approaches such as drawing and photography enable children and youth in qualitative research to have a conversation with themselves by thinking through how they wanted to represent their own perspectives and experiences. Through participatory visual methods, they are able to produce powerful metaphors or literal depictions of their lived realities. Nonetheless, procedural, ethical and relational challenges in working with participatory visual approaches at various stages from activation to interpretation and dissemination can result including issues with data validity and authenticity.</p><p><bold>Conclusions</bold>: The insights derived from the literature and through the research provide standards for the advancement of participatory visual approaches in qualitative research that seeks to advance our understanding of children and youth's perspectives of cancer and cancer prevention. Enhancements to the didactic quality of the research, and considerations for extending participatory visual approaches into care following the completion of research are two areas where these approaches could be developed with great promise.</p></sec><sec id="pbc26772-sec-11540"><label>PO-128</label><title>Navigating Ethical Challenges in Qualitative Research with Children and Youth Living with Cancer and Other Complex Conditions: Sustaining Mindful Presence</title><p><underline underline-style="single">R. Woodgate</underline><sup>1</sup>, P. Tennent<sup>1</sup>, M. Zurba<sup>1</sup></p><p><italic><sup>1</sup>University of Manitoba, Rady Faculty of Health Sciences‐ College of Nursing, Winnipeg, Canada</italic></p><p><bold>Background/Objectives</bold>: A number of ethical challenges can emerge when engaging children and youth in qualitative research. The purpose of this presentation is to discuss how to mitigate ethical challenges in research that seeks to advance our understanding of children and youth living with cancer and other complex conditions.</p><p><bold>Design/Methods</bold>: Ethical challenges in qualitative research are explored by bringing forward examples from the first author's research program that is focused on the significance of multiple perspectives and the value of gauging the needs of young people living with cancer and other complex conditions. The studies address what children and youth think about their illness and contribute to building insights into their lived experience of illness.</p><p><bold>Results</bold>: In addition to highlighting the ethical challenges in working with children and youth in research, a case that ethical considerations need to extend beyond research ethics boards protocols is made. “Sustaining mindful presence” is proposed as a novel and inclusive framework through which researchers can navigate ethical challenges in research and involves moving through the research field with careful forethought, attentive pace and receptive attention to and awareness of what is taking place with the potential for the authentic expression of participants. Sustaining mindful presence includes the following characteristics that can become highly developed within a researcher: (i) openness and curiosity, (ii) empathy and acceptance, (iii) receptive attention and deep listening, (iv) relationally engagement, (v) flexibility and reflexivity, (vi) self‐awareness and self‐regulation, and (vii) being nonjudgmental and respectful.</p><p><bold>Conclusions</bold>: Through sustaining mindful presence, researchers are more able to provide a safe and comfortable research environment, consider the young person's physical and psychological state and avoid placing demands on the young people that could cause harm to them physically or psychologically, and make careful preparations for exiting from the field.</p></sec><sec id="pbc26772-sec-11550"><label>PO-129</label><title>Who do Young Adults Talk to and What do they Talk About Regarding their End‐of‐Life (EOL) Care Preferences</title><p><underline underline-style="single">S. Zadeh Bedoya</underline><sup>1</sup>, H. Battles<sup>1</sup>, M. Lyon<sup>2</sup>, A. Gross<sup>3</sup>, S. Jacobs<sup>4</sup>, K. Zabokrtsky<sup>5</sup>, L. Paredes<sup>5</sup>, K. Fasciano<sup>6</sup>, P. Malinowski<sup>6</sup>, C. Heath<sup>7</sup>, A. Hoeft<sup>7</sup>, L. Wiener<sup>1</sup></p><p><italic><sup>1</sup>National Cancer Institute, Pediatric Oncology Branch, Bethesda, USA; <sup>2</sup>Children's National Medical Center, Center for Translational Research, Washington, USA; <sup>3</sup>Children's National Medical Center, Pediatric Hematology/Oncology, Washington, USA; <sup>4</sup>Children's National Medical Center, Center for Cancer and Blood Disorders, Washington, USA; <sup>5</sup>Children's Hospital of Orange County, Hyundai Cancer Institute, Orange, USA; <sup>6</sup>Dana‐Farber Cancer Institute, Young Adult Program, Boston, USA; <sup>7</sup>Cook Children's Medical Center, AYA Oncology Program, Fort Worth, USA</italic></p><p><bold>Background/Objectives</bold>: About 9,000 young adults (YA) die from cancer each year, making it the 4<sup>th</sup> leading cause of death in this age group (ACS, 2015). Advance care planning (ACP) documents provide patients an opportunity to express their preferences for care and make informed decisions. Both family and providers describe discomfort with initiating these conversations with AYA. This study aims to understand whether AYA are having ACP conversations with family members, friends or health care providers and if not, what barriers they perceive in doing so.</p><p><bold>Design/Methods</bold>: Participants, aged 18‐39, with cancer or other life threatening illnesses were administered a questionnaire to determine whether they had engaged in communication with family, friends, and/or health care providers about preferences for care if they were to become seriously ill. Perceived barriers to having these conversations was also assessed. The study is open at 5 cancer centers.</p><p><bold>Results</bold>: Fifty‐three AYA completed the questionnaire. Fifty‐one percent of participants indicated having had an EoL planning conversation with a family member, while only 30% had spoken with a friend and 17% with a health care provider. Perceived barriers to communication include upsetting family, a desire to maintain normal life with friends, and not feeling comfortable initiating discussion about ACP with their health care providers.</p><p><bold>Conclusions</bold>: Most particpants have not had communication regarding their EoL preferences with either family, friends, or health care providers. Given the importance of end‐of‐life planning and challenges in ensuring these conversations occur with the medical team, interventions are being developed to enhance provider comfort with initiating these discussions and helping helping patients communicate with their family and friends about what is most important to them when their EoL is near.</p></sec></sec><sec id="pbc26772-sec-11560"><title>Epidemiology ‐ Pathway of Care</title><sec id="pbc26772-sec-11570"><label>PO-130</label><title>Incidence of CNS Tumors in Adolescents at a Children Hospital in Ecuador</title><p><underline underline-style="single">A. Borja</underline><sup>1</sup>, M.J. Pesantez<sup>1</sup>, D. Franco<sup>2</sup></p><p><italic><sup>1</sup>Hospital Axxis, Oncología Pediatrica, Quito, Ecuador; <sup>2</sup>Hospital Metropolitano, Patología, Quito, Ecuador</italic></p><p><bold>Background/Objectives</bold>: According to literature about 25% of all tumors in children between 0–14 years old involve CNS. However this percentage decrease at the end of adolescence(2‐5% in adults). Most CNS tumors in childhood are located in <bold>posterior fossa but the most common type are</bold> astrocytomas. Due to differences in epidemiology and management the APP and NCI recommend that children seek diagnose and treatment at specialized pediatric centers for cancer. According to studies, children receiving care in those institutions show 20‐40% higher survival rates. However, survival outcomes in adolescents with CNS tumors have not shown an improvance. This dispartity shows adolescents have a higher mortality, hence, understanding of distribution of CNS cancer in this group will contribute to better, individualized treatments.</p><p>Objetive: Determine incidence of CNS tumors in adolescents at Children Hospital in Ecuador from January 2007 to August 2013.</p><p><bold>Design/Methods</bold>: Descriptive, retrospective study including 406 patients from 0‐15 years old. Inclusion criteria was, age between 9years11months and 14years11months old, and diagnostic of CNS cancer confirmed by Radiology or Pathology area.</p><p><bold>Results</bold>: Only 8.6% (n = 35)children from a total of 406 patients were diagnosed with CNS Tumor. Most of cases were found in males and mean age of diagnosis was ten years old(32%). Fifty‐seven percent corresponded to posterior fosa but globally most common type was Astrocytoma(43%) and least was Ependimoma(3%). Results are similar to previously findings in England and US, only population admitted in this pediatric hospital was enrolled causing selection Bias.</p><p><bold>Conclusions</bold>: Cancer treatment in Adolescents is still being a challenge because poor improvement in survival rates seen despite of changes in management. This study shows that incidence of CNS cancer in adolescents between 10‐15 years old is similar to distribution in children described in previous studies. Therefore, other causes rather than distribution should be related to survival outcomes. New factors need to be investigated.</p></sec><sec id="pbc26772-sec-11580"><label>PO-131</label><title>New Patient Process Documentation at Children's Cancer Hospital Egypt (CCHE) and Recommendations for Improvement</title><p><underline underline-style="single">O. Elmadhoun</underline><sup>1</sup>, N. Ugonabo<sup>1</sup>, I. Albanti<sup>2</sup></p><p><italic><sup>1</sup>Harvard T.H. Chan School of Public Health, Health Policy and Management, Boston, USA; <sup>2</sup>Dana Farber/Boston Children's Hospital, The Global Health Initiative, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: This project at the Children's Cancer Hospital of Egypt‐57357 (CCHE) aimed to define the new patient process for solid tumor patients, study the patient flow and analyze the process to be able to identify root causes and suggest actionable recommendations for improvement. CCHE is the largest specialized children's cancer hospital in the world and is located in Cairo, Egypt. Being the only hospital offering high quality pediatric oncology care completely free of charge, 57357 experiences a very high demand which necessitates continuous improvement in the handling of new patients in order to make the process efficient and enhance the patient experience.</p><p><bold>Design/Methods</bold>: Our project aimed to apply Lean Management – Six Sigma tools to define the new patient process, collect data on the new patient process, study the patient flow and identify root causes. We also used and incorporated the Dana Farber/Boston Children's Quality Improvement policies and toolkits.</p><p><bold>Results</bold>: The key findings of this project include a full process map of the New Patient Solid Tumor Process at both 57357 and Dana Farber/ Boston Children's as well other visual tools utilized in LEAN/Six Sigma. In addition, we drafted a list of ten preliminary recommendations for improvement which we presented to the 57357 team.</p><p><bold>Conclusions</bold>: Those recommendations laid the groundwork for the establishment of a new patient clinic to meet the high patient volumes and enhance the patient experience.</p></sec><sec id="pbc26772-sec-11590"><label>PO-132</label><title>Early Diagnostic of Cancer Children and Adolescents Program in South of Brazil, 8 Years of Activities</title><p><underline underline-style="single">C. Fiori</underline><sup>1</sup>, A. Carla Rosa<sup>1</sup>, C. Santos<sup>1</sup>, S. Buettner<sup>1</sup>, M.I. Melo<sup>1</sup>, F. Neves<sup>1</sup></p><p><italic><sup>1</sup>Hospital do Câncer de Cascavel‐UOPECCAN, Pediatric Oncology, Cascavel, Brazil</italic></p><p><bold>Background/Objectives</bold>: Introduction: In developed countries the cure rate of cancer children exceeds 75%. This reality is far from being achieved in Brazil and the main reason is the difficulty that health professionals have to diagnose the disease early. The Cancer Hospital of Cascavel ‐ UOPECCAN ‐ in partnership with the Ronald McDonald Institute, through the Early Diagnosis of Cancer Children and Adolescents Program, trains professionals of health and pediatrics of the municipalities of Parana‐Brazil.</p><p>Objective: Trainning professionals of health and pediatricians in order to contribute to the early identification of cancer in children and adolescents, reducing the time between the onset of signs and symptoms and diagnosis in a specialized center.</p><p><bold>Design/Methods</bold>: Methodology: Health professionals from several cities of Parana were trained from April / 2008 to December /2016. They received basic information about children cancer and adolescents (Epidemiology; signs and symptoms of suspicion; care needed for the attention to children and adolescents with cancer). The groups were formed with 40 professionals, 16 hours / course.</p><p><bold>Results</bold>: Results There were trained 1805 professionals, 125 doctors, 193 nurses, 305 technicians / nursing assistants, 836 community health agents, 184 upper level and 162 medium‐level professionals or auxiliary.</p><p><bold>Conclusions</bold>: Comments: Among the diagnosed cases of cancer in children in Brazil, many are referred to treatment centers with the disease at an advanced stage. One goal of the campaign is to encourage educational and preventive actions, spreading knowledge for more people about the disease. We observed in the last three years, a cha nge in staging diagnosis of patients who are coming to the reference center. Children are coming up with more localized disease. Shortening the time between the suspicion of cancer and early diagnosis and treatment will certainly contribute to the increasing expectations of cure in developing countries.</p></sec><sec id="pbc26772-sec-11600"><label>PO-133</label><title>Children's Cancer in Morocco: An 11‐Year Retrospective Study</title><p>A. Haimer<sup>1</sup>, F. Habib<sup>2</sup>, A. Soulaymani<sup>1</sup>, A. Mokhtari<sup>1</sup>, <underline underline-style="single">H. Hami</underline><sup>1</sup></p><p><italic><sup>1</sup>Laboratory of Genetics and Biometry‐ Faculty of Science, Ibn Tofail University, Kenitra, Morocco; <sup>2</sup>Al Azhar Oncology Center, Rabat, Morocco</italic></p><p><bold>Background/Objectives</bold>: This study was conducted to determine the epidemiological characteristics of childhood cancer in Morocco.</p><p><bold>Design/Methods</bold>: This is a descriptive retrospective analysis of childhood cancer cases, diagnosed and treated at Al Azhar Oncology Center in Rabat during a period of 11 years (2005‐2015).</p><p><bold>Results</bold>: During the study period, 115 children under the age of 15 were diagnosed with cancer at Al Azhar Oncology Center, accounting for 1.05% of all new cancer cases reported during this period. Nearly two‐thirds were boys with a male‐female ratio of 1.94. The average age at diagnosis was 8.45±3.99 years. More than a quarter of the reported cases were diagnosed during the first five years of life, while the highest rate for children was noted between 10 and 14 years of age. Brain tumors were the most common childhood cancer (15%), followed by cavum cancer (13%). Among all detected cases, 2.6% were diagnosed with metastatic disease and 13.9% died during the study period.</p><p><bold>Conclusions</bold>: Although rare, cancer in children has a substantial impact on public health in Morocco. A national cancer registry will assist in better planning, resource allocation and management including psychosocial support to improve the quality of life of childhood cancer survivors and their families.</p></sec><sec id="pbc26772-sec-11610"><label>PO-134</label><title>Financial Planning of Pediatric Cancer Hospitals in Low‐and‐Middle‐Income Countries: The Unidad Nacional de Oncologia Pediatrica's Experience</title><p><underline underline-style="single">N. Shrivastava</underline><sup>1</sup>, F. Antillón<sup>2</sup>, G. De Dios<sup>3</sup>, I. Albanti<sup>4</sup></p><p><italic><sup>1</sup>Harvard T.H. Chan School of Public Health, Health Policy and Management, Boston, USA; <sup>2</sup>Unidad Nacional de Oncología Pediátrica, Pediatric Oncology, Guatemala City, Guatemala; <sup>3</sup>Fundación Ayúdame a Vivir, Pediatric Oncology, Guatemala City, Guatemala; <sup>4</sup>Dana‐Farber/Boston Children's Cancer and Blood Disorders Center, Pediatric Oncology, Boston, USA</italic></p><p><bold>Background/Objectives</bold>: While financial planning resources for the establishment of new pediatric oncology facilities in low‐and‐middle‐income countries (LMICs) are limited, <italic>Unidad Nacional de Oncología Pediátrica</italic> (UNOP), Guatemala's national pediatric cancer hospital, in partnership with its foundation, <italic>Ayúdame a Vivir</italic> (AYUVI), has sustainably operated for more than 15 years and has recently expanded to a new clinical site. This study aims to examine financial planning practices at UNOP and AYUVI, highlight important lessons learned, and assess the impact of effective budgeting on improving outcomes for children with cancer in Guatemala.</p><p><bold>Design/Methods</bold>: Semi‐structured face‐to‐face key informant interviews were conducted with 9 staff members (physicians, administrators, accountants, and staff in volunteering and fundraising) in English or Spanish at UNOP and AYUVI. Interview content was transcribed and analyzed to identify recurring themes. Informants also provided relevant financial planning documentation.</p><p><bold>Results</bold>: Interviewees emphasized the importance of having diverse funding sources including the government, corporate sponsorships, and both local and international fundraising to prevent reliance on a sole funder. For budgeting, respondents highlighted the importance of gathering local epidemiological data to forecast disease burden and patient demand. These data are used to determine required number of patient beds, necessary quantities of equipment, and required clinical staff, which directly influence the construction, start‐up, and operational budgets. Informants noted several costs unique to pediatric cancer hospitals including the increased need of isolation areas and infectious disease care for immunocompromised patients, and the need to plan for lodging for parents from far‐away locations to stay during longer treatments.</p><p><bold>Conclusions</bold>: UNOP's ability to increase Guatemala's overall survival rate from pediatric cancer from 20% to 70% over 15 years has been made possible in part due to strategic and effective financial management. This institution's continued success highlights the feasibility of providing cost‐effective access to care for children living with cancer in resource‐limited settings.</p></sec></sec><sec id="pbc26772-sec-11620"><title>Late Effects</title><sec id="pbc26772-sec-11630"><label>PO-135</label><title>Rendering of Rehabilitation Help to the Russian Children with Oncohematological Disordes</title><p>E. Zhukovskaya<sup>1</sup>, <underline underline-style="single">A. Rumyantsev</underline><sup>2</sup>, V. Kasatkin<sup>1</sup>, A. Karelin<sup>1</sup>, L. Sidorenko<sup>1</sup></p><p><italic><sup>1</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Rehabilitation Centre “Russkoe Pole”, Moscow, Russia; <sup>2</sup>Federal Research Center of Pediatric Hematology ‐ Oncology ‐ Immunology, Administration, Moscow, Russia</italic></p><p><bold>Background/Objectives</bold>: The long‐term consequences of chemoradiotherapy are preserved until 3‐10 years or more after completion of treatment in children and adolescents.</p><p>The aim of the research is analysis of the rehabilitation care for children and adolescents in Russian Federation cured of malignant neoplasms.</p><p><bold>Design/Methods</bold>: The rehabilitation care to patients with oncohematological pathology in 24 centers and clinics in Russian Federation were studied within the framework of the multicenter study. The sources of the data were official statistical reports and a questionnaire for physicians, including 22 parameters studied, 2,320 parents were interviewed with a prepared questionnaire.</p><p><bold>Results</bold>: Rehabilitation of patients cured of malignant neoplasms is carried out in rehabilitation departments of 3 regional hospitals, 3 specialized rehabilitation centers, in 14 cities, children receive rehabilitation courses during special shifts in children's sanatoriums, dispensaries. “National Scientific and Practical Center of Pediatric Hematology, Oncology and Immunology named after. Dmitry Rogachev» is a methodical center for the delivery and testing of rehabilitation technologies. Only 20% of survivors received rehabilitation courses in connection with insufficient number of the rehabilitation wards. The late effects of antitumor therapy were registered in 68.7% of patients aimed at rehabilitation had organic and functional health disorders, manifestations of deprivation and desocialisation, which caused the need to develop technologies for drug, nutritional, neurocognitive, physical and psychological and social rehabilitation of recovered patients. The parents' survey revealed the interest of families of patients in expanding rehabilitation opportunities; they prefer rehabilitating in the conditions of specialized centers.</p><p><bold>Conclusions</bold>: The doctors emphasize the lack of trained personnel in the field of restorative medicine,absence of the evidence based criterias of the causal patterns of the development revealed symptomatology, premorbid/comorbid conditions that limit the effectiveness of rehabilitation programs for patients with oncohematological diseases.The expense of compulsory medical insurance, social protection system ensures accessibility for families with children cured of malignant tumors.</p></sec></sec></body></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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