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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature</title></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27239400</idno><idno type="pmc">4882159</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882159</idno><idno type="RBID">PMC:4882159</idno><idno type="doi">10.7759/cureus.585</idno><date when="????">????</date><idno type="wicri:Area/Pmc/Corpus">000791</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000791</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature</title></analytic><series><title level="j">Cureus</title><idno type="eISSN">2168-8184</idno><imprint><date when="????">????</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Primary intracranial germ cell tumors are rare, representing less than 5% of all central nervous system tumors. Overall, the majority of germ cell tumors are germinomas and approximately one-third are non-germinomatous germ cell tumors (NGGCT), which include teratoma, embryonal carcinoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, or mixed malignant germ cell tumor. Germ cell tumors may secrete detectable levels of proteins into the blood and/or cerebrospinal fluid, and these proteins can be used for diagnostic purposes or to monitor tumor recurrence. Germinomas have long been known to be highly curable with radiation therapy alone. However, many late effects of whole brain or craniospinal irradiation have been well documented. Strategies have been developed to reduce the dose and volume of radiation therapy, often in combination with chemotherapy. In contrast, patients with NGGCT have a poorer prognosis, with about 60% cured with multimodality chemoradiation. There are no standard approaches for relapsed germ cell tumors. Options may be limited by prior treatment. Radiation therapy has been utilized alone or in combination with chemotherapy or high-dose chemotherapy and transplant. We discuss two cases and review options for frameless radiosurgery or fractionated radiotherapy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kortmann, Rd" uniqKey="Kortmann R">RD Kortmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Echevarria, Me" uniqKey="Echevarria M">ME Echevarría</name></author><author><name sortKey="Fangusaro, J" uniqKey="Fangusaro J">J Fangusaro</name></author><author><name sortKey="Goldman, S" uniqKey="Goldman S">S Goldman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jennings, Mt" uniqKey="Jennings M">MT Jennings</name></author><author><name sortKey="Gelman, R" uniqKey="Gelman R">R Gelman</name></author><author><name sortKey="Hochberg, F" uniqKey="Hochberg F">F Hochberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccarthy, Bj" uniqKey="Mccarthy B">BJ 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cureus</journal-id><journal-id journal-id-type="iso-abbrev">Cureus</journal-id><journal-id journal-id-type="issn">2168-8184</journal-id><journal-title-group><journal-title>Cureus</journal-title></journal-title-group><issn pub-type="epub">2168-8184</issn><publisher><publisher-name>Cureus</publisher-name><publisher-loc>Palo Alto (CA)</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27239400</article-id><article-id pub-id-type="pmc">4882159</article-id><article-id pub-id-type="doi">10.7759/cureus.585</article-id><article-categories><subj-group subj-group-type="heading"><subject>Radiation Oncology</subject></subj-group><subj-group><subject>Pediatrics</subject></subj-group><subj-group><subject>Neurosurgery</subject></subj-group></article-categories><title-group><article-title>Re-irradiation of Recurrent Pineal Germ Cell Tumors with Radiosurgery: Report of Two Cases and Review of Literature</article-title></title-group><contrib-group><contrib contrib-type="editor"><name><surname>Muacevic</surname><given-names>Alexander</given-names></name></contrib><contrib contrib-type="editor"><name><surname>Adler</surname><given-names>John R</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Wong</surname><given-names>Kenneth</given-names></name><xref ref-type="aff" rid="aff-36454">1</xref></contrib><contrib contrib-type="author"><name><surname>Opimo</surname><given-names>Anthony B</given-names></name><xref ref-type="aff" rid="aff-36458">2</xref></contrib><contrib contrib-type="author"><name><surname>Olch</surname><given-names>Arthur J</given-names></name><xref ref-type="aff" rid="aff-36454">1</xref></contrib><contrib contrib-type="author"><name><surname>All</surname><given-names>Sean</given-names></name><xref ref-type="aff" rid="aff-36473">3</xref></contrib><contrib contrib-type="author"><name><surname>Waxer</surname><given-names>Jonathan F</given-names></name><xref ref-type="aff" rid="aff-36472">4</xref></contrib><contrib contrib-type="author"><name><surname>Clark</surname><given-names>Desirae</given-names></name><xref ref-type="aff" rid="aff-36463">5</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Justine</given-names></name><xref ref-type="aff" rid="aff-36464">6</xref></contrib><contrib contrib-type="author"><name><surname>Chlebik</surname><given-names>Alisha</given-names></name><xref ref-type="aff" rid="aff-36463">5</xref></contrib><contrib contrib-type="author"><name><surname>Erdreich-Epstein</surname><given-names>Anat</given-names></name><xref ref-type="aff" rid="aff-36474">7</xref><xref ref-type="aff" rid="aff-36475">8</xref></contrib><contrib contrib-type="author"><name><surname>Krieger</surname><given-names>Mark D</given-names></name><xref ref-type="aff" rid="aff-36467">9</xref></contrib><contrib contrib-type="author"><name><surname>Tamrazi</surname><given-names>Benita</given-names></name><xref ref-type="aff" rid="aff-36469">10</xref></contrib><contrib contrib-type="author"><name><surname>Dhall</surname><given-names>Girish</given-names></name><xref ref-type="aff" rid="aff-37923">11</xref></contrib><contrib contrib-type="author"><name><surname>Finlay</surname><given-names>Jonathan L</given-names></name><xref ref-type="aff" rid="aff-36055">12</xref></contrib><contrib contrib-type="author"><name><surname>Chang</surname><given-names>Eric L</given-names></name><xref ref-type="aff" rid="aff-36454">1</xref></contrib></contrib-group><aff id="aff-36454"><label>1</label> Department of Radiation Oncology, Keck School of Medicine of the University of Southern California, Los Angeles, CA</aff><aff id="aff-36458"><label>2</label> Department of Radiation Oncology, UCLA, Los Angeles, CA</aff><aff id="aff-36473"><label>3</label> College of Medicine, University of Central Florida College of Medicine, Orlando, FL</aff><aff id="aff-36472"><label>4</label> School of Medicine, Tulane University School of Medicine, New Orleans, LA</aff><aff id="aff-36463"><label>5</label> Radiation Oncology Program, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA</aff><aff id="aff-36464"><label>6</label> Mechanical Engineering Department, Massachusetts Institute of Technology, Cambridge, MA</aff><aff id="aff-36474"><label>7</label> Neuro-Oncology Program, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA</aff><aff id="aff-36475"><label>8</label> Department of Pediatrics, Keck School of Medicine of the University of Southern California, Los Angeles, CA</aff><aff id="aff-36467"><label>9</label> Department of Neurosurgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA</aff><aff id="aff-36469"><label>10</label> Department of Radiology, Keck School of Medicine of the University of Southern California, Los Angeles, CA</aff><aff id="aff-37923"><label>11</label> Pediatric Neuro-Oncology, Keck School of Medicine of the University of Southern California, Los Angeles, CA</aff><aff id="aff-36055"><label>12</label> Pediatric Neuro-Oncology, The Ohio State University, Nationwide Children's Hospital</aff><author-notes><corresp id="cor1">Kenneth Wong <email>kewong@chla.usc.edu</email></corresp></author-notes><pub-date date-type="pub" publication-format="electronic"><day>25</day><month>4</month><year>2016</year></pub-date><pub-date date-type="collection" publication-format="electronic"><month>4</month><year>2016</year></pub-date><volume>8</volume><issue>4</issue><elocation-id>e585</elocation-id><history><date date-type="received"><day>11</day><month>4</month><year>2016</year></date><date date-type="accepted"><day>25</day><month>4</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016, Wong et al.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Wong et al.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri xlink:href="http://www.cureus.com/articles/4446-re-irradiation-of-recurrent-pineal-germ-cell-tumors-with-radiosurgery-report-of-two-cases-and-review-of-literature">This article is available from http://www.cureus.com/articles/4446-re-irradiation-of-recurrent-pineal-germ-cell-tumors-with-radiosurgery-report-of-two-cases-and-review-of-literature</self-uri><abstract><p>Primary intracranial germ cell tumors are rare, representing less than 5% of all central nervous system tumors. Overall, the majority of germ cell tumors are germinomas and approximately one-third are non-germinomatous germ cell tumors (NGGCT), which include teratoma, embryonal carcinoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, or mixed malignant germ cell tumor. Germ cell tumors may secrete detectable levels of proteins into the blood and/or cerebrospinal fluid, and these proteins can be used for diagnostic purposes or to monitor tumor recurrence. Germinomas have long been known to be highly curable with radiation therapy alone. However, many late effects of whole brain or craniospinal irradiation have been well documented. Strategies have been developed to reduce the dose and volume of radiation therapy, often in combination with chemotherapy. In contrast, patients with NGGCT have a poorer prognosis, with about 60% cured with multimodality chemoradiation. There are no standard approaches for relapsed germ cell tumors. Options may be limited by prior treatment. Radiation therapy has been utilized alone or in combination with chemotherapy or high-dose chemotherapy and transplant. We discuss two cases and review options for frameless radiosurgery or fractionated radiotherapy.</p></abstract><kwd-group kwd-group-type="author"><kwd>Stereotactic Radiosurgery</kwd><kwd>frameless stereotactic radiotherapy</kwd><kwd>radiation oncology</kwd><kwd>gamma knife</kwd><kwd>linac</kwd><kwd>head immobilization</kwd><kwd>cns germ cell tumor</kwd><kwd>re-irradiation</kwd></kwd-group></article-meta><notes><p content-type="disclaimer">The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.</p></notes></front><body><sec><title>Introduction and background</title><p>Primary intracranial germ cell tumors (IGT) are rare, representing less than 5% of all central nervous system tumors in Western series [<xref rid="REF1" ref-type="bibr">1</xref>-<xref rid="REF2" ref-type="bibr">2</xref>] but may be more common in East Asia [<xref rid="REF3" ref-type="bibr">3</xref>-<xref rid="REF4" ref-type="bibr">4</xref>]. These tumors most commonly occur in the suprasellar cistern and pineal gland and have a male predominance. Overall, the majority of germ cell tumors are germinomas and approximately one-third are non-germinomatous germ cell tumors (NGGCT), which include teratoma, embryonal carcinoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, or mixed malignant germ cell tumor. Embryonal or endodermal sinus tumors are more common in adolescence and young adulthood [<xref rid="REF3" ref-type="bibr">3</xref>]. Germ cell tumors may secrete detectable levels of proteins into the blood and/or cerebrospinal fluid (CSF), and beta-human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) are used for diagnostic purposes and monitor tumor recurrence. Pure germinomas may have elevated HCG [<xref rid="REF5" ref-type="bibr">5</xref>]. Elevated serum or CSF HCG > 50 mIU/mL and/or elevated AFP are generally considered consistent with NGGCT and biopsy is not required.</p><p>Germinomas have long been known to be highly curable with radiation therapy (RT) alone. However, the late effects of whole brain or craniospinal irradiation (CSI) have been well documented, with adverse impacts on hearing, endocrine regulation, neurocognitive function, and risk of secondary malignancies [<xref rid="REF6" ref-type="bibr">6</xref>-<xref rid="REF8" ref-type="bibr">8</xref>]. To mitigate these risks, strategies have been developed to reduce the dose and volume of radiation therapy, often in combination with chemotherapy. In contrast, only about 20-45% of patients with NGGCT can be cured following radiation therapy alone, though results are improved to about 60% with multimodality chemoradiation [<xref rid="REF1" ref-type="bibr">1</xref>].</p><p>The focus of this paper is to discuss treatment options for locally relapsed IGT without dissemination and to investigate patient and/or tumor characteristics that may affect the choice of re-irradiation modalities, such as stereotactic radiosurgery (SRS), hypofractionated fractionated stereotactic radiotherapy (FSRT), or full dose re-irradiation with external beam RT.</p><sec><title>Case reports</title><p>Case 1</p><p>A 16-year-old Hispanic male without prior health problems presented with gradual memory loss and severe headache; an MRI brain with gadolinium revealed an enhancing 3.5 x 3.4 x 3.7 cm pineal gland tumor (Figure <xref ref-type="fig" rid="FIG1">1</xref>). His serum AFP was 49.3 ng/mL and CSF AFP was 33.9 ng/mL (Figure <xref ref-type="fig" rid="FIG2">2</xref>). Both serum and CSF HCG were negative. An MRI spine and CSF cytology were negative. He had hydrocephalus and an intratumoral hemorrhage following a ventriculostomy and ventriculoperitoneal (VP) shunt placement (Table <xref ref-type="table" rid="TAB1">1</xref>). His neurological status deteriorated and he became unresponsive. Because of his intratumoral bleed and performance status, he was treated with systemic chemotherapy as per the Children’s Oncology Group (COG) Trial ACSN0122 with alternating carboplatin/etoposide and ifosfamide/etoposide. Following his first cycle of chemotherapy, he began to neurologically recover and his tumor markers normalized after two cycles of chemotherapy. After six cycles of chemotherapy, his serum and CSF tumor markers remained undetectable with a residual 1.3 x 2.1 x 1.3 cm enhancing pineal gland mass. About six weeks post-chemotherapy and before RT, his serum AFP rose to 8.9 ng/mL (institutional high normal: 7.3 ng/mL). MRI of the spine was negative. Although concerned about relapse, we began whole ventricular irradiation (WVI) and intensity-modulated radiation therapy (IMRT) with an intended dose of 30.6 Gy (Figure <xref ref-type="fig" rid="FIG3">3</xref>). Two weeks after starting WVI, his serum AFP increased to 23.9 ng/mL, and five days later was 15.3 ng/mL. With this AFP elevation, we changed his WVI to 36 Gy and subsequently completed an IMRT boost to the pineal gland to a cumulative total dose of 54 Gy. After peaking at 23.9 ng/mL early during RT, his serum and CSF AFP became undetectable one-month post-RT. His MRI brain showed a continued mild decrease in the size of enhancing residual tissue. Unfortunately, three months after RT, his CSF AFP was elevated at 11.4 ng/mL (serum 5.4 ng/mL), and MRI of the brain showed an interval increase in the size of enhancing tissue of the pineal gland. He was enrolled in a clinical trial of gemcitabine, paclitaxel, and oxaliplatin (GemPOx), and his CSF AFP became undetectable. After three cycles of GemPOx, he proceeded to consolidation chemotherapy with carboplatin, etoposide, and thiotepa, followed by autologous hematopoietic stem cell rescue (ASCR). He tolerated the transplant well and was discharged on Day 20. He was subsequently referred for stereotactic radiosurgery at an adult hospital where he received treatment on Day 97 (Table <xref ref-type="table" rid="TAB2">2</xref>). He was treated with Gamma Knife (Elekta, Stockholm, Sweden) SRS to 18 Gy in one fraction (Figure <xref ref-type="fig" rid="FIG3">3</xref>, Table <xref ref-type="table" rid="TAB3">3</xref>). With 34 months of follow-up post-SRS, his tumor markers remain normal with a stable MRI of the brain.</p><p><fig fig-type="figure" id="FIG1" orientation="portrait" position="float"><label>Figure 1</label><caption><title>Serial sagittal T1-weighted MRI brain scans with gadolinium</title><p>WVI = whole ventricular irradiation; CSI = craniospinal irradiation; FSRT = fractionated stereotactic radiotherapy; RT = radiotherapy</p></caption><graphic xlink:href="cureus-0008-000000000585-i01"></graphic></fig></p><p><fig fig-type="figure" id="FIG2" orientation="portrait" position="float"><label>Figure 2</label><caption><title>Serial values for serum AFP</title></caption><graphic xlink:href="cureus-0008-000000000585-i02"></graphic></fig></p><p><table-wrap id="TAB1" orientation="portrait" position="float"><label>Table 1</label><caption><title>Clinical Characteristics at Presentation, First and Second Recurrences</title><p>M = male; sAFP = serum AFP; cAFP = CSF AFP; VP = ventriculoperitoneal; carbo = carboplatin; ifos = ifosfamide; VP-16 = etoposide; chemo = chemotherapy; WVI = whole ventricular irradiation; CR = complete response; RT = radiation therapy; ETV = endoscopic third ventriculostomy; PR = partial response; GemPOx = gemcitabine, paclitaxel, oxaliplatin; ASCR = autologous hematopoietic stem cell rescue; CSI = craniospinal irradiation; RT = radiotherapy</p></caption><table frame="hsides" rules="groups"><tbody><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Case
</td><td rowspan="1" colspan="1">Age / Sex
</td><td rowspan="1" colspan="1">Histology
</td><td rowspan="1" colspan="1">Extent of Disease
</td><td rowspan="1" colspan="1">Tumor Markers
</td><td rowspan="1" colspan="1">Surgery
</td><td rowspan="1" colspan="1">Chemo
</td><td rowspan="1" colspan="1">Chemo Response
</td><td rowspan="1" colspan="1">Progression
</td><td rowspan="1" colspan="1">Treatment & Response
</td><td rowspan="1" colspan="1">Second Recurrence
</td></tr><tr><td rowspan="1" colspan="1">1
</td><td rowspan="1" colspan="1">16M
</td><td rowspan="1" colspan="1">-
</td><td rowspan="1" colspan="1">Pineal
</td><td rowspan="1" colspan="1">sAFP 49.3 ng/mL, cAFP 33.9 ng/mL
</td><td rowspan="1" colspan="1">Tumor bleed and VP shunt
</td><td rowspan="1" colspan="1">Carbo/VP-16, Ifos/VP-16
</td><td rowspan="1" colspan="1">CR post-6<sup>th</sup> cycle
</td><td rowspan="1" colspan="1">1 month post-chemo, sAFP 8.9 ng/mL
</td><td rowspan="1" colspan="1">WVI 36 Gy, plus boost to 54 Gy, CR
</td><td rowspan="1" colspan="1">3 months post-RT, cAFP 11.4 ng/mL
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">2
</td><td rowspan="1" colspan="1">17M
</td><td rowspan="1" colspan="1">Yolk sac 80% and germinoma 20%
</td><td rowspan="1" colspan="1">Pineal
</td><td rowspan="1" colspan="1">sAFP 755 ng/mL, cAFP 350 ng/mL
</td><td rowspan="1" colspan="1">ETV and biopsy
</td><td rowspan="1" colspan="1">Carbo/VP-16, Ifos/VP-16
</td><td rowspan="1" colspan="1">PR post-6<sup>th</sup> cycle
</td><td rowspan="1" colspan="1">2 months post-chemo, sAFP 17.8 ng/mL
</td><td rowspan="1" colspan="1">GemPOx with ASCR, PR, sAFP 5.2 ng/mL, then CSI 36 Gy, plus boost to 54 Gy, CR
</td><td rowspan="1" colspan="1">29 months post-RT, sAFP 6120 ng/mL, and cAFP 3000 ng/mL
</td></tr></tbody></table></table-wrap></p><p><fig fig-type="figure" id="FIG3" orientation="portrait" position="float"><label>Figure 3</label><caption><title>Comparison of initial and re-irradiation treatment plans (axial, coronal, and sagittal images) for Case 1</title></caption><graphic xlink:href="cureus-0008-000000000585-i03"></graphic></fig></p><p><table-wrap id="TAB2" orientation="portrait" position="float"><label>Table 2</label><caption><title> Clinical Characteristics at Second and Third Recurrences</title><p>FU = Follow up; GemPOx = gemcitabine, paclitaxel, oxaliplatin; ASCR = autologous hematopoietic stem cell rescue; GK SRS = Gamma Knife stereotactic radiosurgery; CR = complete response; ifos = ifosfamide; VP-16 = etoposide; sAFP = serum AFP; PR = partial response; chemo = chemotherapy; FSRT = fractionated stereotactic radiotherapy</p></caption><table frame="hsides" rules="groups"><tbody><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Case
</td><td rowspan="1" colspan="1">Second Recurrence / Extent of Disease
</td><td rowspan="1" colspan="1">Subsequent Treatment
</td><td rowspan="1" colspan="1">Response
</td><td rowspan="1" colspan="1">Third Recurrence
</td><td rowspan="1" colspan="1">Subsequent Treatment
</td><td rowspan="1" colspan="1">Response
</td><td rowspan="1" colspan="1">FU Post-progression
</td></tr><tr><td rowspan="1" colspan="1">1
</td><td rowspan="1" colspan="1">Tumor marker elevation
</td><td rowspan="1" colspan="1">GemPOx with ASCR, GK SRS
</td><td rowspan="1" colspan="1">CR
</td><td rowspan="1" colspan="1">-
</td><td rowspan="1" colspan="1">-
</td><td rowspan="1" colspan="1">-
</td><td rowspan="1" colspan="1">Alive, 34 months
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">2
</td><td rowspan="1" colspan="1">Pineal gross disease and tumor marker elevation
</td><td rowspan="1" colspan="1">Cisplatin/Ifos/VP-16, BCNU/VP-16/Cisplatin
</td><td rowspan="1" colspan="1">PR
</td><td rowspan="1" colspan="1">1 month post-chemo, sAFP 490 ng/mL
</td><td rowspan="1" colspan="1">FSRT followed by oral VP-16 & thalidomide
</td><td rowspan="1" colspan="1">PR, sAFP 19.8 ng/mL
</td><td rowspan="1" colspan="1">Alive, 3 months
</td></tr></tbody></table></table-wrap></p><p><table-wrap id="TAB3" orientation="portrait" position="float"><label>Table 3</label><caption><title>Comparison of Different Radiosurgery Techniques for Case 1 and Case 2</title><p>*dose to PTV overlapping brainstem</p><p>**Indices derived for total PTV (includes volume overlapping brainstem)</p><p>RT1 = first course of radiotherapy; RT2 = second course of radiotherapy; IMRT = intensity-modulated radiation therapy; SRS = stereotactic radiosurgery</p></caption><table frame="hsides" rules="groups"><tbody><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Case
</td><td rowspan="1" colspan="1">Technique & Interval Between RT1 & RT2
</td><td rowspan="1" colspan="1">Immobilization
</td><td rowspan="1" colspan="1">PTV Volume & Prescription Dose
</td><td rowspan="1" colspan="1">Shots / Beams
</td><td colspan="2" rowspan="1">Dose Statistics
</td><td rowspan="1" colspan="1">Conformity
</td><td rowspan="1" colspan="1">Gradient
</td></tr><tr><td rowspan="1" colspan="1">1
</td><td rowspan="1" colspan="1">Gamma Knife RT to SRS: 9.5 months
</td><td rowspan="1" colspan="1">Head frame
</td><td rowspan="1" colspan="1">2.4 cm<sup>3</sup>, 18 Gy to 50% isodose line
</td><td rowspan="1" colspan="1">14 shots
</td><td colspan="2" rowspan="1">18 Gy margin, 36 Gy max
</td><td rowspan="1" colspan="1">1.46
</td><td rowspan="1" colspan="1">2.94
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">2
</td><td rowspan="1" colspan="1">Dose painting IMRT RT to FSRT: 36 months
</td><td rowspan="1" colspan="1">Frameless vacuum-assisted mouthpiece with surface imaging
</td><td rowspan="1" colspan="1">4.3 cm<sup>3</sup>, 25 Gy to 79.4% with limit of 20 Gy to brainstem
</td><td rowspan="1" colspan="1">8 beam non-coplanar IMRT
</td><td rowspan="1" colspan="1">26.4 Gy mean, 31.5 Gy max
</td><td rowspan="1" colspan="1">19.1 Gy* mean, 22.8 Gy* max
</td><td rowspan="1" colspan="1">0.59**
</td><td rowspan="1" colspan="1">0.91**
</td></tr></tbody></table></table-wrap></p><p>Case 2</p><p>A 17-year-old Hispanic male without prior health problems presented with headaches and multiple episodes of vomiting. He had an MRI of the brain, which showed a pineal gland tumor with hydrocephalus (Figure <xref ref-type="fig" rid="FIG1">1</xref>). Upon transfer to our institution, he had an endoscopic third ventriculostomy and biopsy, which revealed a mixed malignant germ cell tumor (80% yolk sac and 20% germinoma). His serum AFP was 755 ng/mL, a normal serum HCG, and the CSF AFP was 350 ng/mL (CSF HCG: 13). An MRI of the brain revealed a 1.5 x 1.3 x 1.3 cm T1-enhancing pineal region mass. An MRI of the spine and CSF cytology were negative. He was also treated as per COG ACNS0122 with six cycles of chemotherapy. His serum AFP reached a nadir of 7 ng/mL and CSF AFP was 17.4 ng/mL; serum and CSF HCG were negative. MRI of the brain showed only a small residual enhancement in the region of the pineal gland. About six weeks after chemotherapy and before his planned RT, his serum AFP rose to 17.8 ng/mL and the CSF AFP rose to 26.5 ng/mL (see inset graph on Figure <xref ref-type="fig" rid="FIG2">2</xref>). Instead of proceeding to RT as in Case 1, our patient was enrolled on the GemPOx clinical trial; after four cycles, his serum and CSF AFP decreased to 4.6 and 5.2 ng/mL, respectively, (Table <xref ref-type="table" rid="TAB1">1</xref>). With post-chemotherapy serum and AFP stable at 5.2 and 6.8 ng/mL, respectively, he proceeded to consolidation chemotherapy with ASCR. After he recovered from the transplant, he started RT with 36 Gy CSI with TomoTherapy® (Accuray, Inc., Sunnyvale, CA) followed by an IMRT boost to the pineal gland for a cumulative dose of 54 Gy (Figure <xref ref-type="fig" rid="FIG4">4</xref>). One month post-RT, his serum and CSF AFP became undetectable. He was then followed for 16.5 months, after which he was lost to follow-up. He returned almost one year later with morning headaches and an MRI of the brain showed a large partially hemorrhagic, enhancing pineal region mass measuring 3.6 x 3.1 x 3.4 cm (Figure <xref ref-type="fig" rid="FIG1">1</xref>). He had a markedly elevated serum AFP, and CSF AFP was over 3,000 ng/mL (Figure <xref ref-type="fig" rid="FIG2">2</xref>). MRI of the spine was negative for leptomeningeal metastases with negative CSF cytology. He was salvaged with systemic chemotherapy (cisplatin, ifosfamide, etoposide for five cycles with one intervening cycle of BCNU, etoposide, and cisplatin). Initially, his serum AFP rapidly declined with chemotherapy but plateaued with a mean of 268 ng/mL. Because of prior treatment, his hematopoietic cell recovery was prolonged. After the sixth cycle of chemotherapy, his serum AFP rose to 490 ng/mL. At this point, he was considered for re-irradiation with SRS. MRI of the brain demonstrated a residual enhancing mass measuring 1.7 x 1.7 x 1.4 cm intimately associated with the thalamus, tectum, and midbrain. With a history of prior RT and involvement of brainstem and thalamus, we decided to offer fractionated stereotactic radiotherapy rather than single fraction SRS. The patient underwent CT simulation with a vacuum-assisted mouthpiece head immobilization system with 1.5 mm slice spacing and intravenous contrast. A gadolinium-enhanced MRI of the brain with 1 mm spacing was obtained and rigidly registered with the simulation CT scan. The gross target volume (GTV) was defined by a team of radiation oncologists, a neuroradiologist, and a neurosurgeon. A 1 mm margin was added to create the planning target volume. A dose of 25 Gy in five fractions was prescribed with a constraint of 20 Gy to the brainstem (Table <xref ref-type="table" rid="TAB3">3</xref>). Dose-painting IMRT (Figure <xref ref-type="fig" rid="FIG4">4</xref>) was planned with the Eclipse treatment planning system, version 13.6 (Varian, Palo Alto, CA), and delivered on a Varian TrueBeam with a PerfectPitch™ 6-DOF (degrees of freedom) couch (Varian, Palo Alto, CA) with kVue couch top (Qfix, Avondale, PA). Cone beam CT (CBCT) daily image guidance was used for alignment to the calcified portion of the residual tumor. Intrafraction real-time optical surface monitoring system (OSMS) was performed with surface imaging using AlignRT (VisionRT, London, UK). The patient tolerated FSRT well with Grade 2 fatigue. At the start of the FSRT, his serum AFP was 656 ng/mL, peaked at 832 ng/mL, and decreased by 40% two weeks after FSRT. Oral etoposide and thalidomide were then added, and 2.5 months post-treatment, the serum AFP fell to 6.9 ng/mL.</p><p><fig fig-type="figure" id="FIG4" orientation="portrait" position="float"><label>Figure 4</label><caption><title>Comparison of initial and re-irradiation treatment plans (axial, coronal, and sagittal images) for Case 2</title></caption><graphic xlink:href="cureus-0008-000000000585-i04"></graphic></fig></p></sec></sec><sec><title>Review</title><p>These two cases contribute insight to the series demonstrating that recurrent germ cell tumors can be sensitive to chemotherapy and re-irradiation [<xref rid="REF9" ref-type="bibr">9</xref>-<xref rid="REF12" ref-type="bibr">12</xref>]. In the series described by Zissiadis, et al. [<xref rid="REF9" ref-type="bibr">9</xref>], one patient with NGGCT recurred after subtotal resection, chemotherapy, and CSI. That patient, who subsequently received high-dose chemotherapy with ASCR and 15 Gy SRS, was alive at 32 months post-salvage therapy. Modak, et al. [<xref rid="REF10" ref-type="bibr">10</xref>] described 21 relapsed IGT patient treated with high-dose chemotherapy and ASCR. There were five survivors among the twelve patients with NGGCT, and of those survivors, two had RT and one was treated focally, but not with SRS. Hasegawa, et al. [<xref rid="REF11" ref-type="bibr">11</xref>] successfully salvaged a patient with chemotherapy and Gamma Knife SRS. In contrast, chemotherapy alone is not likely to be effective up front [<xref rid="REF1" ref-type="bibr">1</xref>, <xref rid="REF13" ref-type="bibr">13</xref>-<xref rid="REF15" ref-type="bibr">15</xref>] or at relapse [<xref rid="REF16" ref-type="bibr">16</xref>], and avoiding RT with high-dose chemotherapy and ASCR is uncertain [<xref rid="REF10" ref-type="bibr">10</xref>, <xref rid="REF12" ref-type="bibr">12</xref>, <xref rid="REF17" ref-type="bibr">17</xref>].</p><p>Consideration for re-irradiation must take into account size and location of tumor recurrence, prior treatments, the time interval from prior radiation therapy, the proximity of organs-at-risk (OAR), and the need for anesthesia. Not all patients are candidates for single fraction radiosurgery. In cases where re-irradiation has been performed with curative intent for medulloblastoma or ependymoma, brainstem toxicity has been an issue [<xref rid="REF18" ref-type="bibr">18</xref>-<xref rid="REF22" ref-type="bibr">22</xref>]. Less toxicity has been described with FSRT or conventional fractionation [<xref rid="REF23" ref-type="bibr">23</xref>-<xref rid="REF24" ref-type="bibr">24</xref>], and thus, these may be safer techniques. Effective palliation in children with recurrent or metastatic tumors with frameless SRS or FSRT can be achieved with attention to cumulative doses to critical structures [<xref rid="REF25" ref-type="bibr">25</xref>]. Similarly, palliation in adults with brainstem metastases with the CyberKnife SRS/FSRT has been described with limited acute brainstem toxicity [<xref rid="REF26" ref-type="bibr">26</xref>].</p><p>Our second case highlights some of the potential advantages of frameless radiosurgery, which include increased patient comfort, ability to fractionate treatment, greater time for the multidisciplinary team review of imaging, contours, and dosimetry, and shorter daily treatment appointments. For children, frame placement may be a higher risk due to their thinner and softer skulls and need for sedation, so frameless FSRT can be more a more acceptable option. When re-irradiation is planned, a diagnostic MRI should be obtained within two weeks of the simulation scan [<xref rid="REF27" ref-type="bibr">27</xref>].</p><p>There are three main types of frameless immobilization: thermoplastic mask, open thermoplastic mask with or without bite block, and upper jaw fixation devices (bite block or vacuum-assisted mouthpieces) [<xref rid="REF28" ref-type="bibr">28</xref>]. These devices are commonly used in conjunction with custom cushions conformed to the head or head and shoulder. Thermoplastic masks and vacuum-assisted mouthpiece systems seem to have similar accuracy and precision [<xref rid="REF29" ref-type="bibr">29</xref>-<xref rid="REF31" ref-type="bibr">31</xref>], although masks tend to be less rigid. In addition, some investigators have found the mask to be more comfortable [<xref rid="REF29" ref-type="bibr">29</xref>]. However, in our experience over the past decade, children by far chose the mouthpiece system over a closed thermoplastic mask, which was described as ”scary” and “too tight.” We have used the vacuum-assisted mouthpiece with high accuracy in infants or edentulous patients [<xref rid="REF32" ref-type="bibr">32</xref>].</p><p>Treatments can be planned with cylindrical collimators, dynamic conformal arcs, 3D conformal beams, IMRT (step-and-shoot or sliding window, coplanar or non-coplanar), volumetric modulated arc therapy (VMAT), or proton beams [<xref rid="REF9" ref-type="bibr">9</xref>, <xref rid="REF25" ref-type="bibr">25</xref>, <xref rid="REF33" ref-type="bibr">33</xref>-<xref rid="REF38" ref-type="bibr">38</xref>]. With the Extend frameless immobilization system (Elekta, Stockholm, Sweden) [<xref rid="REF39" ref-type="bibr">39</xref>], fractionated Gamma Knife radiosurgery is possible [<xref rid="REF40" ref-type="bibr">40</xref>] and is further supported by CBCT in the Icon system (Elekta, Stockholm, Sweden). Case 2 was treated with IMRT in order to reduce the dose to the adjacent brainstem, with IMRT being the best way to achieve dose-painting for a simultaneous integrated boost.</p><p>Treatment delivery can be accomplished on a variety of different platforms with different equipment, including linear accelerators, Gamma Knife, CyberKnife, TomoTherapy, or protons (Table <xref ref-type="table" rid="TAB4">4</xref>). Some consider frameless immobilization systems to be less precise, even though patients can shift within frames and most frame-based systems ignore rotational shifts. To address this concern, orthogonal or stereoscopic kilovoltage (kV) or CBCT imaging guidance can permit shifts to correct for setup or immobilization inaccuracies. The time required for image guidance (acquisition, review, and adjustment) in the second case was a mean of 9 minutes (range: 4-13) and was reasonable and comparable to other investigators [<xref rid="REF34" ref-type="bibr">34</xref>, <xref rid="REF41" ref-type="bibr">41</xref>]. Our workflow was similar to that described by Li, et al. [<xref rid="REF29" ref-type="bibr">29</xref>]. In some centers, as a proxy for intrafraction motion, post-treatment imaging is often performed. More recently, real-time intrafraction monitoring can be performed with surrogate markers or the body surface and can interrupt treatment when movement exceeds a predefined tolerance (1-2 mm and 1°) [<xref rid="REF29" ref-type="bibr">29</xref>, <xref rid="REF41" ref-type="bibr">41</xref>-<xref rid="REF42" ref-type="bibr">42</xref>]. At our institution, we conducted a phantom study, which demonstrated the variability of the OSMS when the region of interest was decreased in size and as the couch angle changed (Figure <xref ref-type="fig" rid="FIG5">5</xref>). Based on these results, we utilized an intermediate patch monitoring the forehead and temples which were not obscured by the mouthpiece system. Over five treatments, the patient had very small intrafraction shifts (Table <xref ref-type="table" rid="TAB5">5</xref>) while immobilized for a mean of 29 minutes (range: 21-42 min) with a mean treatment time of 19 minutes (range: 12-27 min). Mayo, et al. noted that their treatment times with noncoplanar VMAT were about 20 minutes and shorter than the 45-60 minutes required for frame-based treatment [<xref rid="REF34" ref-type="bibr">34</xref>].</p><p><table-wrap id="TAB4" orientation="portrait" position="float"><label>Table 4</label><caption><title>Literature Review of Frameless Radiosurgery (Selected Series)</title><p>Ref = references; Pre-RT = pre-radiation therapy; HD = high definition; TPS = treatment planning system; IR = Infrared camera system with 4-6 reflectors or emitters mounted on bite-block tray; OSMS = optical surface monitoring system (AlignRT); kV = kilovoltage imaging; CBCT = cone beam CT; DOF = degrees of freedom; HD = high definition; MLC = multileaf collimator; SRS = stereotactic radiosurgery; VMAT = volumetric modulated arc therapy; FSRT = fractionated stereotactic radiotherapy; OBI = on-board imaging; GK = Gamma Knife; DCA = dynamic conformal arc; FFF = flattening fillter free; N = number; mets = metastases; OBI = on-board imager; AVM = arteriovenous malformation; CI = conformity index; HI = homogeneity index; GTV = gross target volume; PTV = planning target volume; IMRT = intensity modulate radiation therapy</p></caption><table frame="hsides" rules="groups"><tbody><tr style="background-color:#ccc"><td rowspan="1" colspan="1">First Author [Ref], Institution, Publication year
</td><td rowspan="1" colspan="1">Equipment
</td><td rowspan="1" colspan="1">Image Guidance, Robotic Couch, Intrafraction Motion
</td><td rowspan="1" colspan="1">Pre-RT Scans, Immobilization Devices
</td><td rowspan="1" colspan="1">Patients
</td><td rowspan="1" colspan="1">Technique, TPS
</td><td rowspan="1" colspan="1">Notes, Results, or Conclusions
</td></tr><tr><td rowspan="1" colspan="1">Mancosu [<xref rid="REF43" ref-type="bibr">43</xref>]
Milan-Rozzano
2016
</td><td rowspan="1" colspan="1">Varian Edge
120HD MLC
</td><td rowspan="1" colspan="1">kV/CBCT
6-DOF couch
OSMS
</td><td rowspan="1" colspan="1">CT
MRI
</td><td rowspan="1" colspan="1">Phantom
</td><td rowspan="1" colspan="1">-
</td><td rowspan="1" colspan="1">Study of Edge linac with OSMS and CBCT. Tested ability of OSMS vs. CBCT ability to detect facial movements at isocenter, ability to recognize shifts, at different couch angles, and accuracy of OSMS when a camera is blocked. Submillimeter accuracy with rotational inaccuracy of 0.3 degrees.
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Wen [<xref rid="REF44" ref-type="bibr">44</xref>]
Henry Ford
2015
</td><td rowspan="1" colspan="1">Varian Edge
120HD MLC
</td><td rowspan="1" colspan="1">kV/CBCT
6-DOF couch
OSMS
</td><td rowspan="1" colspan="1">-
</td><td rowspan="1" colspan="1">Commissioning
</td><td rowspan="1" colspan="1">FFF
VMAT
Cones
</td><td rowspan="1" colspan="1">Report of commissioning of Edge radiosurgery system. Deviation between OSMS and CBCT was -0.4, 0.1, and 0 mm in vertical, longitudinal, and lateral dimensions. Beam data and mechanical parameters similar to TrueBeam, with advanced imaging package, 6-DOF couch, and intracranial SRS accessory package.
</td></tr><tr><td rowspan="1" colspan="1">Seravalli [<xref rid="REF45" ref-type="bibr">45</xref>]
MAASTRO
2015
</td><td rowspan="1" colspan="1">Elekta Synergy
10 mm MLC
</td><td rowspan="1" colspan="1">kV/CBCT
Pre- & post- CBCT
</td><td rowspan="1" colspan="1">CT 1.2 mm
MRI 1.2 mm
Mask
(BlueBAG)
</td><td rowspan="1" colspan="1">N = 52
Brain mets
</td><td rowspan="1" colspan="1">SRS
Coplanar
VMAT
(Pinnacle)
</td><td rowspan="1" colspan="1">Process of treatment. End-to-end test. GTV-PTV margin of 2.4 - 3.1 mm. Used Quantec constraints.
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Li [<xref rid="REF29" ref-type="bibr">29</xref>]
MSK
2015
</td><td rowspan="1" colspan="1">Varian Trilogy
kV/CBCT
</td><td rowspan="1" colspan="1">OSMS
</td><td rowspan="1" colspan="1">Bite block
(PinPoint) vs
Open Mask (Freedom)
</td><td rowspan="1" colspan="1">N = 25 Bite block
N = 8 Mask
</td><td rowspan="1" colspan="1">FSRT
Coplanar beams
(iPlan)
</td><td rowspan="1" colspan="1">Process of care diagram. Deliberate forced moves (15 volunteers) on ref Table <xref ref-type="table" rid="TAB1">1</xref>. Study of volunteer comfort ref Table <xref ref-type="table" rid="TAB2">2</xref>.
</td></tr><tr><td rowspan="1" colspan="1">McTyre [<xref rid="REF40" ref-type="bibr">40</xref>]
Wake Forest
2015
</td><td rowspan="1" colspan="1">Gamma Knife Perfexion
</td><td rowspan="1" colspan="1">No OBI
</td><td rowspan="1" colspan="1">CT
MRI
Bite block (Extend)
</td><td rowspan="1" colspan="1">N = 34
</td><td rowspan="1" colspan="1">Fractionated GK
(GammaPlan)
</td><td rowspan="1" colspan="1">Meningioma, schwannoma, metastases. GTV was treated without margin. 16-32 Gy to 50% isodose line over 4-5 fractions. Optic apparatus constrained to 4 Gy tangential to tumor. Daily repositioning errors < 1.2 mm.
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Nanda [<xref rid="REF25" ref-type="bibr">25</xref>]
Emory
2014
</td><td rowspan="1" colspan="1">Novalis Tx
HD MLC
</td><td rowspan="1" colspan="1">kV/CBCT
IR
6-DOF
</td><td rowspan="1" colspan="1">CT 0.625 mm
MRI
</td><td rowspan="1" colspan="1">N = 5
Pediatric
</td><td rowspan="1" colspan="1">SRS/FSRT
Non-coplanar DCA
IMRT
12 beams
</td><td rowspan="1" colspan="1">GTV-PTV 1 mm
4/5 patients required anesthesia
</td></tr><tr><td rowspan="1" colspan="1">Pan [<xref rid="REF41" ref-type="bibr">41</xref>]
UCSD
2012
</td><td rowspan="1" colspan="1">TrueBeam
Trilogy
</td><td rowspan="1" colspan="1">OSMS
</td><td rowspan="1" colspan="1">CT 1.25 mm
MRI 1.25 mm
Open Mask
(CIVCO)
</td><td rowspan="1" colspan="1">N = 44
Adults
</td><td rowspan="1" colspan="1">SRS/FSRT
Multiple beams
Cones or VMAT
(Eclipse)
</td><td rowspan="1" colspan="1">GTV-PTV 1 mm. Beam hold 1-2 mm and 1°. Treatment times – CBCT mean 11 min. Median shifts 1 mm, 2 mm, 1 mm vertical, longitudinal, lateral. Treatment time 15 min (shorter for TrueBeam). Compared local control to other series.
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Schlesinger [<xref rid="REF39" ref-type="bibr">39</xref>]
UVA
2012
</td><td rowspan="1" colspan="1">Gamma Knife Perfexion
</td><td rowspan="1" colspan="1">No OBI
</td><td rowspan="1" colspan="1">CT
MRI
Bite block (Extend)
</td><td rowspan="1" colspan="1">N = first 10
</td><td rowspan="1" colspan="1">Fractionated GK
(GammaPlan)
</td><td rowspan="1" colspan="1">Interfraction and intrafraction performance of Extend. Mean radial setup difference was 0.64 mm, SD 0.24 mm. Mean intrafractional positional difference was 0.47 mm. Cannot account for rotations.
</td></tr><tr><td rowspan="1" colspan="1">Lu [<xref rid="REF35" ref-type="bibr">35</xref>]
BIDMC
2012
</td><td rowspan="1" colspan="1">Proton
</td><td rowspan="1" colspan="1">Orthogonal kV
Three 2 mm gold fiducial spheres
</td><td rowspan="1" colspan="1">CT
Frameless
</td><td rowspan="1" colspan="1">N = 1 AVM
</td><td rowspan="1" colspan="1">Proton
</td><td rowspan="1" colspan="1">Description of novel technique with implanted fiducials to localize AVM identified on angiography and to transfer location information to CT for proton SRS planning.
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Tryggestad [<xref rid="REF30" ref-type="bibr">30</xref>]
JHU
2011
</td><td rowspan="1" colspan="1">Elekta Synergy S
</td><td rowspan="1" colspan="1">Pre- & post- CBCT
</td><td rowspan="1" colspan="1">Mask - 4 types
Nonrandom study
Retrospective
</td><td rowspan="1" colspan="1">N = 121
</td><td rowspan="1" colspan="1">FSRT/external RT
</td><td rowspan="1" colspan="1">Demonstrated masks (ref. Figure <xref ref-type="fig" rid="FIG1">1</xref>). Best was type-S head and shoulder mask with head and shoulder cushion with mouthpiece. Can achieve intrafraction motion of 1 mm or less, and interfraction variability of less than 3 mm.
</td></tr><tr><td rowspan="1" colspan="1">Ramakrishna [<xref rid="REF31" ref-type="bibr">31</xref>]
DFCI
2010
</td><td rowspan="1" colspan="1">Novalis
</td><td rowspan="1" colspan="1">Stereoscopic kV (ExacTrac)
IR
</td><td rowspan="1" colspan="1">Frame
(Radionics)
Mask
(BrainLAB)
</td><td rowspan="1" colspan="1">N = 102 SRS
N = 7 FSRT
</td><td rowspan="1" colspan="1">SRS
</td><td rowspan="1" colspan="1">End-to-end overall accuracy of Novalis Body ExacTrac is 0.7 mm ± 0.3 mm. Approximately 22% of mask-immobilized patients displayed intrafraction displacement of 1-2 mm.
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Peng [<xref rid="REF49" ref-type="bibr">49</xref>]
UF Gainesville
2010
</td><td rowspan="1" colspan="1">Elekta Synergy
Varian Trilogy
</td><td rowspan="1" colspan="1">
</td><td rowspan="1" colspan="1">CT 2 mm
Mask
IR
CBCT
</td><td rowspan="1" colspan="1">N = 15 IR
N = 18 Mask
</td><td rowspan="1" colspan="1">-
</td><td rowspan="1" colspan="1">Comparison of IR tracking system setup with CBCT. Setup with IR resulted in setup errors of 1.2 mm determined by CBCT, versus mask and laser setup errors of 3.2 mm. FSRT should not rely on IR alone.
</td></tr><tr><td rowspan="1" colspan="1">Mayo [<xref rid="REF34" ref-type="bibr">34</xref>]
U Mass
2010
</td><td rowspan="1" colspan="1">Varian Trilogy
5 mm MLC
</td><td rowspan="1" colspan="1">kV/CBCT
</td><td rowspan="1" colspan="1">CT 1.25 mm
MRI 1.25 mm
Mask
(Alpha Cradle)
</td><td rowspan="1" colspan="1">N = 12
Adults
Brain mets
</td><td rowspan="1" colspan="1">SRS
Non-coplanar VMAT
(Eclipse)
</td><td rowspan="1" colspan="1">GTV-PTV 1-2 mm margin. Dosimetric details compared to CyberKnife, TomoTherapy, & IMRT. Reported on CI, gradient, & HI. Phantom end-to-end testing. Compared dose rate vs. survival in cell line (ref Figure 9).
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Keshavarzi [<xref rid="REF50" ref-type="bibr">50</xref>]
UCSD
2009
</td><td rowspan="1" colspan="1">Varian Trilogy
</td><td rowspan="1" colspan="1">IR
</td><td rowspan="1" colspan="1">CT 1.25 mm
MRI 1.5 mm
Mask
(AccuForm)
</td><td rowspan="1" colspan="1">N = 12
Pediatric
</td><td rowspan="1" colspan="1">SRS/FSRT
MLC IMRT
Cones
(Eclipse)
</td><td rowspan="1" colspan="1">GTV-PTV margin 1-3 mm
</td></tr></tbody></table></table-wrap></p><p><fig fig-type="figure" id="FIG5" orientation="portrait" position="float"><label>Figure 5</label><caption><title>Phantom study demonstrating increased variability of OSMS-reported 6-DOF couch shifts as the region of interest size decreases at five couch angles</title><p>OSMS = Optical Surface Monitoring System; DOF = degrees of freedom</p></caption><graphic xlink:href="cureus-0008-000000000585-i05"></graphic></fig></p><p><table-wrap id="TAB5" orientation="portrait" position="float"><label>Table 5</label><caption><title>Six Degrees of Freedom Couch Shifts Based on Daily Image Guidance with CBCT and OSMS</title><p>*Representative real-time delta shifts across non-coplanar treatment couch angles</p><p>OSMS = optical surface monitoring system; CBCT = cone beam CT; FSRT = fractionated stereotactic radiotherapy</p></caption><table frame="hsides" rules="groups"><tbody><tr style="background-color:#ccc"><td rowspan="1" colspan="1">
</td><td colspan="3" rowspan="1">Mean Translational Shifts (mm)
</td><td colspan="3" rowspan="1">Mean Rotational Shifts (°)
</td></tr><tr><td rowspan="1" colspan="1">
</td><td rowspan="1" colspan="1">Vertical
</td><td rowspan="1" colspan="1">Longitudinal
</td><td rowspan="1" colspan="1">Lateral
</td><td rowspan="1" colspan="1">Pitch
</td><td rowspan="1" colspan="1">Roll
</td><td rowspan="1" colspan="1">Rotation
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Localization CBCT
</td><td rowspan="1" colspan="1">3.1 (1.7 to 5.4)
</td><td rowspan="1" colspan="1">0.34 (-0.4 to 1.3)
</td><td rowspan="1" colspan="1">1.0 (0.5 to 1.5)
</td><td rowspan="1" colspan="1">0.4 (0.1 to 0.7)
</td><td rowspan="1" colspan="1">0.1 (0 to 0.2)
</td><td rowspan="1" colspan="1">-0.1 (-0.3 to 0.2)
</td></tr><tr><td rowspan="1" colspan="1">Setup OSMS
</td><td rowspan="1" colspan="1">5.4
</td><td rowspan="1" colspan="1">-0.40
</td><td rowspan="1" colspan="1">0.96
</td><td rowspan="1" colspan="1">0.07
</td><td rowspan="1" colspan="1">-0.08
</td><td rowspan="1" colspan="1">0.18
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Verification CBCT
</td><td rowspan="1" colspan="1">0
</td><td rowspan="1" colspan="1">0.15
</td><td rowspan="1" colspan="1">-0.3
</td><td rowspan="1" colspan="1">0.05
</td><td rowspan="1" colspan="1">0.05
</td><td rowspan="1" colspan="1">0
</td></tr><tr><td rowspan="1" colspan="1">Intrafraction OSMS*
</td><td rowspan="1" colspan="1">0.30
</td><td rowspan="1" colspan="1">-0.29
</td><td rowspan="1" colspan="1">0.02
</td><td rowspan="1" colspan="1">0
</td><td rowspan="1" colspan="1">-0.01
</td><td rowspan="1" colspan="1">0.07
</td></tr><tr style="background-color:#ccc"><td rowspan="1" colspan="1">Post-FSRT CBCT
</td><td rowspan="1" colspan="1">-0.2
</td><td rowspan="1" colspan="1">0.85
</td><td rowspan="1" colspan="1">-0.25
</td><td rowspan="1" colspan="1">0.2
</td><td rowspan="1" colspan="1">0.05
</td><td rowspan="1" colspan="1">0.15
</td></tr></tbody></table></table-wrap></p><p>Some common features of the latest equipment for radiosurgery include: higher mechanical precision, higher dose rate, smaller collimators, image guidance, intrafraction motion detection, and robotic 6DOF couches. Several investigators have performed end-to-end accuracy tests [<xref rid="REF43" ref-type="bibr">43</xref>-<xref rid="REF44" ref-type="bibr">44</xref>] and have found the equipment to be highly accurate and suitable for frameless SRS, with GTV-PTV margins of 1-2 mm [<xref rid="REF31" ref-type="bibr">31</xref>, <xref rid="REF34" ref-type="bibr">34</xref>, <xref rid="REF41" ref-type="bibr">41</xref>]. By comparison, an end-to-end test with older equipment utilizing 10 mm MLC leaves without 6-DOF couch advocated a GTV-PTV margin of 2.8 mm [<xref rid="REF45" ref-type="bibr">45</xref>].</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>Overall, intracranial germ cell tumors are rare. There are no standard approaches for patients with recurrent germ cell tumors. Curative options are limited by prior treatment. For patients with pure germinomas treated initially with either radiation or chemotherapy [<xref rid="REF36" ref-type="bibr">36</xref>, <xref rid="REF46" ref-type="bibr">46</xref>], high salvage rates are achieved. However, for patients with prior chemoradiation or those with relapsed NGGCT, sustained responses to commonly used salvage chemotherapy regimens are difficult to achieve. To date, cure rates of about 50% have been achieved using a salvage paradigm with an initial intensive chemotherapy to achieve minimal residual tumor, followed by high-dose chemotherapy with ASCR. However, compared to germinomas, relapsed NGGCT patients have a worse prognosis with two-thirds progressing within 18 months of treatment.</p><p>When re-irradiating recurrent IGT, the cumulative dose to the optic apparatus or brainstem will often be an issue since these tumors tend to occur in the suprasellar cistern or pineal gland. Data from re-irradiation of pediatric posterior fossa tumors or radiosurgery of lesions near critical structures can inform us about radiobiological dose constraints and guide treatment planning [<xref rid="REF47" ref-type="bibr">47</xref>-<xref rid="REF48" ref-type="bibr">48</xref>]. Fractionated treatments may have a lower risk of toxicity.</p><p>Frameless immobilization is the best choice for multiple repeated treatments. With our current technology and policies and procedures, we can safely and accurately deliver either SRS or FSRT. 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