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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer: a phase II trial</title><author><name sortKey="Fonteyne, Valerie" sort="Fonteyne, Valerie" uniqKey="Fonteyne V" first="Valérie" last="Fonteyne">Valérie Fonteyne</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Dirix, Piet" sort="Dirix, Piet" uniqKey="Dirix P" first="Piet" last="Dirix">Piet Dirix</name><affiliation><nlm:aff id="Aff2">Department of Radiation-Oncology, Iridium Cancer Network, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Junius, Sara" sort="Junius, Sara" uniqKey="Junius S" first="Sara" last="Junius">Sara Junius</name><affiliation><nlm:aff id="Aff3">Department of Radiation-Oncology CH-M/AMPR, Mouscron, Belgium</nlm:aff></affiliation></author><author><name sortKey="Rammant, Elke" sort="Rammant, Elke" uniqKey="Rammant E" first="Elke" last="Rammant">Elke Rammant</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Ost, Piet" sort="Ost, Piet" uniqKey="Ost P" first="Piet" last="Ost">Piet Ost</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="De Meerleer, Gert" sort="De Meerleer, Gert" uniqKey="De Meerleer G" first="Gert" last="De Meerleer">Gert De Meerleer</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2069 7798</institution-id><institution-id institution-id-type="GRID">grid.5342.0</institution-id><institution>Department of Radiotherapy and Experimental Cancer Research,</institution><institution>Ghent University,</institution></institution-wrap>Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Swimberghe, Martijn" sort="Swimberghe, Martijn" uniqKey="Swimberghe M" first="Martijn" last="Swimberghe">Martijn Swimberghe</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Decaestecker, Karel" sort="Decaestecker, Karel" uniqKey="Decaestecker K" first="Karel" last="Decaestecker">Karel Decaestecker</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Urology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>Ghent, Belgium</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28464906</idno><idno type="pmc">5414216</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414216</idno><idno type="RBID">PMC:5414216</idno><idno type="doi">10.1186/s12885-017-3302-9</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000C44</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C44</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer: a phase II trial</title><author><name sortKey="Fonteyne, Valerie" sort="Fonteyne, Valerie" uniqKey="Fonteyne V" first="Valérie" last="Fonteyne">Valérie Fonteyne</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Dirix, Piet" sort="Dirix, Piet" uniqKey="Dirix P" first="Piet" last="Dirix">Piet Dirix</name><affiliation><nlm:aff id="Aff2">Department of Radiation-Oncology, Iridium Cancer Network, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Junius, Sara" sort="Junius, Sara" uniqKey="Junius S" first="Sara" last="Junius">Sara Junius</name><affiliation><nlm:aff id="Aff3">Department of Radiation-Oncology CH-M/AMPR, Mouscron, Belgium</nlm:aff></affiliation></author><author><name sortKey="Rammant, Elke" sort="Rammant, Elke" uniqKey="Rammant E" first="Elke" last="Rammant">Elke Rammant</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Ost, Piet" sort="Ost, Piet" uniqKey="Ost P" first="Piet" last="Ost">Piet Ost</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="De Meerleer, Gert" sort="De Meerleer, Gert" uniqKey="De Meerleer G" first="Gert" last="De Meerleer">Gert De Meerleer</name><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2069 7798</institution-id><institution-id institution-id-type="GRID">grid.5342.0</institution-id><institution>Department of Radiotherapy and Experimental Cancer Research,</institution><institution>Ghent University,</institution></institution-wrap>Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Swimberghe, Martijn" sort="Swimberghe, Martijn" uniqKey="Swimberghe M" first="Martijn" last="Swimberghe">Martijn Swimberghe</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Decaestecker, Karel" sort="Decaestecker, Karel" uniqKey="Decaestecker K" first="Karel" last="Decaestecker">Karel Decaestecker</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Urology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>Ghent, Belgium</nlm:aff></affiliation></author></analytic><series><title level="j">BMC Cancer</title><idno type="eISSN">1471-2407</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Neo-adjuvant chemotherapy followed by radical cystectomy with extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with ≥pT3 tumors develop a pelvic recurrence. We hypothesize that postoperative adjuvant external beam radiotherapy (EBRT) might prevent local and lymph node recurrence and improve disease free- and overall survival as loco-regional recurrence is linked to the development of distant metastasis.</p></sec><sec><title>Methods</title><p>We plan to perform a multicentric prospective phase two study including 76 patients. Eligible patients are patients with MIBC, treated with radical cystectomy and presenting with ≥1 of the following characteristics:<list list-type="bullet"><list-item><p>Pathological (p)T3 stage + presence of lymphovascular invasion on pathological examination</p></list-item><list-item><p>pT4 stage</p></list-item><list-item><p><10 lymph nodes removed</p></list-item><list-item><p>positive lymph nodes</p></list-item><list-item><p>positive surgical margins</p></list-item></list></p><p>Patients will have a <sup>18</sup>F–FDG PET-CT to rule out the presence of distant metastasis prior to EBRT. A median dose of 50 Gy in 25 fractions is prescribed to the pelvic lymph node regions with inclusion of the operative bladder bed in case of a positive surgical margin. Patients with suspected lymph nodes on PET- CT can still be included in the trial, but a simultaneous integrated boost to 74Gy to the positive lymph nodes will be delivered. Blood and urine samples will be collected on day-1 and last day of EBRT for evaluation of biomarkers. The primary endpoint is evaluation of acute ≥Grade 3 intestinal or grade 4 urinary toxicity, in case of a neo-bladder reconstruction, within 12 weeks after EBRT. Secondary endpoints are: assessment of QOL, late RTOG toxicity, local control, disease free survival and overall survival. Biomarkers in urine and blood will be correlated with secondary survival endpoints.</p></sec><sec><title>Discussion</title><p>This is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC.</p></sec><sec><title>Trial registration</title><p>The Ethics committee of the Ghent University Hospital (EC2014/0630) approved this study on 31/07/2014.</p><p>Trial registration on Clinicaltrials.gov (<ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02397434">NCT02397434</ext-link>) on November 19, 2014.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sebastian Antoni, Jf" uniqKey="Sebastian Antoni J">JF Sebastian Antoni</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I Soerjomataram</name></author><author><name sortKey="Znaor, A" uniqKey="Znaor A">A Znaor</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A Jemal</name></author><author><name sortKey="Bray, F" uniqKey="Bray F">F Bray</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zehdner, P" uniqKey="Zehdner P">P Zehdner</name></author><author><name sortKey="Studer, Ue" uniqKey="Studer U">UE Studer</name></author><author><name sortKey="Skineer, Ec" uniqKey="Skineer E">EC Skineer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grossman, Hb" uniqKey="Grossman H">HB Grossman</name></author><author><name sortKey="Natale, Rb" uniqKey="Natale R">RB Natale</name></author><author><name sortKey="Tangen, Cm" uniqKey="Tangen C">CM Tangen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shariat, Sf" uniqKey="Shariat S">SF Shariat</name></author><author><name sortKey="Karakiewicz, Pi" uniqKey="Karakiewicz P">PI Karakiewicz</name></author><author><name sortKey="Palapattu, Gs" uniqKey="Palapattu G">GS Palapattu</name></author><author><name sortKey="Lotan, Y" uniqKey="Lotan Y">Y Lotan</name></author><author><name sortKey="Rogers, Cg" uniqKey="Rogers C">CG Rogers</name></author><author><name sortKey="Amiel, Ge" uniqKey="Amiel G">GE Amiel</name></author><author><name sortKey="Vazina, A" uniqKey="Vazina A">A Vazina</name></author><author><name sortKey="Gupta, A" uniqKey="Gupta A">A Gupta</name></author><author><name sortKey="Bastian, Pj" uniqKey="Bastian P">PJ Bastian</name></author><author><name sortKey="Sagalowsky, Ai" uniqKey="Sagalowsky A">AI Sagalowsky</name></author><author><name sortKey="Schoenberg, Mp" uniqKey="Schoenberg M">MP Schoenberg</name></author><author><name sortKey="Lerner, Sp" uniqKey="Lerner S">SP Lerner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raza, Sj" uniqKey="Raza S">SJ Raza</name></author><author><name sortKey="Wilson, T" uniqKey="Wilson T">T Wilson</name></author><author><name sortKey="Peabody, Jo" uniqKey="Peabody J">JO Peabody</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baumann, Bc" uniqKey="Baumann B">BC Baumann</name></author><author><name sortKey="Guzzo, T" uniqKey="Guzzo T">T Guzzo</name></author><author><name sortKey="He, J" uniqKey="He J">J He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Herr, Hw" uniqKey="Herr H">HW Herr</name></author><author><name sortKey="Faulkner, Jr" uniqKey="Faulkner J">JR Faulkner</name></author><author><name sortKey="Grossman, Hb" uniqKey="Grossman H">HB Grossman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Christodouleas, Jp" uniqKey="Christodouleas J">JP Christodouleas</name></author><author><name sortKey="Baumann, Bc" uniqKey="Baumann B">BC Baumann</name></author><author><name sortKey="He, J" uniqKey="He J">J He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leow, Jj" uniqKey="Leow J">JJ Leow</name></author><author><name sortKey="Martin Doyle, W" uniqKey="Martin Doyle W">W Martin-Doyle</name></author><author><name sortKey="Fay, Ap" uniqKey="Fay A">AP Fay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sternberg, Cn" uniqKey="Sternberg C">CN Sternberg</name></author><author><name sortKey="Sylvester, R" uniqKey="Sylvester R">R Sylvester</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dovedi, S" uniqKey="Dovedi S">S Dovedi</name></author><author><name sortKey="Adlard, Al" uniqKey="Adlard A">AL Adlard</name></author><author><name sortKey="Lipowska Bhalla, G" uniqKey="Lipowska Bhalla G">G Lipowska-Bhalla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reddy, Av" uniqKey="Reddy A">AV Reddy</name></author><author><name sortKey="Pariser, Jj" uniqKey="Pariser J">JJ Pariser</name></author><author><name sortKey="Pearce, Sm" uniqKey="Pearce S">SM Pearce</name></author><author><name sortKey="Weichselbaum, Rr" uniqKey="Weichselbaum R">RR Weichselbaum</name></author><author><name sortKey="Smith, Nd" uniqKey="Smith N">ND Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ploeg, M" uniqKey="Ploeg M">M Ploeg</name></author><author><name sortKey="Kums, Ac" uniqKey="Kums A">AC Kums</name></author><author><name sortKey="Aben, Kk" uniqKey="Aben K">KK Aben</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pollack, A" uniqKey="Pollack A">A Pollack</name></author><author><name sortKey="Zagars, Gk" uniqKey="Zagars G">GK Zagars</name></author><author><name sortKey="Dinney, Cp" uniqKey="Dinney C">CP Dinney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ide, H" uniqKey="Ide H">H Ide</name></author><author><name sortKey="Kikuchi, E" uniqKey="Kikuchi E">E Kikuchi</name></author><author><name sortKey="Miyajima, A" uniqKey="Miyajima A">A Miyajima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huncharek, M" uniqKey="Huncharek M">M Huncharek</name></author><author><name sortKey="Muscat, J" uniqKey="Muscat J">J Muscat</name></author><author><name sortKey="Geschwind, Jf" uniqKey="Geschwind J">JF Geschwind</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaghloul, Ms" uniqKey="Zaghloul M">MS Zaghloul</name></author><author><name sortKey="Awwad, Hk" uniqKey="Awwad H">HK Awwad</name></author><author><name sortKey="Omar, S" uniqKey="Omar S">S Omar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaghloul, Ms" uniqKey="Zaghloul M">MS Zaghloul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reisinger, S" uniqKey="Reisinger S">S Reisinger</name></author><author><name sortKey="Mohiuddin, M" uniqKey="Mohiuddin M">M Mohiuddin</name></author><author><name sortKey="Mulholland, S" uniqKey="Mulholland S">S Mulholland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang Chesebro, A" uniqKey="Wang Chesebro A">A Wang-Chesebro</name></author><author><name sortKey="Xia, P" uniqKey="Xia P">P Xia</name></author><author><name sortKey="Coleman, J" uniqKey="Coleman J">J Coleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fonteyne, V" uniqKey="Fonteyne V">V Fonteyne</name></author><author><name sortKey="Lumen, N" uniqKey="Lumen N">N Lumen</name></author><author><name sortKey="Ost, P" uniqKey="Ost P">P Ost</name></author><author><name sortKey="Van Praet, C" uniqKey="Van Praet C">C Van Praet</name></author><author><name sortKey="Vandecasteele, K" uniqKey="Vandecasteele K">K Vandecasteele</name></author><author><name sortKey="De Gersem, W" uniqKey="De Gersem W">W De Gersem</name></author><author><name sortKey="Villeirs, G" uniqKey="Villeirs G">G Villeirs</name></author><author><name sortKey="De Neve, W" uniqKey="De Neve W">W De Neve</name></author><author><name sortKey="Decaestecker, K" uniqKey="Decaestecker K">K Decaestecker</name></author><author><name sortKey="De Meerleer, G" uniqKey="De Meerleer G">G De Meerleer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vandecasteele, K" uniqKey="Vandecasteele K">K Vandecasteele</name></author><author><name sortKey="De Neve, W" uniqKey="De Neve W">W De Neve</name></author><author><name sortKey="De Gersem, W" uniqKey="De Gersem W">W De Gersem</name></author><author><name sortKey="Delrue, L" uniqKey="Delrue L">L Delrue</name></author><author><name sortKey="Paelinck, L" uniqKey="Paelinck L">L Paelinck</name></author><author><name sortKey="Makar, A" uniqKey="Makar A">A Makar</name></author><author><name sortKey="Fonteyne, V" uniqKey="Fonteyne V">V Fonteyne</name></author><author><name sortKey="De Wagter, C" uniqKey="De Wagter C">C De Wagter</name></author><author><name sortKey="Villeirs, G" uniqKey="Villeirs G">G Villeirs</name></author><author><name sortKey="De Meerleer, G" uniqKey="De Meerleer G">G De Meerleer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baumann, Bg" uniqKey="Baumann B">BG Baumann</name></author><author><name sortKey="Guzzo, Tj" uniqKey="Guzzo T">TJ Guzzo</name></author><author><name sortKey="He, J" uniqKey="He J">J He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Esse, J" uniqKey="Van Esse J">J van Esse</name></author><author><name sortKey="Grosse, J" uniqKey="Grosse J">J Grosse</name></author><author><name sortKey="Pfister, Dj" uniqKey="Pfister D">DJ Pfister</name></author><author><name sortKey="Epplen, R" uniqKey="Epplen R">R Epplen</name></author><author><name sortKey="Heidenreich, A" uniqKey="Heidenreich A">A Heidenreich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alongi, P" uniqKey="Alongi P">P Alongi</name></author><author><name sortKey="Caobelli, F" uniqKey="Caobelli F">F Caobelli</name></author><author><name sortKey="Gentile, R" uniqKey="Gentile R">R Gentile</name></author><author><name sortKey="Stefano, A" uniqKey="Stefano A">A Stefano</name></author><author><name sortKey="Russo, G" uniqKey="Russo G">G Russo</name></author><author><name sortKey="Albano, D" uniqKey="Albano D">D Albano</name></author><author><name sortKey="Baldari, S" uniqKey="Baldari S">S Baldari</name></author><author><name sortKey="Gilardi, Mc" uniqKey="Gilardi M">MC Gilardi</name></author><author><name sortKey="Midiri, M" uniqKey="Midiri M">M Midiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cox, Jd" uniqKey="Cox J">JD Cox</name></author><author><name sortKey="Stetz, J" uniqKey="Stetz J">J Stetz</name></author><author><name sortKey="Pajak, Tf" uniqKey="Pajak T">TF Pajak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trotti, A" uniqKey="Trotti A">A Trotti</name></author><author><name sortKey="Colevas, D" uniqKey="Colevas D">D Colevas</name></author><author><name sortKey="Setser, A" uniqKey="Setser A">A Setser</name></author><author><name sortKey="Rusch, V" uniqKey="Rusch V">V Rusch</name></author><author><name sortKey="Jaques, D" uniqKey="Jaques D">D Jaques</name></author><author><name sortKey="Budach, V" uniqKey="Budach V">V Budach</name></author><author><name sortKey="Langer, C" uniqKey="Langer C">C Langer</name></author><author><name sortKey="Murphy, B" uniqKey="Murphy B">B Murphy</name></author><author><name sortKey="Cumberlin, R" uniqKey="Cumberlin R">R Cumberlin</name></author><author><name sortKey="Coleman, Cn" uniqKey="Coleman C">CN Coleman</name></author><author><name sortKey="Rubin, P" uniqKey="Rubin P">P Rubin</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Rosen, Rc" uniqKey="Rosen R">RC Rosen</name></author><author><name sortKey="Riley, A" uniqKey="Riley A">A Riley</name></author><author><name sortKey="Wagner, G" uniqKey="Wagner G">G Wagner</name></author><author><name sortKey="Osterloh, Ih" uniqKey="Osterloh I">IH Osterloh</name></author><author><name sortKey="Kirkpatrick, J" uniqKey="Kirkpatrick J">J Kirkpatrick</name></author><author><name sortKey="Mishra, A" uniqKey="Mishra A">A Mishra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ter Kuile, Mm" uniqKey="Ter Kuile M">MM Ter Kuile</name></author><author><name sortKey="Brauer, M" uniqKey="Brauer M">M Brauer</name></author><author><name sortKey="Laan, E" uniqKey="Laan E">E Laan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barry, Mj" uniqKey="Barry M">MJ Barry</name></author><author><name sortKey="Fowler, Fj" uniqKey="Fowler F">FJ Fowler</name></author><author><name sortKey="O Eary, Mp" uniqKey="O Eary M">MP O’Leary</name></author><author><name sortKey="Bruskewitz, Rc" uniqKey="Bruskewitz R">RC Bruskewitz</name></author><author><name sortKey="Holtgrewe, Hl" uniqKey="Holtgrewe H">HL Holtgrewe</name></author><author><name sortKey="Mebust, Wk" uniqKey="Mebust W">WK Mebust</name></author><author><name sortKey="Cockett, At" uniqKey="Cockett A">AT Cockett</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Avery, K" uniqKey="Avery K">K Avery</name></author><author><name sortKey="Donovan, J" uniqKey="Donovan J">J Donovan</name></author><author><name sortKey="Peters, Tj" uniqKey="Peters T">TJ Peters</name></author><author><name sortKey="Shaw, C" uniqKey="Shaw C">C Shaw</name></author><author><name sortKey="Gotoh, M" uniqKey="Gotoh M">M Gotoh</name></author><author><name sortKey="Abrama, P" uniqKey="Abrama P">P ABrama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pos, Fj" uniqKey="Pos F">FJ Pos</name></author><author><name sortKey="Hart, G" uniqKey="Hart G">G Hart</name></author><author><name sortKey="Schneider, C" uniqKey="Schneider C">C Schneider</name></author><author><name sortKey="Sminia, P" uniqKey="Sminia P">P Sminia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sargos, P" uniqKey="Sargos P">P Sargos</name></author><author><name sortKey="Baumann, Bc" uniqKey="Baumann B">BC Baumann</name></author><author><name sortKey="Eapen, Lj" uniqKey="Eapen L">LJ Eapen</name></author><author><name sortKey="Bahl, A" uniqKey="Bahl A">A Bahl</name></author><author><name sortKey="Murthy, V" uniqKey="Murthy V">V Murthy</name></author><author><name sortKey="Roubaud, G" uniqKey="Roubaud G">G Roubaud</name></author><author><name sortKey="Orre, M" uniqKey="Orre M">M Orré</name></author><author><name sortKey="Efstathiou, Ja" uniqKey="Efstathiou J">JA Efstathiou</name></author><author><name sortKey="Shariat, S" uniqKey="Shariat S">S Shariat</name></author><author><name sortKey="Larre, S" uniqKey="Larre S">S Larré</name></author><author><name sortKey="Richaus, P" uniqKey="Richaus P">P Richaus</name></author><author><name sortKey="Christodouleas, Jp" uniqKey="Christodouleas J">JP Christodouleas</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Cancer</journal-id><journal-id journal-id-type="iso-abbrev">BMC Cancer</journal-id><journal-title-group><journal-title>BMC Cancer</journal-title></journal-title-group><issn pub-type="epub">1471-2407</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28464906</article-id><article-id pub-id-type="pmc">5414216</article-id><article-id pub-id-type="publisher-id">3302</article-id><article-id pub-id-type="doi">10.1186/s12885-017-3302-9</article-id><article-categories><subj-group subj-group-type="heading"><subject>Study Protocol</subject></subj-group></article-categories><title-group><article-title>Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer: a phase II trial</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-6724-1595</contrib-id><name><surname>Fonteyne</surname><given-names>Valérie</given-names></name><address><phone>+32 9 332 30 15</phone><email>valerie.fonteyne@uzgent.be</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Dirix</surname><given-names>Piet</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Junius</surname><given-names>Sara</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rammant</surname><given-names>Elke</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ost</surname><given-names>Piet</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>De Meerleer</surname><given-names>Gert</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Swimberghe</surname><given-names>Martijn</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Decaestecker</surname><given-names>Karel</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Radiation-Oncology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>De Pintelaan 185, Ghent, Belgium</aff><aff id="Aff2"><label>2</label>Department of Radiation-Oncology, Iridium Cancer Network, Ghent, Belgium</aff><aff id="Aff3"><label>3</label>Department of Radiation-Oncology CH-M/AMPR, Mouscron, Belgium</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2069 7798</institution-id><institution-id institution-id-type="GRID">grid.5342.0</institution-id><institution>Department of Radiotherapy and Experimental Cancer Research,</institution><institution>Ghent University,</institution></institution-wrap>Ghent, Belgium</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0626 3303</institution-id><institution-id institution-id-type="GRID">grid.410566.0</institution-id><institution>Department of Urology,</institution><institution>Ghent University Hospital,</institution></institution-wrap>Ghent, Belgium</aff></contrib-group><pub-date pub-type="epub"><day>2</day><month>5</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>2</day><month>5</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>17</volume><elocation-id>308</elocation-id><history><date date-type="received"><day>23</day><month>1</month><year>2017</year></date><date date-type="accepted"><day>25</day><month>4</month><year>2017</year></date></history><permissions><copyright-statement>© The Author(s). 2017</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p>Neo-adjuvant chemotherapy followed by radical cystectomy with extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with ≥pT3 tumors develop a pelvic recurrence. We hypothesize that postoperative adjuvant external beam radiotherapy (EBRT) might prevent local and lymph node recurrence and improve disease free- and overall survival as loco-regional recurrence is linked to the development of distant metastasis.</p></sec><sec><title>Methods</title><p>We plan to perform a multicentric prospective phase two study including 76 patients. Eligible patients are patients with MIBC, treated with radical cystectomy and presenting with ≥1 of the following characteristics:<list list-type="bullet"><list-item><p>Pathological (p)T3 stage + presence of lymphovascular invasion on pathological examination</p></list-item><list-item><p>pT4 stage</p></list-item><list-item><p><10 lymph nodes removed</p></list-item><list-item><p>positive lymph nodes</p></list-item><list-item><p>positive surgical margins</p></list-item></list></p><p>Patients will have a <sup>18</sup>F–FDG PET-CT to rule out the presence of distant metastasis prior to EBRT. A median dose of 50 Gy in 25 fractions is prescribed to the pelvic lymph node regions with inclusion of the operative bladder bed in case of a positive surgical margin. Patients with suspected lymph nodes on PET- CT can still be included in the trial, but a simultaneous integrated boost to 74Gy to the positive lymph nodes will be delivered. Blood and urine samples will be collected on day-1 and last day of EBRT for evaluation of biomarkers. The primary endpoint is evaluation of acute ≥Grade 3 intestinal or grade 4 urinary toxicity, in case of a neo-bladder reconstruction, within 12 weeks after EBRT. Secondary endpoints are: assessment of QOL, late RTOG toxicity, local control, disease free survival and overall survival. Biomarkers in urine and blood will be correlated with secondary survival endpoints.</p></sec><sec><title>Discussion</title><p>This is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC.</p></sec><sec><title>Trial registration</title><p>The Ethics committee of the Ghent University Hospital (EC2014/0630) approved this study on 31/07/2014.</p><p>Trial registration on Clinicaltrials.gov (<ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT02397434">NCT02397434</ext-link>) on November 19, 2014.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Muscle invasive bladder cancer-adjuvant radiotherapy-toxicity</kwd></kwd-group><funding-group><award-group><funding-source><institution>Kom Op tegen Kanker</institution></funding-source><award-id>0010091</award-id><principal-award-recipient><name><surname>Fonteyne</surname><given-names>Valérie</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2017</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1"><title>Background</title><p>Muscle invasive bladder cancer (MIBC) is the ninth most frequently diagnosed cancer and ranks 13th in terms of causes of death worldwide [<xref ref-type="bibr" rid="CR1">1</xref>]. The incidence of bladder cancer increases steadily with age. Due to improved life expectancy, the number of patients diagnosed with MIBC is expected to increase in the future.</p><p>A radical cystectomy combined with an extended pelvic lymph node dissection (ePLND) is considered to be the treatment of choice. Cisplatin-based neo-adjuvant chemotherapy improves survival outcomes and is recommended for patients with cT2-T4a N0–1 M0 MIBC [<xref ref-type="bibr" rid="CR2">2</xref>, <xref ref-type="bibr" rid="CR3">3</xref>]. Despite this multimodality treatment the outcome did not altered significantly over the last 30 years [<xref ref-type="bibr" rid="CR4">4</xref>] and remains poor with 5-years overall survival rates ranging between 50 [<xref ref-type="bibr" rid="CR5">5</xref>] and 60% [<xref ref-type="bibr" rid="CR6">6</xref>] to 65% [<xref ref-type="bibr" rid="CR7">7</xref>]. For patients with ≥pT3 MIBC the 5-year overall survival even drops to as low as 22% [<xref ref-type="bibr" rid="CR8">8</xref>]. Others have reported somewhat better results with a 5-year bladder cancer specific survival of 31 and 48% for T4 and T3 MIBC patients respectively [<xref ref-type="bibr" rid="CR6">6</xref>].</p><p>Besides the high rate of systemic recurrences, loco-regional control is equally important. Approximately 30% of patients with ≥pT3 tumors develop a pelvic recurrence [<xref ref-type="bibr" rid="CR8">8</xref>–<xref ref-type="bibr" rid="CR10">10</xref>]. For instance, in a contemporary monocentric analysis from a high-volume, tertiary center focusing on 334 pT3–4 pN0–1 MIBC patients, 31% of patients developed a pelvic recurrence, 34% of which had loco-regional only failure. Chemotherapy, whether immediately postoperative (adjuvant) or delayed at time of recurrence, might improve the outcome of patients with MIBC as was suggested in a recent meta-analysis [<xref ref-type="bibr" rid="CR11">11</xref>]. Unfortunately, these results are based on very inhomogeneous data. The conclusions of this meta-analysis are not considered to be robust and it remains unclear which patients really benefit from it [<xref ref-type="bibr" rid="CR12">12</xref>]. Generally, neo-adjuvant chemotherapy is preferred, which does not interfere with this trial. Currently, there are also several trials already running or being initiated looking at the use of adjuvant immunotherapy with MIBC. While this approach looks promising, eventual adjuvant immunotherapy does not exclude adjuvant radiotherapy. In fact, there might be an additional benefit in the combination [<xref ref-type="bibr" rid="CR13">13</xref>].</p><p>The rationale for adjuvant radiotherapy also reflects that attempts to salvage patients with pelvic failures are rarely successful [<xref ref-type="bibr" rid="CR14">14</xref>]. Indeed, 1- and 2-years survival for patients developing a local recurrence after cystectomy is only 8 and 3% respectively, with a median survival of <4 months [<xref ref-type="bibr" rid="CR15">15</xref>]. For patients with lymph node recurrence prognosis is somewhat better, but nevertheless still disappointing with reported 1- and 2 years survival of 42 and 11% respectively [<xref ref-type="bibr" rid="CR15">15</xref>]. Moreover, pelvic recurrences are often debilitating with pain, lymphedema and venous thrombosis as known morbidities. If patients with local or lymph node recurrence are treated with external beam radiotherapy (EBRT), 1-year survival is significantly improved from 2% (no EBRT) to 27% [<xref ref-type="bibr" rid="CR15">15</xref>]. Apparently, improving loco-regional control can impact survival in MIBC. We hypothesize that an earlier implementation of pelvic EBRT i.e. in the immediate postoperative (i.e. adjuvant) setting, will prevent local and pelvic nodal recurrence and improve disease free- and overall survival as loco-regional recurrence is linked to the development of distant metastasis [<xref ref-type="bibr" rid="CR16">16</xref>, <xref ref-type="bibr" rid="CR17">17</xref>].</p><p>Little is known about the timing of EBRT combined with radical cystectomy in MIBC. Preoperative EBRT can prevent intra-operative seeding of tumor cells and sterilizes microscopic extensions in the perivesical tissues. However, a meta-analysis of six randomized trials showed no clear benefit for preoperative irradiation [<xref ref-type="bibr" rid="CR18">18</xref>]. Adjuvant EBRT also has the advantage of dealing with microscopic cells along with a better identification of patients who are really at increased risk of developing local recurrence based on histological information of the primary tumor. Already two decennia ago, adjuvant EBRT was tested in a prospective randomized trial and resulted in a 20% increase in 5-year disease free survival (DFS) [<xref ref-type="bibr" rid="CR19">19</xref>, <xref ref-type="bibr" rid="CR20">20</xref>]. These results were supported by a non-randomized controlled Radiation Therapy Oncology Group trial [<xref ref-type="bibr" rid="CR21">21</xref>]. Also in the era of modern surgery it is suggested that adjuvant radiotherapy improves outcome. Shariat et al. found that, although a limited number of patients, adjuvant radiotherapy was independently associated with lower disease recurrence (HR: 3.3, 95% CI: 2.2–4.9; <italic>p</italic> < 0.001) and improved disease specific survival (HR: 2.4, 95% CI: 1.6–3.7; <italic>p</italic> < 0.001) while in the same study the impact of adjuvant chemotherapy on similar outcomes was less clear [<xref ref-type="bibr" rid="CR6">6</xref>]. Despite those encouraging results, severe intestinal toxicity rates hampered the enthusiasm to use adjuvant EBRT, in fact till now [<xref ref-type="bibr" rid="CR19">19</xref>, <xref ref-type="bibr" rid="CR21">21</xref>]. However, the technology that was used in the above-mentioned trials is outdated and conclusions concerning toxicity do not apply to the current technologies such as intensity-modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) and image guided radiotherapy [<xref ref-type="bibr" rid="CR22">22</xref>–<xref ref-type="bibr" rid="CR24">24</xref>]. Therefore, it is reasonable and even desirable to reconsider the use of adjuvant EBRT in properly selected MIBC patients.</p><p>This “proper” selection should be based on clinical, pathological, radiological and biological predictors for local and locoregional failure. Well-known clinical and pathological predictors are T-stage, lymph node status [<xref ref-type="bibr" rid="CR6">6</xref>, <xref ref-type="bibr" rid="CR25">25</xref>], presence of lymphovascular invasion [<xref ref-type="bibr" rid="CR6">6</xref>] and surgical margin status [<xref ref-type="bibr" rid="CR10">10</xref>].</p><p>To select those MIBC patients who will benefit most from postoperative EBRT it is important to first rule out distant metastasis. So far, conventional imaging techniques fail to detect recurrences or metastasis from bladder cancer at an early stage. Although only few studies have evaluated the potential role of <sup>18</sup>F–FDG-PET-CT in the loco-regional staging of patients with MIBC, specificity and negative predictive values mounts to >90% rendering it an interesting tool in the staging of MIBC patients, although its use is currently recommended only within clinical trials [<xref ref-type="bibr" rid="CR26">26</xref>]. <sup>18</sup>F–FDG-PET-CT has also been studied in the recurrent setting. Although the evidence is limited it has been suggested that a good diagnostic performance is obtained with <sup>18</sup>F–FDG-PET-CT in the recurrent setting of MIBC [<xref ref-type="bibr" rid="CR27">27</xref>]. By implementing <sup>18</sup>F–FDG-PET-CT prior to the start of adjuvant radiotherapy we aim to exclude patients with distant metastasis as these patients are less likely to benefit from this treatment approach.</p><p>Additionally, circulating biomarkers can be used to identify patients who are at increased risk for local and pelvic nodal relapse for whom this multimodality therapy is presumed to be most beneficial. Biomarkers will be evaluated to determine if they can help in selecting those patients most likely to benefit from adjuvant radiotherapy.</p></sec><sec id="Sec2"><title>Methods/design</title><p>This study is approved by the Ethics committee of the Ghent University Hospital (EC2014/0630) and is registered on <ext-link ext-link-type="uri" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</ext-link> (NCT02397434). Patients with high risk (see below) of developing local or pelvic nodal recurrence after radical cystectomy with ePLND will be offered adjuvant EBRT within a multicentric prospective phase II trial.</p><sec id="Sec3"><title>Objectives</title><p><list list-type="bullet"><list-item><p><italic>Primary endpoint</italic><list list-type="bullet"><list-item><p>○ Acute toxicity defined as toxicity occurring during or within 3 months following adjuvant EBRT and scored by:<list list-type="bullet"><list-item><p>▪ Acute Radiation Therapy Oncology Group (RTOG) small and large intestine toxicity [<xref ref-type="bibr" rid="CR28">28</xref>] and Common toxicity criteria version 4.0 (CTC v4.0) [<xref ref-type="bibr" rid="CR29">29</xref>]</p></list-item><list-item><p>▪ Acute RTOG [<xref ref-type="bibr" rid="CR28">28</xref>] and CTC v4.0 [<xref ref-type="bibr" rid="CR29">29</xref>] bladder toxicity for patients with a neobladder only</p></list-item></list></p></list-item></list></p></list-item><list-item><p><italic>Secondary endpoints</italic><list list-type="bullet"><list-item><p>○ Quality of life (QOL) scoring using the EORTC QLQ-C30 supplemented with QLQ-BLM30 prior to, at the end and 1 month after adjuvant EBRT, then 3-monthly during the first year and 6-monthly up to 2 years.</p></list-item><list-item><p>○ Assessment of quality-adjusted-life-years with the EuroQol classification system (EQ-5D) [<xref ref-type="bibr" rid="CR30">30</xref>]. A written consent to use this system was obtained from the EuroQol Group Foundation.</p></list-item><list-item><p>○ Assessment of erectile function using the International Index of Erectile Function (IIEF) questionnaire [<xref ref-type="bibr" rid="CR31">31</xref>] in males and sexual function in females [<xref ref-type="bibr" rid="CR32">32</xref>].</p></list-item><list-item><p>○ Assessment of voiding pattern using the International prostate Symptom Score (I-PSS) [<xref ref-type="bibr" rid="CR33">33</xref>] and International Consultation on Incontinence Modular Questionnaire Urinary Incontinence (ICIQ-UI) Short Form [<xref ref-type="bibr" rid="CR34">34</xref>] for patients with a neobladder.</p></list-item><list-item><p>○ Late toxicity due to radiotherapy will be scored using RTOG [<xref ref-type="bibr" rid="CR28">28</xref>] and CTC v4.0 [<xref ref-type="bibr" rid="CR29">29</xref>] scoring systems. Late toxicity is defined as toxicity lasting more than 3 months after cessation of adjuvant EBRT, or starting more than 3 months after the end of adjuvant radiotherapy.</p></list-item><list-item><p>○ Local control rate defined as absence of recurrence within the pelvis. This will be evaluated on pelvic CT scans performed on predefined time-points (see below) or in case of suspicion of recurrence.</p></list-item><list-item><p>○ DFS defined as survival without evidence of disease recurrence (neither local recurrence, recurrence in lymph nodes or distant metastasis) and is calculated from date of radical cystectomy till diagnosis of local, regional or distant recurrence on CT scan at predefined time-points or in case of suspicion of recurrence.</p></list-item><list-item><p>○ Bladder cancer specific survival calculated from date of radical cystectomy till death due to MIBC.</p></list-item><list-item><p>○ Overall survival calculated from date of radical cystectomy till death of any cause.</p></list-item><list-item><p>○ Serum samples and urine samples after cystectomy will be collected and stored in a biobank. Biomarkers will be evaluated on all samples in duplicate and correlated with DFS and bladder cancer specific survival.</p></list-item></list></p></list-item></list></p></sec><sec id="Sec4"><title>Inclusion criteria</title><p>Eligible patients are patients with M0-MIBC, treated with radical cystectomy and ePLND with ≥1 of the following characteristics:<list list-type="bullet"><list-item><p>pathological (p)T3-MIBC with presence of lymphovascular invasion on pathological examination</p></list-item><list-item><p>pT4 -MIBC</p></list-item><list-item><p><10 lymph nodes removed</p></list-item><list-item><p>presence of pathological positive lymph nodes</p></list-item><list-item><p>positive surgical margins</p></list-item></list></p><p>and<list list-type="bullet"><list-item><p>WHO performance state 0–2</p></list-item><list-item><p>Age ≥ 18 years old</p></list-item><list-item><p>Willing and able to provide a signed informed consent</p></list-item></list></p></sec><sec id="Sec5"><title>Exclusion criteria</title><p><list list-type="bullet"><list-item><p>Presence of distant metastasis at time of inclusion</p></list-item><list-item><p>Previous pelvic irradiation</p></list-item><list-item><p>Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule</p></list-item><list-item><p>Presence of a second primary tumour other than accidental finding of completely removed prostate cancer, non-melanoma skin tumour or tumour diagnosed ≥5 years ago</p></list-item></list></p></sec><sec id="Sec6"><title>Evaluation and inclusion</title><p>A flow chart presenting the different steps from inclusion until treatment is presented in Fig. <xref rid="Fig1" ref-type="fig">1</xref>. EBRT should start during week 6–12 after radical cystectomy.<fig id="Fig1"><label>Fig. 1</label><caption><p>Overview of study flow chart. Abbreviations: p: pathological; EBRT: external beam radiotherapy; RC: radical cystectomy</p></caption><graphic xlink:href="12885_2017_3302_Fig1_HTML" id="MO1"></graphic></fig></p></sec><sec id="Sec7"><title>Intervention</title><p>A <sup>18</sup>F–FDG-PET-CT is recommended but not obligatory within 4–10 weeks after radical cystectomy to rule out distant metastases.</p><p>All patients receive a planning CT on week 5–10 after radical cystectomy. Planning CT is performed in supine position with 3 mm CT slice thickness from the lung top till mid femur.</p><p>The target volume comprises the pelvic lymph node areas at risk in all cases. This stems from the observation that most recurrences are in the pelvic sidewall region so that the central pelvis, and the cystectomy bed in particular, might reasonably be spared treatment unless margins are involved [<xref ref-type="bibr" rid="CR8">8</xref>, <xref ref-type="bibr" rid="CR11">11</xref>]. The lymph node regions at risk are the lymph nodes located along the common, internal and external iliac artery, the lymph nodes in the obturator fossa and the presacral nodes. Suspicious lymph nodes on <sup>18</sup>F–FDG-PET-CT imaging are delineated separately. All delineated lymph node regions at risk are then summed to a structure named as Lnn. The clinical target volume (CTV)_Lnn is then created using an isotropic expansion of 2 mm around the Lnn. The planning target volume (PTV)_Lnn is created using a 5 mm margin around the CTN_Lnn.</p><p>The bladder bed is only included in the radiation field if there is a positive surgical margin [<xref ref-type="bibr" rid="CR8">8</xref>, <xref ref-type="bibr" rid="CR14">14</xref>]. Pre cystectomy imaging as well as information obtained from the surgical report and anatomopathological evaluation is used for delineation of the bladder bed.</p><p>A median dose of 50 Gy is prescribed to the pelvic lymph nodes ± bladder bed and is delivered in 25 fractions, 5 times a week. A simultaneous integrated boost up to 70 Gy (corresponding to a normalised iso-effective dose of 74 Gy in 2 Gy fractions calculated with an α/β of 10 [<xref ref-type="bibr" rid="CR35">35</xref>]) to the positive lymph nodes, detected on (<sup>18</sup>F–FDG-PET-)CT, is prescribed. VMAT is used. The treatment is delivered on a linear accelerator using 6–18 MV photons and multileaf collimation [<xref ref-type="bibr" rid="CR23">23</xref>, <xref ref-type="bibr" rid="CR24">24</xref>]. Patient positioning during treatment is controlled by daily cone beam CT.</p></sec><sec id="Sec8"><title>Follow up</title><p>Patients are followed weekly during therapy, 1 month after therapy and 3- monthly thereafter. After the end of radiotherapy and at each follow up visit a standard blood control (including sedimentation, erythrocytes, leucocytes (including formula), thrombocytes, creatinine, electrolytes, liver parameters, alkaline phosphatase) is performed. In asymptomatic patients imaging (CT thorax/abdomen/pelvis) will be performed 3–6-monthly after the end of radiotherapy during the first year and 6-monthly thereafter up to a period of 5 years and yearly thereafter or until progression.</p></sec><sec id="Sec9"><title>Statistical analysis</title><sec id="Sec10"><title>Sample size</title><p>We plan to perform a multicentric prospective phase 2 study in which 76 patients will be enrolled. With this sample size there is 95% likelihood that no more than 25% ± 10% [<xref ref-type="bibr" rid="CR21">21</xref>] of the patients will develop severe toxicity (i.e. grade ≥ 3 toxicity requiring hospitalization and/or surgical re-intervention) after adjuvant radiotherapy. This number takes into account 5% percentage of missing data.</p></sec></sec><sec id="Sec11"><title>Data analysis</title><p>The primary endpoint is acute toxicity defined as any toxicity from start of adjuvant EBRT up to 3 months following adjuvant EBRT.</p><p>The incidence of late toxicity will be recorded. Actuarial risk estimates for developing late toxicity will be calculated using Kaplan Meier analysis.</p><p>QOL will be evaluated pre-radiotherapy, at the end of radiotherapy and 1 month after radiotherapy. Thereafter a 3 monthly evaluation will be performed during the first year and 6-monthly up to 2 years after radiotherapy.</p><p>DFS, bladder cancer specific survival and overall survival will also be calculated using Kaplan Meier actuarial analysis. Survival times are defined from the date of radical cystectomy until an event or last follow up.</p></sec></sec><sec id="Sec12"><title>Discussion</title><p>For patients with MIBC neo-adjuvant chemotherapy and radical surgery is standard of care [<xref ref-type="bibr" rid="CR3">3</xref>]. Unfortunately the outcome remains poor for high-risk MIBC patients and the overall survival hasn’t improved significantly over the past years. Further efforts to improve the outcome of these patients are therefore mandatory. Previous trials showed that adjuvant radiotherapy can improve DFS at the cost of severe toxicity [<xref ref-type="bibr" rid="CR9">9</xref>–<xref ref-type="bibr" rid="CR20">20</xref>]. The latter limited the enthusiasm to propose adjuvant radiotherapy to patients with high-risk MIBC. In the last decade, major technological advancements in radiotherapy delivery have been realized, resulting in a better coverage of the target volume while sparing more normal tissue (mainly small bowel) and in a more precise delivery of radiation. VMAT is such a technique that can significantly reduce late toxicity [<xref ref-type="bibr" rid="CR23">23</xref>, <xref ref-type="bibr" rid="CR24">24</xref>]. Furthermore, better insights in the pattern of local relapse, based on large surgical data [<xref ref-type="bibr" rid="CR8">8</xref>–<xref ref-type="bibr" rid="CR10">10</xref>], enable us to tailor and restrict the radiation field to the area that is at highest risk of developing recurrence. Based on these observations there is a renewed interest in reevaluating the place of adjuvant radiotherapy in those MIBC patients who are at increased risk of developing disease recurrence [<xref ref-type="bibr" rid="CR36">36</xref>]. The aim of this prospective phase 2 trial is to support the hypothesis that with modern radiotherapy toxicity of adjuvant radiotherapy after radical cystectomy is acceptable.</p></sec></body><back><glossary><title>Abbreviations</title><def-list><def-item><term>c</term><def><p>Clinical stage</p></def></def-item><def-item><term>CT</term><def><p>Computed tomography</p></def></def-item><def-item><term>CTC</term><def><p>Common toxicity criteria</p></def></def-item><def-item><term>CTV</term><def><p>Clinical target volume</p></def></def-item><def-item><term>DFS</term><def><p>Disease free survival</p></def></def-item><def-item><term>EBRT</term><def><p>External beam radiotherapy</p></def></def-item><def-item><term>EORTC</term><def><p>European Organisation for Research and Treatment of Cancer</p></def></def-item><def-item><term>ePLND</term><def><p>Extended pelvic lymph node dissection</p></def></def-item><def-item><term>EQ-5D</term><def><p>EuroQol classification system</p></def></def-item><def-item><term>Gy</term><def><p>Gray</p></def></def-item><def-item><term>ICIQ_UI</term><def><p>International Consultation on Incontinence Modular Questionnaire Urinary Incontinence</p></def></def-item><def-item><term>IIEF</term><def><p>International Index of Erectile Function</p></def></def-item><def-item><term>IMRT</term><def><p>Intensity-modulated radiotherapy</p></def></def-item><def-item><term>Lnn</term><def><p>Lymph nodes</p></def></def-item><def-item><term>MIBC</term><def><p>Muscle invasive bladder cancer</p></def></def-item><def-item><term>p</term><def><p>Pathological stage</p></def></def-item><def-item><term>PTV</term><def><p>Planning target volume</p></def></def-item><def-item><term>QOL</term><def><p>Quality of life</p></def></def-item><def-item><term>RTOG</term><def><p>Radiation Therapy Oncology Group</p></def></def-item><def-item><term>VMAT</term><def><p>Volumetric arc therapy</p></def></def-item></def-list></glossary><ack><p>This study is funded by a grant of Kom op tegen Kanker (ref: 0010091). The granting bodies are not involved in data collection or analysis.</p><sec id="FPar1"><title>Availability of data and materials</title><p>The data set used and/or analysed during the current study are available from the corresponding author on reasonable request. Not all data are obtained yet since the study is still ongoing.</p></sec><sec id="FPar2"><title>Authors’ contributions</title><p>Study Conception: VF. Initial study design: VF. Revision of study design and protocol: VF, KD, GDM, PO. Study coordination: VF, PD, SJ, ER, MS. Participating centers: SJ, PD, GDM. All authors read and approved the final manuscript.</p></sec><sec id="FPar3"><title>Authors’ information</title><p>Not applicable.</p></sec><sec id="FPar4"><title>Competing interests</title><p>The authors declare that they have no competing interests.</p><p>The study did not receive funding from a commercial organization.</p></sec><sec id="FPar5"><title>Consent for publication</title><p>A signed informed consent is obtained from all patients included in the trial.</p></sec><sec id="FPar6"><title>Ethics approval and consent to participate</title><p>Approval was obtained by the ethical committee of Ghent University Hospital on 31/07/2014 (EC2014/0630).</p></sec><sec id="FPar7"><title>Publisher’s Note</title><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></sec></ack><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sebastian Antoni</surname><given-names>JF</given-names></name><name><surname>Soerjomataram</surname><given-names>I</given-names></name><name><surname>Znaor</surname><given-names>A</given-names></name><name><surname>Jemal</surname><given-names>A</given-names></name><name><surname>Bray</surname><given-names>F</given-names></name></person-group><article-title>Bladder cancer incidence and mortality: a global overview and recent trends</article-title><source>Eur Urol</source><year>2017</year><volume>71</volume><issue>1</issue><fpage>96</fpage><lpage>107</lpage><pub-id pub-id-type="doi">10.1016/j.eururo.2016.06.010</pub-id><pub-id pub-id-type="pmid">27370177</pub-id></element-citation></ref><ref id="CR2"><label>2.</label><mixed-citation publication-type="other">Yin M, Joshi M, Meijer RP, Glantz M, Holder S, Harvey HA, Kaag M, Fransen van dePutte EE, Horenblas S, Drabick JJ. Neo-adjuvant chemotherapy for muscle invaisve bladder cancer: as systematic review and two-step meta-analysis. Oncologist 2016; 21 (6): 708-715.</mixed-citation></ref><ref id="CR3"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>Advanced Bladder Cancer (ABC) Meta-analysis collaboration</collab></person-group><article-title>Neo-adjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data</article-title><source>Eur Urol</source><year>2005</year><volume>48</volume><fpage>202</fpage><lpage>206</lpage><pub-id pub-id-type="doi">10.1016/j.eururo.2005.04.006</pub-id><pub-id pub-id-type="pmid">15939524</pub-id></element-citation></ref><ref id="CR4"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zehdner</surname><given-names>P</given-names></name><name><surname>Studer</surname><given-names>UE</given-names></name><name><surname>Skineer</surname><given-names>EC</given-names></name><etal></etal></person-group><article-title>Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades</article-title><source>BJU Int</source><year>2013</year><volume>112</volume><fpage>51</fpage><lpage>58</lpage><pub-id pub-id-type="doi">10.1111/bju.12215</pub-id></element-citation></ref><ref id="CR5"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Grossman</surname><given-names>HB</given-names></name><name><surname>Natale</surname><given-names>RB</given-names></name><name><surname>Tangen</surname><given-names>CM</given-names></name><etal></etal></person-group><article-title>Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer</article-title><source>N Engl J Med</source><year>2003</year><volume>349</volume><fpage>859</fpage><lpage>866</lpage><pub-id pub-id-type="doi">10.1056/NEJMoa022148</pub-id><pub-id pub-id-type="pmid">12944571</pub-id></element-citation></ref><ref id="CR6"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shariat</surname><given-names>SF</given-names></name><name><surname>Karakiewicz</surname><given-names>PI</given-names></name><name><surname>Palapattu</surname><given-names>GS</given-names></name><name><surname>Lotan</surname><given-names>Y</given-names></name><name><surname>Rogers</surname><given-names>CG</given-names></name><name><surname>Amiel</surname><given-names>GE</given-names></name><name><surname>Vazina</surname><given-names>A</given-names></name><name><surname>Gupta</surname><given-names>A</given-names></name><name><surname>Bastian</surname><given-names>PJ</given-names></name><name><surname>Sagalowsky</surname><given-names>AI</given-names></name><name><surname>Schoenberg</surname><given-names>MP</given-names></name><name><surname>Lerner</surname><given-names>SP</given-names></name></person-group><article-title>Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemproary series from the bladder cancer research consortium</article-title><source>J Urol</source><year>2006</year><volume>176</volume><fpage>2414</fpage><lpage>2422</lpage><pub-id pub-id-type="doi">10.1016/j.juro.2006.08.004</pub-id><pub-id pub-id-type="pmid">17085118</pub-id></element-citation></ref><ref id="CR7"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Raza</surname><given-names>SJ</given-names></name><name><surname>Wilson</surname><given-names>T</given-names></name><name><surname>Peabody</surname><given-names>JO</given-names></name><etal></etal></person-group><article-title>Long-term oncologic outcomes following robot-assisted radical cystectomy: results from the international robotic Cystectomy consortium</article-title><source>Eur Urol</source><year>2015</year><volume>68</volume><fpage>721</fpage><lpage>728</lpage><pub-id pub-id-type="doi">10.1016/j.eururo.2015.04.021</pub-id><pub-id pub-id-type="pmid">25985883</pub-id></element-citation></ref><ref id="CR8"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Baumann</surname><given-names>BC</given-names></name><name><surname>Guzzo</surname><given-names>T</given-names></name><name><surname>He</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Bladder cancer patterns of pelvic failure: implications for adjuvant radiation therapy</article-title><source>Int J Radiat Oncol Biol Phys</source><year>2013</year><volume>85</volume><fpage>363</fpage><lpage>369</lpage><pub-id pub-id-type="doi">10.1016/j.ijrobp.2012.03.061</pub-id><pub-id pub-id-type="pmid">22658217</pub-id></element-citation></ref><ref id="CR9"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Herr</surname><given-names>HW</given-names></name><name><surname>Faulkner</surname><given-names>JR</given-names></name><name><surname>Grossman</surname><given-names>HB</given-names></name><etal></etal></person-group><article-title>Surgical factors influence bladder cancer outcomes: a cooperative group report</article-title><source>J Clin Oncol</source><year>2004</year><volume>22</volume><fpage>2781</fpage><lpage>2789</lpage><pub-id pub-id-type="doi">10.1200/JCO.2004.11.024</pub-id><pub-id pub-id-type="pmid">15199091</pub-id></element-citation></ref><ref id="CR10"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Christodouleas</surname><given-names>JP</given-names></name><name><surname>Baumann</surname><given-names>BC</given-names></name><name><surname>He</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Optimizing bladder cancer locoregional failure risk stratification after radical cystectomy using SWOG 8710</article-title><source>Cancer</source><year>2014</year><volume>120</volume><fpage>1272</fpage><lpage>1280</lpage><pub-id pub-id-type="doi">10.1002/cncr.28544</pub-id><pub-id pub-id-type="pmid">24390799</pub-id></element-citation></ref><ref id="CR11"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Leow</surname><given-names>JJ</given-names></name><name><surname>Martin-Doyle</surname><given-names>W</given-names></name><name><surname>Fay</surname><given-names>AP</given-names></name><etal></etal></person-group><article-title>A systematic review and meta-analysis od adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma</article-title><source>Eur Urol</source><year>2014</year><volume>66</volume><fpage>529</fpage><lpage>541</lpage><pub-id pub-id-type="doi">10.1016/j.eururo.2014.03.003</pub-id><pub-id pub-id-type="pmid">24680361</pub-id></element-citation></ref><ref id="CR12"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sternberg</surname><given-names>CN</given-names></name><name><surname>Sylvester</surname><given-names>R</given-names></name></person-group><article-title>Thoughts on a systematic review and meta-analysis of adjuvant chemotherapy in muscle-invasive bladder cancer</article-title><source>Eur Urol</source><year>2014</year><volume>66</volume><fpage>55</fpage><lpage>56</lpage><pub-id pub-id-type="doi">10.1016/j.eururo.2014.01.008</pub-id><pub-id pub-id-type="pmid">24484605</pub-id></element-citation></ref><ref id="CR13"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dovedi</surname><given-names>S</given-names></name><name><surname>Adlard</surname><given-names>AL</given-names></name><name><surname>Lipowska-Bhalla</surname><given-names>G</given-names></name><etal></etal></person-group><article-title>Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade</article-title><source>Cancer Res</source><year>2014</year><volume>74</volume><issue>19</issue><fpage>5458</fpage><lpage>5468</lpage><pub-id pub-id-type="doi">10.1158/0008-5472.CAN-14-1258</pub-id><pub-id pub-id-type="pmid">25274032</pub-id></element-citation></ref><ref id="CR14"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reddy</surname><given-names>AV</given-names></name><name><surname>Pariser</surname><given-names>JJ</given-names></name><name><surname>Pearce</surname><given-names>SM</given-names></name><name><surname>Weichselbaum</surname><given-names>RR</given-names></name><name><surname>Smith</surname><given-names>ND</given-names></name><etal></etal></person-group><article-title>Patterns of failure after radical Cystectomy for pT3-4 bladder cancer: implications for adjuvant radiation therapy</article-title><source>Int J Radiat Oncol Biol Phys</source><year>2016</year><volume>94</volume><fpage>1031</fpage><lpage>1039</lpage><pub-id pub-id-type="doi">10.1016/j.ijrobp.2015.10.051</pub-id><pub-id pub-id-type="pmid">27026309</pub-id></element-citation></ref><ref id="CR15"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ploeg</surname><given-names>M</given-names></name><name><surname>Kums</surname><given-names>AC</given-names></name><name><surname>Aben</surname><given-names>KK</given-names></name><etal></etal></person-group><article-title>Prognostic factors for survival in patients with recurrence of muscle invasive bladder cancer after treatment with curative intent</article-title><source>Clin Genitourin Cancer</source><year>2011</year><volume>9</volume><fpage>14</fpage><lpage>21</lpage><pub-id pub-id-type="doi">10.1016/j.clgc.2011.05.004</pub-id><pub-id pub-id-type="pmid">21723794</pub-id></element-citation></ref><ref id="CR16"><label>16.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pollack</surname><given-names>A</given-names></name><name><surname>Zagars</surname><given-names>GK</given-names></name><name><surname>Dinney</surname><given-names>CP</given-names></name><etal></etal></person-group><article-title>Preoperative radiotherapy for muscle-invasive bladder carcinoma. Long term follow up and prognostic factors for 338 patients</article-title><source>Cancer</source><year>1994</year><volume>74</volume><fpage>2819</fpage><lpage>2827</lpage><pub-id pub-id-type="doi">10.1002/1097-0142(19941115)74:10<2819::AID-CNCR2820741013>3.0.CO;2-L</pub-id><pub-id pub-id-type="pmid">7954243</pub-id></element-citation></ref><ref id="CR17"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ide</surname><given-names>H</given-names></name><name><surname>Kikuchi</surname><given-names>E</given-names></name><name><surname>Miyajima</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>The predictability of local recurrence after radical cystectomy in patients with invasive bladder cancer</article-title><source>Jpn J Clin Oncol</source><year>2008</year><volume>38</volume><fpage>360</fpage><lpage>364</lpage><pub-id pub-id-type="doi">10.1093/jjco/hyn036</pub-id><pub-id pub-id-type="pmid">18490370</pub-id></element-citation></ref><ref id="CR18"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huncharek</surname><given-names>M</given-names></name><name><surname>Muscat</surname><given-names>J</given-names></name><name><surname>Geschwind</surname><given-names>JF</given-names></name></person-group><article-title>Planned preoperative radiation therapy in muscle invasive bladder cancer; results of a meta-analysis</article-title><source>Anticancer Res</source><year>1998</year><volume>18</volume><fpage>1931</fpage><lpage>1934</lpage><pub-id pub-id-type="pmid">9677446</pub-id></element-citation></ref><ref id="CR19"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zaghloul</surname><given-names>MS</given-names></name><name><surname>Awwad</surname><given-names>HK</given-names></name><name><surname>Omar</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Postoperative radiotherapy of carcinoma in bilharzial bladder. Improved disease-free survival through improving local control</article-title><source>Int J Radiat Oncol Biol Phys</source><year>1992</year><volume>22</volume><fpage>511</fpage><lpage>517</lpage><pub-id pub-id-type="doi">10.1016/0360-3016(92)90005-3</pub-id><pub-id pub-id-type="pmid">1735689</pub-id></element-citation></ref><ref id="CR20"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zaghloul</surname><given-names>MS</given-names></name></person-group><article-title>Distant metastasis from bilharzial bladder cancer</article-title><source>Cancer</source><year>1996</year><volume>77</volume><fpage>743</fpage><lpage>749</lpage><pub-id pub-id-type="doi">10.1002/(SICI)1097-0142(19960215)77:4<743::AID-CNCR21>3.0.CO;2-#</pub-id><pub-id pub-id-type="pmid">8616767</pub-id></element-citation></ref><ref id="CR21"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reisinger</surname><given-names>S</given-names></name><name><surname>Mohiuddin</surname><given-names>M</given-names></name><name><surname>Mulholland</surname><given-names>S</given-names></name></person-group><article-title>Combined pre- and postoperative adjuvant radiotherapy for bladder cancer – a 10 year experience</article-title><source>Int J Radiat Oncol Biol Phys</source><year>1992</year><volume>24</volume><fpage>463</fpage><lpage>468</lpage><pub-id pub-id-type="doi">10.1016/0360-3016(92)91060-Z</pub-id><pub-id pub-id-type="pmid">1399731</pub-id></element-citation></ref><ref id="CR22"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang-Chesebro</surname><given-names>A</given-names></name><name><surname>Xia</surname><given-names>P</given-names></name><name><surname>Coleman</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer</article-title><source>Int J Radiat Oncol Biol Phys</source><year>2006</year><volume>66</volume><fpage>654</fpage><lpage>662</lpage><pub-id pub-id-type="doi">10.1016/j.ijrobp.2006.05.037</pub-id><pub-id pub-id-type="pmid">17011444</pub-id></element-citation></ref><ref id="CR23"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fonteyne</surname><given-names>V</given-names></name><name><surname>Lumen</surname><given-names>N</given-names></name><name><surname>Ost</surname><given-names>P</given-names></name><name><surname>Van Praet</surname><given-names>C</given-names></name><name><surname>Vandecasteele</surname><given-names>K</given-names></name><name><surname>De Gersem</surname><given-names>W</given-names></name><name><surname>Villeirs</surname><given-names>G</given-names></name><name><surname>De Neve</surname><given-names>W</given-names></name><name><surname>Decaestecker</surname><given-names>K</given-names></name><name><surname>De Meerleer</surname><given-names>G</given-names></name></person-group><article-title>Hypofractionated intensity-modulated arc therapy for lymph node metastasized prostate cancer: toxicity and 3-years clinical outcome</article-title><source>Radiother Oncol</source><year>2013</year><volume>109</volume><fpage>229</fpage><lpage>234</lpage><pub-id pub-id-type="doi">10.1016/j.radonc.2013.08.006</pub-id><pub-id pub-id-type="pmid">24016677</pub-id></element-citation></ref><ref id="CR24"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vandecasteele</surname><given-names>K</given-names></name><name><surname>De Neve</surname><given-names>W</given-names></name><name><surname>De Gersem</surname><given-names>W</given-names></name><name><surname>Delrue</surname><given-names>L</given-names></name><name><surname>Paelinck</surname><given-names>L</given-names></name><name><surname>Makar</surname><given-names>A</given-names></name><name><surname>Fonteyne</surname><given-names>V</given-names></name><name><surname>De Wagter</surname><given-names>C</given-names></name><name><surname>Villeirs</surname><given-names>G</given-names></name><name><surname>De Meerleer</surname><given-names>G</given-names></name></person-group><article-title>Intensity-modulated arc therapy with simultaneous integrated boost in the treatment of primary irresectable cervical cancer. Treatment planning, quality control, and clinical implementation</article-title><source>Strahlenther Onkol</source><year>2009</year><volume>185</volume><issue>12</issue><fpage>799</fpage><lpage>807</lpage><pub-id pub-id-type="doi">10.1007/s00066-009-1986-8</pub-id><pub-id pub-id-type="pmid">20013089</pub-id></element-citation></ref><ref id="CR25"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Baumann</surname><given-names>BG</given-names></name><name><surname>Guzzo</surname><given-names>TJ</given-names></name><name><surname>He</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>A novel risk stratification to predict local-regional failures in urothelial carcinoma of the bladder after radical cystectomy</article-title><source>Int J Radiat Oncol Biol Phys</source><year>2012</year><volume>85</volume><fpage>81</fpage><lpage>88</lpage><pub-id pub-id-type="doi">10.1016/j.ijrobp.2012.03.007</pub-id><pub-id pub-id-type="pmid">22543204</pub-id></element-citation></ref><ref id="CR26"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Esse</surname><given-names>J</given-names></name><name><surname>Grosse</surname><given-names>J</given-names></name><name><surname>Pfister</surname><given-names>DJ</given-names></name><name><surname>Epplen</surname><given-names>R</given-names></name><name><surname>Heidenreich</surname><given-names>A</given-names></name></person-group><article-title>Evaluation of (18F) FDG-PET-CT for preoperative lymph node staging of bladder cancer</article-title><source>J Clin Oncol</source><year>2012</year><volume>30</volume><fpage>275</fpage></element-citation></ref><ref id="CR27"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alongi</surname><given-names>P</given-names></name><name><surname>Caobelli</surname><given-names>F</given-names></name><name><surname>Gentile</surname><given-names>R</given-names></name><name><surname>Stefano</surname><given-names>A</given-names></name><name><surname>Russo</surname><given-names>G</given-names></name><name><surname>Albano</surname><given-names>D</given-names></name><name><surname>Baldari</surname><given-names>S</given-names></name><name><surname>Gilardi</surname><given-names>MC</given-names></name><name><surname>Midiri</surname><given-names>M</given-names></name></person-group><article-title>Recurrent bladder carcinoma: clinical and prognostic role of 18 F-FDG PET/CT</article-title><source>Eur J Nucl Med Mol Imaging</source><year>2016</year></element-citation></ref><ref id="CR28"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cox</surname><given-names>JD</given-names></name><name><surname>Stetz</surname><given-names>J</given-names></name><name><surname>Pajak</surname><given-names>TF</given-names></name></person-group><article-title>Toxicity criteria of the radiation therapy Oncology group (RTOG) and the European Organization for Research and Treatment of cancer (EORTC)</article-title><source>Int J Radiat Oncol Biol Phys</source><year>1995</year><volume>31</volume><fpage>1341</fpage><lpage>1346</lpage><pub-id pub-id-type="doi">10.1016/0360-3016(95)00060-C</pub-id><pub-id pub-id-type="pmid">7713792</pub-id></element-citation></ref><ref id="CR29"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Trotti</surname><given-names>A</given-names></name><name><surname>Colevas</surname><given-names>D</given-names></name><name><surname>Setser</surname><given-names>A</given-names></name><name><surname>Rusch</surname><given-names>V</given-names></name><name><surname>Jaques</surname><given-names>D</given-names></name><name><surname>Budach</surname><given-names>V</given-names></name><name><surname>Langer</surname><given-names>C</given-names></name><name><surname>Murphy</surname><given-names>B</given-names></name><name><surname>Cumberlin</surname><given-names>R</given-names></name><name><surname>Coleman</surname><given-names>CN</given-names></name><name><surname>Rubin</surname><given-names>P</given-names></name></person-group><article-title>CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment</article-title><source>Semi Radiat Oncol</source><year>2003</year><volume>13</volume><issue>3</issue><fpage>176</fpage><lpage>181</lpage><pub-id pub-id-type="doi">10.1016/S1053-4296(03)00031-6</pub-id></element-citation></ref><ref id="CR30"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>EuroQol Group</collab></person-group><article-title>EuroQOL- a new facility for the measurement of health-related quality of life. The EuroQol group</article-title><source>Health Policy</source><year>1990</year><volume>16</volume><issue>3</issue><fpage>199</fpage><lpage>208</lpage><pub-id pub-id-type="doi">10.1016/0168-8510(90)90421-9</pub-id><pub-id pub-id-type="pmid">10109801</pub-id></element-citation></ref><ref id="CR31"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rosen</surname><given-names>RC</given-names></name><name><surname>Riley</surname><given-names>A</given-names></name><name><surname>Wagner</surname><given-names>G</given-names></name><name><surname>Osterloh</surname><given-names>IH</given-names></name><name><surname>Kirkpatrick</surname><given-names>J</given-names></name><name><surname>Mishra</surname><given-names>A</given-names></name></person-group><article-title>The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction</article-title><source>Urology</source><year>1997</year><volume>49</volume><issue>6</issue><fpage>822</fpage><lpage>883</lpage><pub-id pub-id-type="doi">10.1016/S0090-4295(97)00238-0</pub-id><pub-id pub-id-type="pmid">9187685</pub-id></element-citation></ref><ref id="CR32"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ter Kuile</surname><given-names>MM</given-names></name><name><surname>Brauer</surname><given-names>M</given-names></name><name><surname>Laan</surname><given-names>E</given-names></name></person-group><article-title>The female sexual function index (FSFI) and the female sexual distress scale (FSDS): psychomteric properties within a Dutch population</article-title><source>J Sex Marital Ther</source><year>2006</year><volume>32</volume><fpage>289</fpage><lpage>304</lpage><pub-id pub-id-type="doi">10.1080/00926230600666261</pub-id><pub-id pub-id-type="pmid">16709550</pub-id></element-citation></ref><ref id="CR33"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barry</surname><given-names>MJ</given-names></name><name><surname>Fowler</surname><given-names>FJ</given-names></name><name><surname>O’Leary</surname><given-names>MP</given-names></name><name><surname>Bruskewitz</surname><given-names>RC</given-names></name><name><surname>Holtgrewe</surname><given-names>HL</given-names></name><name><surname>Mebust</surname><given-names>WK</given-names></name><name><surname>Cockett</surname><given-names>AT</given-names></name></person-group><article-title>The American urological association symptom index for benign prostatic hyperplasia. The measurement Committee of the American Urolohical Association</article-title><source>J Urol</source><year>1992</year><volume>148</volume><issue>5</issue><fpage>1549</fpage><lpage>1557</lpage><pub-id pub-id-type="pmid">1279218</pub-id></element-citation></ref><ref id="CR34"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Avery</surname><given-names>K</given-names></name><name><surname>Donovan</surname><given-names>J</given-names></name><name><surname>Peters</surname><given-names>TJ</given-names></name><name><surname>Shaw</surname><given-names>C</given-names></name><name><surname>Gotoh</surname><given-names>M</given-names></name><name><surname>ABrama</surname><given-names>P</given-names></name></person-group><source>Neurourol Urodyn</source><year>2004</year><volume>23</volume><issue>4</issue><fpage>322</fpage><lpage>330</lpage><pub-id pub-id-type="doi">10.1002/nau.20041</pub-id><pub-id pub-id-type="pmid">15227649</pub-id></element-citation></ref><ref id="CR35"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pos</surname><given-names>FJ</given-names></name><name><surname>Hart</surname><given-names>G</given-names></name><name><surname>Schneider</surname><given-names>C</given-names></name><name><surname>Sminia</surname><given-names>P</given-names></name></person-group><article-title>Radical radiotherapy for invasive bladder cancer: what dose and fractionation schedule to choose?</article-title><source>Int J Radiat Oncol Biol Phys</source><year>2006</year><volume>15</volume><issue>64</issue><fpage>1168</fpage><lpage>1173</lpage><pub-id pub-id-type="doi">10.1016/j.ijrobp.2005.09.023</pub-id></element-citation></ref><ref id="CR36"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sargos</surname><given-names>P</given-names></name><name><surname>Baumann</surname><given-names>BC</given-names></name><name><surname>Eapen</surname><given-names>LJ</given-names></name><name><surname>Bahl</surname><given-names>A</given-names></name><name><surname>Murthy</surname><given-names>V</given-names></name><name><surname>Roubaud</surname><given-names>G</given-names></name><name><surname>Orré</surname><given-names>M</given-names></name><name><surname>Efstathiou</surname><given-names>JA</given-names></name><name><surname>Shariat</surname><given-names>S</given-names></name><name><surname>Larré</surname><given-names>S</given-names></name><name><surname>Richaus</surname><given-names>P</given-names></name><name><surname>Christodouleas</surname><given-names>JP</given-names></name></person-group><article-title>Adjuvant radiotherapy for pathological high-risk muscle invasive bladder cancer: time to reconsider?</article-title><source>Transl Androl Urol</source><year>2016</year><volume>5</volume><issue>5</issue><fpage>702</fpage><lpage>710</lpage><pub-id pub-id-type="doi">10.21037/tau.2016.08.18</pub-id><pub-id pub-id-type="pmid">27785427</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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