ESTRO 37 Abstract book

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ESTRO 37

involved in both DNA damage response and differentiation of multipotent tissues and may thus play a role in GCT treatment resistance. Material and Methods Impact of H2Bub1 knockdown by siRNA or the CDK9 inhibitor LCD000067 on DNA repair efficiency was assessed in HeLa cells by immunofluorescence and specific repair substrates as a proof of principle. Non- seminoma cell lines NTera-2, NCCIT and 2102EP, and two respective Cisplatin-resistant sub-lines (NCCIT-R, 2102EP- R) served as in vitro GCT models. H2Bub1 expression was assessed by western blotting and correlated to pluripotency markers NANOG and Oct3/4 after differentiation induction with all-trans retinoic acid (ATRA). MTT assay and colony formation assay were applied to investigate the impact of H2Bub1 knockdown on response to genotoxic treatment (CDDP, irradiation). A tissue microarray (TMA) comprising 97 primary GCT samples was immunohistochemically analyzed for H2Bub1 formation. Results H2Bub1 expression was found to be higher in cisplatin- resistant non-seminoma cell lines compared to the sensitive parental cell lines. ATRA treatment increased H2Bub1 levels, and decreased sensitivity to cisplatin in pluripotent non-seminoma cell lines. Moreover, inhibition of H2Bub1 formation (by siRNA or CDK9i) significantly impaired DNA repair and decreased cellular survival in vitro , yielding enhanced sensitivity towards genotoxic Treatment including CDDP and irradiation. In TMA analysis, H2Bub1 formation was found to be heterogeneous in both seminomas and non-seminomas. Conclusion H2Bub1 is heterogeneously present in GCTs in vivo , and seems to be related to both differentiation and treatment resistance in vitro . Inhibition of H2Bub1 formation by CDK9 inhibition leads to impaired DNA damage response and re-sensitizes cells towards genotoxic treatment, which warrants further investigation of this target in treatment resistant GCTs. EP-1619 Radiotherapy for Kidney Transplant Recipient With Urothelial Carcinoma: A Retrospective Analysis H. Sheng-Ping 1 , K.H. FAN 1 , C. Yang-Jen 2 1 Chang Gung Memorial Hospital, Radiation Oncology, Taoyuan, Taiwan 2 Chang Gung Memorial Hospital, Division of Transplant and General Urology, Taoyuan, Taiwan Purpose or Objective Kidney transplant recipients are at higher risk of malignancy including urothelial carcinoma(UC). Besides, the incidence of advanced stage UC was also higher in this population. Radiation therapy (RT) had been proven effective for treatment of urothelial cancer. However, most renal grafts are located near the irradiation target and graft injury would be a important concern when radiotherapy is indicated. The goal of this study is to verify the safeness of RT for kidney transplant recipients with UC. Material and Methods Ten kidney transplant recipients who developed UC and received radiation therapy with or without chemotherapy in our hospital were identified as study group. All the patients were treated by 3-dimensional conformal radiation therapy(3D-CRT) or intense modulated radiation therapy (IMRT). The first priority of radiotherapy treatment plan was to match V20Gy < 32% of renal graft. The allograft failure was defined as irreversible

decreasing clearance of creatinine (cCr) which turned patient into hemodialysis or peritoneal dialysis. Tolerance dose of kidney was defined as QUANTEC report for evaluation. Radiation associated allograft failure was defined as irreversible renal function decline without identified reason besides excessive radiation exposure. The reason of graft failure was determined by a specialist of renal transplant. Results There were five male and five female patients in the study group with median age at 63 years old. These patients were diagnosed with 5 bladder cancers, 2 renal pelvic cancers, 1 ureter cancer and 1 double primary kidney/ bladder cancer. Half patients were treated by 3D-CRT and the others were treated by IMRT. Only 2 treatment plans’ dose distribution violated tolerance dose of QUANTEC report (V6Gy<30%), but neither of them induced renal graft failure. There were four renal graft failure found in study group, which resulted from different reason, including recurrent infection, tumor recurrence, chronic allograft nephropathy and chemotherapy related. Although most radiation dose was distributed to gastrointestinal (GI) tract to protect graft, the GI toxicities were all tolerable. No patients had their radiotherapy course shortened or terminated because of toxicities. Conclusion Based on our results, we assumed that current irradiation technique is quite safe for kidney allograft when treating UC and can comply nearly all the constrains suggested by QUENTEC report. Radiotherapy for patients with kidney transplant is safe and feasible. EP-1620 Muscle-Invasive Bladder Cancer Bladder- Preservation by Combined-Modality Therapy: Long- Term Outcomes A. Soler 1 , M. López 1 , D. Martínez 1 , A. Benedicto 2 , A. Navarro 1 , J.L. Monroy 1 , M. Albert 1 , C. Domingo 1 , M. Soler 1 1 Hospital Universitario de la Ribera, Radiation Oncology, Alzira, Spain 2 Hospital Universitario de la Ribera, Urology, Alzira, Spain Purpose or Objective Muscle-Invasive Bladder Cancer is an aggressive entity and a major health problem. Radical cystectomy is elective treatment, but the best of them is nonetheless mutilating. We present the results of our Institution's Long-Term Combined-Modality treatment. Material and Methods From January 2002 to December 2015, 128 bladder cancer patients have been treated with radical intention, but only 101 accomplished the criteria for study. The median age at diagnosis was 72 years (range: 41-85 years). All with confirmed transitional cancer histology. All of them were subjected to maximum TURBT and CT- Scan staging. 96% had G3. Initial stages were: 76% T2, 16% T3, 5% T4, and 3% T1; 85% N0, 15% N1-N2. RT was delivered over first and second nodal station at 45- 50.4Gy, followed dose 59.4-66Gy over bladder; the first 15 cases had split course with re-staging TURBT between phases. Chemotherapy (CT) platinum based were, neo- adjuvant-concurrent 72%, neoadjuvant 3%, concurrent 11%, and none 14%. Results After a mean follow-up of 118 months (17-182), Overall Survival was 39%, and Cancer-Specific survival was 72%. After local relapse, radical cystectomy was performed in 6 patients, meanwhile TURBT in 3 cases. Death at the