Abstract Book

S871

ESTRO 37

Material and Methods Consecutive RCC patients underwent a contrast enhanced MRI scan. Five physicians received a MRI dataset (T2, pre- and post-contrast T1, DWI, and ADC), on which they contoured the tumor. On four datasets the tumor was delineated without instructions (development phase). With help of an expert radiologist new delineation guidelines were made based on these initial delineations. Next, another 10 new cases were delineated following these guidelines and subsequently evaluated (evaluation phase). The volumes, conformity index (CI) and distance between centers of the mass (dCOM) were calculated. Results Four RCC cases were delineated in the development phase and 10 RCC cases in the evaluation phase by 5 observers. The agreement between observers in the evaluation phase resulted in a mean CI of 0.77, ranging from 0.59-0.88. The mean dCOM was 0.55 mm. Conclusion A delineation guideline for RCC on MRI has been created, based on T2 weighted MR imaging with help of contrast enhanced T1 weighted imaging and DWI. Inter-observer delineation variations were limited. The recommendations for contouring and sequences used can be helpful in the introduction of MRI guided radiotherapy in the clinic. EP-1618 Monoubiquitinylated histone H2B as a potential target in treatment resistant germ cell tumors C. Oing 1 , S. Dyshlovoy 1 , F. Honecker 2 , L. Nordquist 3 , K. Rothkamm 3 , C. Bokemeyer 1 , C. Petersen 4 , W.Y. Mansour 3 1 Universitaetsklinikum Hamburg-Eppendorf, Oncology- Hematology and Bone Marrow Transplantation with 3 Universitaetsklinikum Hamburg-Eppendorf, Laboratory of Radiobiology and Radiation Oncology, Hamburg, Germany 4 Universitaetsklinikum Hamburg-Eppendorf, Radiotherapy and Radiation Oncology, Hamburg, Germany Purpose or Objective To investigate the role of histone H2B monoubiquitination (H2Bub1) in treatment resistance and as a therapeutic target in treatment resistant germ cell tumors (GCTs). Up to 30% of patients with advanced GCT disease suffer from treatment-resistant disease and have a dismal prognosis. Treatment resistance is of multifactorial origin, where tissue differentiation and DNA repair alterations play critical roles. A better understanding of resistance mechanisms and identification of new therapeutic targets are urgently needed to improve outcomes. H2Bub1 is 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 section of Pneumology, Hamburg, Germany 2 ZeTuP, Breast and Tumor Center, St. Gallen, Switzerland

(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