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with curative intent, three or fewer extracranial metastatic lesions on choline PET-CT and serum testosterone levels >50 ng/ml. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was done with PSA follow-up every 3 months with repeated imaging at PSA progression or clinical suspicion for progression. Randomisation was balanced dynamically on two factors: PSA doubling time (≤3 vs. > 3 months) and nodal vs non-nodal metastases. The primary endpoint was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to >3 metastases or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (IQR 2.3 – 3.75), the median ADT-free survival (figure) was 13 months (80% CI: 12-17) for the surveillance group and 21 months (80% CI: 14-29) for the MDT group (hazard ratio 0.60 [80% CI: 0.40 – 0.90], log-rank p=0.11). On subgroup analysis, no significant interaction was observed between the effect of MDT and PSA doubling time or location of metastases (p-value of interaction: 0.35 and 0.31 respectively). The PSA change is depicted as a waterfall plot as the largest change in PSA. In total, 74% of patients treated with MDT had a PSA decline as compared to 42% in the surveillance arm. The median time until PSA progression for the ITT was 6 months (95%CI: 3.85 – 8.15) for the surveillance group as compared to 10 months (5.46 – 14.55) for the MDT group (HR = 0.53, 95%CI: 0.30- 0.94, p = 0.03). Quality of life was similar between arms at baseline and remained comparable at 3 months and 1 year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2-5 toxicity was observed.

blood vessels network to distribute chemotherapy or therapeutic molecules to tumour cells. It is also a main actor of tumour aggressiveness and resistance to radiotherapy through hypoxic zones. In a previous study, we showed that standard fractionated RT (2Gy/day) was able to improve vascular morphology and functionality by improving pericyte coverage, increasing blood perfusion and reducing hypoxia in prostate tumours. However, hypofractionated schedules are frequently used and in vitro studies suggest that high single doses above 7Gy could induce massive endothelial cell death and major hypoxia. The aim of this work was to investigate the consequences of different clinically relevant hypofractionated schedules on tumour vasculature and their impact on blood perfusion, hypoxia and small Mice with subcutaneous tumours received localised RT during 2 weeks, according to the following fractionation schedules: 2x12Gy, 3x8Gy, 6x4Gy, 10x2Gy. Two tumour models were used: the highly proliferative LLC lung cancer and the moderately proliferative PC3 prostate cancer. Tumour hypoxia (pimonidazole), blood perfusion (hoechst perfusion), microvascular density (CD31) and pericyte coverage (αSMA and Desmin) were assessed by immunohistochemistry. Chemotherapy diffusion was assessed by doxorubicin intravenous injections. Results After 2 weeks, all RT schedules induced a tumour volume reduction in the PC3 model and a tumour growth slowdown in the LLC model. In both models, RT substantially improved vascular pericyte coverage regardless of the fractionation schedule and chemotherapy diffusion was majored. Unlike vascular morphologic changes, hypoxia and perfusion modifications occurred differently according to the dose per fraction. In the slowly proliferative PC3 model, despite microvascular density was unchanged, hypoxia was reduced from -26% to -85% and perfusion was majored from +28% to +203% compare to control, in a dose per fraction-dependent manner. In the highly proliferative LLC model, microvascular density was affected but perfusion was surprisingly improved with the highest doses per fraction. Hypoxia was reduced in all the hypofractionated schedules. In this model, hypoxia, perfusion and microvascular density changes were observed within 3 days after last RT session and compensated after 7 days whereas the changes were more stable in the PC3 model. Conclusion In our tumour models, hypofractionated RT improves tumour perfusion, reduces hypoxia and increases pericyte coverage. The differences between the 2 models suggest that the duration of radio-induced hypoxia and perfusion improvement could be balanced by the tumor growth rate. These finding will help better understanding the radiobiological effects of high doses per fraction and modeling hypofractionated RT schedules. OC-0377 Targeting a Novel Function for SAMHD1 in DNA Repair for Radiation Therapy and PARP Inhibition D. Yu 1 , W. Daddacha 1 , A. Koyen 1 , A. Bastien 1 , P. Head 1 , V. Dhere 1 , G. Nabeta 1 , E. Connolly 1 , E. Werner 1 , M. Madden 1 , M. Daly 1 , E. Minten 1 , D. Whelan 2 , H. Zhang 1 , R. Anand 3 , C. Shepard 4 , R. Sundaram 5 , X. Deng 1 , W. Dynan 1 , Y. Wang 1 , R. Bindra 5 , P. Cejka 3 , E. Rothenberg 2 , P. Doetsch 1 , B. Kim 4 1 Emory University, Radiation Oncology, Atlanta GA, USA 2 NYU, Biochemistry and Molecular Pharmacology, New Yoprk, USA 3 Università della Svizzera italiana, Institute for Research in Biomedicin, Bellinzona, Switzerland 4 Emory University, Pediatrics, Atlanta GA, USA 5 Yale University School of Medicine, Department of Radiation Oncology, New Haven, USA molecules distribution. Material and Methods

Conclusion ADT-free survival was longer with metastasis-directed therapy than with surveillance alone for oligorecurrent PCa, suggesting that metastasis-directed therapy should be further explored in phase III trials.

Proffered Papers: RB 4: Targeting tumour biology

OC-0376 Hypofractionated RT: fractionation schedule affects tumour vascular morphology and functionality K. Clement-Colmou 1 , V. Potiron 1 , M. Guillonneau 1 , E. Jouglar 1 , F. Paris 1 , S. Supiot 2 1 CRCiNA, UMR 1232 INSERM, Nantes, France 2 Institut de Cancérologie de l'Ouest, Radiation Oncology, Nantes, France Purpose or Objective Tumour vascular microenvironment is a crucial actor in response to systemic treatments through the ability of