ESTRO 37 Abstract book

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ESTRO 37

however, certain limitations related to the physics and hardware that make protons less favorable in treatment of metastases. With the present technology, the lateral penumbra of scanned protons is less sharp than for IMRT, especially in treatment of smaller targets. On the other hand, the low dose volume and thereby the integral dose is always reduced with protons. Treatment of small targets with PBS is vulnerable and less robust to anatomical changes from day to day and during treatment and uncertainties in stopping power estimation. For SBRT of small lung and liver metastases, respiration related motion of ribs may degrade the planned proton dose distribution. The more resource- demanding proton SRT/SBRT is only preferred over conventional SRT/SBRT when it is related to a reduced risk of morbidity. In principle, scanned protons my be preferred for treatment of large metastases embedded in organs with large volume effects (parallel organized) that is sensitive to the integral or median dose whereas small metastases in close relationship to organs with low volume effects (serial organized) benefit from the less costly IMRT. This presentation will focus on the potential possibilities, the present knowledge and on the limitations in terms of physics and hardware for proton therapy of metastases and it will discuss how improvement of the technology with i.e. reduced spot size and collimated scanned beam may increase the usefulness of protons in treatment of metastases. SP-0375 Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence P. Ost 1 , D. Reynders 2 , K. Decaestecker 3 , V. Fonteyne 1 , N. Lumen 3 , A. De Bruycker 1 , B. Lambert 4 , L. Delrue 5 , R. Bultijnck 1 , E. Goetghebeur 2 , K. De Man 6 , G. De Meerleer 7 1 Ghent University Hospital, Radiation oncology, Gent, Belgium 2 Ghent University, Applied Mathematics- Computer Science and Statistics, Ghent, Belgium 3 Ghent University Hospital, Urology, Ghent, Belgium 4 Ghent University, Radiology and Nuclear Medicine, Ghent, Belgium 5 Ghent University Hospital, Radiology, Gent, Belgium 6 Ghent University Hospital, Nuclear Medicine, Ghent, Belgium 7 Ghent University, Radiation oncology, Gent, Belgium Purpose or Objective Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Material and Methods In this multicentre, randomised, phase II study, asymptomatic PCa patients were eligible in case of a biochemical recurrence following primary PCa treatment 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.

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 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

molecules distribution. Material and Methods

Mice with subcutaneous tumours received localised RT during 2 weeks, according to the following fractionation schedules: 2x12Gy, 3x8Gy, 6x4Gy, 10x2Gy. Two tumour