ESTRO 2020 Abstract Book

S242

ESTRO 2020

PD analyses demonstrate a significant reduction in PAR levels in PBMCs during olaparib treatment (>95% at +3hrs after olaparib intake for all dose levels, >90% at +12hrs in the 25mg BID dose level and 66-99% at +24hrs in the 25mg QD dose level; all p<0.0001). In pre-treatment samples, ex vivo radiation induced PAR levels by 66-fold (range 23- 174). This radiation induced PARylation was abolished during olaparib treatment. Compared to corresponding pre-treatment PBMC samples, PAR levels in pre-treatment tumor biopsy samples were higher in all but one patient (median 7-fold, range 0.6-60), and ex vivo radiation induced PARylation was lower (only 1.5-fold). Also, in tumors, olaparib abolished radiation induced PARylation. PAR levels were reduced by 89% (range 83-99.7%, Olaparib doses as low as 25mg once and twice daily inhibit PARP activation by irradiation and reduce PAR levels >95% in PBMCs and >83% in tumors, thereby showing biological effectivity. The tumor olaparib concentrations determined in this study were all within a range that has been shown to radiosensitize in preclinical models. Together this supports further development of PARP inhibitors as radiosensitizer at low doses. OC-0439 Quantifying the benefit of online adaptive radiotherapy for rectal cancer compared to plan selection R. De Jong 1 , J. Visser 1 , K. Crama 1 , N. Van Wieringen 1 , J. Wiersma 1 , D. Geijsen 1 , A. Bel 1 1 Amsterdam UMC, Radiation Oncology, Amsterdam, The Netherlands Purpose or Objective To assess the added value of online adaptive radiotherapy (online ART) for rectal cancer, by comparing online ART to a clinically implemented plan selection strategy (PS) and quantifying the benefit in terms of target coverage and dose to the organs at risk (OAR). p<0.0001). Conclusion

online ART (Figure 1). We calculated coverage as the percentage of the prescribed dose received by 99% of the CTV volume (D99%). We calculated the volume of normal tissue irradiated with 95% of the prescribed dose per fraction by calculating the difference of the volume receiving 95% of the prescribed dose minus the volume of the CTV and the volume of different DVH parameters on the OARs per fraction (V15Gy, V30Gy, V40Gy, V45Gy, V95% and Dmean).

Results In total, 10 short (SCRT) and 10 long (LCRT) course radiotherapy treatment schedules were included, resulting in 300 fractions for evaluation. Coverage, expressed as D99% remained the same. For the total cohort the median volume of the normal tissue irradiated with 95% of the prescribed dose dropped from 642 cm 3 (PS) to 237 cm 3 (online ART), which was statistically significant (Figure 2). Online ART reduced dose to the bowel bag and bladder for all tested dose levels significantly for both SCRT and LCRT. The average difference for bowel bag was -127 cm 3 for the volume receiving 0.6Gy per fraction in LCRT and -57 cm 3 the volume receiving 95% of the prescribed dose in SCRT. The average difference for bladder was -24% for the volume receiving 0.6Gy per fraction in LCRT and -9% and for the volume receiving 95% of the prescribed dose in SCRT. The average difference for the total cohort in Dmean for bladder was -7%. Conclusion Radiotherapy with online ART of locally advanced rectal cancer reduces dose to the bladder and small bowel significantly for large volumes, compared to a clinically implemented plan selection strategy.

Material and Methods For this study Conebeam CT (CBCT) scans of the first 20 consecutive patients treated with PS between May and September 2016 were included. New dual arc VMAT plans were generated using auto planning (Plan Explorer, Raystation) for both the online ART and the PS strategy. - For the PTV of the PS strategy the ventral margins were variable for the CTV of the upper part of the mesorectum, the remaining CTV had fixed population based margins. - The PTV margin for online ART was a 3mm expansion of the entire CTV in all directions. For each fraction bowel bag, bladder and mesorectum were delineated on the daily CBCT. The dose distribution planned was used to calculate daily DVHs for both PS and

Proffered Papers: Proffered papers 21: Protons

OC-0440 Proton Therapy Reduces Patient-Reported Adverse Events: A Neural Network for Large-Volume Practice T. DeWees 1 , M. Golafshar 2 , M. Petersen 2 , T.J. Whitaker 3 , A. Amundson 4 , K. Klein 4 , T. Pisansky 4 , B. Davis 4 , K. Corbin 4 , B. Stish 4 , C.R. Choo 4 , C. Hallemeier 4 , R. Mutter 4 , W. Wong 5 , I. Petersen 4 , S. Park 4 , T. Daniels 5 , L. McGee 5 , N. Laack 4 , A. Dueck 2 , C. Vargas 5 1 Mayo Clinic, Health Sciences Research- Radiation Oncology, Scottsdale, USA ; 2 Mayo Clinic, Health Sciences Research, Scottsdale, USA ; 3 Baylor University, Radiation