Impact of treatment sequence and dose response on outcomes in locally advanced pancreatic cancer treated with hypofractionated proton beam therapy using simultaneous integrated boost technique.

Abstract

To evaluate the efficacy and safety of hypofractionated simultaneous integrated boost (SIB) - proton beam therapy (PBT) with systemic treatment and also to explore survival-related prognostic factors, including treatment sequencing and dose-response. We reviewed 225 consecutive patients with LAPC treated with SIB-PBT (45-50 Gy[RBE] for PTV1 and 30 Gy[RBE] for PTV2 in 10 fractions). The patients were grouped by treatment sequence as follows: PBT after stable disease post-induction chemotherapy (Group I, 48.9 %), PBT after progression post-induction chemotherapy (Group II, 15.6 %), and PBT followed by maintenance chemotherapy (Group III, 35.6 %). Median overall survival (OS) from first treatment and PBT was 24.2 (95 % CI, 21.7-26.7) and 19.5 (95 % CI, 17.4-21.7) months, respectively. Group I had significantly longer OS than Groups II and III from first treatment (31.1 vs. 21.1 and 19.1 months) and PBT (23.7 vs. 9.9 and 19.1 months) (p < 0.05 each). Patients receiving 50 Gy(RBE) had significantly better OS from first treatment (25.6 vs. 19.3 months; p = 0.001) and a trend towards better OS from PBT (20.3 vs. 18.3 months; p = 0.062). Most acute adverse events were grade 1-2, with late grade ≥ 3 gastrointestinal events in 4 %. This largest to-date study on PBT for LAPC suggests that hypofractionated SIB-PBT could be a safe and effective local treatment for LAPC. Favorable outcomes were observed with PBT after stable disease following induction chemotherapy, and a potential dose-response relationship was suggested. However, further prospective studies are required to validate our findings.