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

PURPOSE: 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. METHODS: 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 %). RESULTS: 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 %. CONCLUSION: 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.