Intensified systemic therapy and stereotactic ablative radiotherapy dose for patients with unresectable pancreatic adenocarcinoma

Purpose: We aimed to report the long-term impact of modern chemotherapy and SABR dose regimens on oncologic outcomes of unresectable pancreatic adenocarcinoma (PA). Materials and methods: We reviewed the treatment characteristics and outcomes of all patients who received multi-fraction SABR for unresectable PA between February 2007 and August 2018 at our institution. Time-to-events were calculated from date of diagnosis treating death as a competing risk. Results: A total of 149 patients were identified. Median follow-up was 15 months (range: 5–47). Median SABR dose was 33 Gy (range: 20–45) delivered in 5 fractions in 143 patients, and 3 or 6 fractions in 6 patients. 107 patients (72%) received gemcitabine-based chemotherapy while 31 (21%) received modified FOLFIRINOX (mFFX). Median OS was 16 months (95% CI, 14–17), with a 1-year cumulative incidence of LF of 14%. The combination of SABR doses ≥40 Gy and mFFX (n = 21) showed a superior PFS and OS to the use of GEM-based chemotherapy with <40 Gy SABR doses (median PFS: 14 vs. 10 months, HR: 0.46, 95% CI: 0.29–0.71, P = 0.003; median OS: 24 vs. 14 months, HR: 0.36, 95% CI: 0.22–0.59, P = 0.002), with 1-year PFS and OS of 67% and 90% compared to 35% and 59% for those who received GEM-based chemotherapy with <40 Gy SABR doses, respectively. Conclusions: The use of mFFX and a SABR dose ≥40 Gy in 5 fractions may be superior compared to regimens that utilize gemcitabine-based chemotherapy or SABR doses <40 Gy.