Improved Survival with Modified Folfirinox and Higher Doses of Stereotactic Body Radiation Therapy for Treatment of Locally Advanced Pancreatic Adenocarcinoma

Abstract

As higher doses of stereotactic body radiation therapy (SBRT) continue to show local control benefit, stronger regimens of systemic therapy have also shown to improve outcomes for locally advanced pancreatic adenocarcinoma (LPA). This study was completed to report the long-term impacts of modern chemotherapy and dose regimens of SBRT on survival outcomes of LPA. We reviewed the treatment characteristics and outcomes of all patients who received multi-fraction SBRT for LPA between February 2007 and August 2017 at our institution. SBRT for metastatic and locoregional recurrent cases were excluded. Disease progression was analyzed by computed tomography (CT), using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and when available, by positron emission tomography (PET). Cumulative incidences of local and distant failure (LF, DF) were calculated from date of diagnosis treating death as a competing risk, with Gray’s test to compare groups. Survival (OS) was calculated using Kaplan Meier method. A total of 115 patients were identified. Median follow-up was 15.3 months (range 5.3-47.3 months). Median age was 67 years (range 37-92 years). Median SBRT dose was 33 Gy (range 20-45 Gy) delivered in 5 fractions in 110 patients, and 3 or 6 fractions in 5 patients. 86 patients (74.8%) received gemcitabine-based chemotherapy and 29 (25.2%) received mFOLFIRINOX. For the whole group, median OS was 16.2 months (95% confidence interval [CI] 14-18 months), with a 1- and 2- year cumulative incidence of LF of 12.2% and 21.8%, respectively, and a 1- and 2- year cumulative incidence of DF of 41.5% and 59%, respectively. Higher SBRT doses (≥40 Gy) (n=34) and mFOLFIRINOX (n=27), each, was associated with superior OS; with patients who were treated with doses ≥40 Gy and mFOLFIRINOX (n=19) having significantly longer median OS compared with patients treated with gemcitabine-based regimen and/or SBRT doses <40 Gy (24 vs 15 months, P=0.002). DF rates for patients treated with higher SBRT doses (≥40 Gy) were lower compared to those who received lower SBRT doses (2 yr 46.1% vs 64.2% P=0.03). mFOLFIRINOX with an SBRT regimen of 40 Gy in 5 fractions is superior when compared to gemcitabine-based SBRT regimens using doses <40 Gy.