Chemotherapy with or without definitive radiation therapy in locally advanced pancreatic cancer.

Abstract

4103 Background: The recently reported LAP07 randomized trial calls into question the role of radiation therapy (RT) in the modern treatment of locally advanced pancreatic cancer (LAPC). However, advances in chemotherapy and RT limit application of the LAP07 results to current clinical practice. Here we utilize the National Cancer Database (NCDB) to evaluate the effects of RT in patients receiving chemotherapy for LAPC. Methods: Using the NCDB, patients with AJCC clinical stage T2-T4, N0-1, M0 adenocarcinoma of the pancreas from 2004-2014 were analyzed. Only those that received chemotherapy and did not undergo surgery were included. Patients were stratified into chemotherapy only (CT) and chemoradiation (CRT) cohorts. Patients undergoing definitive RT, defined as at least 20 fractions (fxs) or ≥ 5 Gy per fraction (i.e. SBRT) were included in the CRT cohort. Propensity-score matching (PSM) and landmark analysis were used to address selection bias and lead-time bias, respectively. The primary endpoint was overall survival (OS). Results: 13,004 patients met inclusion criteria, of which 7,034 (54%) received CT and 5,970 (46%) received CRT. After PSM, 5,215 patients remained in each cohort. Median follow-up was 22.6 months. The CRT group had younger median age (65 vs. 67) and less treatment at academic centers (44 vs. 51%); performance status was similar between groups. The median fractionated RT dose was 50.4 Gy in 28 fxs and SBRT dose was 24 Gy in 3 fxs. The CRT cohort demonstrated better OS compared with CT alone, with median and 1-yr OS of 12 vs. 10 months, and 50% and 41%, respectively (p < 0.001). On multivariable analysis, CRT was associated with superior OS with a hazard ratio (HR) of 0.79 (95% confidence interval (CI): 0.76-0.83, p < 0.001) compared with CT alone. The SBRT subgroup demonstrated the best survival (HR 0.71 [95% CI: 0.64-0.80], p < 0.001). OS was superior for CRT after PSM and for all patient subsets. Conclusions: In unresected LAPC, the addition of definitive radiotherapy to chemotherapy is associated with superior OS when compared with chemotherapy alone. Survival was greatest when SBRT was used. Definitive radiotherapy should remain a standard option for LAPC but optimal selection criteria remain unclear.