Survival Outcomes of Patients With Borderline Resectable and Resectable Pancreatic Adenocarcinoma Treated With Neoadjuvant Short-Course Chemoradiotherapy With Capecitabine-Based vs. Gemcitabine-Based Concurrent Chemotherapy

PURPOSE/OBJECTIVE(S) Neoadjuvant chemoradiotherapy is a critical treatment for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). The PREOPANC trials employ a short course chemoradiation (SCCRT) regimen of 3600 cGy in 15 fractions with concurrent gemcitabine (GEM)-based chemotherapy, but little is known about the relative efficacy of capecitabine (CAPE)-based concurrent chemotherapy in this population. We hypothesize that patients treated with SCCRT with CAPE-based concurrent chemotherapy will have superior overall survival (OS) compared to GEM-based strategies. MATERIALS/METHODS Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC between 1/2005 and 12/2020. Patients treated with neoadjuvant SCCRT were included in the analysis. Descriptive statistics were quantified for baseline characteristics. OS was estimated using Kaplan-Meier estimates, statistical difference was determined using the log-rank test. Multivariate Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors. RESULTS Thirty-one (n = 31) patients were included in the analysis. 71% of patients (n = 22) were treated with CAPE-based concurrent chemotherapy, while 29% of patients (n = 9) were treated with GEM-based concurrent chemotherapy. Median age at diagnosis was 65 (interquartile range (IQR): 60 to 71) for the CAPE group, compared to 66 (IQR: 63 to 71) for the GEM group, P = 0.414. 100% of patients in the CAPE group were borderline resectable, compared to 82% of patients in the GEM group, P = 0.171. 44% of patients in the CAPE group were treated with neoadjuvant FOLFIRINOX, compared to 14% in the GEM group, P = 0.016. Patients treated with concurrent 5-CAPE-based chemotherapy had a longer median OS than other concurrent chemotherapy approaches: Not reached (95% confidence interval (CI): 24 to not reached) vs. 17 months (95% CI: 6 to 22 months), P < 0.0001. Multivariate Cox proportional hazards models, controlling for borderline vs. resectable status, age at diagnosis, and use of neoadjuvant FOLFIRINOX, demonstrated that CAPE-based concurrent chemotherapy had a HR of death of 0.081 (95% CI: 0.018 to 0.369, P = 0.0012) compared to GEM-based concurrent chemotherapy. CONCLUSION Patients diagnosed with (B)RPC have many therapeutic options; this study suggests a benefit to CAPE-based concurrent chemotherapy when treating patients with SCCRT, even after controlling for significant confounding by greater use of neoadjuvant FOLFIRINOX with CAPE-based concurrent chemotherapy. SCCRT may be more effective with concurrent capecitabine instead of concurrent gemcitabine for (B)RPC.