Dose escalation of radiation therapy with or without induction chemotherapy for unresectable locally advanced pancreatic cancer

BackgroundDose escalation of conventionally fractionated radiation therapy (CFRT) above 45-54Gy has an unclear survival benefit. Prior National Cancer Database (NCDB) analyses have shown improved overall survival with induction chemotherapy (iC) prior to concurrent chemoradiation (CRT) in locally advanced pancreatic cancer. Our study compared dose-escalated CFRT with and without iC.MethodsThe NCDB was queried for primary stage III, cT4N0-1M0 LAPC treated with CRT with or without iC (2004-2015). CFRT was stratified by <55Gy and55Gy. Cohort iC+CRT and CRT included those with and without iC, respectively. The primary endpoint was overall survival (OS). Kaplan-Meier analysis, Cox proportional hazards method, and propensity score matching were used.ResultsAmong 2029 patients, cohort iC+CRT had 738 patients (n=601 for 45-55Gy and n=137 for 55Gy) and cohort CRT had 1291 patients (n=1066 for 45-55Gy and n=225 for 55Gy). Median follow-up was 24.3months and 24.6months for cohorts iC+CRT and CRT, respectively. Dose escalation showed improved survival in the multivariable analysis in cohort iC+CRT (HR 0.77, p=0.013) but not in cohort CRT (HR 0.91, p=0.19). Using 2:1 propensity score matching, a total of 387 patients for cohort iC+CRT and 549 patients for cohort CRT were matched. After matching, dose escalation remained significant for improved overall survival in cohort iC+CRT (median OS 16.2 vs 15.2months; 2-yr OS 33.4% vs 25.4%; p=0.022) but not in cohort CRT (median OS 11.8 vs 10.6months; 2-yr OS 13.3% vs 10.1%; p=0.16).ConclusionsPatients with locally advanced pancreatic cancer who undergo iC have improved survival with radiation dose escalation above 55Gy. For patients without iC, there is no clear association between radiation dose escalation and survival.