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

BACKGROUND: Dose escalation of conventionally fractionated radiation therapy (CFRT) above 45–54 Gy 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. METHODS: The NCDB was queried for primary stage III, cT4 N0–1 M0 LAPC treated with CRT with or without iC (2004–2015). CFRT was stratified by < 55 Gy and ≥ 55 Gy. 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. RESULTS: Among 2029 patients, cohort iC + CRT had 738 patients (n = 601 for 45–55 Gy and n = 137 for ≥55 Gy) and cohort CRT had 1291 patients (n = 1066 for 45–55 Gy and n = 225 for ≥55 Gy). Median follow-up was 24.3 months and 24.6 months 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 15.2 months; 2-yr OS 33.4% vs 25.4%; p = 0.022) but not in cohort CRT (median OS 11.8 vs 10.6 months; 2-yr OS 13.3% vs 10.1%; p = 0.16). CONCLUSIONS: Patients with locally advanced pancreatic cancer who undergo iC have improved survival with radiation dose escalation above 55 Gy. For patients without iC, there is no clear association between radiation dose escalation and survival.