A comparison of outcomes for patients with localized pancreatic ductal adenocarcinoma receiving neoadjuvant chemotherapy with and without radiation prior to curative-intent resection: an analysis of the National Cancer Database.

BACKGROUND: Neoadjuvant chemotherapy has been demonstrated as playing a key role in improving the prognosis of patients receiving surgical resection for local pancreatic ductal adenocarcinoma (PDAC) when compared to up-front surgery. However, the addition of radiation to chemotherapy remains controversial. As such, our study aims to characterize differences in characteristics and outcomes for patients receiving neoadjuvant chemotherapy with radiation (NCR) versus those receiving neoadjuvant chemotherapy alone (NC).

METHODS: We conducted a retrospective analysis of the National Cancer Database (NCDB) from 2015 to 2020. Patients with localized PDAC (stages I-III) who received neoadjuvant chemotherapy and curative-intent resection were included. Individuals were classified into NC and NCR cohorts based on the treatment they received, with NCR being defined as radiation starting at least 30 days after chemotherapy commencement. Patients receiving adjuvant chemotherapy were included. Univariate models assessed for heterogeneity between cohorts for demographic and tumor characteristics. Multivariate logistic regressions and propensity-matched Cox proportional hazards models assessed for treatment outcomes and survival analysis, respectively. Kaplan-Meier curves were generated to visualize survival between cohorts. Linear regressions quantified utilization trends for these two cohorts as well.

RESULTS: This study included 6,472 patients total (NCR: 2,117; NC: 4,355). The NCR patients were younger (64.6 vs. 65.8 years, P<0.001), had differences in tumor primary site (P<0.001), clinical and pathologic staging (P<0.001), and Charleson-Deyo comorbidity score (P<0.001). On multivariate analysis, the NCR cohort had higher odds of tumor downstaging [odds ratio (OR) =2.15, 95% confidence interval (CI): 1.70-2.71, P<0.001], lower odds for pathologic node status (OR =0.42, 95% CI: 0.38-0.48, P<0.001), and lower odds of receiving adjuvant chemotherapy (OR =0.56, 95% CI: 0.49-0.64, P<0.001) but no difference in R0 resection was noted (OR =0.95, 95% CI: 0.80-1.12, P=0.52). Propensity-matched models revealed that NCR was associated with improved overall survival (OS) when compared to NC [hazard ratio (HR) =0.88, 95% CI: 0.80-0.97, P=0.01]. Lastly, the NC cohort had an increase of +166.7 cases/year (P<0.001), but the NCR cohort did not show a significant trend (+35.1 cases/year, P=0.07) from 2015-2020.

CONCLUSIONS: In patients with localized PDAC who receive curative-intent resection, the addition of radiation to neoadjuvant chemotherapy is associated with improved tumor downstaging, negative node status, and superior survival outcomes. As such, our work supports the use of radiation in the neoadjuvant setting to supplement chemotherapy and highlights further evaluation of its benefits.