The Impact of Adjuvant Therapy Delay on Survival Following Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Abstract

Background: In this study we leveraged a large administrative database to investigate temporal and comparative effects of adjuvant chemotherapy (AC) and adjuvant chemoradiotherapy (ACRT) following pancreaticoduodenectomy (PD) for pancreas adenocarcinoma (PAC). Methods: NCDB was queried for patients with PAC who underwent PD between 2010-2018. Only patients with complete data were included. Patients who received neoadjuvant, as well as those who never received any adjuvant therapy, were excluded. Cox multivariable regression analyses were performed. Results: 8763 patients met inclusion criteria. Delay of ≥60-days to AC was seen in 39.1% of the patients. While early vs. delayed initiation of AC afforded no survival benefit to the margin-negative cohort (p=0.263), AC <60 vs. ≥60-days suggested a small survival benefit among margin-positive patients (No Delay-AC vs. Delay-AC, 16.6 vs 16.3 months), and when corrected for confounders this effect was significant (p=0.041, HR 0.845, 95%CI 0.704-0.998). In contrast, among margin-positive patients, ACRT with and without delay was associated with statistically identical outcome (No Delay vs. Delay, 19.9 vs 19.4 months, p=0.054), with similar results across margin-positive treatment subgroups after correcting for confounders (No delay-AC vs Delay-ACRT, p=0.74, HR 1.031, 95%CI 0.861-1.234). Conclusion: Delay of AC ≥60-days may be associated with worse survival in patients with positive margins following PD for PAC. This negative effect was not observed among margin-positive patients with a delay of ACRT ≥60-days. These findings suggest that consideration should be given to delivery of ACRT rather than AC in patients with positive margins when delay of adjuvant therapy ≥60-days cannot be avoided.