Intraoperative Radiation Mitigates the Effect of Microscopically Positive Tumor Margins on Survival Among Pancreatic Adenocarcinoma Patients Treated with Neoadjuvant FOLFIRINOX and Chemoradiation.

Background: Microscopically positive margins (R1) negatively impact survival in pancreatic ductal adenocarcinoma (PDAC). For patients with close/positive margins, intraoperative radiotherapy (IORT) can improve local control. The prognostic impact of an R1 resection in patients who receive total neoadjuvant therapy (TNT; FOLFIRINOX with chemoradiation) and IORT is unknown.
Methods: Clinicopathologic data were retrospectively collected for borderline/locally advanced (BR/LA) PDAC patients who received TNT and underwent resection between 2011 and 2019. Disease-free (DFS) and overall survival (OS) measured from time of diagnosis were compared between groups.
Results: Two hundred one patients received TNT and were resected, with a median DFS and OS of 24 months and 47 months, respectively. Eighty-eight patients (44%) received IORT; of these, 69 (78%) underwent an R0 and 19 (22%) an R1 resection. There was no significant difference in clinicopathologic factors between the IORT and no-IORT groups, except for resectability status (LA: IORT 69%, no-IORT 53%, p = 0.021) and surgeons' concern for a positive/close margin. R1 resection was associated with worse DFS and OS in the no-IORT population. However, among patients who received IORT, there was no difference in DFS (R0: 29 months, IQR 14-47 vs R1: 20 months, IQR 15-28; p = 0.114) or OS (R0: 48 months, IQR 25-not reached vs R1: 37 months, IQR 30-47; p = 0.307) between patients who underwent R0 vs R1 resection. In multivariate analysis, within the IORT group, R1 resection was not associated with DFS or OS.
Conclusion: IORT may mitigate the adverse effect of an R1 resection on DFS and OS in BR/LA PDAC patients receiving TNT.