Multimodal Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma (PDAC) With Vascular Involvement: What Is the Impact of Radiation on Perioperative Outcomes, Local Control, and Survival?

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ABSTRACT Objectives Neoadjuvant chemoradiation for PDAC with vascular invasion remains understudied. The aim of this study is to compare neoadjuvant chemotherapy with chemoradiation (NAC + CRT) versus neoadjuvant chemotherapy (NAC) for PDAC with vascular involvement. Methods The National Cancer Database was reviewed between 2018 and 2023, including patients with T4 PDAC initiating NAC or NAC + CRT. The primary outcome of overall survival (OS) was examined among unresected and resected cohorts. Secondary outcomes included pathologic complete response (pCR), node‐negative (ypN0) pathology, and R0 resection. Multilevel logistic and Cox models were fit to identify factors associated with outcomes. Results In total, 2950 patients met inclusion, of which 1407 (47.7%) underwent NAC + CRT. In total, 1291 (44.4%) underwent surgery. Use of NAC + CRT declined by 2.8%/year ( p < 0.001). Compared with NAC, use of NAC + CRT was associated with R0 resection (OR: 0.62, 95% CI: [0.43, 0.89], p = 0.010) and ypN0 (OR: 2.19, 95% CI: [1.63, 2.93], p < 0.001) but not pCR (OR: 1.78, 95% CI: [0.99, 3.20], p = 0.056). NAC + CRT was associated with improved OS among the full cohort (hazard ratio [HR]: 0.67, 95% CI: [0.60, 0.74], p < 0.001) but not the resected cohort (HR: 0.98, 95% CI: [0.81, 1.19], p = 0.848). Conclusions Neoadjuvant chemoradiation for T4 PDAC yielded mixed effects on local response with no survival difference among patients undergoing resection.