Vasculitis Associated with Preoperative Cheomoradiation Therapy for Pancreatic Cancer: A Preliminary Analysis

Abstract

Introduction: Despite the widespread use of neoadjuvant chemotherapy (NAC) or neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer, little is known about its effects on vascular structures and surgical outcomes. In this study, we attempted to identify the primary loci of inflammation by conducting a pathological evaluation. Clinicopathological and transcriptome analysis were also performed to characterize vasculitis-associated changes. Methods: Patients who underwent preoperative NACRT between 2014 and 2019 were retrieved and specimens were subjected to pathologic evaluation and gene expression analysis. A total of 31 and 30 patients were included in the NACRT group and the NAC group, respectively. Results: All NACRT patients had preoperative SBRT of 30-33 Gy/5 fractions. Vascular inflammation or vasculitis (defined as vascular-associated myxoid change, vascular lymphocyte/macrophage infiltration) were more frequently observed in the RT group (38.7% vs 16.7%, p=0.067, HR: 3.2, CI 0.9-12.1). Within the NACRT group, subgroup analysis showed that longer “Duration from NAC to surgery” and “Postoperative complication > grade2” correlated with increased risk for vasculitis ([108.2 vs 85.0 days (median), p=0.017 ] and 66.7% vs 30%, p=0.027, HR: 5.3 CI 1.16-27.1], respectively). Gene set enrichment analysis(Subramanian et al. 2005) showed inflammation-related sets were up-regulated in the vasculitis group as defined by histopathologic features. Conclusion: Our preliminary analysis shows more vasculitis was observed in the NACRT group. RNAseq analysis suggested that the inflammatory pathway was up-regulated with histopathological evidence of vasculitis. The presence of vasculitis in the RT group correlated with postoperative complications. This suggests that vasculitis associated with NACRT might affect the surgical outcomes.