Portal venous circulating tumor cells as a biomarker for relapse prediction in resected pancreatic cancer.

Abstract

Background: Pancreatic cancer is an aggressive disease with poor prognosis. The only potentially curative treatment option is surgical resection, however recurrence is common. Biomarkers to detect minimal residual disease, assist with risk stratification, relapse and real time monitoring, are required. Circulating tumor cells (CTCs) are a promising liquid biopsy biomarker for solid tumors. However, their role in monitoring minimal residual disease in pancreatic cancer remains to be determined. Our study aimed to investigate whether detection and enumeration of CTCs could predict recurrence and provide monitoring of disease status.

Method: Participants planned for Whipple procedure or partial pancreatectomy were enrolled in this prospective pilot study. Intraoperatively, 7.5 mL of portal and peripheral venous blood were collected, and peripheral venous blood was also collected post-surgery. CTC identification and enumeration were performed using the AccuCyte-CyteFinder platform and CellSieve microfiltration.

Results: Of 29 participants, 20 were confirmed to have epithelial cancer by histopathology, where 15 had pancreatic ductal adenocarcinoma. In those with epithelial cancer, CTCs were detected intraoperatively in 75% of portal venous blood samples, in contrast to 40% detected in peripheral venous blood (median: 6 and 0 per 7.5mL respectively). Only portal venous CTC detection was predictive of pancreatic ductal adenocarcinoma relapse. The positive (> 5) portal venous CTC group had a 6.67 times higher risk of recurring (odds ratio = 20.43, sensitivity = 1.00, specificity = 0.625). Detection of peripheral venous CTCs post-surgery was also correlated with relapse in a small subset of patients.

Conclusions: If validated, CTCs may provide a prognostic and monitoring biomarker in patients with pancreatic cancer undergoing surgery.