Increased neutrophil-to-lymphocyte ratio after neoadjuvant therapy is associated with worse survival after resection of borderline resectable pancreatic ductal adenocarcinoma

Abstract

Background: The neutrophil-to-lymphocyte ratio (neutrophil count divided by lymphocyte count) is a marker of inflammation associated with poor cancer outcomes. The role of neutrophil-to-lymphocyte ratio in borderline resectable pancreatic ductal adenocarcinoma is unknown. We hypothesized that increased neutrophil-to-lymphocyte ratio in patients with borderline resectable pancreatic ductal adenocarcinoma after neoadjuvant therapy is inversely associated with survival.

Methods: We used our borderline resectable pancreatic ductal adenocarcinoma database to identify patients who had completed neoadjuvant therapy and underwent resection. The neutrophil-to-lymphocyte ratio difference was calculated as the neutrophil-to-lymphocyte ratio after neoadjuvant therapy minus the neutrophil-to-lymphocyte ratio before neoadjuvant therapy. Patients were assigned to the increased neutrophil-to-lymphocyte ratio cohort if the difference was ≥2.5 units; all others were assigned to the stable neutrophil-to-lymphocyte ratio cohort. Statistical analyses were performed with t test and regression.

Results: Of 62 patients identified, 43 were assigned to the stable neutrophil-to-lymphocyte ratio cohort, and 19 to the increased neutrophil-to-lymphocyte ratio cohort. There were no differences in stage, age, or sex. The preneoadjuvant neutrophil-to-lymphocyte ratio was 3.1 ± 2.4, whereas the postneoadjuvant neutrophil-to-lymphocyte ratio was 4.4 ± 3.5 (P = .002). Overall survival was worse in the increased neutrophil-to-lymphocyte ratio cohort compared with the stable neutrophil-to-lymphocyte ratio cohort (P = .009) with a Cox hazard ratio of 2.9 (P = .02). N0 disease conferred a survival advantage over N1 disease (Cox hazard ratio = 0.3, P = .01). On multivariate Cox hazard regression analysis, both increased neutrophil-to-lymphocyte ratio and N1 stage were associated with worse survival (P < .01).

Conclusion: This investigation shows an independent, inverse association between survival and decreased neutrophil-to-lymphocyte ratio in patients with borderline resectable pancreatic ductal adenocarcinoma. These findings support exploring predictive inflammatory biomarkers, such as neutrophil-to-lymphocyte ratio, to investigate inflammation and improve outcomes.