E. S. Glazer1, O. Rashid1, J. Pimiento1, P. J. Hodul1, M. P. Malafa1 1Moffitt Cancer Center,Gastrointestinal Oncology,Tampa, FL, USA
Introduction: The neutrophil to lymphocyte ratio (NLR, neutrophil count divided by lymphocyte count) is a marker for systemic inflammation and has been studied as a prognostic biomarker in numerous cancers. An NLR value greater than ~3-5 is associated with systemic inflammation. We hypothesized that changes to this ratio in patients undergoing neoadjuvant therapy for borderline pancreatic carcinoma would be predictive of long term survival after resection.
Methods: All patients in our borderline resectable pancreatic carcinoma database (2006-13) were included if they completed neoadjuvant chemoradiotherapy, underwent resection, and complete data was available. Neoadjuvant chemotherapy usually consisted of gemcitabine, docetaxel, & capecitabine while radiotherapy was usually 40 Gy with SBRT. The difference in NLR was calculated as the NLR before surgery (after neoadjuvant therapy) minus the NLR before neoadjuvant therapy. A clinically significant increase in NLR was defined as an increase by 2.5 or more units while any differences less than 2.5 units (including negative differences) were defined as stable NLR. Statistical significance was α = 0.05, survival was investigated with the Kaplan-Meier method, and uncertainties are standard deviations.
Results: 58 patients were identified; all patients completed neoadjuvant therapy and 97% had R0 margins. The mean age was 65 ± 9 years; 60% were male. The mean pre-neoadjuvant NLR was 3.1 ± 2.4 while the mean post-neoadjuvant/pre-surgical NLR was 4.4 ± 3.5. Overall survival was significantly worse in the increased NLR group compared to the stable NLR group (see figure, P = 0.009) with a Cox hazard ratio of 2.9 (P = 0.02). There were no significant differences in age, gender, tumor location, or Ca19-9 levels between the 2 groups. Survival was not associated with adjuvant chemotherapy administration (P = 0.4) or AJCC tumor stage (P = 0.9), but N0 disease conferred a survival advantage over N1 disease (Cox hazard ratio = 3.0, P = 0.01). There was no association between changes in NLR and nodal stage (P = 0.8). On multivariate Cox regression analysis, both increased NLR and N1 disease remained independent predictors of worse survival (P < 0.008 for both).
Conclusion: This is the first investigation demonstrating an independent, inverse association between survival and increase in NLR after neoadjuvant therapy followed by resection for patients with borderline resectable pancreatic carcinoma. We theorize that a pro-inflammatory state is related to worse survival despite a high rate of R0 resections. It is unclear if modulation of inflammation will improve survival in patients with pancreatic carcinoma, but we are actively investigating this in the laboratory.
