Objective: The purpose of this study was to investigate the role of pre and post-stereotactic body radiation therapy (SBRT) neutrophil-to-lymphocyte ratio (NLR) in a cohort of patients with borderline resectable and locally advanced pancreatic adenocarcinoma (BRPC/LAPC) who was treated with multi-agent induction chemotherapy followed by anti-programmed cell death protein-1 (PD-1) antibody and SBRT.

Methods: Patients with BRPC/LAPC who were treated multi-agent induction chemotherapy followed by anti-PD-1 antibody and SBRT and had laboratory values available for review were included in the study. Median pre and post-SBRT laboratory values were compared with the Mann-Whitney U test. Univariate (UVA) and multivariable analyses (MVA) were performed to identify variables associated with clinical outcomes. Linear regression was performed to determine correlations between variables and laboratory values.

Results: A total of 68 patients were included in the study. The percent change between median pre and post-SBRT absolute lymphocyte count (ALC), absolute neutrophil count, and NLR were -44.0% (p<0.001), -10.0% (p=0.190), and +43.2% (p=0.003), respectively. Median overall survival (OS) after SBRT was 22.4 months, with 1-year, 2-year, and 3-year OS rates of 66.9%, 47.3%, and 28.2%, respectively. On UVA, pre-SBRT CA 19-9 (hazard ratio [HR]=1.00, 95% CI 1.00-1.00, p=0.031), post-SBRT ALC (HR=0.33, 95% CI 0.11-0.91, p=0.031), and post-SBRT NLR (HR=1.13, 95% CI 1.04-1.22, p=0.009) were associated with OS. On MVA, induction chemotherapy duration (HR=0.75, 95% CI 0.57-0.99, p=0.048) and post-SBRT NLR (HR=1.14, 95% CI 1.04-1.23, p=0.002) were significant predictors of OS. The optimal post-SBRT NLR threshold in predicting OS was 3.2. Patients with post-SBRT NLR > 3.2 had a median OS of 15.6 months versus 27.6 months in patients with post-SBRT NLR < 3.2 (p=0.009). On MVA linear regression, log10CTV had a significant negative correlation with post-SBRT ALC (regression coefficient: -0.314, 95% CI -0.626 to -0.003, p=0.048).  

Conclusion: Elevated NLR after SBRT is primarily due to depletion of lymphocytes and associated with worse survival outcomes in BRPC/LAPC treated with anti-PD-1 antibody. Larger CTVs were associated with decreased post-SBRT lymphocyte count.