High neutrophil-to-lymphocyte ratio following stereotactic body radiation therapy is associated with poor clinical outcomes in patients with borderline resectable and locally advanced pancreatic cancer

Background: The purpose of this study is to report on the prognostic role of pre- and post-stereotactic body radiation therapy (SBRT) neutrophil-to-lymphocyte ratio (NLR) in a cohort of patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) who was treated with multi-agent induction chemotherapy followed by five-fraction SBRT. Methods: Patients treated with multi-agent induction chemotherapy followed by SBRT from August 2016 to January 2019 and who had laboratory values available for review were included in the study. Univariate (UVA) and multivariate analyses (MVA) were performed to determine associations between pre-/postSBRT NLR and overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Results: A total of 156 patients were treated with multi-agent induction chemotherapy followed by SBRT and had laboratory values available for review. On UVA, chemotherapy duration ≥4 months, poorly differentiated disease, inability to undergo resection, pre-SBRT ANC ≥3.7 No./μL, pre-SBRT NLR ≥2.3, and post-SBRT NLR ≥2.6 were associated with worse OS. Patients with post-SBRT NLR ≥2.6 had a median OS of 16.7 months versus median OS not yet reached in patients with post-SBRT <2.6 (P=0.009). On MVA, poorly differentiated disease [hazard ratio (HR) =1.82, 95% CI: 1.04–3.18, P=0.035], inability to undergo resection (HR =2.17, 95% CI: 1.25–3.70, P=0.006), and post-SBRT NLR ≥2.6 (HR =2.55, 95% CI: 1.20–5.45, P=0.015) were associated with inferior OS. On UVA, baseline CA 19-9 ≥219 U/mL, pre-SBRT platelet count ≥157×1,000/μL, and post-SBRT NLR ≥2.6 were associated with inferior LPFS. Patients with post-SBRT NLR ≥2.6 had a median LPFS of 18.3 months versus median LPFS not yet reached in patients with post-SBRT <2.6 (P=0.028). On MVA, only post-SBRT NLR ≥2.6 was associated with worse LPFS (HR =3.22, 95% CI: 1.04–9.98, P=0.043). Conclusions: Post-SBRT NLR ≥2.6 predicted for inferior OS and LPFS in BRPC/LAPC patients treated with multi-agent chemotherapy and SBRT. These findings highlight the importance of further elucidating the immunologic effects of radiation therapy in this setting, which may have significant implications on both radiation design as well as combination strategies.