Post-treatment Neutrophil-to-Lymphocyte Ratio as a Predictor of Overall Survival in Melanoma Brain Metastases treated with Stereotactic Radiosurgery

Abstract

Systemic inflammation is known to play an important role in the progression of cancer. Specifically, an increase in the neutrophil-to-lymphocyte ratio (NLR) has been associated with shorter survival in patients with various malignancies; however, this effect has yet to be elucidated for patients with melanoma brain metastases (MBM). Pathology reviews have shown that stereotactic radiosurgery (SRS) results in a leukocyte predominant inflammatory response. The aim of this study is to investigate if NLR is associated with outcomes of patients with MBM treated with SRS. After IRB approval, patients with MBM treated with SRS from 2005-2013 were retrospectively identified. NLR was calculated from full blood counts obtained from the most proximal follow-up examination following SRS. Overall survival and intracranial outcomes were calculated using the Kaplan-Meier method and cumulative incidence with competing risk for death, respectively. Multivariable Cox models were applied to adjust for confounders. Seventy-seven consecutive patients with 138 MBM received SRS for which post-treatment NLR could be calculated. Of these, 50 patients (64.9%) with 90 MBM (65.2%) had a NLR <5. The cutoff point of 5 was chosen for NLR based on results from prior studies. Baseline patient characteristics, including active systemic disease and controlled primary, were well balanced, with only lower rates of prior immune therapy (48% vs. 22%, P = 0.002) in the NLR ≥5 cohort being different. SRS treatment parameters, including number of fractions, total dose, margin size, and treatment volume (GTV and PTV), were similarly well balanced. The median time to death or last imaging follow-up was 9.12 months overall (6.8 vs. 10.2 months for NLR ≥5 vs. NLR <5). A statistically significant (P = 0.004) survival advantage was seen in patients with a NLR <5 at 6 (81.4% vs. 61.3%), 12 (54.2% vs. 26.3%), and 24 months (35.7% vs. 11.7%). Post-SRS NLR (P = 0.005) and prior immune therapy (P = 0.014) were significant on univariate analysis. Multivariable analysis confirmed that post-SRS NLR ≥5 predicted for worse survival (Hazard Ratio: 2.02; 95% confidence interval, 1.16-3.54, P = 0.013), while prior immune therapy was no longer significant. No statistically significant differences were noted in 1-year local failure (8.1% vs. 11.2%), distal failure (66.3% vs. 72.9%), or radiation necrosis (9.3% vs. 16.0%) between NLR <5 and ≥5. The post-treatment NLR value, a potential marker for post-SRS inflammatory response, is inversely associated with survival for MBM treated with SRS. If prospectively validated, NLR could be deployed as a predictive biomarker and as a stratification and/or eligibility variable in clinical research.