Pre-treatment Neutrophil to Lymphocyte ratio (NLR) is a Prognostic Biomarker for Overall Survival in Localized Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy

Abstract

High neutrophil-to-lymphocyte ratio (NLR), as measured on peripheral complete blood count (CBC), has been studied as a biomarker related to tumor aggressiveness and overall prognosis, given the known role of inflammation in the pathogenesis and progression of cancer and health. Studies have demonstrated NLR as a prognostic marker associated with inferior outcomes in NSCLC treated with surgery, however NLR has been less studied in the setting of lung SBRT. It is believed that tumors with an unfavorable prognosis may promote or be associated with excess inflammation. We hypothesized that high pre-treatment NLR may be associated with inferior outcomes in localized NSCLC treated with stereotactic body radiotherapy (SBRT). This is a retrospective chart review of patients diagnosed with localized NSCLC treated with SBRT at our institution between 2008 and 2017. The NLR was calculated from CBC values (absolute neutrophil and lymphocyte counts) obtained within 6 months before starting treatment. The primary outcome was overall survival (OS), calculated from last SBRT treatment to last follow up or date of death. Secondary outcomes were primary tumor, lobar, nodal and distant failure. Cox regression univariate analysis was used to assess the association between OS and CBC parameters, which were dichotomized as high and low by the median. A total of 161 patients and 170 treated tumors were included. One hundred twenty (70.6%) tumors were T1, 38 (31.7%) were T2, 6 (5%) were T3, and 6 (5%) were T4 (T3/4 tumors were classified due to having 2 separate nodules). Median follow-up was 14.3 months. Median SBRT total dose, dose per fraction, and number of fractions was 50 Gy, 10 Gy and 5 fractions respectively. Median NLR of the cohort was 3.5 (range 0.18 to 41.8). Higher pre-treatment NLR was significantly associated with worse OS (HR=2.0, 95% CI 1.2-2.9, p=0.004). However, elevated NLR was not found to be statistically significant for secondary outcomes of failure, including primary tumor (p=0.81), lobar (p=0.13), regional (p=0.44) or distant failure (p=0.35). A CBC is a routinely ordered laboratory test that can serve a novel function in potentially prognosticating patients with localized NSCLC treated with SBRT. We identified that high pre-treatment NLR is associated with worse overall survival in patients treated with SBRT. These findings require validation in a large, independent patient cohort.