Optimal Threshold of Neutrophil-Lymphocyte Ratio and its Association with Survival Outcome Among Patients with Head and Neck Cancer in the United States

Abstract

<h3>Purpose/Objective(s)</h3> Given the role of inflammation in cancer progression, neutrophil-lymphocyte ratio (NLR) from peripheral blood has been suggested as a read-out of systemic inflammation and a prognostic marker in several solid malignancies. However, optimal threshold for NLR in North American head and neck cancer patients remains unclear. We performed an observational cohort study to determine the optimal NLR threshold as a prognostic biomarker for survival outcomes. <h3>Materials/Methods</h3> A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent radiation therapy from January 2005 to April 2021. A threshold for NLR was determined by Cox proportional hazard model for OS using restricted cubic splines (RCS), and patients were then stratified into two cohorts by above versus below the model-derived threshold for their NLR. Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze overall survival (OS) and disease-specific survival (DSS) outcomes. Logistic MVA was performed to identify variables associated with elevated NLR. To reduce selection bias, propensity score matching was used based on nearest neighbor method in a 1:1 ratio without replacements. <h3>Results</h3> A total of 753 patients were included for analysis. Median follow up was 29.7 months (interquartile range 17.8-57.8). Cox MVA using RCS showed a threshold of NLR at 4.82, with worsening OS in a continuous fashion without plateau as NLR increases. High NLR above 4.82 was associated with worse OS (adjusted hazards ratio [aHR] 1.73, 95% confidence interval [CI] 1.26-2.37, p<0.001) and DSS (aHR 1.77, 95% CI 1.22-2.56, p=0.003). Similar findings were noted in 103 matched pairs (OS: aHR 1.85, 95% CI 1.19-2.90, p=0.007; DSS: aHR 1.91, 95% CI 1.11-3.28, p=0.02). On logistic MVA, patients were more likely to have high NLR if they had a higher T staging (adjusted odds ratio [aOR] 1.75, 95% CI 1.14-2.73, p=0.01), but less likely if they had a good performance status (aOR 0.45, 95% CI 0.29-0.69, p<0.001). Among 466 patients with available HPV data, high NLR was not associated with OS (aHR 1.38, 0.89-2.15, p=0.15) and DSS (aHR 1.15, 95% CI 0.67-1.97, p=0.62). <h3>Conclusion</h3> High NLR based on a model-derived threshold was associated with worse survival. Patients with significant primary disease burden and poor performance status were more likely to have high NLR. Further studies would be warranted to investigate the role of such prognostic marker to identify patients at risk to tailor interventions.