Prognostic Nomograms in Oral Squamous Cell Carcinoma: The Negative Impact of Low Neutrophil to Lymphocyte Ratio

Objectives: To investigate the prognostic significance of preoperative neutrophil to lymphocyte ratio (NLR) and the impact of different clinical-pathologic factors in a series of primary oral squamous cell carcinomas (OSCC). Materials and Methods: All naive OSCCs treated with upfront surgery between 2000 and 2014 were retrospectively reviewed. Patients with distant metastasis, synchronous head and neck cancer, immunological disorders, or who had received previous chemotherapy and/or radiation of the head and neck area were excluded. The main outcomes were overall (OS), disease-specific (DSS), loco-regional free (LRFS), and distant metastasis free (DMFS) survivals. Univariate (Kaplan-Meier) and multivariate (Cox regression model) analysis were performed, and nomograms developed for each outcome. NLR was analyzed as a continuous variable using restricted cubic spline multivariable Cox regression models. Results: One-hundred-eighty-two patients were included. Five-year estimates for LRFS, DMFS, DSS, and OS were 67, 83.7, 69.5, and 61.2%, respectively. NLR had a complex influence on survival and risk of recurrence: negative for very low and high values, while positive in case of intermediate ratios. At univariate analysis, T classification, 7th AJCC stage, nodal metastasis, perineural spread, and lymphovascular invasion were statistically significant. At multivariate analysis, extranodal extension (ENE) and perineural spread were the most powerful independent prognostic factors. NLR was an independent prognosticator for the risk of recurrence. In nomograms, NLR and ENE had the strongest prognostic effect. Conclusions: In OSCC, very low preoperative NLR values have a negative prognostic impact on survival and recurrence, similarly to high ratios. ENE and perineural spread are the most important clinical-pathologic prognosticators.