Post-operative radiation effects on lymphopenia, neutrophil to lymphocyte ratio, and clinical outcomes in palatine tonsil cancers

Objective: To evaluate radiation-induced lymphopenia associated with unilateral vs. bilateral neck radiation and to test post-treatment neutrophil to lymphocyte ratio (NLR) as a prognostic clinical biomarker. Methods: This was a single academic center retrospective review of palatine tonsil squamous cell cancer patients treated with post-operative intensity modulated radiation therapy (IMRT) from 1997 to 2013. Absolute lymphocyte count (ALC) and NLR were evaluated during and after radiation for up to a year. Correlations of lab values with loco-regional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were assessed. Results: Ninety-nine patients with median follow up 5.8 years had ALC recorded at least at baseline and within one year of starting RT. Acute grade 3-4 lymphopenia (< 10 weeks from RT start) occurred in 79% of bilateral neck RT patients (n = 70) and 58% of unilateral neck RT patients (n = 29), p = 0.03. There was no significant difference in late grade 3-4 (p = 0.12) lymphopenia. In a multivariable Cox regression model, acute NLR > 11.875 correlated with worse OS (HR = 4.4, 95% CI 1.2-16). Late NLR > 6.875 independently correlated with significantly worse FFDM (HR = 16, 95% CI 1.9-137) and OS (HR = 12, 95% CI 3.0-48). Conclusions: Unilateral neck radiation may prevent acute iatrogenic immunosuppression. In exploratory analyses, elevated post-treatment NLR was associated with risk for distant metastases and death.