Neutrophil-to-Lymphocyte Ratio in Laryngeal SQCC Treated by Radiotherapy: Prognostic and Predictive Value

Laryngeal squamous cell carcinoma (SQCC), in both early and advanced stages, is often treated non-surgically with definitive-intent radiotherapy or chemoradiotherapy. In advanced-stage disease, uninvolved lymphatic structures of the neck are electively irradiated, whereas in early-stage disease the larynx alone is irradiated. The neutrophil-to-lymphocyte ratio (NLR) has been implicated as a prognostic marker in head and neck SQCC. As lymphocytes are extremely radiosensitive, the absolute lymphocyte count (ALC) may fluctuate during and after radiotherapy, and consequently, the NLR may vary across these time points. This study aimed to evaluate dynamic changes in NLR, ALC, and absolute neutrophil count (ANC) during and after radiotherapy and to assess their association with oncologic outcomes in patients with laryngeal SQCC. We retrospectively reviewed the charts of patients treated with definitive-intent radiotherapy or chemoradiotherapy for laryngeal carcinoma at our institution between 2015 and 2021. NLR, ANC, and ALC values were recorded at three time points: treatment initiation, treatment completion, and three to six months after treatment completion. Oncologic outcomes were also recorded. A total of 174 patients treated for laryngeal SQCC were included. The mean NLR level was significantly higher at treatment completion than at treatment initiation (6.23 ± 4.61 vs. 3.12 ± 3.32, P < 0.001) and was significantly lower at 3-6 months after treatment than at treatment completion (3.75 ± 2.15 vs. 6.23 ± 4.61, P < 0.001). An NLR level above 4 at treatment completion was associated with worse overall survival (log-rank P = 0.005). NLR above 4 at treatment completion and 3-6 months afterward was associated with worse disease-free survival (log-rank P = 0.047 and P = 0.011, respectively). Mean ALC declined from 1.91 ± 0.70 × 103/µL at baseline to 0.90 ± 0.51 × 103/µL at treatment completion and partially recovered to 1.36 ± 0.52 × 103/µL at follow-up, whereas ANC remained relatively stable (4.95 ± 1.70, 4.38 ± 1.99, and 4.38 ± 1.44 × 103/µL, respectively). NLR significantly increases during oncologic treatment. Our study demonstrates a novel association between NLR at the end of treatment for laryngeal SQCC and survival. Patients whose NLR remains high 3-6 months after treatment experience worse disease-free survival. The transient rise in NLR appears to be largely driven by radiation-induced lymphocyte depletion. These findings support routine monitoring of both NLR and ALC in patients undergoing radiotherapy for laryngeal cancer.