Pretreatment platelet-to-lymphocyte ratio and survival after definitive radio(chemo)therapy for head and neck squamous cell carcinoma: an exploratory cohort study

Abstract

Background Current staging provides limited prognostic accuracy in head and neck squamous cell carcinoma (HNSCC). We evaluated whether pretreatment systemic inflammatory ratios and 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) metabolic parameters are associated with survival in patients treated with definitive radio(chemo)therapy. Methods We retrospectively studied 110 patients with HNSCC treated with definitive radio(chemo)therapy at a single center. Inflammatory ratios, including the platelet-to-lymphocyte ratio (PLR), were derived from a pretreatment blood count. Metabolic parameters were obtained from staging [ 18 F]FDG PET/CT. The primary endpoints were overall survival (OS) and disease-specific survival (DSS). A Cox model comprising PLR, p16 status, cT category and age was fitted for each endpoint. Missing p16 status was handled by multiple imputation. Results A higher PLR was independently associated with worse OS (HR per interquartile range 1.61, 95% CI 1.13–2.28; p = 0.008) and DSS (HR 1.78, 95% CI 1.21–2.60; p = 0.003), alongside p16-negativity. cT4 category and age were also independently associated with OS. p16 was missing in 30% of patients, mostly non-oropharyngeal tumors. Complete-case analysis was therefore restricted to 77 patients, in which the point estimates were similar, but the association no longer reached significance. PLR correlated weakly with cT category (Spearman ρ = 0.275, p = 0.004) without collinearity. In exploratory analyses, the association between a high PLR and worse survival was clear in oropharyngeal tumors but weaker in other subsites. Metabolic parameters did not demonstrate an independent association with survival after adjustment. Conclusions Pretreatment PLR was independently associated with worse OS and DSS in HNSCC treated with definitive radio(chemo)therapy in the primary multiple-imputation analysis. Effect estimates were consistent in direction and magnitude across all three approaches to missing p16 status. A higher PLR indicates a worse prognosis, but the association is modest and does not guide treatment selection. Prospective validation with prespecified cutoffs is required before clinical use.