Impact of Suboptimal Cisplatin Dosing on Mortality in Locally Advanced Head and Neck Cancer: Insights from a Decade of Real-World Data

Background Cisplatin and radiotherapy have been the standard treatment for locally advanced squamous cell carcinoma of the head and neck (LAHNSC) for over 20 years. Achieving a cumulative cisplatin dose ≥200 mg/m ² has been associated with improved overall survival (OS); however, this target is often not met in clinical practice. Methods This retrospective cohort study was conducted at Instituto de Cancerología Las Américas (Medellín, Colombia) from 2014-2024. Demographic and clinical factors were analyzed to evaluate the relationship between ineffective cisplatin doses (<200 mg/m ² ) and OS. Survival analysis was performed using the log-rank test and Kaplan-Meier curves. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR), and a Poisson regression model to calculate relative risks (RR). Results 326 patients were included. OS was longer in patients receiving ≥200 mg/m ² of cisplatin (median 72.4 vs. 31.8 months), with an HR of 1.46 (95% CI 0.98–2.18, p=0.064). Multivariable analysis showed that an ineffective dose was associated with increased mortality (HR 1.54, 95% CI 1.00–2.37, p=0.049). Factors associated with worse OS included low functional status, primary oral carcinoma, subsidized health insurance, and leukocytosis. Patients with low body mass index, hypertension, male sex, or GFR <60 mL/min/1.73 m ² were at higher risk of receiving an ineffective dose. Acute kidney injury during treatment doubled this risk. Conclusions This real-world study supports that failure to achieve a cisplatin dose ≥200 mg/m ² increases mortality in LAHNSC. Identifying high-risk patients and optimizing management strategies are essential to improve treatment outcomes.