Background: No randomized studies have compared low-dose or high-dose concurrent chemoradiotherapy (CRT). Methods: In this study, 7219 patients with stage III or IV head and neck squamous cell carcinoma (HNSCC) were enrolled and categorized into 2 groups: group 1, comprising those undergoing low-dose concurrent CRT (n = 1575), and group 2, comprising those receiving high-dose concurrent CRT (n = 5644). Results: Cox regression analyses revealed that age ≥65 years, male, high Charlson comorbidity index (CCI) scores, radiotherapy (RT) duration ≥7.5 weeks, clinical stage IV cancer, oral cavity cancers, tobacco smoking, and total cisplatin dose ≥240 mg/m2 were significant independent prognostic risk factors for overall survival (OS). After adjustment for confounders, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) for overall mortality was 0.83 (0.78-0.89; P < .001) in patients with oral cavity HNSCC undergoing high-dose concurrent CRT and 0.82 (0.77-0.94; P < .001) in patients with nonoral cavity HNSCC receiving high-dose concurrent CRT. Conclusion: High-dose concurrent CRT can reduce the incidence of death in patients with stage III or IV HNSCC.
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