Efficacy and Safety of Induction Chemotherapy Followed by Concurrent Chemoradiotherapy in Locoregionally Advanced Hypopharyngeal Carcinoma.

PURPOSE: For locoregionally advanced hypopharyngeal carcinoma (LAHPC), organ preservation via induction chemotherapy followed by concurrent chemoradiotherapy (IC-CCRT) is a key strategy, yet robust data from homogeneous cohorts treated with modern radiation therapy are scarce. This prospective study evaluated the efficacy and safety of IC-CCRT in a contemporary LAHPC cohort.

METHODS AND MATERIALS: From January 2015 to December 2021, 259 patients with LAHPC receiving curative-intent IC-CCRT with intensity-modulated radiation therapy were enrolled. Endpoints included survival with functional larynx (SFL), overall survival, progression-free survival, and disease control measures.

RESULTS

The 5-year rates for SFL, overall survival, progression-free survival, local failure-free survival, locoregional failure-free survival, and distant metastasis-free survival (DMFS) were 49.9%, 51.5%, 43.3%, 50.2%, 48.6%, and 46.4%, respectively. Outcomes declined sharply with advancing American Joint Committee on Cancer (AJCC) stage. The 5-year SFL was 89.0% for stage III, 47.0% for stage IVA (hazard ratio [HR] 4.02; 95% CI, 1.66-9.77; P = .002), and 31.7% for stage IVB (HR 2.77; 95% CI, 1.01-7.58; P = .048). T4b classification independently predicted the poorest outcomes, with a 5-year SFL of 25.2% versus 69.9% for T1-3 tumors (HR 3.23; 95% CI, 1.70-6.12; P < .001). AJCC stage and T classification, but not N stage, remained independent prognostic factors across all endpoints. Age was also an independent prognostic factor. Based on these factors, a prognostic nomogram was developed, demonstrating good discrimination (C-index 0.696) and calibration, with decision curve analysis confirming its clinical utility. Grade 3 to 4 hematologic toxicity occurred in 13.9% of patients. Functional impairments were common, including hoarseness (42.1%) and dysphagia (23.2%), with 14.3% requiring feeding tube dependence.

CONCLUSIONS

IC-CCRT provides meaningful survival and larynx preservation in LAHPC, but efficacy is highly dependent on AJCC stage and T classification. Patients with T4b tumors have particularly poor outcomes. The developed nomogram offers a practical tool for individual outcome prediction. Treatment should be individualized, balancing survival benefits against significant treatment-related toxicities.