External Validation of Pre‐Treatment Primary Tumor Volume as a Prognostic Factor in Head and Neck Cancer Treated With (Chemo)Radiotherapy

ABSTRACT Background Primary tumor volume (GTVp) is a key prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC) treated with radiotherapy. We aimed to externally validate this association and assess its relevance in other head and neck sites. Methods Patients from the RADCURE dataset were analyzed using Cox regression for local failure, progression‐free survival (PFS), and overall survival (OS). Subgroup analyses included HPV status, chemotherapy use, and separate evaluations for hypopharyngeal and laryngeal cancers. Model performance was assessed using the concordance index (C‐index). Results Among 1286 OPSCC patients, increasing GTVp was associated with a higher risk of local failure and reduced PFS and OS, consistent across HPV and chemotherapy subgroups. Similar associations were observed in hypopharyngeal ( n = 157) and laryngeal ( n = 803) cancers. Model performance was strong (C‐index up to 0.82). Conclusion Primary tumor volume is a robust prognostic factor across head and neck cancer sites, supporting risk stratification in curative radiotherapy.