Involved Neck Only Versus Mucosal Radiation Therapy for Head and Neck Squamous Cell Cancer of Unknown Primary (HNSCCUP): A National Retrospective Multicenter Cohort Study.

PURPOSE: Target volumes for irradiation remain ill-defined for head and neck squamous cell cancer of unknown primary (HNSCCUP). The aim of this study was to compare 2 commonly used radiation therapy strategies for patients diagnosed with HNSCCUP: ipsilateral or involved neck only (INO) versus bilateral neck and/or mucosal (MUC) radiation therapy, evaluating disease-related outcomes and enteral feeding rates.

METHODS AND MATERIALS: This was a retrospective, observational, multicenter cohort study. Patients diagnosed with unilateral HNSCCUP between 2015 and 2023 who underwent radical (chemo) radiation therapy were eligible for analysis. All patients underwent 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography - Computed Tomography (PET-CT). HNSCCUP was a diagnosis of exclusion made on the basis of negative investigations to detect a primary site. Patient and tumor characteristics, treatment details, toxicities, and disease control were recorded and compared between the 2 radiation therapy strategies.

RESULTS

One hundred ninety-five patients were eligible for analysis, 66% had human papillomavirus-associated disease. Seventy-three patients received INO (37%) and 122 patients received MUC radiation therapy (63%). The median duration of follow-up was 58 months (IQR, 42-72 months). The rate of primary site emergence was 2.7% in the INO and 0.8% in the MUC cohorts, P = .56. Five-year overall survival was 80% (95% CI, 70%-90%) for INO and 82% (95% CI, 75%-90%) for MUC radiation therapy, P = .74. Those undergoing INO radiation therapy were more likely to die from HNSCCUP (17.8% vs 5.7%), and those receiving MUC were more likely to die from a non-HNSCCUP cause (15.6% vs 4.1%). The need for enteral feeding ≥12 months from radiation therapy was 5.7% for MUC versus 0% for INO (P = .046).

CONCLUSIONS

This is the largest series to date of patients with unilateral HNSCCUP treated radically with radiation therapy in the human papillomavirus and FDG PET-CT era. Acceptably low rates of primary site emergence, lower toxicity, and no difference in overall survival when compared with prophylactic MUC radiation therapy suggest that INO radiation therapy in HNSCCUP may be a feasible alternative in contemporary practice.