Comparable Outcomes Without Routine Pan-mucosal Irradiation in Head and Neck Carcinoma of Unknown Primary

Evaluate whether adding pan-mucosal irradiation (50 Gy) reduces recurrence or improves survival in head and neck carcinoma of unknown primary.

Retrospective 2-center analysis (center 1, 2009-2018, and center 2, 2005-2023). All patients underwent neck dissection with adjuvant irradiation to lymphatic drainage or definitive radiochemotherapy; center 2 additionally received 50 Gy pan-mucosal irradiation to the upper aerodigestive tract. Definitive radiation therapy/chemoradiation therapy was used for advanced nodal disease.

Of 164 screened, 134 were included (center 1, n = 88, and center 2, n = 46). Median follow-up was 72 months (95% CI, 48-96). Sixty-five patients (42%) died (37 vs 28). Overall survival did not differ between centers (log-rank P = .899). Combining centers 1 and 2, there were 39 recurrences in 134 patients; 24 out of 88 patients (27.3%) in center 1 and 15 out of 46 patients in center 2 (32.6%), P = .519. There were no differences noted in time-to-event analysis (log-rank P = .724). Mucosal recurrences occurred in 13 patients (9 vs 4; P = .282); all arose more than 36 months after diagnosis and exclusively in persistent smokers.

In thoroughly staged head and neck carcinoma of unknown primary, adding pan-mucosal irradiation to standard nodal irradiation was not associated with improved survival or lower mucosal recurrence rates compared with nodal-only fields. The late occurrence of mucosal events and their association with persistent smoking suggest second primary tumors rather than missed index lesions. Given potential toxicity and quality-of-life trade-offs, routine pan-mucosal irradiation may not be warranted, and treatment should be individualized.