Radiotherapy Outcomes and Prognostic Factors in Head and Neck NUT Carcinoma: A Single‐Center Cohort Analysis

BACKGROUND: NUT carcinoma is a rare, aggressive malignancy defined by NUTM1 gene rearrangement, with the head and neck as the second most common site. Its prognosis is poor, and current treatment references other cancers. Although radiotherapy is key in managing head and neck tumors, its efficacy and prognostic factors in head and neck NUT carcinoma are unclear. METHODS: We retrospectively analyzed 31 patients with locally advanced or recurrent/metastatic head and neck NUT carcinoma treated with radiotherapy. OS and PFS were estimated by Kaplan-Meier, and prognostic factors were identified using Cox regression. RESULTS: Among 31 patients (64.5% male, median age 37), nasal cavity/paranasal sinuses were the most common primary site (51.6%). Most received intensity-modulated radiotherapy with ≥ 66 Gy. Median OS and PFS were 18.73 and 3 months, respectively. Nasal cavity/paranasal sinus primaries had the worst prognosis (median OS: 16.7 months). Locally advanced cases had significantly better survival than recurrent/metastatic disease (median OS: 30.43 vs. 13.93 months; PFS: 5.83 vs. 2.3 months). High-dose radiotherapy (≥ 66 Gy) was associated with improved OS, and R0 resection combined with ≥ 66 Gy achieved median OS of 27.9 months. In surgical patients, GTV longest diameter > 3.5 cm independently predicted worse PFS (HR = 5.01, p = 0.01). Recurrent/metastatic status was the most critical independent adverse prognostic factor for both PFS (HR = 4.56) and OS (HR = 10.12). Adjuvant therapy after radiotherapy prolonged PFS, particularly in locally advanced patients. BETi-based regimens before radiotherapy showed potential for improved locoregional and distant control in postoperative recurrence/metastasis. CONCLUSIONS: Prognosis in head and neck NUT carcinoma treated with radiotherapy is affected by disease status, primary site, radiotherapy dose, and adjuvant therapy. Locally advanced patients benefit most from high-dose radiotherapy and adjuvant therapy. GTV > 3.5 cm identifies high-risk populations requiring intensified treatment, while BETi may improve outcomes in postoperative recurrence/metastasis.