<scp>NUT</scp> Midline Carcinoma of the Head and Neck: A Systematic Review and Pooled Survival Analysis

BACKGROUND: NUT midline carcinoma (NMC) is an aggressive malignancy driven by NUTM1 fusions in poorly differentiated tumor cells. This pooled analysis evaluates the impact of primary tumor location on overall survival (OS) in head and neck (HN) NMC. METHODS: A systematic review of case reports was performed. Kaplan-Meier survival analysis was used to assess OS differences by subsite, age, and genetic profile. RESULTS: Of 261 screened articles, 81 met inclusion criteria. Overall, 138 cases were included in demographic analyzes and 65 in survival analyzes. Tracheo-laryngopharyngeal tumors trended toward worse OS (HR 2.45, 95% CI 1.01-5.95, p = 0.047). Orbito-sinonasal tumors trended toward improved OS (HR 0.75, 95% CI 0.46-1.24, p = 0.25). BRD4-NUTM1 fusions were associated with worse OS (HR 8.3, 95% CI 4.26-16.23, p = 0.0003). CONCLUSIONS: HN NMC carries a poor prognosis, and BRD4-NUTM1 fusions have worse outcomes. Primary subsite is a potential prognostic variable that may inform future studies.