Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Introduction: NUT carcinoma (NC) is a rare, aggressive form of poorly differentiated squamous cell carcinoma (SCC) characterized by chromosomal translocations involving the NUTM1 gene, commonly fusing with BRD4 or BRD3. Once considered a pediatric cancer, NC is now increasingly recognized and diagnosed across a wider age spectrum. Survival outcomes for well-differentiated SCC of the head and neck differ by primary tumor site; however, this association remains less understood for head and neck NUT carcinoma (HNNC). Therefore, a systematic review and pooled survival analysis were conducted to describe HNNC patient characteristics and compare survival outcomes by tumor subsite.
Methods: The PubMed and Scopus databases were searched through June 2024 using search terms generated by a head and neck surgeon. Before data extraction, a written protocol was published in PROSPERO (CRD42024530021). PRISMA guidelines were adhered to. All original English-language studies reporting HNNC patient outcomes were included. Two authors independently screened studies for inclusion and performed data extraction. A third author resolved any discrepancies. Demographic, clinical, pathological, treatment, metastasis, recurrence, and survival data were extracted for pooled analysis. Tumor sites were grouped into four categories: orbito-sinonasal, oral, major salivary glands, and tracheo-laryngopharyngeal. Survival analyses were conducted using the Kaplan-Meier method, and comparisons between subsites were measured using the Log-rank (LR) and Gehan-Breslow-Wilcoxon (GBW) tests. Median survival, where the patient’s probability of survival is 50%, was reported in weeks. Statistical significance was determined at p < 0.05.
Results: The search yielded 261 articles. After screening, a total of 81 articles and 138 patients were identified. The average age at diagnosis was 36 (SD=18.4), and most patients were diagnosed in their 30s (n=28, 20%). The most common primary site was the sinonasal region (n=78, 56.5%), followed by the parotid (n=15, 10.9%) and larynx (n=13, 9.4%). Of those with recurrence or metastasis data (n=100), 72% had recurrence and/or metastasis. Of those with reported survival status (n=122), 62.3% died of disease. Median survival was 56.5 weeks (range 3 to 113 weeks). Of those with treatment data (n=115), the most common regimen was combined surgery, radiation, and chemotherapy (54.8%). Among cases with diagnostic timelines (n?=?96), 59.3% were initially misdiagnosed and revised to NC after further testing.
Survival analysis included 65 patients. Orbito-sinonasal tumors were trending towards better overall survival (n= 35, median OS: 65.18 weeks, p>0.05, HR 0.75, 95% CI 0.46-1.24). Tracheo-laryngopharyngeal tumors had significantly worse survival (n= 10, median OS: 34.76 weeks, p<0.05; HR 2.45, 95% CI 1.01-5.95). Age was not a significant predictor of survival (p>0.05; HR 0.66, 95% CI 0.33-1.32).
Discussion: HNNC predominantly affects adults and occurs most commonly in the orbito-sinonasal region. Tracheo-laryngopharyngeal tumors are significantly linked to worse survival, stressing the need for early, accurate diagnosis and appropriate treatment. Despite aggressive treatments, the prognosis for HNNC remains poor, with a median survival of approximately 13 months and a high recurrence and metastasis rate of 72%. Study limitations include selection bias and data heterogeneity inherent in retrospective case reports. Prospective studies are needed to improve diagnosis and treatment.