Clinical and demographic determinants of overall survival in early-onset head and neck cancers: A multicenter database study.

e18118 Background: The incidence of early-onset (EO) head and neck cancers (HNC), defined as diagnosis before age 50 years, is increasing. EO-HNC exhibits a heterogeneous clinical course, and factors influencing overall survival (OS) remain incompletely characterized. We sought to identify clinical and demographic variables associated with OS in patients with EO-HNC. Methods: We conducted a multicenter retrospective cohort study using the TriNetX Research Network, a federated database of de-identified electronic health records. Adults diagnosed with EO-HNC were identified. The association between clinical and demographic covariates and OS was evaluated using Cox proportional hazards regression. Covariates included age at diagnosis, sex, race, primary tumor site, nicotine dependence, alcohol use disorder, obesity, type 2 diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (COPD). Results: A total of 39,358 patients with EO-HNC were identified, of whom 56.9% were male. Factors significantly associated with increased mortality included male sex (HR 1.72; 95% CI, 1.59–1.85; P<0.0001), increasing age at diagnosis (HR 1.03; 95% CI, 1.02–1.03; P<0.0001), primary tumor site at the base of tongue (HR 2.81; 95% CI, 2.00–3.94; P<0.0001) or oropharynx (HR 2.05; 95% CI, 1.38–3.04; P<0.0001), White race (HR 1.09; 95% CI, 1.00–1.19; P=0.04), Black or African American race (HR 1.44; 95% CI, 1.27–1.62; P<0.0001), nicotine dependence (HR 1.29; 95% CI, 1.14–1.45; P<0.0001), alcohol use disorder (HR 1.61; 95% CI, 1.32–1.96; P<0.0001), COPD (HR 1.58; 95% CI, 1.22–2.05; P=0.001), and hypertension (HR 1.21; 95% CI, 1.08–1.36; P=0.001). Primary tumor site at the tonsil was associated with improved survival (HR 0.55; 95% CI, 0.32–0.94; P=0.029). Primary site at the palate or larynx, obesity, type 2 diabetes mellitus, and HPV status were not significantly associated with OS. Conclusions: In this large multicenter cohort of patients with EO-HNC, survival was adversely affected by male sex, increasing age at diagnosis, race, select primary tumor sites, tobacco and alcohol use, and cardiopulmonary comorbidities. Tonsillar primary tumors were associated with improved outcomes likely secondary to impressive response rates to chemoradiation in this often HPV positive cohort. These findings underscore the prognostic heterogeneity of EO-HNC and may aid in risk stratification and patient counseling.