Importance: Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignant tumors worldwide. There is conflicting evidence regarding the indications for and benefits of adjuvant radiation therapy for advanced CSCC tumors of the head and neck. Objective: To assess indications for adjuvant radiation therapy in patients with CSCC. Design, Setting, and Participants: Retrospective analysis of 349 patients with head and neck CSCC treated with primary resection with or without adjuvant radiation therapy at 2 tertiary referral centers from January 1, 2008, to June 30, 2016. Main Outcomes and Measures: Data were compared between treatment groups with a χ2 analysis. Disease-free survival (DFS) and overall survival (OS) were analyzed using a Kaplan-Meier survival analysis with log-rank test and a Cox proportional hazards multivariate regression. Results: A total of 349 patients had tumors that met the inclusion criteria (mean [SD] age, 70  years; age range, 32-94 years; 302 [86.5%] male), and 191 (54.7%) received adjuvant radiation therapy. The 5-year Kaplan-Meier estimates were 59.4% for DFS and 47.4% for OS. Patients with larger, regionally metastatic, poorly differentiated tumors with perineural invasion (PNI) and younger immunosuppressed patients were more likely to receive adjuvant radiation therapy. On Cox proportional hazards multivariate regression, patients with periorbital tumors (hazard ratio [HR], 2.48; 95% CI, 1.00-6.16), PNI (HR, 1.90; 95% CI, 1.12-3.19), or N2 or greater nodal disease (HR, 2.16; 95% CI, 1.13-4.16) had lower DFS. Immunosuppressed patients (HR, 2.17; 95% CI, 1.12-4.17) and those with N2 or greater nodal disease (HR, 2.43; 95% CI, 1.42-4.17) had lower OS. Adjuvant radiation therapy was associated with improved OS for the entire cohort (HR, 0.59; 95% CI, 0.38-0.90). In a subset analysis of tumors with PNI, adjuvant radiation therapy was associated with improved DFS (HR, 0.47; 95% CI, 0.23-0.93) and OS (HR, 0.44; 95% CI, 0.24-0.86). Adjuvant radiation therapy was also associated with improved DFS (HR, 0.36; 95% CI, 0.15-0.84) and OS (HR, 0.30; 95% CI, 0.15-0.61) in patients with regional disease. Conclusions and Relevance: Among patients with advanced CSCC, receipt of adjuvant radiation therapy was associated with improved survival in those with PNI and regional disease.
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