Survival Outcomes With Concurrent Systemic Therapy in Patients With a Medical Contraindication to Cisplatin in the Non-Operative Management of Locally Advanced HNSCC, an NCDB Study.

Demircioglu, Deniz Can; Singh, Sohil; Belcher, Johnny; Wong, Stuart J; Zenga, Joseph; Awan, Musaddiq · Head Neck · 2026

retrospective_cohort · Level III

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Abstract

Patients with locally advanced head and neck squamous cell carcinoma who are medically ineligible for cisplatin lack a standard concurrent systemic therapy. We used the National Cancer Database to identify patients diagnosed from 2015 onward with non-metastatic, locally advanced squamous HNSCC treated with definitive radiation therapy and concurrent systemic therapy, receiving either chemotherapy or cetuximab (using immunotherapy as a surrogate for cetuximab in the NCDB). Cisplatin-ineligibility was defined using the age and comorbidity criteria from NRG-HN004. Overall survival was compared using Kaplan-Meier analysis and an inverse probability weighted Cox proportional hazards model. The final cohort included 6045 patients: 5441 receiving chemotherapy and 604 receiving cetuximab. In the weighted Cox model, chemotherapy was not significantly associated with improved overall survival compared to cetuximab (HR, 1.08; 95% CI, 0.94-1.23; p = 0.281). In this retrospective analysis, no survival advantage was found with chemotherapy over cetuximab in cisplatin-ineligible patients. Future, randomized trials are necessary to define optimal systemic therapy in this population.