Phase 2 trial of response-adapted postoperative therapy after neoadjuvant chemoimmunotherapy for LA-HNSCC

Neoadjuvant chemoimmunotherap9 NACI) demonstrates promising efficacy in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), yet its effect on postoperative radiotherapy/chemoradiotherapy (PORT/POCRT) is undefined. A phase 2 trial at Huazhong University of Science and Technology (Wuhan, China) assessed NACI efficacy and its role in guiding adaptive PORT/POCRT). Primary endpoint was major pathologic response (MPR; 0-10% residual tumor) rate. Thirty resectable stage III-IVB HNSCC patients received sintilimab plus chemotherapy, followed by surgery and response-adapted PORT/POCRT. Patients with MPR received low-dose PORT (9-54 Gy), while patients without MPR received standard PORT/POCRT. The MPR rate was 59.1% (95% CI 38.7-76.7). The MPR with low-dose group showed higher 2-year overall survival rate (100% versus 77.8%) and disease-free survival rate (100% versus 55.6%) with fewer radiotherapy-related adverse events than non-WPR with standard-dose group (all p<0.05). The authors conclude that adaptive radiation de-escalation maintains survival while reducing toxicity, representing a new strategy for LA-HNSCC.