Mature results of a randomized trial of accelerated hyperfractionated versus conventional radiotherapy in head-and-neck cancer.

Purpose To evaluate long-term late adverse events and treatment outcome of a randomized, multicenter Phase III trial of continuous, hyperfractionated, accelerated radiotherapy (CHART) compared with conventional radiotherapy (CRT) in 918 patients with advanced squamous cell carcinomas of the head and neck. Methods and Materials Survival estimates were obtained for locoregional relapse-free survival, local relapse-free survival, overall survival, disease-specific survival, disease-free survival and for late adverse events. Results The 10-year estimates (±1 standard error) for locoregional relapse-free survival, overall survival, disease-free survival, and disease-specific survival were 43% ± 2% for CHART and 50% ± 3% with CRT (log-rank p = 0.2); 26% ± 2% and 29% ± 3% ( p = 0.4), respectively; 41% ± 2% and 46% ± 3% ( p = 0.3), respectively; and 56% ± 3% and 58% ± 3% ( p = 0.5), respectively. There was a small but significant reduction in the incidence of slight or worse and moderate or worse epidermal adverse events with CHART ( p = 0.002 to 0.05). Severe xerostomia, laryngeal edema, and mucosal necrosis were also significantly lower with CHART ( p = 0.02 to 0.05). Conclusions Despite the reduction in total dose from 66 Gy to 54 Gy, control of locoregional disease and survival with CHART were similar to those with CRT. These findings, together with the low incidence of long-term severe adverse events, suggest that CHART is a treatment option for patients with low-risk disease and for those unable to withstand the toxicity of concurrent chemoradiotherapy.