Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction.
15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74 % ) patients had stage III–IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3·4 % at 5 years (hazard ratio 0·92, 95 % CI 0·86–0·97; p=0·003). The benefit was significantly higher with hyperfractionated radiotherapy (8 % at 5 years) than with accelerated radiotherapy (2 % with accelerated fractionation without total dose reduction and 1·7 % with total dose reduction at 5 years, p=0·02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6·4 % at 5 years; p<0·0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (hazard ratio 0·78 [0·65–0·94] for under 50 year olds, 0·95 [0·83–1·09] for 51–60 year olds, 0·92 [0·81–1·06] for 61–70 year olds, and 1·08 [0·89–1·30] for over 70 year olds; test for trends p=0·007).
Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.