Preoperative hyperfractionated accelerated radiotherapy and radical surgery in advanced head and neck cancer: A prospective phase II study

Background and purpose To evaluate whether preoperative hyperfractionated accelerated radiotherapy (RT) combined with major radical surgery is feasible and successful in the treatment of advanced primary head and neck cancer. Patients and methods Ninety four patients with histologically confirmed head and neck squamous cell cancer (HNSCC) in the oral cavity (41/96; 43%), supraglottis (14/96; 15%), glottis (5/96; 5%), oropharynx (16/96; 17%), nasal cavity/paranasal sinuses (8/96; 8%), nasopharynx (3/96; 3%), hypopharynx (7/96; 7%) and two (2%) with unknown primary tumour and large cervical lymph nodes entered into the study. 21/96 patients (22%) had stage II, 17/96 (18%) stage III and 58/96 patients (60%) stage IV disease. The patients received preoperative hyperfractionated RT 1.6 Gy twice a day, 5 days a week to a median tumour dose of 63 Gy with a planned break for 11 days (median) after the median dose of 37 Gy. Then, after a median of 27 days the patients underwent major radical surgery of the primary tumour and metastatic lymph nodes including reconstructions with pedicled or microvascular free flaps when indicated as a part of the scheduled therapy. 12/96 patients had only ipsilateral or bilateral neck dissections. Results After a median follow-up time of 37.2 mos 77/96 (80.2%) patients had complete locoregional control. All but 2 patients had complete histological remission after surgery. 40/96 pts were alive without disease, two of them after salvage surgery. 32/96 patients had relapsed; 15 had locoregional and 13 distant relapses, 4 patients relapsed both locoregionally and distantly. Fifty patients have died; 29 with locoregional and/or distant relapse, eight patients died of second malignancy, and 19 had intercurrent diseases. Disease-specific and overall survival at 3 years was 67.7 and 51%, respectively. Acute grade three mucosal reactions were common, but transient and tolerable. Late grade 3–4 adverse effects were few. Conclusions Preoperative hyperfractionated accelerated RT can be successfully combined with major radical surgery in the treatment of HNSCC. The amount of serious late adverse effects was not increased.