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BACKGROUND: The standard treatment for older patients (aged ≥70 years) with localised, unresectable head and neck squamous-cell carcinoma is standard fractionated radiotherapy (SF-RT). However, its high toxicity and multiple fractions lead physicians to deliver tailored hypofractionated split-course radiotherapy (HSC-RT). The aim of the study was to compare these two radiotherapy methods in older patients. METHODS: This non-inferiority, multicentre, open-label, randomised controlled trial was done in 30 treating centres (cancer centres, university and general hospitals, and private clinics) across France and Monaco. Patients aged 70 years or older, assessed as frail by geriatric evaluation, with stage II-IV head and neck squamous-cell carcinoma and in curative intent were randomly assigned (1:1) to receive either SF-RT (70 Gy, 35 fractions over 7 weeks) or HSC-RT (55 Gy, 20 fractions, two courses of 2 weeks with 2 weeks stop). Randomisation was done by minimisation, and physicians and patients were not masked to the treatment group. The primary endpoint was the proportion of patients alive with complete locoregional response at 6 months, analysed in all randomly assigned patients (intention-to-treat population). The non-inferiority margin was set at 16%. The study was sponsored by the Groupe d'Oncologie Radiothérapie Tête et Cou (GORTEC) and is registered with ClinicalTrials.gov, NCT01864850. FINDINGS: Between Oct 21, 2013, and Aug 22, 2018, 102 patients were randomly assigned to the HSC-RT group and 100 patients to the SF-RT group. One patient in the HSC-RT group refused treatment and follow-up and so was excluded, resulting in 101 patients in the HSC-RT group. Median age was 82 years (IQR 77-86); 145 (72%) were male and 56 (28%) were female. Median follow-up for overall survival was 56·6 months (IQR 41-69). In the intent-to-treat population, 35 (35%) of 101 patients were alive with complete locoregional response at 6 months in the HSC-RT group versus 33 (33%) of 100 patients in the SF-RT group (difference +2%, 95% CI -11 to 15). In the per-protocol population, 35 (36%) of 97 patients were alive with complete locoregional response at 6 months in the HSC-RT group versus 33 (35%) of 95 patients in the SF-RT group (difference +1%, -12 to 15). Median overall survival was 13·0 months (95% CI 10·3 to 17·0) in the HSC-RT group versus 18·9 months (14·3 to 30·9) in the SF-RT group (hazard ratio 1·32, 95% CI 0·97 to 1·81). Eight patients died between radiotherapy start and 30 days after radiotherapy end (five 5% in the HSC-RT group and three 3% in the SF-RT group). One patient in the HSC-RT group had a grade 4 adverse event (kidney failure), as did four in the SF-RT group (two mucositis, one septic shock, and one hemiplegia). Acute adverse events grade 3-5 occurred in 33 (36%) of 91 patients in the HSC-RT group and in 44 (47%) of 93 patients in the SF-RT group (p=0·13; difference -11%, 95% CI -25 to 3). INTERPRETATION: Compared with SF-RT, HSC-RT did not decrease the 6-month complete locoregional response rate and could be an option for frail older patients. However, given the survival results, it should only be offered to patients deemed unsuitable for SF-RT after geriatric assessment. FUNDING: French programme PAIR-VADS 2011 (sponsored by the French National Cancer Institute, Fondation ARC, and Ligue Contre le Cancer), GEMLUC, and GEFLUC.
Ortholan et al. (Thu,) studied this question.