Fast track — ArticlesHyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis
Introduction
Head and neck squamous cell carcinomas are frequent tumours, with more than 550 000 new cases of oral cavity, oropharynx, hypopharynx, and larynx cancer every year worldwide.1 About 40% of patients have locally advanced disease at diagnosis. Surgery, radiation therapy, or both, have been used for decades to achieve locoregional control; the most commonly used schedule when radiotherapy is given alone is 2 Gy in a single fraction per day, 5 days a week, for 7 weeks. Despite these treatments, the prognosis of patients with head and neck squamous cell carcinomas with locally advanced disease remains poor, with 5-year survival rates of 30–35%.2
In the past decade, new radiotherapy regimens for the treatment of head and neck squamous cell carcinomas have been assessed. These regimens were designed to increase the dose-intensity by delivering a higher total dose in the same time,3, 4, 5, 6 the same total dose in 5–6 weeks instead of 7 weeks,6, 7, 8, 9, 10, 11, 12 or a smaller total dose given in 3–4 weeks.13, 14, 15, 16, 17 Reducing the total treatment time—ie, accelerating the treatment—should reduce the repopulation of tumour cells between sessions, resulting in improved locoregional control. In hyperfractionated regimens, two to three fractions are delivered each day, with a reduced dose per fraction equal to 1·1–1·2 Gy. The reduction of the dose per fraction might reduce the risk of late toxicity, despite an increased total dose. Acceleration and hyperfractionation can be combined, in particular for regimens in which overall treatment time is reduced.
In some randomised trials, altered fractionated radiotherapy has proved to be of benefit in locoregional control,3, 4, 5, 6, 9, 11, 17 although no benefit in survival was generally detected. The use of altered fractionated radiotherapy is associated with some increase in toxicity, mostly due to mucositis,6, 7, 8, 9, 17 and can add some practical constraints in radiotherapy departments3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17—eg, treatment two to three times a day or at a weekend—that need to be balanced by substantial benefit.
A meta-analysis of updated individual patient data is the most reliable way to assess whether altered fractionated radiotherapy could affect survival. This meta-analysis was undertaken by the MARCH (Meta-Analysis of Radiotherapy in Carcinomas of Head and neck) Collaborative Group. The main objective was to study the effect of altered fractionation in overall survival. A comparison between the effects of the three types of altered fractionated radiotherapy was also planned.
Section snippets
Selection of trials
The methods were specified in a protocol published in the Cochrane Library.18 The collaborative group's steering committee prespecified three groups of trials with different modifications of fractionation that correspond to three distinct biological questions. The first group (hyperfractionation) examined the effect of a higher total dose in the same overall time than in the reference arm.3, 4, 5, 6 The second group (accelerated group) represented a pure test of the effect of accelerating
Results
Of 26 potentially eligible randomised trials, nine were excluded: three were post-operative trials, one had biased randomisations, two used unconventional radiotherapy in the reference group, and three used hypofractionated radiotherapy in the experimental group (webappendix). Data from one eligible trial (212 patients) were lost.25 15 trials fulfilled all the inclusion criteria and data were available for 6515 patients.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 The length of follow-up
Discussion
This meta-analysis of individual patient data showed that different types of altered fractionated radiotherapy could improve the effectiveness of radiotherapy in head and neck squamous cell carcinomas, compared with conventional radiotherapy, with a small but significant benefit in survival and a more pronounced benefit in locoregional and local control. Our findings provide strong evidence that altered fractionated radiotherapy can improve survival in this disease. The survival benefit was
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Dr Hliniak died in 2005