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Hyperfractionated or accelerated radiotherapy for head and neck cancer

  • Review
  • Intervention

Authors


Abstract

Background

Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear.

Objectives

The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival.

Search methods

We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 8 August 2010.

Selection criteria

We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck squamous cell carcinomas and grouped trials into three pre-specified treatment categories: hyperfractionated, accelerated and accelerated with total dose reduction. Trials were eligible if they began recruitment after 1969 and ended before 1998.

Data collection and analysis

We obtained updated individual patient data. Overall survival was the main outcome measure. The secondary outcome measures were local or regional control rates (or both), distant control rates and cause-specific mortality.

Main results

We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five 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 (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007).

Authors' conclusions

Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress.

Plain language summary

Hyperfractionated or accelerated radiotherapy for head and neck cancer

Radiotherapy is often used to treat head and neck cancers. The dosage of radiation is measured in Gray (Gy). When radiotherapy is given alone, the most commonly used schedule is 2 Gy in a single fraction per day, five days a week, for seven weeks. However, alternative radiotherapy regimens to reduce the total treatment time for head and neck cancers have been assessed. 'Acceleration' of the treatment (delivering the same total dose in a shorter time) should reduce the regrowth of the tumour between sessions, resulting in improved local control of the disease. In 'hyperfractionated' regimens, two to three fractions are delivered each day, with a reduced dose per fraction equal to 1.1 to 1.2 Gy. The reduction of the dose per fraction may 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.

This Cochrane Review is an individual patient data based meta-analysis and the aim was to assess whether this type of radiotherapy could improve survival. We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck cancers and grouped trials into three pre-specified categories: hyperfractionated, accelerated without total dose reduction and accelerated with total dose reduction. The results of this meta-analysis suggest that altered fractionation radiotherapy improves survival in patients with head and neck cancer. Comparison of the different types of altered fractionation radiotherapy suggests that hyperfractionation provides the greatest benefit.

Individual patient data meta-analysis is a long process and this review included all eligible trials which had completed recruiting patients by 1998. A major update of the analysis, including data from more recent trials, is currently underway.

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