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Meta-Analysis
. 2010 Dec 8;2010(12):CD002026.
doi: 10.1002/14651858.CD002026.pub2.

Hyperfractionated or accelerated radiotherapy for head and neck cancer

Bertrand Baujat  1 , Jean Bourhis, Pierre Blanchard, Jens Overgaard, Kian K Ang, Michelle Saunders, Aurélie Le Maître, Jacques Bernier, Jean Claude Horiot, Emilie Maillard, Thomas F Pajak, Michael G Poulsen, Abderrahmane Bourredjem, Brian O'Sullivan, Werner Dobrowsky, Hliniak Andrzej, Krzystof Skladowski, John H Hay, Luiz Hj Pinto, Karen K Fu, Carlo Fallai, Richard Sylvester, Jean Pierre Pignon; MARCH Collaborative Group
Affiliations
Meta-Analysis

Hyperfractionated or accelerated radiotherapy for head and neck cancer

Bertrand Baujat et al. Cochrane Database Syst Rev. .

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 strategy: 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Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials.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.

PubMed Disclaimer

Conflict of interest statement

Sanofi‐Aventis had a general agreement with Institut Gustave Roussy to support meta‐analyses on lung and head and neck cancers. Sanofi‐Aventis played no role in the study design, data collection, data analysis, data interpretation or writing of the publications. Sanofi‐Aventis is a pharmaceutical company with, to the best of the authors' knowledge, no interest in radiotherapy material.

We declare that we have no conflict of interest.

H Andrzej is deceased; no declaration of interest available.

Figures

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Description of trials comparing altered fractionated with conventional radiotherapy: patients characteristics BCCA = British Columbia Cancer Agency; CAIR = Continuous Accelerated Irradiation; CHART = Continuous Hyperfractionated Accelerated Radiation Therapy; DAHANCA = Danish Head and Neck Cancer Study Group; EORTC = European Organisation for Research and Treatment of Cancer; GORTEC = Groupe d'Oncologie Radiothérapie Tête et Cou; KBN = Komiet Badan Naukowych (Committee for Scientific Research); PMH‐Toronto = Princess Margaret Hospital, Toronto; RTOG = Radiation Therapy Oncology Group; TROG = Trans‐Tansman Radiation Oncology Group Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Description of patients included in trials comparing altered fractionated radiotherapy with conventional radiotherapy by arm (n = 7073). Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. None of the studies of altered fractionation used a sham procedure for radiotherapy blinding, but overall survival is a robust endpoint that should not be sensitive to this absence of blinding.
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4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study. None of the studies of altered fractionation used a sham procedure for radiotherapy blinding, but overall survival is a robust endpoint that should not be sensitive to this absence of blinding.
5
5
Survival curves by treatment arm for all trials and for the three groups of trials according to the type of altered fractionated radiotherapy. The slopes of the broken lines from year 6 to year >= 7 are based on the overall death rates in the seventh and subsequent years. RT = radiotherapy Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Non‐cancer death and cancer death survival curves for all trials and for the three groups of trials according to the altered fractionated radiotherapy. The slopes of the broken lines from year 6 to year >= 7 are based on the overall death rates in the seventh and subsequent years. RT = radiotherapy Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Description of patients included in trials comparing conventional radiotherapy with altered fractionated radiotherapy by group of altered fractionated radiotherapy (n = 7073). Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Distribution of type of first failure by arm. Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Locoregional failure by treatment arm according to the type of radiotherapy. The slopes of the broken lines from year 6 to year >= 7 are based on the overall death rates in the seventh and subsequent years. RT = radiotherapy Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Hazard ratio (95% CI) of altered fractionated radiotherapy versus conventional radiotherapy on overall population and type of radiotherapy for locoregional, local, regional, and metastatic control (n = 7073). Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
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Hazard ratio of death with altered fractionated radiotherapy versus conventional radiotherapy by age, sex, performance status, stage and site of tumour. Test for trend was significant for age (P = 0.007). Figure from Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J et al on behalf of MARCH collaborative group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta‐analysis. Lancet 2006;368:843‐54 reproduced with permission from Elsevier Ltd.
1.1
1.1. Analysis
Comparison 1 Altered fractionated radiotherapy versus conventional radiotherapy, Outcome 1 Hazard ratio of death.
1.2
1.2. Analysis
Comparison 1 Altered fractionated radiotherapy versus conventional radiotherapy, Outcome 2 Hazard ratio of head and neck cancer death.
1.3
1.3. Analysis
Comparison 1 Altered fractionated radiotherapy versus conventional radiotherapy, Outcome 3 Hazard ratio of locoregional control.
1.4
1.4. Analysis
Comparison 1 Altered fractionated radiotherapy versus conventional radiotherapy, Outcome 4 Hazard ratio of local control.
See this image and copyright information in PMC

Update of

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References to other published versions of this review

Bourhis 2006
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MeSH terms