title: Hyperfractionated or accelerated radiotherapy for head and neck cancer.
abstract: 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.
  
  
  
  The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival.
  
  
  
  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Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials.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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Head and Neck Surgery, Hôpital Foch, 40 rue Worth, Suresnes, France, 92150.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Baujat
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
authors.forename: Kian K
authors.initials: KK
authors.lastname: Ang
authors.forename: Michelle
authors.initials: M
authors.lastname: Saunders
authors.forename: Aurélie
authors.initials: A
authors.lastname: Le Maître
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernier
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Horiot
authors.forename: Emilie
authors.initials: E
authors.lastname: Maillard
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Pajak
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poulsen
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Bourredjem
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Werner
authors.initials: W
authors.lastname: Dobrowsky
authors.forename: Hliniak
authors.initials: H
authors.lastname: Andrzej
authors.forename: Krzystof
authors.initials: K
authors.lastname: Skladowski
authors.forename: John H
authors.initials: JH
authors.lastname: Hay
authors.forename: Luiz Hj
authors.initials: LH
authors.lastname: Pinto
authors.forename: Karen K
authors.initials: KK
authors.lastname: Fu
authors.forename: Carlo
authors.initials: C
authors.lastname: Fallai
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Pignon
mesh_terms: D000367:Age Factors; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D011878:Radiotherapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic