title: Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.
abstract: BACKGROUND
  Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival.
  
  
  METHODS
  Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction.
  
  
  RESULTS
  15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years (hazard ratio 0.92, 95% CI 0.86-0.97; p=0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years, p=0.02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at 5 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 (hazard ratio 0.78 [0.65-0.94] for under 50 year olds, 0.95 [0.83-1.09] for 51-60 year olds, 0.92 [0.81-1.06] for 61-70 year olds, and 1.08 [0.89-1.30] for over 70 year olds; test for trends p=0.007).
  
  
  CONCLUSIONS
  Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.
authors.affiliation: Radiation Oncology Department, Institut Gustave Roussy, Villejuif, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
authors.forename: Hélène
authors.initials: H
authors.lastname: Audry
authors.forename: Kian K
authors.initials: KK
authors.lastname: Ang
authors.forename: Michele
authors.initials: M
authors.lastname: Saunders
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernier
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Horiot
authors.forename: Aurélie
authors.initials: A
authors.lastname: Le Maître
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Pajak
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poulsen
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Werner
authors.initials: W
authors.lastname: Dobrowsky
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hliniak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Skladowski
authors.forename: John H
authors.initials: JH
authors.lastname: Hay
authors.forename: Luiz H J
authors.initials: LH
authors.lastname: Pinto
authors.forename: Carlo
authors.initials: C
authors.lastname: Fallai
authors.forename: Karen K
authors.initials: KK
authors.lastname: Fu
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate / Q000639:trends