title: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site.
abstract: BACKGROUND
  The recently updated meta-analysis of chemotherapy in head and neck cancer (MACH-NC) demonstrated the benefit of the addition of chemotherapy in terms of overall survival in head and neck squamous cell carcinoma (HNSCC). The magnitude of the benefit according to tumour site is unknown as well as their potential interactions with patient or trial characteristics.
  
  
  METHODS
  Eighty seven randomized trials performed between 1965 and 2000 were included in the present analysis. Patients were divided into four categories according to tumour location: oral cavity, oropharynx, hypopharynx and larynx. Patients with other tumour location were excluded (999, 5.7%). For each tumour location and chemotherapy timing, the logrank-test, stratified by trial, was used to compare treatments. The hazard ratios of death or relapse were calculated. Interactions between patient or trial characteristics and chemotherapy effect were studied.
  
  
  RESULTS
  Individual patient data of 16,192 patients were analysed, with a median follow-up of 5.6years. The benefit of the addition is consistent in all tumour locations, with hazard ratios between 0.87 and 0.88 (p-value of interaction=0.99). Chemotherapy benefit was higher for concomitant administration for all tumour locations, but the interaction test between chemotherapy timing and treatment effect was only significant for oropharyngeal (p<0.0001) and laryngeal tumours (p=0.05), and not for oral cavity (p=0.15) and hypopharyngeal tumours (p=0.30). The 5-year absolute benefits associated with the concomitant chemotherapy are 8.9%, 8.1%, 5.4% and 4% for oral cavity, oropharynx, larynx and hypopharynx tumours, respectively.
  
  
  CONCLUSIONS
  The benefit of the addition of chemotherapy to locoregional treatment is consistent in all tumour locations of HNSCC. The higher benefit of concomitant schedule was demonstrated only for oropharyngeal and laryngeal tumours but this may be only a consequence of a lack of power.
authors.affiliation: Biostatistics and Epidemiology Department, Institut Gustave Roussy, Villejuif, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Baujat
authors.forename: Victoria
authors.initials: V
authors.lastname: Holostenco
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Bourredjem
authors.forename: Charlotte
authors.initials: C
authors.lastname: Baey
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors