title: Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study.
abstract: OBJECTIVE
  To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx.
  
  
  METHODS
  Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis.
  
  
  RESULTS
  From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10).
  
  
  CONCLUSIONS
  Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT.
authors.affiliation: Department of Radiation Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. gisangui@utmb.edu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sanguineti
authors.forename: Antonella
authors.initials: A
authors.lastname: Richetti
authors.forename: Mario
authors.initials: M
authors.lastname: Bignardi
authors.forename: Renzo
authors.initials: R
authors.lastname: Corvo'
authors.forename: Pietro
authors.initials: P
authors.lastname: Gabriele
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Paolo
authors.initials: P
authors.lastname: Antognoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000601:surgery; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000532:radiotherapy / Q000601:surgery; D007822:Laryngeal Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D009959:Oropharyngeal Neoplasms / Q000532:radiotherapy / Q000601:surgery; D010610:Pharyngeal Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D013223:Statistics as Topic; D017211:Treatment Failure