title: A dose escalation study of hyperfractionated accelerated radiation delivered with integrated neck surgery (HARDWINS) for the management of advanced head and neck cancer.
abstract: OBJECTIVE
  To determine toxicity and outcome of radiation dose escalation with hyperfractionated accelerated radiation delivered with neck surgery (HARDWINS) for head and neck cancer.
  
  
  METHODS
  Patients with stage III and IV squamous cell carcinoma of the oropharynx, hypopharynx or larynx were enrolled. Dose levels of 60, 62 and 64Gy were delivered with twice daily fractionation in 40 fractions over 4 weeks. Involved and at-risk nodal regions received microscopic dose (46.5-48Gy) with neck dissection for node positive patients 8 weeks after radiation.
  
  
  RESULTS
  One hundred and sixty-nine patients were enrolled (60Gy n=22, 62Gy n=26, 64Gy n=121). No grade 4 acute toxicity was observed. Incidence of acute grade 3 toxicity was: skin (2%), larynx (6%), pharynx and esophagus (66%) and mucous membrane (75%). Feeding tube dependence was observed in 14% of patients receiving 64Gy. Overall survival, and relapse free rate at 5 years were 65% and 63%, respectively. Local, nodal and distant relapse free rates at 5 years were 77%, 94% and 81% (median follow-up 3.8 years).
  
  
  CONCLUSIONS
  HARDWINS can be delivered without acute grade 4 toxicity but significant grade 3 acute toxicity. A significant proportion of the patients have prolonged swallowing dysfunction. Outcomes suggest this regimen represents an alternative to chemoradiation.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Hospital and the University of Toronto, Canada. john.waldron@rmp.uhn.on.ca
authors.forename: John
authors.initials: J
authors.lastname: Waldron
authors.forename: Padraig
authors.initials: P
authors.lastname: Warde
authors.forename: Jon
authors.initials: J
authors.lastname: Irish
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Susanna
authors.initials: S
authors.lastname: Sellmann
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.forename: Bernard
authors.initials: B
authors.lastname: Cummings
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Payne
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.forename: Dale
authors.initials: D
authors.lastname: Brown
authors.forename: Jeremy
authors.initials: J
authors.lastname: Freeman
authors.forename: Ralph
authors.initials: R
authors.lastname: Gilbert
authors.forename: Patrick
authors.initials: P
authors.lastname: Gullane
authors.forename: Ian
authors.initials: I
authors.lastname: Witterick
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000601:surgery*; D003131:Combined Modality Therapy; D003680:Deglutition Disorders / Q000453:epidemiology; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D009364:Neoplasm Recurrence, Local; D009959:Oropharyngeal Neoplasms / Q000532:radiotherapy* / Q000601:surgery*; D011379:Prognosis; D011832:Radiation Injuries / Q000453:epidemiology; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome