title: Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).
abstract: OBJECTIVE
  Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT.
  
  
  METHODS
  A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system.
  
  
  RESULTS
  Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025).
  
  
  CONCLUSIONS
  In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in patients who smoked during therapy.
authors.affiliation: Department of Medical Oncology, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: Robert G
authors.initials: RG
authors.lastname: Mackenzie
authors.forename: Abdenour
authors.initials: A
authors.lastname: Nabid
authors.forename: Ian D
authors.initials: ID
authors.lastname: Hodson
authors.forename: Samy
authors.initials: S
authors.lastname: El-Sayed
authors.forename: Laval
authors.initials: L
authors.lastname: Grimard
authors.forename: Michael
authors.initials: M
authors.lastname: Brundage
authors.forename: James
authors.initials: J
authors.lastname: Wright
authors.forename: John
authors.initials: J
authors.lastname: Hay
authors.forename: Pradip
authors.initials: P
authors.lastname: Ganguly
authors.forename: Carson
authors.initials: C
authors.lastname: Leong
authors.forename: Jane
authors.initials: J
authors.lastname: Wilson
authors.forename: Richard C K
authors.initials: RC
authors.lastname: Jordan
authors.forename: Melanie
authors.initials: M
authors.lastname: Walker
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Wendy
authors.initials: W
authors.lastname: Parulekar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm; D015897:Comorbidity; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000532:radiotherapy*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000453:epidemiology* / Q000517:prevention & control; D011878:Radiotherapy / Q000379:methods* / Q000706:statistics & numerical data*; D018570:Risk Assessment / Q000379:methods*; D013280:Stomatitis / Q000453:epidemiology* / Q000517:prevention & control; D014481:United States / Q000453:epidemiology