title: Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial.
abstract: BACKGROUND
  Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy.
  
  
  METHODS
  We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres. Patients were randomly assigned in a 1:1:1 ratio to receive conventional or hypofractionated high-dose intensity-modulated radiotherapy, and all were given with 3-6 months of neoadjuvant androgen suppression. Computer-generated random permuted blocks were used, with risk of seminal vesicle involvement and radiotherapy-treatment centre as stratification factors. The conventional schedule was 37 fractions of 2 Gy to a total of 74 Gy. The two hypofractionated schedules involved 3 Gy treatments given in either 20 fractions to a total of 60 Gy, or 19 fractions to a total of 57 Gy. The primary endpoint was proportion of patients with grade 2 or worse toxicity at 2 years on the Radiation Therapy Oncology Group (RTOG) scale. The primary analysis included all patients who had received at least one fraction of radiotherapy and completed a 2 year assessment. Treatment allocation was not masked and clinicians were not blinded. Stage 3 of this trial completed the planned recruitment in June, 2011. This study is registered, number ISRCTN97182923.
  
  
  RESULTS
  153 men recruited to stages 1 and 2 were randomly assigned to receive conventional treatment of 74 Gy, 153 to receive 60 Gy, and 151 to receive 57 Gy. With 50·5 months median follow-up (IQR 43·5-61·3), six (4·3%; 95% CI 1·6-9·2) of 138 men in the 74 Gy group had bowel toxicity of grade 2 or worse on the RTOG scale at 2 years, as did five (3·6%; 1·2-8·3) of 137 men in the 60 Gy group, and two (1·4%; 0·2-5·0) of 143 men in the 57 Gy group. For bladder toxicities, three (2·2%; 0·5-6·2) of 138 men, three (2·2%; 0·5-6·3) of 137, and none (0·0%; 97·5% CI 0·0-2·6) of 143 had scores of grade 2 or worse on the RTOG scale at 2 years.
  
  
  CONCLUSIONS
  Hypofractionated high-dose radiotherapy seems equally well tolerated as conventionally fractionated treatment at 2 years.
  
  
  BACKGROUND
  Stage 1 was funded by the Academic Radiotherapy Unit, Cancer Research UK programme grant; stage 2 was funded by the Department of Health and Cancer Research UK.
authors.affiliation: Royal Marsden NHS Foundation Trust, London, UK. david.dearnaley@icr.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.forename: Isabel
authors.initials: I
authors.lastname: Syndikus
authors.forename: Georges
authors.initials: G
authors.lastname: Sumo
authors.forename: Margaret
authors.initials: M
authors.lastname: Bidmead
authors.forename: David
authors.initials: D
authors.lastname: Bloomfield
authors.forename: Catharine
authors.initials: C
authors.lastname: Clark
authors.forename: Annie
authors.initials: A
authors.lastname: Gao
authors.forename: Shama
authors.initials: S
authors.lastname: Hassan
authors.forename: Alan
authors.initials: A
authors.lastname: Horwich
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
authors.forename: Vincent
authors.initials: V
authors.lastname: Khoo
authors.forename: Peter
authors.initials: P
authors.lastname: Kirkbride
authors.forename: Helen
authors.initials: H
authors.lastname: Mayles
authors.forename: Philip
authors.initials: P
authors.lastname: Mayles
authors.forename: Olivia
authors.initials: O
authors.lastname: Naismith
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
authors.forename: Helen
authors.initials: H
authors.lastname: Patterson
authors.forename: Martin
authors.initials: M
authors.lastname: Russell
authors.forename: Christopher
authors.initials: C
authors.lastname: Scrase
authors.forename: Chris
authors.initials: C
authors.lastname: South
authors.forename: John
authors.initials: J
authors.lastname: Staffurth
authors.forename: Emma
authors.initials: E
authors.lastname: Hall
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019583:Dose Fractionation, Radiation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D017430:Prostate-Specific Antigen