title: Dose-volume constraints to reduce rectal side effects from prostate radiotherapy: evidence from MRC RT01 Trial ISRCTN 47772397.
abstract: OBJECTIVE
  Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>/=50 Gy). Evidence is emerging that lower doses could also be important.
  
  
  METHODS
  Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity.
  
  
  RESULTS
  A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<or=80%, V40<or=65%, V50<or=55%, V60<or=40%, V65<or=30%, V70<or=15%, and V75<or=3%.
  
  
  CONCLUSIONS
  Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.
authors.affiliation: Joint Department of Physics, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, Sutton, United Kingdom.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gulliford
authors.forename: Kerwyn
authors.initials: K
authors.lastname: Foo
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Morgan
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Aird
authors.forename: A Margaret
authors.initials: AM
authors.lastname: Bidmead
authors.forename: Helen
authors.initials: H
authors.lastname: Critchley
authors.forename: Philip M
authors.initials: PM
authors.lastname: Evans
authors.forename: Stefano
authors.initials: S
authors.lastname: Gianolini
authors.forename: W Philip
authors.initials: WP
authors.lastname: Mayles
authors.forename: A Rollo
authors.initials: AR
authors.lastname: Moore
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Nieto
authors.forename: Mike
authors.initials: M
authors.lastname: Partridge
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sydes
authors.forename: Steve
authors.initials: S
authors.lastname: Webb
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
mesh_terms: D004307:Dose-Response Relationship, Radiation; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000150:complications / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D012002:Rectal Diseases / Q000209:etiology; D012007:Rectum / Q000473:pathology / Q000528:radiation effects*