title: Technical quality assurance during the TROG 03.04 RADAR prostate radiotherapy trial: are the results reflected in observed toxicity rates?
abstract: BACKGROUND
  Multicentre radiotherapy clinical trials can incorporate quality assurance (QA) procedures for ensuring consistent application of the trial protocol in the planning, delivery and reporting of participant treatments. Subsequently detected variations from trial protocol have previously been shown to reduce treatment efficacy, although little has been shown for toxicity rates. The purpose of this study was to investigate the association of QA measures and protocol variations on toxicity incidence in the context of a prostate radiotherapy trial.
  
  
  METHODS
  Using QA records from the TROG 03.04 RADAR trial, the impact of variations on gastrointestinal (GI) and genito-urinary (GU) toxicities was investigated.
  
  
  RESULTS
  Protocol variation rates were lower than reported in previous studies, and showed little correlation with GI toxicity outcomes. Variations classified as 'major' showed a non-significant trend for increased toxicity relative to those classified as 'minor'. Results from a Level III phantom-based dosimetry study showed some correlation with GI toxicity, whereas ranking on a set-up accuracy study did not impact on toxicity. Toxicity in general increased with the number of participants accrued per centre, at odds with previous reports relating to disease progression, with a potential link to increases in low-mid-range rectal doses in the cohort from higher-accruing centres. No QA-related variables correlated with GU toxicities.
  
  
  CONCLUSIONS
  Besides non-significant trends, minimal association was observed between QA variables and toxicity rates for the RADAR trial. The intention of the trial's QA programme was to reduce treatment variations and minimise toxicity in the context of a relevantly advanced treatment approach.
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, University of Western Australia, Perth, Australia; School of Physics, University of Western Australia, Perth, Australia.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Ebert
authors.forename: Max
authors.initials: M
authors.lastname: Bulsara
authors.forename: Annette
authors.initials: A
authors.lastname: Haworth
authors.forename: Rachel
authors.initials: R
authors.lastname: Kearvell
authors.forename: Sharon
authors.initials: S
authors.lastname: Richardson
authors.forename: Angel
authors.initials: A
authors.lastname: Kennedy
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Spry
authors.forename: Sean A
authors.initials: SA
authors.lastname: Bydder
authors.forename: David J
authors.initials: DJ
authors.lastname: Joseph
authors.forename: James W
authors.initials: JW
authors.lastname: Denham
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D015984:Causality; D015897:Comorbidity; D005767:Gastrointestinal Diseases / Q000453:epidemiology*; D019983:Guideline Adherence / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008297:Male; D052801:Male Urogenital Diseases / Q000453:epidemiology*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000532:radiotherapy*; D011785:Quality Assurance, Health Care / Q000592:standards*; D011832:Radiation Injuries / Q000453:epidemiology*; D011835:Radiation Protection / Q000592:standards*; D061106:Radiotherapy Setup Errors / Q000517:prevention & control / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
keywords: clinical trail; quality assurance; radiation oncology; toxicity