title: Impact of treatment planning and delivery factors on gastrointestinal toxicity: an analysis of data from the RADAR prostate radiotherapy trial.
abstract: BACKGROUND
  To assess the impact of incremental modifications of treatment planning and delivery technique, as well as patient anatomical factors, on late gastrointestinal toxicity using data from the TROG 03.04 RADAR prostate radiotherapy trial.
  
  
  METHODS
  The RADAR trial accrued 813 external beam radiotherapy participants during 2003-2008 from 23 centres. Following review and archive to a query-able database, digital treatment plans and data describing treatment technique for 754 patients were available for analysis. Treatment demographics, together with anatomical features, were assessed using uni- and multivariate regression models against late gastrointestinal toxicity at 18-, 36- and 54-month follow-up. Regression analyses were reviewed in the context of dose-volume data for the rectum and anal canal.
  
  
  RESULTS
  A multivariate analysis at 36-month follow-up shows that patients planned using a more rigorous dose calculation algorithm (DCA) was associated with a lower risk of stool frequency (OR: 0.435, CI: 0.242-0.783, corrected p = 0.04). Patients using laxative as a method of bowel preparation had higher risk of having increased stool frequency compared to patients with no dietary intervention (OR: 3.639, CI: 1.502-8.818, corrected p = 0.04). Despite higher risks of toxicities, the anorectum, anal canal and rectum dose-volume histograms (DVH) indicate patients using laxative had unremarkably different planned dose distributions. Patients planned with a more rigorous DCA had lower median DVH values between EQD23 = 15 Gy and EQD23 = 35 Gy. Planning target volume (PTV), conformity index, rectal width and prescription dose were not significant when adjusted for false discovery rate. Number of beams, beam energy, treatment beam definition, positioning orientation, rectum-PTV separation, rectal length and mean cross sectional area did not affect the risk of toxicities.
  
  
  CONCLUSIONS
  The RADAR study dataset has allowed an assessment of technical modifications on gastrointestinal toxicity. A number of interesting associations were subsequently found and some factors, previously hypothesised to influence toxicity, did not demonstrate any significant impact. We recommend trial registries be encouraged to record technical modifications introduced during the trial in order for more powerful evidence to be gathered regarding the impact of the interventions.
authors.affiliation: School of Physics, University of Western Australia, Crawley, Western Australia, Australia. noorazrul.yahya@research.uwa.edu.au.|School of Health Sciences, National University of Malaysia, Bangi, Malaysia. noorazrul.yahya@research.uwa.edu.au.
authors.forename: Noorazrul
authors.initials: N
authors.lastname: Yahya
authors.affiliation: School of Physics, University of Western Australia, Crawley, Western Australia, Australia. Martin.Ebert@health.wa.gov.au.|Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. Martin.Ebert@health.wa.gov.au.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Ebert
authors.affiliation: Institute for Health Research, University of Notre Dame, Fremantle, Western Australia, Australia. max.bulsara@nd.edu.au.
authors.forename: Max
authors.initials: M
authors.lastname: Bulsara
authors.affiliation: Department of Physical Sciences, Peter MacCallum Cancer Centre, Victoria, Australia. annette.haworth@petermac.org.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia. annette.haworth@petermac.org.
authors.forename: Annette
authors.initials: A
authors.lastname: Haworth
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. Rachel.Kearvell@health.wa.gov.au.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kearvell
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. kerwyn.foo@sydney.edu.au.
authors.forename: Kerwyn
authors.initials: K
authors.lastname: Foo
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. Angel.Kennedy@health.wa.gov.au.
authors.forename: Angel
authors.initials: A
authors.lastname: Kennedy
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. Sharon.Richardson@health.wa.gov.au.
authors.forename: Sharon
authors.initials: S
authors.lastname: Richardson
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. Michele.Krawiec@health.wa.gov.au.
authors.forename: Michele
authors.initials: M
authors.lastname: Krawiec
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. David.Joseph@health.wa.gov.au.|School of Surgery, University of Western Australia, Crawley, Western Australia, Australia. David.Joseph@health.wa.gov.au.
authors.forename: David J
authors.initials: DJ
authors.lastname: Joseph
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. jim.denham@newcastle.edu.au.
authors.forename: Jim W
authors.initials: JW
authors.lastname: Denham
mesh_terms: D000465:Algorithms; D041981:Gastrointestinal Tract / Q000528:radiation effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods*