title: Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications.
abstract: BACKGROUND
  Derivation of dose-volume correlated with toxicity for multi-modal treatments can be difficult due to the perceived need for voxel-by-voxel dose accumulation. With data available for a single-institution cohort with long follow-up, an investigation was undertaken into rectal dose-volume effects for gastrointestinal toxicities after deformably-registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR) brachytherapy prostate treatment.
  
  
  METHODS
  One hundred and eighteen patients received EBRT in 23 fractions of 2 Gy and HDR (TG43 algorithm) in 3 fractions of 6.5 Gy. Results for the Late Effects of Normal Tissues - Subjective, Objective, Management and Analytic toxicity assessments were available with a median follow-up of 72 months. The HDR CT was deformably-registered to the EBRT CT. Doses were corrected for dose fractionation. Rectum dose-volume histogram (DVH) parameters were calculated in two ways. (1) Distribution-adding: parameters were calculated after the EBRT dose distribution was 3D-summed with the registered HDR dose distribution. (2) Parameter-adding: the EBRT DVH parameters were added to HDR DVH parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate parameters with late peak toxicity (dichotomised at grade 1 or 2).
  
  
  RESULTS
  The 48-80, 40-63 and 49-55 Gy dose regions from distribution-adding were significantly correlated with rectal bleeding, urgency/tenesmus and stool frequency respectively. Additionally, urgency/tenesmus and anorectal pain were associated with the 25-26 Gy and 44-48 Gy dose regions from distribution-adding respectively. Parameter-adding also indicated the low-mid dose region was significantly correlated with stool frequency and proctitis.
  
  
  CONCLUSIONS
  This study confirms significant dose-histogram effects for gastrointestinal toxicities after including deformable registration to combine phases of EBRT/HDR prostate cancer treatment. The findings from distribution-adding were in most cases consistent with those from parameter-adding. The mid-high dose range and near maximum doses were important for rectal bleeding. The distribution-adding mid-high dose range was also important for stool frequency and urgency/tenesmus. We encourage additional studies in a variety of institutions using a variety of dose accumulation methods with appropriate inter-fraction motion management.
  
  
  BACKGROUND
  NCT NCT00193856 . Retrospectively registered 12 September 2005.
authors: School of Physics (M013), University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia. calyn.moulton@research.uwa.edu.au.
authors: Calyn R
authors: CR
authors: Moulton
authors: School of Physics (M013), University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors: Michael J
authors: MJ
authors: House
authors: Radiation Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia.
authors: Victoria
authors: V
authors: Lye
authors: Radiation Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia.
authors: Colin I
authors: CI
authors: Tang
authors: Radiation Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia.
authors: Michele
authors: M
authors: Krawiec
authors: Radiation Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia.|School of Surgery, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors: David J
authors: DJ
authors: Joseph
authors: School of Medicine and Population Health, University of Newcastle, University Drive, Callaghan, NSW, 2308, Australia.
authors: James W
authors: JW
authors: Denham
authors: School of Physics (M013), University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.|Radiation Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia.
authors: Martin A
authors: MA
authors: Ebert
mesh_terms: D001918:Brachytherapy / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000209:etiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D011467:Prostate / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D012042:Registries; D012984:Software; D014057:Tomography, X-Ray Computed
keywords: Deformable registration; Distribution-adding; Gastrointestinal toxicity