title: Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397).
abstract: OBJECTIVE
  In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects.
  
  
  METHODS
  The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires.
  
  
  RESULTS
  In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade >or=2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade >or=2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade >or=2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively.
  
  
  CONCLUSIONS
  There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.
authors.affiliation: Clatterbridge Centre for Oncology, Bebington, United Kingdom.
authors.forename: Isabel
authors.initials: I
authors.lastname: Syndikus
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Morgan
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sydes
authors.forename: John D
authors.initials: JD
authors.lastname: Graham
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
mesh_terms: D003967:Diarrhea / Q000453:epidemiology / Q000209:etiology*; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008297:Male; D009367:Neoplasm Staging; D011349:Proctitis / Q000453:epidemiology / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D012002:Rectal Diseases / Q000453:epidemiology / Q000209:etiology*; D012007:Rectum / Q000528:radiation effects; D006113:United Kingdom