title: Late rectal toxicity on RTOG 94-06: analysis using a mixture Lyman model.
abstract: OBJECTIVE
  To estimate the parameters of the Lyman normal-tissue complication probability model using censored time-to-event data for Grade ≥2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group 94-06, a dose-escalation trial designed to determine the maximum tolerated dose for three-dimensional conformal radiotherapy of prostate cancer.
  
  
  METHODS
  The Lyman normal-tissue complication probability model was fitted to data from 1,010 of the 1,084 patients accrued on Radiation Therapy Oncology Group 94-06 using an approach that accounts for censored observations. Separate fits were obtained using dose-volume histograms for whole rectum and dose-wall histograms for rectal wall.
  
  
  RESULTS
  With a median follow-up of 7.2 years, the crude incidence of Grade ≥2 late rectal toxicity was 15% (n = 148). The parameters of the Lyman model fitted to dose-volume histograms data, with 95% profile-likelihood confidence intervals, were TD(50) = 79.1 Gy (75.3 Gy, 84.3 Gy), m = 0.146 (0.107, 0.225), and n = 0.077 (0.041, 0.156). The fit based on dose-wall histogram data was not significantly different. Patients with cardiovascular disease had a significantly higher incidence of late rectal toxicity (p = 0.015), corresponding to a dose-modifying factor of 5.3%. No significant association with late rectal toxicity was found for diabetes, hypertension, rectal volume, rectal length, neoadjuvant hormone therapy, or prescribed dose per fraction (1.8 Gy vs. 2 Gy).
  
  
  CONCLUSIONS
  These results, based on a large cohort of patients from a multi-institutional trial, are expected to be widely representative of the ability of the Lyman model to describe the long-term risk of Grade ≥2 late rectal toxicity after three-dimensional conformal radiotherapy of prostate cancer.
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA. sltucker@mdanderson.org
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Walter R
authors.initials: WR
authors.lastname: Bosch
authors.forename: Jeff
authors.initials: J
authors.lastname: Michalski
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winter
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.forename: James A
authors.initials: JA
authors.lastname: Purdy
authors.forename: Deborah
authors.initials: D
authors.lastname: Kuban
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Lee
authors.forename: M Rex
authors.initials: MR
authors.lastname: Cheung
authors.forename: Howard D
authors.initials: HD
authors.lastname: Thames
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications; D048909:Diabetes Complications / Q000453:epidemiology; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D020714:Maximum Tolerated Dose; D008954:Models, Biological; D015233:Models, Statistical; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology*; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D012007:Rectum / Q000033:anatomy & histology / Q000528:radiation effects*; D013997:Time Factors