title: Rectal bleeding, fecal incontinence, and high stool frequency after conformal radiotherapy for prostate cancer: normal tissue complication probability modeling.
abstract: OBJECTIVE
  To analyze whether inclusion of predisposing clinical features in the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model improves the estimation of late gastrointestinal toxicity.
  
  
  METHODS
  This study includes 468 prostate cancer patients participating in a randomized trial comparing 68 with 78 Gy. We fitted the probability of developing late toxicity within 3 years (rectal bleeding, high stool frequency, and fecal incontinence) with the original, and a modified LKB model, in which a clinical feature (e.g., history of abdominal surgery) was taken into account by fitting subset specific TD50s. The ratio of these TD50s is the dose-modifying factor for that clinical feature. Dose distributions of anorectal (bleeding and frequency) and anal wall (fecal incontinence) were used.
  
  
  RESULTS
  The modified LKB model gave significantly better fits than the original LKB model. Patients with a history of abdominal surgery had a lower tolerance to radiation than did patients without previous surgery, with a dose-modifying factor of 1.1 for bleeding and of 2.5 for fecal incontinence. The dose-response curve for bleeding was approximately two times steeper than that for frequency and three times steeper than that for fecal incontinence.
  
  
  CONCLUSIONS
  Inclusion of predisposing clinical features significantly improved the estimation of the NTCP. For patients with a history of abdominal surgery, more severe dose constraints should therefore be used during treatment plan optimization.
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Stephanie T H
authors.initials: ST
authors.lastname: Peeters
authors.forename: Mischa S
authors.initials: MS
authors.lastname: Hoogeman
authors.forename: Wilma D
authors.initials: WD
authors.lastname: Heemsbergen
authors.forename: Augustinus A M
authors.initials: AA
authors.lastname: Hart
authors.forename: Peter C M
authors.initials: PC
authors.lastname: Koper
authors.forename: Joos V
authors.initials: JV
authors.lastname: Lebesque
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017326:Clinical Trials, Phase III as Topic; D016001:Confidence Intervals; D003672:Defecation / Q000528:radiation effects*; D005242:Fecal Incontinence / Q000209:etiology*; D006471:Gastrointestinal Hemorrhage / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011336:Probability; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012007:Rectum / Q000528:radiation effects*