title: The benefits of including clinical factors in rectal normal tissue complication probability modeling after radiotherapy for prostate cancer.
abstract: OBJECTIVE
  To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial.
  
  
  METHODS
  Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits.
  
  
  RESULTS
  Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was "previous abdominal surgery." As second significant (p = 0.012-0.016) factor, "cardiac history" was included in all three rectal bleeding fits, whereas including "diabetes" was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D(50). Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints.
  
  
  CONCLUSIONS
  Comparable prediction models were obtained with LKB, RS, and logistic NTCP models. Including clinical factors improved the predictive power of all models significantly.
authors.affiliation: Radiation Oncology Department, University Hospitals Leuven, Leuven, Belgium. gilles.defraene@uzleuven.be
authors.forename: Gilles
authors.initials: G
authors.lastname: Defraene
authors.forename: Laura
authors.initials: L
authors.lastname: Van den Bergh
authors.forename: Abrahim
authors.initials: A
authors.lastname: Al-Mamgani
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
authors.forename: Wilma
authors.initials: W
authors.lastname: Heemsbergen
authors.forename: Frank
authors.initials: F
authors.lastname: Van den Heuvel
authors.forename: Joos V
authors.initials: JV
authors.lastname: Lebesque
mesh_terms: D000005:Abdomen / Q000601:surgery; D000368:Aged; D019540:Area Under Curve; D002318:Cardiovascular Diseases / Q000150:complications; D005242:Fecal Incontinence / Q000209:etiology*; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology*; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D015233:Models, Statistical; D011336:Probability; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D012372:ROC Curve; D011832:Radiation Injuries / Q000150:complications*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D012007:Rectum / Q000528:radiation effects*