title: Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models.
abstract: OBJECTIVE
  Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade > or = 2 rectal bleeding.
  
  
  METHODS
  Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD, (3) serial reconstruction unit (RU) model, (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation.
  
  
  RESULTS
  Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models.
  
  
  CONCLUSIONS
  Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse.
authors.affiliation: Section for Biomedical Physics, University Hospital for Radiation Oncology, Tübingen, Germany. Matthias.Soehn@med.uni-tuebingen.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Söhn
authors.forename: Di
authors.initials: D
authors.lastname: Yan
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.forename: Elisa
authors.initials: E
authors.lastname: Meldolesi
authors.forename: Carlos
authors.initials: C
authors.lastname: Vargas
authors.forename: Markus
authors.initials: M
authors.lastname: Alber
mesh_terms: D016001:Confidence Intervals; D004307:Dose-Response Relationship, Radiation; D006471:Gastrointestinal Hemorrhage / Q000209:etiology*; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D015233:Models, Statistical; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000150:complications*; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012007:Rectum / Q000528:radiation effects*; D018570:Risk Assessment