title: Normal tissue complication probability (NTCP) models for late rectal bleeding, stool frequency and fecal incontinence after radiotherapy in prostate cancer patients.
abstract: Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects.
  
  
  
  The study sample was composed of 262 patients with localized or locally advanced prostate cancer (stage T1-3). Anorectal toxicity was prospectively assessed using a standardized follow-up program. Different anatomical subregions within and around the anorectum were delineated. A LASSO logistic regression analysis was used to analyze dose volume effects on toxicity.
  
  
  
  In the univariable analysis, rectal bleeding, increase in stool frequency and fecal incontinence were significantly associated with a large number of dosimetric parameters. The collinearity between these predictors was high (VIF>5). In the multivariable model, rectal bleeding was associated with the anorectum (V70) and anticoagulant use, fecal incontinence was associated with the external sphincter (V15) and the iliococcygeal muscle (V55). Finally, increase in stool frequency was associated with the iliococcygeal muscle (V45) and the levator ani (V40). No significant associations were found for rectal pain.
  
  
  
  Different anorectal side effects are associated with different anatomical substructures within and around the anorectum. The dosimetric variables associated with these side effects can be used to optimize radiotherapy treatment planning aiming at prevention of specific side effects and to estimate the benefit of new radiation technologies.
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands; Research Group Healthy Ageing, Allied Health Care and Nursing, Hanze University of Applied Sciences, Groningen, The Netherlands. Electronic address: w.schaake@pl.hanze.nl.
authors.forename: Wouter
authors.initials: W
authors.lastname: Schaake
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: van der Schaaf
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Lisanne V
authors.initials: LV
authors.lastname: van Dijk
authors.affiliation: Department of Radiology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Alfons H H
authors.initials: AH
authors.lastname: Bongaerts
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Alfons C M
authors.initials: AC
authors.lastname: van den Bergh
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
mesh_terms: D000368:Aged; D003672:Defecation / Q000528:radiation effects*; D005242:Fecal Incontinence / Q000209:etiology*; D006471:Gastrointestinal Hemorrhage / Q000209:etiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D058958:Organs at Risk; D011336:Probability; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012002:Rectal Diseases / Q000209:etiology*; D012007:Rectum / Q000528:radiation effects
keywords: Dose–volume effects; NTCP; Prediction; Prostate; Side effects; Toxicity