title: Statistical validation of normal tissue complication probability models.
abstract: OBJECTIVE
  To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models.
  
  
  METHODS
  A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve.
  
  
  RESULTS
  Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing.
  
  
  CONCLUSIONS
  Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. c.j.xu@umcg.nl
authors.forename: Cheng-Jian
authors.initials: CJ
authors.lastname: Xu
authors.forename: Arjen
authors.initials: A
authors.lastname: van der Schaaf
authors.forename: Aart A
authors.initials: AA
authors.lastname: Van't Veld
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.forename: Cornelis
authors.initials: C
authors.lastname: Schilstra
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D058958:Organs at Risk / Q000528:radiation effects*; D010306:Parotid Gland / Q000528:radiation effects; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012044:Regression Analysis; D013363:Submandibular Gland / Q000528:radiation effects; D035501:Uncertainty; D014987:Xerostomia / Q000175:diagnosis / Q000209:etiology*