title: Multivariable modeling of radiotherapy outcomes, including dose-volume and clinical factors.
abstract: OBJECTIVE
  The probability of a specific radiotherapy outcome is typically a complex, unknown function of dosimetric and clinical factors. Current models are usually oversimplified. We describe alternative methods for building multivariable dose-response models.
  
  
  METHODS
  Representative data sets of esophagitis and xerostomia are used. We use a logistic regression framework to approximate the treatment-response function. Bootstrap replications are performed to explore variable selection stability. To guard against under/overfitting, we compare several analytical and data-driven methods for model-order estimation. Spearman's coefficient is used to evaluate performance robustness. Novel graphical displays of variable cross correlations and bootstrap selection are demonstrated.
  
  
  RESULTS
  Bootstrap variable selection techniques improve model building by reducing sample size effects and unveiling variable cross correlations. Inference by resampling and Bayesian approaches produced generally consistent guidance for model order estimation. The optimal esophagitis model consisted of 5 dosimetric/clinical variables. Although the xerostomia model could be improved by combining clinical and dose-volume factors, the improvement would be small.
  
  
  CONCLUSIONS
  Prediction of treatment response can be improved by mixing clinical and dose-volume factors. Graphical tools can mitigate the inherent complexity of multivariable modeling. Bootstrap-based variable selection analysis increases the reliability of reported models. Statistical inference methods combined with Spearman's coefficient provide an efficient approach to estimating optimal model order.
authors.affiliation: Department of Radiation Oncology, Washington University, St. Louis, MO 63110, USA. deasy@wustl.edu
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bradley
authors.forename: Angel I
authors.initials: AI
authors.lastname: Blanco
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Lindsay
authors.forename: Milos
authors.initials: M
authors.lastname: Vicic
authors.forename: Andrew
authors.initials: A
authors.lastname: Hope
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D004941:Esophagitis / Q000209:etiology*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000532:radiotherapy*; D015233:Models, Statistical; D015999:Multivariate Analysis; D011336:Probability; D011832:Radiation Injuries; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014987:Xerostomia / Q000209:etiology*