title: A predictive model for dysphagia following IMRT for head and neck cancer: introduction of the EMLasso technique.
abstract: OBJECTIVE
  Design a model for prediction of acute dysphagia following intensity-modulated radiotherapy (IMRT) for head and neck cancer. Illustrate the use of the EMLasso technique for model selection.
  
  
  METHODS
  Radiation-induced dysphagia was scored using CTCAE v.3.0 in 189 head and neck cancer patients. Clinical data (gender, age, nicotine and alcohol use, diabetes, tumor location), treatment parameters (chemotherapy, surgery involving the primary tumor, lymph node dissection, overall treatment time), dosimetric parameters (doses delivered to pharyngeal constrictor (PC) muscles and esophagus) and 19 genetic polymorphisms were used in model building. The predicting model was achieved by EMLasso, i.e. an EM algorithm to account for missing values, applied to penalized logistic regression, which allows for variable selection by tuning the penalization parameter through crossvalidation on AUC, thus avoiding overfitting.
  
  
  RESULTS
  Fifty-three patients (28%) developed acute ≥ grade 3 dysphagia. The final model has an AUC of 0.71 and contains concurrent chemotherapy, D2 to the superior PC and the rs3213245 (XRCC1) polymorphism. The model's false negative rate and false positive rate in the optimal operation point on the ROC curve are 21% and 49%, respectively.
  
  
  CONCLUSIONS
  This study demonstrated the utility of the EMLasso technique for model selection in predictive radiogenetics.
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Belgium. kim.deruyck@UGent.be
authors.forename: Kim
authors.initials: K
authors.lastname: De Ruyck
authors.forename: Fréderic
authors.initials: F
authors.lastname: Duprez
authors.forename: Joke
authors.initials: J
authors.lastname: Werbrouck
authors.forename: Nick
authors.initials: N
authors.lastname: Sabbe
authors.forename: De Langhe
authors.initials: de L
authors.lastname: Sofie
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.forename: Indira
authors.initials: I
authors.lastname: Madani
authors.forename: Olivier
authors.initials: O
authors.lastname: Thas
authors.forename: De Neve
authors.initials: de N
authors.lastname: Wilfried
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D003680:Deglutition Disorders / Q000209:etiology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*
keywords: Dysphagia; EMLasso; Genetic polymorphisms; Predictive model; Radiotherapy