title: NTCP models for patient-rated xerostomia and sticky saliva after treatment with intensity modulated radiotherapy for head and neck cancer: the role of dosimetric and clinical factors.
abstract: OBJECTIVE
  The purpose of this multicentre prospective study was to develop multivariable logistic regression models to make valid predictions about the risk of moderate-to-severe patient-rated xerostomia (XER(M6)) and sticky saliva 6 months (STIC(M6)) after primary treatment with intensity modulated radiotherapy (IMRT) with or without chemotherapy for head and neck cancer (HNC).
  
  
  METHODS
  The study population was composed of 178 consecutive HNC patients treated with IMRT. All patients were included in a standard follow up programme in which acute and late side effects and quality of life were prospectively assessed, prior to, during and after treatment. The primary endpoints were XER(M6) and STIC(M6) as assessed by the EORTC QLQ-H&N35 after completing IMRT. Organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate-to-severe xerostomia or sticky saliva, respectively, at baseline were excluded. The optimal number of variables for a multivariate logistic regression model was determined using a bootstrapping method.
  
  
  RESULTS
  Eventually, 51.6% of the cases suffered from XER(M6). The multivariate analysis showed that the mean contralateral parotid gland dose and baseline xerostomia (none vs. a bit) were the most important predictors for XER(M6). For the multivariate NTCP model, the area under the receiver operating curve (AUC) was 0.68 (95% CI 0.60-0.76) and the discrimination slope was 0.10, respectively. Calibration was good with a calibration slope of 1.0. At 6 months after IMRT, 35.6% of the cases reported STIC(M6). The mean contralateral submandibular gland dose, the mean sublingual dose and the mean dose to the minor salivary glands located in the soft palate were most predictive for STIC(M6). For this model, the AUC was 0.70 (95% CI 0.61-0.78) and the discrimination slope was 0.12. Calibration was good with a calibration slope of 1.0.
  
  
  CONCLUSIONS
  The multivariable NTCP models presented in this paper can be used to predict patient-rated xerostomia and sticky saliva. The dose volume parameters included in the models can be used to further optimise IMRT treatment.
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. i.beetz@umcg.nl
authors.forename: Ivo
authors.initials: I
authors.lastname: Beetz
authors.forename: Cornelis
authors.initials: C
authors.lastname: Schilstra
authors.forename: Arjen
authors.initials: A
authors.lastname: van der Schaaf
authors.forename: Edwin R
authors.initials: ER
authors.lastname: van den Heuvel
authors.forename: Patricia
authors.initials: P
authors.lastname: Doornaert
authors.forename: Peter
authors.initials: P
authors.lastname: van Luijk
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
authors.forename: Bernard F A M
authors.initials: BF
authors.lastname: van der Laan
authors.forename: Charles R
authors.initials: CR
authors.lastname: Leemans
authors.forename: Henk P
authors.initials: HP
authors.lastname: Bijl
authors.forename: Miranda E M C
authors.initials: ME
authors.lastname: Christianen
authors.forename: Roel J H M
authors.initials: RJ
authors.lastname: Steenbakkers
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011336:Probability; D011446:Prospective Studies; D011874:Radiometry; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012463:Saliva; D012469:Salivary Glands / Q000528:radiation effects; D014987:Xerostomia / Q000209:etiology*