title: Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy.
abstract: Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning.
  
  
  
  Predictive models of severe acute mucositis were generated using radiotherapy dose (dose-volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models.
  
  
  
  The dose-volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis.
  
  
  
  The RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence.
authors.affiliation: Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. Electronic address: jamie.dean@icr.ac.uk.
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Dean
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Kee H
authors.initials: KH
authors.lastname: Wong
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Liam C
authors.initials: LC
authors.lastname: Welsh
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Ann-Britt
authors.initials: AB
authors.lastname: Jones
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schick
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Newbold
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Shreerang A
authors.initials: SA
authors.lastname: Bhide
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Nutting
authors.affiliation: Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gulliford
mesh_terms: D000208:Acute Disease; D000066491:Clinical Decision-Making; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D016015:Logistic Models; D000069550:Machine Learning; D008297:Male; D008962:Models, Theoretical; D011336:Probability; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D013280:Stomatitis / Q000209:etiology*
keywords: Dose–response modelling; Head and neck radiotherapy; Machine learning; NTCP modelling; Oral mucositis; Spatial dose metrics