title: Evaluation of the Risk of Grade 3 Oral and Pharyngeal Dysphagia Using Atlas-Based Method and Multivariate Analyses of Individual Patient Dose Distributions.
abstract: OBJECTIVE
  The study aimed to apply the atlas of complication incidence (ACI) method to patients receiving radical treatment for head and neck squamous cell carcinomas (HNSCC), to generate constraints based on dose-volume histograms (DVHs), and to identify clinical and dosimetric parameters that predict the risk of grade 3 oral mucositis (g3OM) and pharyngeal dysphagia (g3PD).
  
  
  METHODS
  Oral and pharyngeal mucosal DVHs were generated for 253 patients who received radiation (RT) or chemoradiation (CRT). They were used to produce ACI for g3OM and g3PD. Multivariate analysis (MVA) of the effect of dosimetry, clinical, and patient-related variables was performed using logistic regression and bootstrapping. Receiver operating curve (ROC) analysis was also performed, and the Youden index was used to find volume constraints that discriminated between volumes that predicted for toxicity.
  
  
  RESULTS
  We derived statistically significant dose-volume constraints for g3OM over the range v28 to v70. Only 3 statistically significant constraints were derived for g3PD v67, v68, and v69. On MVA, mean dose to the oral mucosa predicted for g3OM and concomitant chemotherapy and mean dose to the inferior constrictor (IC) predicted for g3PD.
  
  
  CONCLUSIONS
  We have used the ACI method to evaluate incidences of g3OM and g3PD and ROC analysis to generate constraints to predict g3OM and g3PD derived from entire individual patient DVHs. On MVA, the strongest predictors were radiation dose (for g3OM) and concomitant chemotherapy (for g3PD).
authors.affiliation: Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Otter
authors.affiliation: Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schick
authors.affiliation: Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gulliford
authors.affiliation: Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow India.
authors.forename: Punita
authors.initials: P
authors.lastname: Lal
authors.affiliation: Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Franceschini
authors.affiliation: Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Newbold
authors.affiliation: Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nutting
authors.affiliation: Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.affiliation: Department of Clinical Oncology, Royal Marsden Hospital, Sutton and London, UK; The Institute of Cancer Research, London, UK; Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Milan, Italy. Electronic address: shreerang.bhide@icr.ac.uk.
authors.forename: Shreerang
authors.initials: S
authors.lastname: Bhide
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage; D003196:Computer Graphics; D003680:Deglutition Disorders / Q000453:epidemiology* / Q000209:etiology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000453:epidemiology* / Q000209:etiology; D015999:Multivariate Analysis; D058958:Organs at Risk / Q000000981:diagnostic imaging; D012372:ROC Curve; D011859:Radiography; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D018570:Risk Assessment
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil