title: Dosimetric predictors of dysphonia after intensity-modulated radiotherapy for oropharyngeal carcinoma.
abstract: OBJECTIVE
  To investigate dosimetric predictors of voice changes after whole-field intensity-modulated radiotherapy (IMRT).
  
  
  METHODS
  Patients treated with whole-field IMRT for oropharyngeal/unknown primary tumours were selected for the present retrospective study having grossly uninvolved larynx at the time of radiotherapy and at least one follow-up visit. Voice changes were prospectively scored at each follow-up examination according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 scale and self-reported by two items (HN4 and HN10) of the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-HN) questionnaire. Predictors of toxicity were investigated at logistic regression, including various patient and tumour characteristics, as well as individual dosimetric data.
  
  
  RESULTS
  With a median follow-up of 18 months (range 3-46 months), peak CTCAE dysphonia was graded as 2 in 13 patients (10.5%), whereas 45 patients (36.3%) reported peak grade 0-1 voice changes according to FACT-HN4. Communication (FACT-HN10) was barely affected. At multivariate analysis, the mean laryngeal dose was an independent predictor of both grade 2 CTCAE dysphonia (odds ratio = 1.10, 95% confidence interval 1.01-1.20, P = 0.025) and grade 0-1 FACT-HN4 voice changes (odds ratio = 1.11, 95% confidence interval 1.04-1.18, P = 0.001). Further stratification optimised by a receiver operating characteristic (ROC) analysis showed that, to minimise the risk of grade 0-1 FACT-HN4 voice changes, the mean dose to the larynx has to be kept ≤ 49.4 Gy.
  
  
  CONCLUSIONS
  Voice changes after whole-field IMRT are common, but mild, and are strictly correlated to the dose received by the uninvolved larynx; in order to minimise the risk of side-effects, the mean dose to the larynx should be kept ≤ 50 Gy.
authors.affiliation: Radiation Oncology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: gsangui1@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Sanguineti
authors.affiliation: Radiation Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: F
authors.initials: F
authors.lastname: Ricchetti
authors.affiliation: Radiation Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: McNutt
authors.affiliation: Radiation Oncology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.affiliation: Physics, Ospedale San Raffaele, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fiorino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D055154:Dysphonia / Q000209:etiology* / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D011874:Radiometry; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Dosimetric predictors; radiotherapy; voice changes