title: Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.
abstract: OBJECTIVE
  To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models.
  
  
  METHODS
  Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion.
  
  
  RESULTS
  Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy.
  
  
  CONCLUSIONS
  The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.
authors.affiliation: Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Bakhshandeh
authors.forename: Bijan
authors.initials: B
authors.lastname: Hashemi
authors.forename: Seied Rabi Mehdi
authors.initials: SR
authors.lastname: Mahdavi
authors.forename: Alireza
authors.initials: A
authors.lastname: Nikoofar
authors.forename: Maryam
authors.initials: M
authors.lastname: Vasheghani
authors.forename: Anoshirvan
authors.initials: A
authors.lastname: Kazemnejad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016001:Confidence Intervals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000209:etiology*; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D058958:Organs at Risk / Q000528:radiation effects; D011336:Probability; D011446:Prospective Studies; D011832:Radiation Injuries / Q000097:blood / Q000150:complications*; D011859:Radiography; D011880:Radiotherapy Planning, Computer-Assisted; D018709:Statistics, Nonparametric; D013961:Thyroid Gland / Q000528:radiation effects*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine