title: Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: normal tissue complication probability modeling with latent time correction.
abstract: OBJECTIVE
  To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.
  
  
  METHODS
  Patients with HNSCC receiving definitive radiotherapy with 66-68Gy without surgery were followed up with serial post-treatment thyrotropin (TSH) assessment. HT was defined as TSH >4.0mU/l. Data were analyzed with both a logistic and a mixture model (correcting for latency) to determine risk factors for HT and develop an NTCP model based on mean thyroid dose (MTD) and thyroid volume.
  
  
  RESULTS
  203 patients were included. Median follow-up: 25.1months. Five-year estimated risk of HT was 25.6%. In the mixture model, the only independent risk factors for HT were thyroid volume (cm(3)) (OR=0.75 [95% CI: 0.64-0.85], p<0.001) and MTD (Gy) (OR=1.12 [95% CI: 1.07-1.20], p<0.001). From the mixture NTCP-model individual dose constraints for a 25% risk of HT were 26, 38, 48 and 61Gy for thyroid volumes of 10, 15, 20 and 25cm(3), respectively.
  
  
  CONCLUSIONS
  Comparing the logistic and mixture models demonstrates the importance of latent-time correction in NTCP-modeling. Thyroid dose constraints in treatment planning should be individualized based on thyroid volume.
authors.affiliation: Department of Oncology, Odense University Hospital, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: Marianne.roenjom@rsyd.dk.
authors.forename: Marianne Feen
authors.initials: MF
authors.lastname: Rønjom
authors.forename: Carsten
authors.initials: C
authors.lastname: Brink
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
authors.forename: Jørgen
authors.initials: J
authors.lastname: Johansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D015331:Cohort Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011336:Probability; D011832:Radiation Injuries / Q000209:etiology*; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D013972:Thyrotropin / Q000097:blood
chemical_list: D013972:Thyrotropin
keywords: Head-and-neck cancer; Hypothyroidism; Mixture model; Normal tissue complication probability; Radiotherapy; Thyroid gland constraint