title: Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.
abstract: BACKGROUND
  To determine the risk of thyroid dysfunction and subsequent thyroid cancer among childhood acute lymphoblastic leukemia (ALL) survivors.
  
  
  METHODS
  Rates of self-reported thyroid dysfunction and thyroid cancer were determined among 3,579 ALL survivors participating in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of pediatric cancers diagnosed from 1970 to 1986, and compared with 3,846 siblings and population rates, respectively.
  
  
  RESULTS
  The cumulative incidence of hypo- and hyperthyroidism among survivors 15 years following leukemia diagnosis was 1.6% (95% CI 1.1, 2.1) and 0.6% (95% CI 0.3, 1.1), respectively, both significantly increased compared with siblings. In multivariate analysis, survivors who received >or=20 Gy cranial radiotherapy plus any spinal radiotherapy had the highest risk of subsequent hypothyroidism (HR 8.3, 95% CI 3.3, 20.5) compared with those treated with chemotherapy alone. Craniospinal radiotherapy also was associated with an increased risk of subsequent hyperthyroidism (HR 6.1, 95% CI 1.1, 34.2) compared with chemotherapy alone, as well as an increased risk of subsequent thyroid cancers (SIR 30.3, 95% CI 14.5, 55.7) compared with population rates. In radiation dosimetry analysis, pituitary doses >or=20 Gy combined with thyroid doses >or=10 Gy were associated with hypothyroidism, whereas pituitary doses >or=20 Gy combined with thyroid doses >or=15 Gy were associated with hyperthyroidism.
  
  
  CONCLUSIONS
  The risk of thyroid dysfunction and thyroid cancer was increased among childhood ALL survivors treated with craniospinal radiotherapy. In these individuals, long-term surveillance is warranted as no obvious plateau in risk was seen, even after 25 years of follow-up.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA. ericchow@u.washington.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Chow
authors.forename: Debra L
authors.initials: DL
authors.lastname: Friedman
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: John A
authors.initials: JA
authors.lastname: Whitton
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000401:mortality* / Q000628:therapy; D012307:Risk Factors; D017741:Survivors; D013959:Thyroid Diseases / Q000209:etiology*; D013964:Thyroid Neoplasms / Q000209:etiology*