title: Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study.
abstract: BACKGROUND
  Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group.
  
  
  METHODS
  As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1,607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS.
  
  
  RESULTS
  One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (>/= 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7-21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1-694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1-238.2), and osteoporosis (RR = 24.7; 95% CI 9.9-61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7-109.8), blood clots (RR = 5.7; 95% CI 3.2-10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5-2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy.
  
  
  CONCLUSIONS
  Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. gurney@upi.umn.edu
authors.forename: James G
authors.initials: JG
authors.lastname: Gurney
authors.forename: Nina S
authors.initials: NS
authors.lastname: Kadan-Lottick
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Neglia
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
authors.forename: Judy A
authors.initials: JA
authors.lastname: Punyko
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: H Stacy
authors.initials: HS
authors.lastname: Nicholson
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wolden
authors.forename: Dawn E
authors.initials: DE
authors.lastname: McNeil
authors.forename: Ann C
authors.initials: AC
authors.lastname: Mertens
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects; D001932:Brain Neoplasms / Q000628:therapy*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D002648:Child; D004700:Endocrine System Diseases / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D011878:Radiotherapy / Q000009:adverse effects; D012306:Risk; D017741:Survivors
chemical_list: D000970:Antineoplastic Agents