title: Impact of treatment exposures on cardiovascular risk and insulin resistance in childhood cancer survivors.
abstract: BACKGROUND
  Childhood cancer survivors (CCS) are more insulin resistant and have higher levels of several cardiovascular risk factors even while still children. This study examines specific treatment exposures associated with cardiovascular risk factors and insulin resistance.
  
  
  METHODS
  CCS of ages 9 to 18 years at study entry and in remission 5 years or more from diagnosis (n = 319) and 208 sibling controls were recruited into this cross-sectional study that included physiologic assessment of insulin resistance (hyperinsulinemic euglycemic clamp) and assessment of cardiovascular risk factors. Regression and recursive tree modeling were used to ascertain treatment combinations associated with insulin resistance and cardiovascular risk.
  
  
  RESULTS
  Mean current age of CCS was 14.5 years and 54% were male (siblings 13.6 years, 54% male). Diagnoses included leukemia (35%), brain tumors (36%), solid tumors (33%), or lymphoma (6%). Among CCS, analysis of individual chemotherapy agents failed to find associations with cardiovascular risk factors or insulin resistance. Compared with siblings, insulin resistance was significantly higher in CCS who received platinum plus cranial radiotherapy (CRT, 92% brain tumors) and in those who received steroids but no platinum (majority leukemia). Insulin resistance did not differ between CCS who received surgery alone versus siblings. Within survivor comparisons failed to elucidate treatment combinations that increased insulin resistance compared with those who received surgery only.
  
  
  CONCLUSIONS
  Exposure to platinum, CRT, or steroids is associated with insulin resistance and cardiovascular risk factors and should be taken into consideration in the development of screening recommendations for cardiovascular risk.
  
  
  CONCLUSIONS
  Earlier identification of CCS who may benefit from targeted prevention efforts may reduce their future risk of cardiovascular disease.
authors.affiliation: Authors' Affiliations: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; University of California San Diego & Rady Children's Hospital, San Diego, California; Children's Hospitals and Clinics of Minnesota; and Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Chow
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Goodman
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Dietz
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Perkins
authors.forename: Lisa
authors.initials: L
authors.lastname: Chow
authors.forename: Alan
authors.initials: A
authors.lastname: Sinaiko
authors.forename: Antoinette
authors.initials: A
authors.lastname: Moran
authors.forename: Anna
authors.initials: A
authors.lastname: Petryk
authors.forename: Julia
authors.initials: J
authors.lastname: Steinberger
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D016014:Linear Models; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D017741:Survivors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents