title: Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study.
abstract: OBJECTIVE
  To test the hypotheses that (1) the increased risk of stroke conferred by childhood cranial radiation therapy (CRT) persists into adulthood; and (2) atherosclerotic risk factors further increase the stroke risk in cancer survivors.
  
  
  METHODS
  The Childhood Cancer Survivor Study is a multi-institutional retrospective cohort study of 14,358 5-year survivors of childhood cancer and 4023 randomly selected sibling controls with longitudinal follow-up. Age-adjusted incidence rates of self-reported late-occurring (≥5 years after diagnosis) first stroke were calculated. Multivariable Cox proportional hazards models were used to identify independent stroke predictors.
  
  
  RESULTS
  During a mean follow-up of 23.3 years, 292 survivors reported a late-occurring stroke. The age-adjusted stroke rate per 100,000 person-years was 77 (95% confidence interval [CI] 62-96), compared with 9.3 (95% CI 4-23) for siblings. Treatment with CRT increased stroke risk in a dose-dependent manner: hazard ratio 5.9 (95% CI 3.5-9.9) for 30-49 Gy CRT and 11.0 (7.4-17.0) for 50+ Gy CRT. The cumulative stroke incidence in survivors treated with 50+ Gy CRT was 1.1% (95% CI 0.4-1.8%) at 10 years after diagnosis and 12% (95% CI 8.9-15.0%) at 30 years. Hypertension increased stroke hazard by 4-fold (95% CI 2.8-5.5) and in black survivors by 16-fold (95% CI 6.9-36.6).
  
  
  CONCLUSIONS
  Young adult pediatric cancer survivors have an increased stroke risk that is associated with CRT in a dose-dependent manner. Atherosclerotic risk factors enhanced this risk and should be treated aggressively.
authors.affiliation: Department of Neurology, Pediatrics and Neurosurgery, University of California, San Francisco, San Francisco, California 94158, USA. muellers@neuropeds.ucsf.edu
authors.forename: Sabine
authors.initials: S
authors.lastname: Mueller
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Fullerton
authors.forename: Kayla
authors.initials: K
authors.lastname: Stratton
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Rita E
authors.initials: RE
authors.lastname: Weathers
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Robert E
authors.initials: RE
authors.lastname: Goldsby
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bowers
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D050197:Atherosclerosis / Q000150:complications*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications; D015994:Incidence; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000208:ethnology / Q000532:radiotherapy*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology; D017741:Survivors; D055815:Young Adult