title: Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy.
abstract: OBJECTIVE
  To assess, in a retrospective cohort study, rates and predictors of first and recurrent stroke in patients treated with cranial irradiation (CRT) and/or cervical irradiation at ≤18 years of age.
  
  
  METHODS
  We performed chart abstraction (n=383) and phone interviews (n=104) to measure first and recurrent stroke in 383 patients who received CRT and/or cervical radiation at a single institution between 1980 and 2009. Stroke was defined as a physician diagnosis and symptoms consistent with stroke. Incidence of first stroke was number of first strokes per person-years of observation after radiation. We used survival analysis techniques to determine cumulative incidence of first and recurrent stroke.
  
  
  RESULTS
  Among 325 subjects with sufficient follow-up data, we identified 19 first strokes (13 ischemic, 4 hemorrhagic, 2 unknown subtype) occurring at a median age of 24 years (interquartile range 17-33 years) in patients treated with CRT. Imaging was reviewed when available (n=13), and the stroke was confirmed in 12. Overall rate of first stroke was 625 (95% confidence interval [CI] 378-977) per 100,000 person-years. The cumulative incidence of first stroke was 2% (95% CI 0.01%-5.3%) at 5 years and 4% (95% CI 2.0%-8.4%) at 10 years after irradiation. With each 100-cGy increase in the radiation dose, the stroke hazard increased by 5% (hazard ratio 1.05; 95% CI 1.01-1.09; P=.02). We identified 6 recurrent strokes; 5 had available imaging that confirmed the stroke. Median time to recurrence was 15 months (interquartile range 6 months-3.2 years) after first stroke. The cumulative incidence of recurrent stroke was 38% (95% CI 17%-69%) at 5 years and 59% (95% CI 27%-92%) at 10 years after first stroke.
  
  
  CONCLUSIONS
  Cranial irradiation puts childhood cancer survivors at high risk of both first and recurrent stroke. Stroke prevention strategies for these survivors are needed.
authors.affiliation: Department of Neurology, University of California, San Francisco, California 94148, USA. muellers@neuropeds.ucsf.edu
authors.forename: Sabine
authors.initials: S
authors.lastname: Mueller
authors.forename: Katherine
authors.initials: K
authors.lastname: Sear
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Hills
authors.forename: Nassim
authors.initials: N
authors.lastname: Chettout
authors.forename: Shervin
authors.initials: S
authors.lastname: Afghani
authors.forename: Erica
authors.initials: E
authors.lastname: Gastelum
authors.forename: Daphne
authors.initials: D
authors.lastname: Haas-Kogan
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Fullerton
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016371:Cranial Irradiation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D009333:Neck; D009369:Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012008:Recurrence; D012189:Retrospective Studies; D012306:Risk; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology*; D016019:Survival Analysis; D017741:Survivors; D055815:Young Adult