Heather J Fullerton1, Kayla Stratton1, Sabine Mueller2, Wendy W Leisenring1, Greg T Armstrong1, Rita E Weathers1, Marilyn Stovall1, Charles A Sklar1, Robert E Goldsby1, Les L Robison1, Kevin R Krull1. 1. From the Departments of Neurology (H.J.F., S.M.), Pediatrics (H.J.F., S.M., R.E.G.), and Neurosurgery (S.M.), University of California, San Francisco; the Fred Hutchinson Cancer Research Center (K.S., W.W.L.), Clinical Statistics and Cancer Prevention Programs, Seattle, WA; St. Jude Children's Research Hospital (G.T.A., L.L.R., K.R.K.), Memphis, TN; the University of Texas M.D. Anderson Cancer Center (R.E.W., M.S.), Houston; and Memorial Sloan-Kettering Cancer Center (C.A.S.), New York, NY. 2. From the Departments of Neurology (H.J.F., S.M.), Pediatrics (H.J.F., S.M., R.E.G.), and Neurosurgery (S.M.), University of California, San Francisco; the Fred Hutchinson Cancer Research Center (K.S., W.W.L.), Clinical Statistics and Cancer Prevention Programs, Seattle, WA; St. Jude Children's Research Hospital (G.T.A., L.L.R., K.R.K.), Memphis, TN; the University of Texas M.D. Anderson Cancer Center (R.E.W., M.S.), Houston; and Memorial Sloan-Kettering Cancer Center (C.A.S.), New York, NY. muellers@neuropeds.ucsf.edu.
Abstract
OBJECTIVE: To estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970-1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis. RESULTS: Among 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years (range 0-53), and 70 reported a second stroke at a median age of 32 years (range 1-56). In a multivariable Cox proportional hazards model, independent predictors of recurrent stroke included cranial radiation therapy (CRT) dose of ≥50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence interval [CI] 1.4-13.7), hypertension (HR 1.9; 95% CI 1.0-3.5), and older age at first stroke (HR 6.4; 95% CI 1.8-23; for age ≥40 vs age 0-17 years). The 10-year cumulative incidence of late recurrent stroke was 21% (95% CI 16%-27%) overall, and 33% (95% CI 21%-44%) for those treated with ≥50 Gy of CRT. CONCLUSION: Survivors of childhood cancer, particularly those previously treated with high-dose cranial radiation, have a high risk of recurrent stroke for decades after a first stroke. Although these strokes are mostly occurring in young adulthood, hypertension, an established atherosclerotic risk factor, independently predicts recurrent stroke in this population.
OBJECTIVE: To estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970-1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis. RESULTS: Among 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years (range 0-53), and 70 reported a second stroke at a median age of 32 years (range 1-56). In a multivariable Cox proportional hazards model, independent predictors of recurrent stroke included cranial radiation therapy (CRT) dose of ≥50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence interval [CI] 1.4-13.7), hypertension (HR 1.9; 95% CI 1.0-3.5), and older age at first stroke (HR 6.4; 95% CI 1.8-23; for age ≥40 vs age 0-17 years). The 10-year cumulative incidence of late recurrent stroke was 21% (95% CI 16%-27%) overall, and 33% (95% CI 21%-44%) for those treated with ≥50 Gy of CRT. CONCLUSION: Survivors of childhood cancer, particularly those previously treated with high-dose cranial radiation, have a high risk of recurrent stroke for decades after a first stroke. Although these strokes are mostly occurring in young adulthood, hypertension, an established atherosclerotic risk factor, independently predicts recurrent stroke in this population.
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