Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer

A report from the childhood cancer survivor study

Sabine Mueller, Heather J. Fullerton, Kayla Stratton, Wendy Leisenring, Rita E. Weathers, Marilyn Stovall, Gregory Armstrong, Robert E. Goldsby, Roger J. Packer, Charles A. Sklar, Daniel C. Bowers, Leslie L. Robison, Kevin R. Krull

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose: 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 and Materials: 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)649-655
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume86
Issue number4
DOIs
StatePublished - Jul 15 2013
Externally publishedYes

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strokes
Survivors
cancer
Stroke
Radiation
Pediatrics
confidence
radiation
radiation therapy
Confidence Intervals
Radiotherapy
intervals
Neoplasms
Radiation Dosage
hazards
Siblings
incidence
hypertension
dosage
Incidence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer : A report from the childhood cancer survivor study. / Mueller, Sabine; Fullerton, Heather J.; Stratton, Kayla; Leisenring, Wendy; Weathers, Rita E.; Stovall, Marilyn; Armstrong, Gregory; Goldsby, Robert E.; Packer, Roger J.; Sklar, Charles A.; Bowers, Daniel C.; Robison, Leslie L.; Krull, Kevin R.

In: International Journal of Radiation Oncology Biology Physics, Vol. 86, No. 4, 15.07.2013, p. 649-655.

Research output: Contribution to journalArticle

Mueller, S, Fullerton, HJ, Stratton, K, Leisenring, W, Weathers, RE, Stovall, M, Armstrong, G, Goldsby, RE, Packer, RJ, Sklar, CA, Bowers, DC, Robison, LL & Krull, KR 2013, 'Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer: A report from the childhood cancer survivor study', International Journal of Radiation Oncology Biology Physics, vol. 86, no. 4, pp. 649-655. https://doi.org/10.1016/j.ijrobp.2013.03.034
Mueller, Sabine ; Fullerton, Heather J. ; Stratton, Kayla ; Leisenring, Wendy ; Weathers, Rita E. ; Stovall, Marilyn ; Armstrong, Gregory ; Goldsby, Robert E. ; Packer, Roger J. ; Sklar, Charles A. ; Bowers, Daniel C. ; Robison, Leslie L. ; Krull, Kevin R. / Radiation, atherosclerotic risk factors, and stroke risk in survivors of pediatric cancer : A report from the childhood cancer survivor study. In: International Journal of Radiation Oncology Biology Physics. 2013 ; Vol. 86, No. 4. pp. 649-655.
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abstract = "Purpose: 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 and Materials: 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). Conclusion: 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.",
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AU - Leisenring, Wendy

AU - Weathers, Rita E.

AU - Stovall, Marilyn

AU - Armstrong, Gregory

AU - Goldsby, Robert E.

AU - Packer, Roger J.

AU - Sklar, Charles A.

AU - Bowers, Daniel C.

AU - Robison, Leslie L.

AU - Krull, Kevin R.

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AB - Purpose: 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 and Materials: 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). Conclusion: 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.

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