Stroke Rounds: Recurrent Stroke Risk High for Childhood Cancer Survivors

Second strokes occur at double the rate seen in the general population

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• by Salynn Boyles
  Contributing Writer

• This article is a collaboration between MedPage Today® and:
  

Action Points

• Note that this observational cohort study found a high rate of recurrent stroke among childhood cancer survivors who had suffered a first stroke.
• Be aware that cranial irradiation was a powerful risk factor for recurrent stroke.

Survivors of childhood cancer who suffer strokes during young adulthood have a high risk of recurrent stroke for decades to come, especially when they have been treated with high-dose cranial radiation, researchers reported.
The analysis of data from the retrospective Childhood Cancer Survivor Study (CCSS) revealed a 2-fold greater risk of recurrent stroke in survivors of childhood cancer, compared to the general population matched for age.
Having a history of cranial radiation (≥50 Gy) was associated with a three-fold increase in recurrent stroke risk, Heather Fullerton, MD, of the University of California San Francisco, and colleagues wrote online in Neurology. Hypertension and older age at first stroke were also associated with an increased risk for recurrent stroke.
The study is the first large analysis of recurrent stroke rates among survivors of childhood cancer, and the findings have important implications for the medical follow-up of this population.
Current screening guidelines do not include a recommendation for routine vascular disease assessment, the researchers noted.
"A better understanding of risk factors for stroke, and the underlying mechanism, creates opportunities for primary and secondary stroke prevention," they wrote. "A role for accelerated atherosclerosis suggests particularly low-hanging fruit for risk modification in this population: the early identification and treatment of modifiable atherosclerotic risk factors like hypertension."
Median Age at Second Stroke was 32
The CCSS includes 14,358 cancer survivors diagnosed between 1970 and 1986 before the age of 21 who had survived for 5 years or more following their cancer diagnosis. The study cohort has been followed since 1994.
A total of 443 surveyed survivors reported a first stroke. To assess the rate of recurrent stroke, the researchers sent a second survey to these study participants asking them to confirm their first stroke and report any subsequent strokes.
Among 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years, and 70 reported a second stroke at a median age of 32 years. The median time from cancer diagnosis to first stroke was 10 years (interquartile range 21 years) and the most common cancer type among participants who had strokes were brain tumors (44%) and leukemia (22%).
The median time from cancer diagnosis to second stroke was 23 years (IQR 19 years).
Independent predictors of stroke recurrence (revealed using multivariate Cox proportional hazard model analysis) included:

• Cranial radiation therapy dose of ≥50 Gy (versus none, hazard ratio 4.4, 95% CI 1.4 to 13.7)
• Hypertension (HR 1.9, 95% CI 1.0 to 3.5)
• Older age at first stroke (HR 6.4, 95% CI 1.8 to 23 for age ≥40 versus age 0-17 years)
• 10 year cumulative incidence of late recurrent stroke was 21% (95% CI 16 to 27%) overall and 33% (95% CI 21 to 44%) among participants treated with ≥50 Gy of cranial radiation therapy

The majority of the participants who had strokes had received cranial radiation, although 22% had received neither cranial nor neck radiation. Stroke survivors who had not received cranial radiation had a recurrent stroke risk of 11% at 10 years.
Radiation May Accelerate Vessel Disease
"The cumulative rate of recurrent stroke in the general population of young adults (≤50 years of age) has been estimated at approximately 10% by 10 years after a first ischemic stroke," the researchers wrote. "In our cohort of childhood cancer survivors, the first strokes tended to occur in young adulthood, but the recurrent stroke rate was, overall, double that for young adults in general."
Potential study limitations cited by the researchers included the fact that the stroke data were self reported, the exclusion of children who died within the first 5 years following their cancer diagnosis, and the lack of access to vascular imaging data.
Neck radiation is a known risk factor for vascular disease, and the researchers suggested that cranial radiation may increase stroke risk by accelerating intracranial atherosclerosis development.
In a previous analysis of the CCSS data, hypertension and black race were found to be independent predictors of first stroke risk in childhood cancer survivors. Another CCSS analysis, published in 2014, found survivors of childhood cancer to have an increased risk for premature aging and early onset cardiovascular disease.
"This (study) lends further support to the hypothesis that early onset atherosclerosis is on the causal pathway from cranial radiation to ischemic stroke, and suggests that earlier screening for modifiable atherosclerotic risk factors could be an avenue for improving both cardiovascular and cerebrovascular outcomes," the researchers wrote.
From the American Heart Association:

• Long-term Cardiovascular Toxicity and Cancer Therapy

The research was funded by the National Cancer Institute, Cancer Center Support, and the American Lebanese-Syrian Associated Charities.
The researchers reported no relevant relationships with industry.

• Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

last updated 08.28.2015

• Primary Source

  Neurology

  Source Reference: Fullerton HJ, et al "Recurrent stroke in childhood cancer survivors" Neurology 2015; DOI: 10.1212/WNL.0000000000001951.