Stroke is exceptionally rare among otherwise healthy young adults. Although several single institution reports have described small series of strokes among cancer survivors,26–30
it has been difficult to determine the prevalence of stroke and risk factors for stroke among childhood cancer survivors. The large number of childhood cancer survivors in the CCSS cohort makes it possible to determine the rate and identify certain diagnostic risk groups as being at a relatively high risk of stroke with onset at greater than 5 years after cancer diagnosis.31,32
Compared with the sibling control group, which had a similar rate of stroke to that reported among otherwise healthy adults, there was an increased relative risk of stroke among survivors of leukemia (RR = 6.4; 95% CI, 3.0 to 13.8), brain tumor (RR = 29; 95% CI, 13.8 to 60.7), and HD (RR = 4.32; 95% CI, 2.01 to 9.29).
RT is the most prominent treatment risk factor associated with subsequent stroke. Furthermore, RT treatment fields and doses appear to contribute to the risk.31,32
For example, there was an increased relative risk of stroke among leukemia survivors treated with a dose of greater than 30 Gy cranial RT (RR = 7.74; 95% CI, 2.6 to 23.3) compared with leukemia survivors treated with no cranial RT or lower dose cranial RT. Also, there was an increased relative risk of stroke among brain tumor survivors treated with a dose of greater than 50 Gy cranial RT (RR = 3.3; 95% CI, 1.5 to 7.1) compared with brain tumor survivors treated without cranial RT. Among HD survivors who developed stroke, nearly all had received mantle radiation doses of 40 Gy.
Among leukemia survivors, there was an increased stroke risk among those who suffered relapse (RR = 21.6; 95% CI, 8.6 to 54.2).31
Among brain tumor survivors, there was an increased relative risk of stroke after treatment with both cranial RT and alkylating agents (RR = 78.3; 95% CI, 35.1 to 174.5).31
Both of these associations suggest an association with a relative increased intensity of therapy and need further investigation. Finally, among survivors of childhood HD, there was an increased risk of stroke if the cancer survivor reported smoking more than 10 cigarettes in their lifetime (RR = 3.37; 95% CI, 1.21 to 10.77). This is the first identified potentially modifiable risk factor for cerebrovascular disease among survivors of HD.
Implications for Risk-Based Screening of Cerebrovascular Disease
Head and neck radiation increases the risk for a variety of cerebrovascular complications including stroke, moyamoya, and occlusive vasculopathy. Among cohorts studied in the CCSS, radiation dose appears to significantly impact risk. Diagnostic groups most likely to present with cerebrovascular complications include survivors of brain tumors, leukemia, and HD. In most cases, a clinical presentation with motor and/or sensory deficits leads to neuroimaging that establishes the diagnosis. Consequently, risk-based surveillance should focus on history and neurological and neurocognitive assessment. Survivors at risk for extracranial vascular disease involving the carotid or subclavian vessels may have bruits or discrepant peripheral pulses on physical examination. Smoking is associated with a three-fold excess risk of stroke in HD survivors in the CCSS cohort, emphasizing the importance of promoting abstinence from smoking in this group.