Childhood Cancer Treatment Increases Stroke Risk

More than half of all childhood cancers are diagnosed as either brain cancer or leukemia, and as high survival rates are resulting in greater numbers of  long-term survivors, investigators have begun examining the consequences of how they are treating these diseases. Cranial radiotherapy (CRT) has been known to have significant long-term consequences. Efforts to reduce radiation during treatment have been made, but completely avoiding its use is not always an option. Now, in addition to being vulnerable to neurocognitive deficits, hormone deficiencies, cardiac dysfunction, and obesity, childhood cancer survivors may also have an increased risk for stroke, and the course of treatment may further increase that risk, according to research published in the November 20 Journal of Clinical Oncology.

Daniel C. Bowers, MD, and colleagues examined data from 4,828 childhood leukemia survivors and 1,871 childhood brain tumor survivors and compared their risk of stroke with that of a random sample of 3,846 siblings of childhood cancer survivors, as a part of the Childhood Cancer Survivor Study. All cancer survivors had received a diagnosis between 1970 and 1986, when they were younger than 21. Mean ages at interview were in the mid to late 20s for all three groups, though the siblings in the comparison group were significantly older than the cancer survivors.

Overall, strokes were reported in 1.5% of the leukemia survivors and 6.3% of the brain tumor survivors, compared to 0.2% of the siblings. Late-occurring strokes, defined as those experienced five or more years after cancer diagnosis, were reported in 37 leukemia survivors and 63 brain cancer survivors, at an average of 9.8 and 13.9 years after diagnosis, respectively. The relative risk of late-occurring stroke was significantly increased, to 6.4 for leukemia survivors and 29 for brain cancer survivors, as compared with the sibling group.

Risk for stroke persisted when the investigators examined the treatments utilized. Those treated only with chemotherapy had a significantly greater risk of stroke than the sibling controls (4.0 in leukemia survivors and 12.9 in brain tumor survivors), though the authors described the increases as modest. However, the relative risk for stroke increased further with the use of CRT—to 5.9 in leukemia survivors and 37.5 in brain cancer survivors. While the risk of late-occurring stroke did not differ between leukemia survivors who had not received CRT and those treated with low doses (less than 30 Gy), more intense CRT treatments (greater than 30 Gy in leukemia patients and greater than 50 Gy in brain tumor patients) further increased the risk of stroke to 7.7 in leukemia survivors and 3.3 in brain tumor survivors. The investigators also observed a dose-dependent relationship between CRT to segments 2, 3, and 4 of the brain, as a treatment for either type of cancer, and the risk of late-occurring stroke.

Cancer relapses and the use of alkylating agents during treatment further increased the risk of stroke in survivors who had been treated with CRT. Of the 100 survivors who had a late-occurring stroke, 18 leukemia patients and 18 brain tumor patients had experienced a cancer relapse. Fourteen and 16 of those strokes occurred within one year of the cancer relapse. The relative risks for late-occurring stroke in relapsed leukemia and brain tumor survivors were 21.6 and 64.5, respectively. The authors stated this higher risk was likely a reflection of the additional therapies required to treat the cancer progression. The use of an alkylating agent led to a relative risk of 78.3 for late-occurring stroke in brain cancer survivors only. However, the authors cautioned against naming the agent as the cause of stroke: “[W]e suspect that this finding may reflect more aggressive therapy for high-risk brain tumor patients rather than an interaction between alkylating agents and CRT.”

The authors noted that while the risk of stroke was increased for these childhood cancer survivors, stroke “is still a relatively uncommon event during the first two decades after the cancer diagnosis.” While admitting that further characterization was needed, including the type and location of the strokes experienced by both populations, they concluded that the dose-dependent relationship between CRT and the risk of stroke “justifies efforts to continue to reduce radiation doses among both leukemia and brain tumor treatment regimens whenever practical.”           

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