Surviving Childhood Hodgkin’s Increases Stroke Risk Sharply
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Surviving Hodgkin’s lymphoma in childhood quadruples the risk of a stroke later in life, researchers here say.
Investigators had expected to see an increased risk of a second cancer or heart failure, but stroke was unexpected, said David Bowers, M.D., of the University of Texas Southwestern Medical Center here. “We were surprised,” he said.
The finding, published online in the Oct. 13 issue of the Journal of Clinical Oncology, was based on an analysis of 1,926 long-term survivors of Hodgkin’s lymphoma as part of the multi-institutional Childhood Cancer Survivor Study, a cohort study that compares cancer survivors with unaffected siblings.
In 2003, a major analysis of the cohort, published in the Journal of the American Medical Association, showed that childhood cancer survivors were more likely to report adverse general or mental health effects, activity limitations, and functional impairment than were people in the sibling cohort.
Other studies have found a higher risk of second tumors, including breast cancer.
But stroke as a consequence of childhood cancer therapy—including neck and mantle radiation—had not been examined, Dr. Bowers and colleagues noted.
The investigators compared 1,926 survivors who had been diagnosed between Jan. 1, 1970, and Dec. 31, 1986 with 3,846 people in a sibling cohort. The mean age of the survivors at diagnosis was 13.8 and at the time of the study was 33.8.
Of the cancer survivors, 24 reported strokes more than five years after diagnosis, for a rate of 83.6 per 100,000 person-years. At the same time, nine of the siblings reported a stroke, for a rate of eight per 100,000 person-years. The expected range for adults aged 18 to 44 in the general population is between 10 and 23 per 100,000 person-years.
After adjusting for age, sex, and race, the relative risk of stroke for Hodgkin’s survivors compared with sibling controls was 4.32; the 95% confidence interval ranged from 2.01 to 9.29 and the result was significant at the p=0.0002 level.
Not all the Hodgkin’s survivors received the same therapy; in particular, the 24 who had strokes had all received mantle radiation, with a median dose of 40 Gy.
The rate of stroke for those treated with mantle radiation was 109.8 per 100,000 person-years and, compared with siblings, the relative risk of stroke was 5.62, with the 95% confidence interval ranging from 2.59 to 12.25 and the statistical significance at the p=0.0001 level.
Cigarette smoking may also play a role, the researchers found. Sixty-three percent of survivors who had a stroke also said they had smoked, compared with 34% of survivors who did not have a stroke. The difference was significant at the p=0.0042 confidence level.
The mechanism involved remains unclear, Dr. Bowers and colleagues noted. One possibility is radiation-induced damage to the carotid artery, while another is damage to the heart itself.
“We are clearly recognizing that cancer survivors have unique and long-term cancer-specific side effects,” Dr. Bowers said in a statement.
He said studies are needed to see what happens if lower doses of radiation have fewer long-term consequences. “Does a reduction in radiation dose cause a decrease in the frequency of stroke?” Dr. Bowers said. “It certainly would be a logical expectation, but we don’t know that.”
Source: Journal of Clinical Oncology
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