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Clinicians can use information available at the end of cancer treatment to predict individual risk of ischemic heart disease and stroke in childhood cancer survivors through to age 50, according to researchers.

The new risk prediction model, which uses information such as sex, chemotherapy and radiotherapy exposures to head, neck and chest, was developed using data from 13,060 participants in the Childhood Cancer Survivor Study (CCSS) participants, said Eric J. Chow, MD, MPH, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

With median follow-up of 19 years, risk scores based on a standard prediction model achieved an area under the curve of 0.70 for ischemic heart disease and 0.63 for stroke, the study authors reported online in the .

After the risk scores were collapsed to form three statistically distinct risk groups, CCSS survivors in the low-risk group had cumulative incidences at age 50 years <5% compared with approximately 20% for high-risk groups (P<0.001). When compared to low-risk survivors, a cohort of 4,023 siblings had a cumulative incidence of only 1% (P<0.001) at 50 years.

"We believe these validated models can be useful tools for counseling survivors of childhood cancer who have recently completed therapy, particularly among survivors with potentially modifiable cardiovascular risk factors," Chow and colleagues wrote. "These models also provide a stronger evidence base for developing and testing potential screening and intervention strategies for high-risk patients, and could help pinpoint potential reductions in late toxicity in future clinical trials."

In the study, the investigators analyzed CCSS cohort data of five-year childhood cancer survivors from 26 institutions in the United States and Canada. All were diagnosed between 1970 and 1986 before the age of 21.

The CCSS models were validated using 1,842 participants from the St. Jude Lifetime Cohort Study and 1,362 from the Emma Children's Hospital cohort, and achieved a concordance statistic of 0.70 for ischemic heart disease and 0.66 for stroke.

At the age of 50 years, 265 childhood cancer survivors had ischemic heart disease and 295 had had a stroke (cumulative incidence of 7.7% and 6.3%, respectively).

Comparison with the siblings cohort, which was used to establish baseline population risk, showed that the prevalence of heart disease was much lower in siblings at the age of 50 than it was in their brothers and sisters who had survived cancer. A total of 26 siblings had ischemic heart disease and 19 had had a stroke for a cumulative incidence of 1.2% and 1.1%, respectively.

Recently, the investigators used the same approach to develop models that predict risk of cardiomyopathy and heart failure in survivors of childhood cancer. Just knowing the presence or absence of exposures allowed them to accurately segregate survivors into lower and higher risk groups, and led to the development of an .

"In general, the predictive influence of chemotherapy agents in our models pales in comparison with radiotherapy exposure," Chow and colleagues noted. While newer methods to deliver radiotherapy may spare more healthy tissue and possibly reduce cardiovascular and other organ toxicity in future, many of the historical CCSS treatment combinations are still in use, they pointed out.

Cancer treatment may also precipitate the development of conditions such as neuropathy, potentially causing poorer cardiovascular health. "This may explain the increased risk observed among our low-risk group compared with siblings as well as in other studies of survivors of cancer," the study authors said.

These findings also suggest that the increased risks to health are ongoing for survivors of childhood cancer. "Thus far, available data from CCSS and other cohorts do not suggest a plateau in the risks of late effects among survivors of cancer compared with the general population," Chow and colleagues said. "If anything, the data suggest further continued increased risk."

In another recent analysis of the CCSS cohort, investigators found that childhood cancer survivors 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.

Currently, there are more than 400,000 survivors of childhood cancer in the United States, who are to have a 10-fold increased risk of ischemic heart disease and stroke compared with siblings, the investigators pointed out.

These statistics can be deceiving, they added, because they mask the significant variation in risk that exists between childhood cancer survivors. In addition to genetic predisposition, these variations could be caused by individual cancer treatment exposures as well as conventional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes.

An earlier assessment carried out in CCSS survivors at a median of 15 years after cancer diagnosis showed that at the age of 23 years, many didn't have conventional cardiovascular risk factors such as obesity, hypertension, diabetes, dyslipidemia and current smoking status, the study authors noted.

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