PEDIATRIC CANCER SURVIVORS AND CARDIOVASCULAR RISK

January 7, 2010 — Exposure to total-body irradiation or abdominal plus chest radiation and a sedentary lifestyle among survivors of childhood cancer are associated with the development of risk factors that can predispose them to metabolic syndrome and subsequent cardiovascular disease, according to new research published in the January issue of Cancer Epidemiology, Biomarkers & Prevention.

The new study is part of a growing body of evidence that indicates that childhood cancer survivors are at higher risk of developing metabolic syndrome than the general population.

The authors found that adult survivors of childhood cancer were about 1.9 times more likely to be taking medication for hypertension, 1.6 times more likely to be taking medication for dyslipidemia, and 1.7 times more likely to be taking medication for diabetes as those in the study's sibling comparison group.

Other studies have shown that pediatric cancer survivors are at high risk for a number of physical and psychosocial conditions as a result of the cancer and its treatment. These include stroke, problems with neurocognitive function and academic achievement, and subsequent malignant neoplasms, as previously reported by Medscape Oncology.

Recently published data from the Childhood Cancer Survivor Study (CCSS) found that nearly three quarters of survivors had at least 1 chronic health condition, the authors note. The risk for cardiovascular disease was approximately 10 times higher among survivors than among their siblings.

Lillian R. Meacham, MD, medical director of the Cancer Survivor Program and professor of pediatrics at Emory University, in Atlanta, Georgia, and colleagues used data from the CCSS to determine the prevalence of and factors associated with the development and clustering of cardiovascular risk factors.

More Likely to Develop Metabolic Syndrome

The authors defined Cardiovascular Risk Factor Cluster (CVRFC), which they used as a substitute for metabolic syndrome, as having at least 3 of the following 4 risk factors: obesity, hypertension, dyslipidemia, and diabetes mellitus or impaired glucose tolerance.

The CCSS is a multi-institutional study of individuals who survived 5 years after a childhood cancer that was diagnosed from 1970 to 1986. The current analysis includes 8599 of the cancer survivors and 2936 of their siblings who were evaluated for a body mass index of 30 kg/m² or more, based on self-reported heights and weights. The self-reported use of pharmacologic agents for the treatment of hypertension, dyslipidemia, and impaired glucose metabolism was also evaluated.

More than half of the survivors (59.2%) received radiation as part of their initial cancer therapy, 33.5% received 100 mg/m² or more of anthracyclines, and 4.7% were treated with platinum therapy.

Three of the hallmarks of metabolic syndrome (hypertension, dyslipidemia, and diabetes) were more commonly found in survivors than in their siblings, but there was no difference in the prevalence of obesity between the 2 groups (20.6% for survivors vs 20.8% for their siblings).

The authors noted that older age at the time of the questionnaire (40 years or older vs younger than 30 years) was associated with each cardiovascular risk factor, and a sedentary lifestyle was associated with CVRFC and each risk factor except for dyslipidemia.

Type of Treatment Influences Risk

In terms of risk and treatment modalities:

• Exposure to more than 100 mL/m² of an anthracycline was associated with a 50% increase in the odds of hypertension.
• Patients who received cranial radiation were more likely to be obese than those who did not receive radiation.
• Those who received more than 300 mg/m² of anthracyclines were less likely to be obese.
• Individuals who received either abdomen or chest radiation or who were currently receiving steroid therapy showed increased risk for hypertension.
• Total-body irradiation and radiation to the craniospinal axis, abdomen plus chest, and chest alone were associated with treatment for dyslipidemia.
• Diabetes was associated with total-body irradiation and radiation to the abdomen and to both the abdomen and chest.
• CVRFC was associated with total-body irradiation and abdominal plus chest radiation.

The authors also evaluated the association between the cardiovascular disease events reported in the 2000 follow-up survey and the cardiovascular risk factors that were observed in the most recent follow-up. Among the survivors, there were 83 reports of cardiac events (which included coronary artery disease, atherosclerosis, and myocardial infarction), and 151 patients reported a history of stroke at either the baseline or the first follow-up questionnaire. Except for stroke, all the previously reported cardiac events were associated with an increased risk of reporting CVRFC at second follow-up (P = .003).

"In light of the high prevalence of chronic health conditions, including cardiac disease and associated increased rates of death, it behooves all healthcare providers to be proactive in the early recognition and treatment of cardiovascular risk factors in this population," the authors conclude.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Meacham reports receiving a commercial research grant from Genentech, Novo Nordisk, and Pfizer. Coauthor Charles Sklar, MD, from Memorial Sloan-Kettering Cancer Center in New York City, reports being a member of the consultant/advisory board of EMD Serono.

Cancer Epidemiol Biomarkers Prev. 2010:19:170-181.