Call for Stepped-Up Monitoring of Cardiovascular Predisposing Factors in Childhood Cancer Survivors (2010)

Although it has been known that long-term survivors of childhood cancer face a higher risk of developing various chronic diseases, new research shows that many of those diseases may be preceded by diabetes, dyslipidemia, and hypertension—risk factors that can sometimes be controlled. “Many of the risks are modifiable,” said Kevin Oeffinger, MD, Director of Memorial Sloan-Kettering Cancer Center's Adult Long-Term Follow-Up Program. “With activity and proper diet, the likelihood of these problems is much lower.” In a study published in the January issue of Cancer Epidemiology, Biomarkers & Prevention, Dr. Oeffinger and his fellow researchers examined four cardiovascular risk factors–obesity, hypertension, dyslipidemia, and diabetes and found that adult survivors of pediatric cancer had a higher than average risk for at least one of those predisposing factor. The study—led by Lillian R. Meacham, MD, Professor of Pediatrics at Emory University and Medical Director of the Aflac Cancer Center of Children's Healthcare of Atlanta Cancer Survivor Program—is one of several based on the Childhood Cancer Survivor Study (CCSS) survey of some 14,000 long-term survivors of pediatric cancer. Survivors were diagnosed between 1970 and 1986, and have been cancer-free at least five years. Healthy siblings of a similar age served as controls.KEVIN C. OEFFINGER, MD: “Many of the risks are modifiable. With activity and proper diet, the likelihood of these problems is much lower…. We strongly encourage all cancer survivors to have a treatment summary.”Risks Specific to Treatments and Cancer Types Earlier studies of CCSS data revealed that nearly three quarters of adult survivors of pediatric cancer suffered from chronic health conditions and that their risk of cardiac death was more than eight times higher than expected. Research also has shown a clear link between high doses of anthracycline and cardiomyopathy. But until the new study, little was know about cancer treatment's effect on the more subtle cardiovascular risk factors that may also lead to cardiovascular disease. “We now see a global cardiac risk,” said Steven Lipshultz, MD, Chairman of the Pediatrics Department at the University of Miami School of Medicine and Chief of Staff at Holtz Children's Hospital, who led earlier studies of cardiac risk in CCSS participants. “It's not only symptomatic cardiomyopathy, but also heart disease from hypertension and dyslipidemia,” he said. Although hypertension, high cholesterol, and diabetes are widespread among today's increasingly overweight adults, the causes differ in cancer survivors. The researchers were surprised to discover that many survivors with cardiovascular risk factors were not obese. Their obesity rate was 20.6%, nearly the same as their sibling controls. Yet survivors were 1.9 times more likely than siblings to be taking medication for hypertension, 1.6 times more likely to be taking it for dyslipidemia, and 1.7 times more likely to be taking it for diabetes. “What surprised me,” Dr. Meacham said, “was that obesity was not the driver—there were significant risks even in survivors who were not as obese as their siblings.” Another difference between the survivors and most patients with cardiovascular risk factors in the study is their youth: An abnormally high number of CCSS respondents had one or more risk factor even though their average age was only 32.LILLIAN R. MEACHAM, MD: “What surprised me was that obesity was not the driver. There were significant risks even in survivors who were not as obese as their siblings.”“These are problems we commonly see in older adults,” Dr. Oeffinger said. Few survivors had all the cardiovascular risk factors studied—i.e., metabolic syndrome. The one or two risk factors survivors did have varied depending on their diagnoses and type treatment. “Survivors as a whole were not more likely to have all of the risk factors,” said another of the study's coauthor's, Eric Chow, MD, MPH, Medical Director of the Seattle Children's Pediatric Cancer Long-Term Follow-up Program, “but certain subsets were at increased risk for individual risk factors.” More Prevalent with Radiation Therapy The risk factors generally were more prevalent in survivors treated with radiation. Hypertension was associated with radiation to the chest or abdomen. Dyslipidemia was linked to radiation of the chest, abdomen, craniospinal axis, and total body irradiation (TBI). TBI and radiation to the abdomen and chest also were associated with diabetes. Survivors treated with TBI or chest or abdominal radiation also faced the greatest risk of having three or more cardiovascular risk factors. Anthracyclines were associated with hypertension—survivors who had doses higher than 100 mL/m2 had a 50% higher incidence of hypertension. Obesity was more prevalent in survivors of acute lymphoblastic leukemia (ALL) and central nervous system tumors, especially in females exposed to cranial radiation. Dr. Meacham said she suspects that the obesity might be linked to radiation's known inhibition of growth hormone. Earlier Age By sounding the alarm on the problem, Dr. Meacham and her coauthors hope to protect this group of childhood cancer survivors from chronic disability and early death.PETER C. ADAMSON, MD: “We should stress the importance of behavioral changes—managing weight and exercise. The need is probably even greater than for a healthy counterpart.”“We need to start looking for high blood pressure, high lipids, and diabetes at an earlier age than before,” she said, explaining that when those risk factors are found, the team has been recommending lifestyle changes along with medication. Close Collaboration with Primary Care MDs Asked for his opinion for this article, Peter Adamson, MD, Professor of Pediatrics and Director of the Office of Clinical and Translational Research at Children's Hospital of Philadelphia, said, “We should stress the importance of behavioral changes—managing weight and exercise. The need is probably greater than for a healthy counterpart.” Earlier studies have shown that 20% to 52% of adult survivors of childhood cancer are sedentary, about the same rate as other adults. ALL survivors and those who received cranial radiation are more likely to be sedentary. These are the same survivors who are most likely to be obese. The task of screening and treating survivors for cardiovascular risk factors most likely will fall in the hands of primary care physicians. Children's cancer centers typically provide follow-up care only to adulthood. Because primary care physicians might not have a lot of experience with long-term, pediatric-cancer survivors, though, oncologists are encouraging collaboration. “Close collaboration is the most effective way [to minimize morbidity] as these children become young adults,” said Dr. Adamson, Chair-Elect of the Children's Oncology Group. A first step is to provide survivors with a treatment summary to give their physicians. Cancer centers keep such data on patients even years after their discharge. “We strongly encourage all cancer survivors to have a treatment summary,” Dr. Oeffinger said. With the summary in hand, a physician can consult survivorship guidelines for likely long-term effects and their recommended treatments. The Children's Oncology Group has comprehensive, up-to-date guidelines free at www.survivorshipguidelines.org. Dr. Oeffinger encourages primary care physicians to go beyond the written guidelines and consult pediatric oncologists. “It's important for primary care physicians to keep in touch with cancer centers,” he said. “There's great potential in the shared-care model.” www.oncology-times.com