Childhood Cancer Survivors May Experience Heart Problems Sooner

June 01, 2003

Childhood cancer survivors may develop earlier and more extensive cardiovascular disease than doctors originally thought, according to two major clinical studies. Researchers at the University of Rochester Medical Center have found survivors as soon as five years after therapy showed signs of cardiomyopathy and premature atherosclerosis – which can lead to congestive heart failure and heart attacks.

While scientists have long known that some cancer treatments can damage the heart, the new studies offer a comprehensive, global view of what effects chemotherapy and radiation have on the cardiovascular system as the children grow into adulthood. The studies were presented at the American Society of Clinical Oncology’s annual meeting June 1 in Chicago.

"Long-term childhood cancer survivors may be at significant risk of serious cardiovascular problems at a much younger age," says Steven Lipshultz, M.D., chief of pediatric cardiology, associate chair of pediatrics, and professor of oncology at the University of Rochester Medical Center. "We need to be cognizant of this and closely monitor their cardiovascular health as part of a comprehensive coordinated program far sooner than most doctors would expect. And we need to help them with prevention of risks for heart failure and heart attacks as much as possible."

Cardiovascular screening is performed while children are undergoing treatment that could cause heart problems. Lipshultz recommends doctors continue periodic cardiovascular screenings soon after the patient completes treatment to monitor the condition of their cardiovascular health.

A team of multidisciplinary researchers at the URMC Long-Term Childhood Cancer Survivors Program closely examined nearly 300 young adults who survived cancer and their siblings. They found the survivors had signs of cardiomyopathy and premature atherosclerosis, Lipshultz says.

"We’ve known that there was a link between cancer treatment and cardiomyopathy, but there haven’t been any comprehensive studies of the many ways chemotherapy and radiation affect patients’ cardiovascular systems as they grow older, including premature atherosclerosis, reduced physical activity, and obesity," Lipshultz says. "It’s alarming that we’ve found such dramatic heart damage and blood vessel risk in some survivors who are just 10 or 15 years from treatment."

One study, funded by the National Cancer Institute’s Office of Cancer Survivorship, analyzed 176 survivors and 64 siblings. The former patients – who were treated for leukemia, lymphoma, Hodgkin’s disease, sarcoma, Wilms’ tumor and other less common tumors -- were on average 18 to 21 years old and about 15 years from therapy. They generally reported feeling healthy.

These patients were divided into two groups – those treated with anthracycline chemotherapy and radiation therapy, known to potentially affect the cardiovascular system, and those who were treated with other therapies that are not believed to be harmful to the heart.

The researchers analyzed echocardiograms, exercise stress tests and a number of blood tests that may predict cardiovascular disease to determine the survivors’ and siblings’ overall health. The results showed that some members of both groups of cancer survivors had experienced some cardiovascular damage. These changes included both weakened heart muscle and increased signs of premature atherosclerosis, which forces the heart to work harder and increases the risk for symptomatic heart disease.

In addition, the childhood cancer survivors, when compared to their siblings, were less active and had markedly different body compositions with less muscle and more fat – putting them at higher risk of elevated blood pressure and other metabolic diseases.

"When compared to their siblings, the cancer survivors were not as physically active, which is interesting and merits more study," Lipshultz says, citing that there could be a number of environmental and behavioral reasons for that finding.

This research was one of the first studies funded by the Office of Cancer Survivorship of the National Cancer Institute, in response to the growing need to understand the late effects of therapy for cancer, and is under the scientific oversight of Noreen Aziz, M.D., Ph.D., program director of the office.

Lipshultz worked closely with Tracie Miller, M.D., chief of pediatric gastroenterology and nutrition, and Louis S. Constine, M.D., associate chair of radiation oncology, and Carol French, M.P.H., associate in pediatrics, on the study. He also worked closely with Andrea Hinkle, M.D., and Cindy Proukou, P.N.P., who direct the URMC Long-Term Childhood Cancer Survivors Program.

The second study, funded by the Food and Drug Administration, focused on 48 Boston area adults treated for Hodgkin’s disease between 1970 and 1991, when they were under the age of 25. Each had received radiation therapy to an area that included the heart in order to treat the disease.

Lipshultz and M. Jacob Adams, M.D., Fellow in community and preventive medicine, pediatric cardiology and a Wilmot Cancer Fellow, conducted a careful analysis of how the radiation affected the survivors’ cardiovascular systems. A general health questionnaire was reviewed in addition to echocardiograms and stress tests.

While these patients, now mostly in their 30s, reported feeling healthy in the survey, results of clinical testing showed early signs of cardiovascular disease. According to the study, there were signs of cardiomyopathy, heart valve irregularities, electrical malfunctions and distress during exercise.

"Unbeknownst to them, they had heart damage. There was even one person who had a heart attack and didn’t know it," Lipshultz says.

Interestingly, the individuals reported that they felt fine, but when researchers looked closely at their survey answers, they found reports of fatigue during normal daily activities such as climbing stairs, doing household chores or undergoing a hectic day at work.

"The evidence of cardiovascular disease was there, but these people hadn’t noticed it yet," Lipshultz says. "That is exactly why we doctors need to be responsible in our treatment of long-term survivors and closely monitor them for late effects of their treatment. The problems begin long before we originally thought."

Lipshultz says patients benefit greatly from follow-up in a comprehensive multidisciplinary program like the URMC Long-Term Childhood Cancer Survivors Program. Coordinated efforts to monitor the impact of cancer treatments are crucial for optimal patient care and the advancement of medical science, he says.

Established in 1987, the URMC Long-Term Childhood Cancer Survivors Program is one of the oldest late effects clinics in the nation. The program monitors survivors of childhood and adolescent cancers for late effects of their treatment. The multi-specialty team studies the many ways cancer therapy impacts the body, providing fresh insights for innovative techniques to prevent potentially fatal problems.

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