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1.17.2013

Landmark Study Finds Pediatric Cancer Survivors Have Reduced Exercise Capacity

Pediatric cancer survivors have significantly lower exercise capacity than their siblings, according to a groundbreaking Miller School study led by Tracie L. Miller, M.D., professor of pediatrics and associate chair of pediatrics for clinical research.

“Most children who have survived cancer have undergone known cardiotoxic treatments, including radiation and chemotherapy,” said Miller, who is also co-director of the Clinical Interaction Resources component of the CTSI. “They should have a complete cardiac evaluation before starting an exercise program and be monitored closely as they participate.”

Miller said that the exercise capacity of the siblings also was below average, possibly due to environmental or genetic factors. “Their exercise capacity, although better than the cancer survivors, was generally in the poor range,” she said. “One of the lessons of the study is that both cancer survivors and their siblings are at risk for low exercise tolerance and this study elucidated a number of characteristics in cancer survivors that could affect their exercise tolerance.”

Recently published online in Pediatric Blood & Cancer, the study, “Exercise Capacity in Long-Term Survivors of Pediatric Cancer: An Analysis From the Cardiac Risk Factors in Childhood Cancer Survivors Study,” will appear in the April issue of the journal with an accompanying commentary that, published online January 17, calls the paper “landmark.” The study’s lead author was former graduate student Angela M. Miller, M.S.P.H.; other Miller School authors were Gabriela Lopez-Mitnik, M.S. M.Phil., former senior research associate; Gabriel Somarriba, D.P.T., assistant professor of clinical pediatrics; and Steven E. Lipshultz, M.D., professor of pediatrics, the George Batchelor Endowed Chair in Pediatric Cardiology, and Director of the Batchelor Children’s Research Institute.

In the commentary, titled “Increasing Exercise in Long-Term Survivors of Pediatric Cancer and Their Siblings: Should Treatment be a Family Affair?” oncologist Rudolf Steiner, M.D., a professor at the University of Zurich in Switzerland, noted that, “Few studies have compared long-term survivors of different types of pediatric cancer and treatments with their siblings on exercise capacity and risk factors for reduced physical capacity.”

“Although pediatric cancer survivors carry a number of risk factors for low physical activity relating to their cancer and treatments, this study eloquently shows the inextricable link between low physical performance and sociodemographic influences,” Steiner wrote. “It provides compelling evidence that survivors had significantly lower exercise capacity, less endurance, and lower anaerobic thresholds than did their siblings.”

More than 11,000 children in the United States are diagnosed with cancer annually, and have a five-year survival rate of nearly 80 percent. Today, there are more than 300,000 childhood cancer survivors who should be monitored regularly for late effects from cancer treatment or cancer itself, including cardiovascular, endocrine, pulmonary, and musculoskeletal abnormalities, Tracie Miller said.

Some cancer survivors, particularly those treated at a young age, have restrictive cardiomyopathy, a potentially life-threatening condition due to a heart muscle that is too small or too stiff to pump blood effectively during periods of physical exertion.

“A child treated for cancer at age 2 or 3 may have a heart that never grows to normal size,” Miller said, adding that adult cancer survivors are less likely to have restrictive cardiomyopathy because their hearts were fully developed at the time of treatment. Survivors with restrictive cardiomyopathy may become symptomatic with mild exercise so their identification allows individualized exercise prescriptions.

The study compared 72 cancer survivors at least four years after cancer diagnosis to 32 siblings. Exercise capacity was determined by several factors, including maximal myocardial oxygen consumption (VO2 max), the maximal achievable level of oxidative metabolism involving large muscle groups. “We evaluated associations between VO2 max and age, sex, treatments, cardiac structure and function, biomarkers, endocrine function, and physical activity,” Miller said. “In age- and sibling-pair adjusted analyses, VO2 max was lower in survivors than siblings, and female survivors had lower exercise capacity than male survivors.”

Participants were recruited from the Long-Term Survivors of Childhood Cancer Program at the University of Rochester Medical Center in Rochester, New York, between 1999 and 2003 as part of a prospective, longitudinal study of cardiac risk factors. Healthy siblings were invited to participate when survivors enrolled, according to Lipshultz, who was principal investigator for the program.

“Because exercise is so important in promoting good health, we need to develop effective programs for cancer survivors who are at high risk for heart disease,” Lipshultz said. “As we learn more about their impairments, we can find better strategies to help them become more active and physically fit.”

Other co-authors of the study were Stuart R. Lipsitz, D.Sc., of Harvard University, and Andrea S. Hinkle, M.D., and Louis S. Constine, M.D., both of the University of Rochester.

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