Miller School Pediatrics Chairman Publishes Editorial on Cardiotoxicity After Childhood Cancer

New Study Builds on UM Doctor’s Breakthrough Finding

Steven E. Lipshultz, M.D., professor and chairman of pediatrics and associate executive dean for child health at the University of Miami Miller School of Medicine, co-authored an editorial in the Journal of Clinical Oncology that was released online February 8. The editorial, written with M. Jacob Adams, M.D., M.P.H., of the University of Rochester School of Medicine and Dentistry, is titled: “Cardiotoxicity After Childhood Cancer: Beginning With the End in Mind.” The editorial specifically comments on an original article in the same journal titled: “Role of Cancer Treatment in Long-Term Overall and Cardiovascular Mortality After Childhood Cancer.”

Lipshultz is a leading authority on the late effects of treatment on survivors of childhood cancer, specifically the effects on the cardiovascular system when the survivors reach adulthood. In the editorial, the authors underscore the importance of further research to more specifically pinpoint specific treatments and the specific cardiovascular causes of death. As they point out, “the goal of childhood cancer treatment is not only to cure the patient, but to try to ensure that the patient lives as long and as normal a life as possible.”

In the early 1980s, Lipshultz began noticing a high number of older children who had been treated for childhood cancer were experiencing cardiovascular effects later in life. As he and Adams state in their editorial, survivors of childhood cancer are five to 10 times more likely than their healthy siblings to experience heart disease.

This latest study involved a large population of over 4,000 survivors of childhood cancer with more than 86,000 patient-years of follow up and survivors who have died. Lipshultz says this work not only “confirms his concerns by showing the dramatic impact of cancer during childhood,” it also adds new information about late cardiac effects by specifically calculating radiation doses to the heart as a factor to assess cardiovascular mortality. Children who received higher anthracycline doses (drugs such as Adriamycin) had more than a four-fold higher risk of having a cardiac death than children who did not receive anthracycline chemotherapy. This study found that as little as 5 Gy of radiation to the heart increased the risk of cardiovascular deaths. Hodgkin’s lymphoma patients are treated with an average of 35 to 40 Gy of radiation.

Lipshultz and Adams argue that using genomics, proteomics and biomarkers to identify those childhood cancer survivors who are most at risk for cardiotoxicity requires much more research. Genetic predispositions along with personal health habits may also play a role. Lipshultz admits that devising cardio-protective treatments to avoid late heart failure is difficult because of an inadequate understanding of the risk-benefit ratio and the inherent challenges of running pediatric clinical trials, but points out the clear need. “Our work over the past 25 years has identified this as one of the largest new populations at risk for premature symptomatic cardiovascular disease, with one in every 560 young adults in the U.S. aged 20-45 years being a survivor of childhood cancer.”

Until less toxic cancer therapies or better screening models are developed, these doctors encourage research involving all childhood cancer survivors and vigilant monitoring for possible cardiovascular disease. These findings however suggest that deliberate and intentional serial cardiac monitoring of childhood cancer survivors is needed not just for the children for whom recommendations exist, such as those treated with anthracyclines, but also for those who have received radiation to the heart or other chemotherapy identified in this study to be associated with cardiac mortality that was not previously noted to be cardiotoxic. In the meantime, Lipshultz says “it appears that for some of these survivors we have substituted one fatal disease of early childhood (cancer) for another fatal disease in early adult life.”

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