Cardiovascular Disease

Abstract

Although important advances have been made in curing childhood cancer in the last several decades, long-term survivors face considerable morbidity and mortality because of late effects from their initial anticancer therapy. By 30 years after treatment, the cumulative mortality from treatment-related medical illness actually exceeds that of mortality from cancer recurrence. Cardiovascular disease, in particular, is a leading threat to the well-being of adult survivors of childhood cancers. Unfortunately, the mechanisms of these late cardiac effects are understudied and poorly understood. This article reviews cardiotoxicity associated with 2 major anticancer regimens used in treating childhood cancer patients: anthracycline treatment and radiation therapy. The known pathophysiology and clinical cardiac risk factors that further predispose these patients to late-onset cardiac events are discussed. Basic and translational research is urgently needed to clarify pathophysiologic mechanisms of late cardiac effects and to develop therapies to improve both long-term survival and quality of life of adults cured of pediatric cancers. (Circ Res. 2011;108:619-628.) Key Words: anthracycline Ⅲ radiation Ⅲ cardiotoxicity Ⅲ cancer survivor Ⅲ childhood T he great majority of children who develop childhood cancer today are cured. In the last 40 years, the 5-year survival for childhood cancers has increased from 30% to 80%. 1 Currently, there are an estimated 328 000 childhood cancer survivors in the United States, 2 and it is estimated that 1 in 640 young adults between the ages of 20 and 39 is a survivor of childhood cancer. 1,3 This ever-increasing population of young adult cancer survivors is a testament to the enormous progress made by modern anticancer therapeutics and medical care.Despite a high cure rate, childhood cancer survivors exhibit a long-term survival rate that significantly lags behind ageand gender-matched population controls ( Figure 1A). These patients face considerable mortality during adulthood; excess risks in patients may shorten the lifespan of a survivor by an average of 10 years, as compared with the general population of the United States. 4 Surprisingly, it is not recurrence of the original cancer that is the cause; instead, the intensity of anticancer therapy to achieve cure increases the risk of treatment-related medical illnesses, organ dysfunction, andOriginal received August 27, 2010; resubmission received August 27, 2010; revised resubmission received October 30, 2010; accepted November 16, 2010. In October 2010, the average time from submission to first decision for all original research papers submitted to Circulation Research was 13.9 days. secondary cancers. These "late effects," defined as medical complications occurring greater than 5 years after cancer treatment, significantly reduce the long-term health of childhood cancer survivors. The risk of late effects progressively increases with time following completion of anticancer therapy so that, at 30 years after cancer therapy,...

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