Cardiotoxicity After Childhood Cancer: Beginning With the End in Mind

Worldwide, more than 28 million people live with cancer. This number could triple by 2030. With the increasing number of patients with cancer and improvements in cancer management that continue to reduce cancer death rates, the number of cancer survivors is projected to increase rapidly, in particular, those afflicted during childhood. In children and adolescents, the survival rate has jumped from fewer than 50% in the mid-1970s to 80% today. The growing population of childhood survivors is notable for its vulnerability to adverse health outcomes, many of which may not become clinically apparent until years after the completion of therapy. Despite surviving their initial cancer, childhood cancer survivors continue to face considerable premature mortality as adults. The excess risk of dying from other causes that contributes most to loss of life expectancy is the increased incidence of chronic conditions among survivors of childhood cancer. We need to monitor the health of these survivors and to minimize the use of therapies with late toxicities in newly diagnosed patients. Survivors also experience a higher prevalence of chronic conditions, with as many as two thirds of childhood cancer survivors reporting at least one chronic condition and one fourth reporting a severe, disabling, or life-threatening condition. Survivors of childhood cancer are 5 to 10 times more likely than their healthy siblings to experience heart disease. The incidence of these conditions increases with time, so the full extent of disease- and treatment-related late effects has yet to be realized. Survivors of childhood cancer are a new, large, emerging population at risk for acquired premature symptomatic cardiovascular disease. The report by Tukenova et al 1 provides important information on late excess cardiovascular mortality in childhood cancer survivors and on the factors associated with this mortality. Their report adds new information about late cardiac effects in childhood cancer survivors by specifically using carefully calculated radiation doses to the heart as a factor to assess overall mortality and cardiovascular mortality. Importantly, this study also evaluated the potential classes of medications for their association with cardiovascular mortality. This article not only validates previous studies of overall cardiac mortality, 2-7 it also provides new data on cumulative anthracycline dose, cumulative radiation dose, and the contribution of other agents. Although the dose-dependent risk of congestive heart failure and related deaths associated with anthracyclines among childhood cancer survivors is established, and although radiation exposure to the heart has also been associated with increased risk of cardiovascular disease, this article’s evaluation of the association between the dose of radiation and the dose of anthracyclines on cardiovascular mortality in the same cohort is important. Studies have generally looked only at radiation as a dichotomous variable, although others have looked at treat