Surviving Childhood Cancer but Succumbing to Long-Term Cardiovascular Disease

The National Cancer Institute estimates that there were 12 million U.S. cancer survivors in 2007, approximately three times more than there were 30 years ago. As the population of cancer survivors grows, more patients are at risk for long-term complications from cancer therapies. Although excess risk for treatment-associated secondary cancers in this population is well established, investigators sought to characterize better the long-term cardiovascular complications of therapy in 4122 French and British patients who received cancer diagnoses before age 15 years (diagnoses made between 1942 and 1986) and who survived at least 5 years after diagnosis. Patients who had childhood leukemias were excluded.

Nephroblastoma was the most common diagnosis (21%), followed by brain cancer (16%), neuroblastoma (14%), soft tissue sarcoma (12%), non-Hodgkin lymphoma (10%), and Hodgkin disease (8%). Almost half of patients were treated with a combination of chemotherapy and radiation; almost one quarter received radiation only, about 20% received chemotherapy only, and the rest were treated with surgery only. At median follow-up of 26 years, 603 patients (15%) had died — about eight times the mortality expected in age- and sex-matched patients in the general population. Although most deaths resulted from first or secondary cancers, 11 deaths were attributed to vascular causes and 21 to cardiac causes, corresponding to death rates that were four and six times higher, respectively, than expected. After adjustment for several factors, risk for cardiovascular mortality was higher in patients who were treated with vinca alkaloids, and risk for cardiac mortality was higher in patients with cumulative exposure to anthracyclines above 360 mg/m². Cardiac-related mortality rose after cardiac irradiation, substantially so at doses ≥5 Gy.