Abstract
Increased risks of cardiac morbidity and mortality among childhood cancer survivors have been described previously. However, little is known about the very long-term risks of cardiac mortality and whether the risk has decreased among those more recently diagnosed. We investigated the risk of long-term cardiac mortality among survivors within the recently extended British Childhood Cancer Survivor Study. The British Childhood Cancer Survivor Study is a population-based cohort of 34 489 five-year survivors of childhood cancer diagnosed from 1940 to 2006 and followed up until February 28, 2014, and is the largest cohort to date to assess late cardiac mortality. Standardized mortality ratios and absolute excess risks were used to quantify cardiac mortality excess risk. Multivariable Poisson regression models were used to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity and trends. Overall, 181 cardiac deaths were observed, which was 3.4 times that expected. Survivors were 2.5 times and 5.9 times more at risk of ischemic heart disease and cardiomyopathy/heart failure death, respectively, than expected. Among those >60 years of age, subsequent primary neoplasms, cardiac disease, and other circulatory conditions accounted for 31%, 22%, and 15% of all excess deaths, respectively, providing clear focus for preventive interventions. The risk of both overall cardiac and cardiomyopathy/heart failure mortality was greatest among those diagnosed from 1980 to 1989. Specifically, for cardiomyopathy/heart failure deaths, survivors diagnosed from 1980 to 1989 had 28.9 times the excess number of deaths observed for survivors diagnosed either before 1970 or from 1990 on. Excess cardiac mortality among 5-year survivors of childhood cancer remains increased beyond 50 years of age and has clear messages in terms of prevention strategies. However, the fact that the risk was greatest in those diagnosed from 1980 to 1989 suggests that initiatives to reduce cardiotoxicity among those treated more recently may be having a measurable impact.
Highlights
Increased risks of cardiac morbidity and mortality among childhood cancer survivors have been described previously
Excess cardiac mortality among 5-year survivors of childhood cancer remains increased beyond 50 years of age and has clear messages in terms of prevention strategies
We have investigated the risk of cardiac mortality among nearly 35 000 survivors of childhood cancer included in the BCCSS (British Childhood Cancer Survivor Study), the largest study to assess mortality in survivors of childhood cancer.[5]
Summary
The British Childhood Cancer Survivor Study is a populationbased cohort of 34 489 five-year survivors of childhood cancer diagnosed from 1940 to 2006 and followed up until February 28, 2014, and is the largest cohort to date to assess late cardiac mortality. The cohort was the first national populationbased study of survivors of childhood cancer to be untaken in Great Britain and was identified from the National Registry of Childhood Tumors, which has an ≈99% ascertainment rate.[6] The study is maintained at the Center for Childhood Cancer Survivor Studies, where research on a wide spectrum of possible adverse health outcomes of childhood cancer and its treatment is undertaken. Additional details relating to the study may be found online[7] and in the descriptive article concerned with methodological aspects underlying the BCCSS.[8] Ethics approval for the study was obtained from the National Research Ethics Service, and legal approval to process identifiable data without consent was approved by the Confidentiality Advisory Group.
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