Survival After Childhood Cancer: Stymied by Cardiac Disease?

Study Questions:

Among survivors of childhood cancer, what are dose-response relationships between treatment characteristics (radiotherapy, chemotherapy) and medically confirmed cardiac diseases in a cohort with very long-term follow-up?

Methods:

This was a retrospective analysis of 3,162 five-year survivors of childhood cancer treated in France. Cardiac diseases included myocardial infarction, angina, heart failure, valvular diseases, cardiac arrhythmia, conduction system disease, or pericardial disease. Cardiac diseases were coded from multiple sources: grade 3-defined symptomatic cardiovascular and that which was life-threatening or having led to death.

Results:

The cumulative incidence of any type of cardiac disease at age 40 years was 11.0% (95% confidence interval [CI], 9.5-12.7) and 7.4% (95% CI, 6.2-8.9) when only the cardiac diseases of grade 3 or more were considered. Compared to patients who received no anthracycline and either no radiotherapy or heart radiation dose <0.1 Gy, the risk was multiplied by 18.4 (95% CI, 7.1-48.0) in patients who had received anthracycline and no radiotherapy, by 60.4 (95% CI, 22.4-163) in those who had received no anthracycline and a heart radiation dose ≥30 Gy, and 61.5 (95% CI, 19.6-192.8) in those who received both anthracycline and a heart radiation dose ≥30 Gy.

Conclusions:

Among survivors of childhood cancers treated with radiotherapy and/or anthracycline, there is high dose-dependent risk of developing cardiac disease.

Perspective:

This is a valuable study that adds to our understanding of the impact of radiotherapy and chemotherapy for childhood cancer on long-term risk for cardiac disease. Such information is particularly relevant as long-term survival rates following childhood cancer improve. A key finding is that a high heart radiation dose during treatment for childhood cancer is associated with a very high risk of later cardiac disease and different from that conferred by anthracycline. Certainly, future studies should characterize the mechanisms of cardiotoxicity related to anthracyclines and radiotherapy.

Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, Heart Failure and Cardiomyopathies, Prevention, Valvular Heart Disease, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Anthracyclines, Angina Pectoris, Arrhythmias, Cardiac, Cardiotoxins, Heart Diseases, Heart Failure, Heart Valve Diseases, Myocardial Infarction, Neoplasms, Radiation Effects, Secondary Prevention, Survival Rate, Cardiotoxicity


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