Cardiac Disease in Childhood Cancer Survivors: Risk Prediction, Prevention, and Surveillance: JACC CardioOncology State-of-the-Art Review

Abstract

Cardiac diseases in the growing population of childhood cancer survivors are of major concern. Cardiotoxicity as a consequence of anthracyclines and chest radiotherapy continues to be relevant in the modern treatment era. Mitoxantrone has emerged as an important treatment-related risk factor and evidence on traditional cardiovascular risk factors in childhood cancer survivors is accumulating. International surveillance guidelines have been developed with the aim to detect and manage cardiac diseases early and prevent symptomatic disease. There is growing interest in risk prediction models to individualize prevention and surveillance. This State-of-the-Art Review summarizes literature from a systematic PubMed search focused on cardiac diseases after treatment for childhood cancer. Here, we discuss the prevalence, risk factors, prevention, risk prediction, and surveillance of cardiac diseases in survivors of childhood cancer.

Keywords: CAD, coronary artery disease; CCS, childhood cancer survivors; ECG, electrocardiogram; FS, fractional shortening; GLS, global longitudinal strain; IGHG, International Late Effects of Childhood Cancer Guideline Harmonization Group; LV, left ventricle; LVEF, left ventricular ejection fraction; RCT, randomized controlled trial; cardiotoxicity; cardiovascular risk factors; chest RT, chest-directed radiotherapy; childhood cancer survivors; prevention; risk prediction.

Graphical abstract

Central Illustration

Overview of Clinical Practice in Childhood Cancer Survivors at Risk for Cardiotoxicity The prevalence of cardiac diseases, risk prediction models, preventive measures, and surveillance recommendations are illustrated based on available evidence and promising research topics of cardiotoxicity in childhood cancer survivors. Numbers derived from Siegel et al., 2019 (122); Feijen et al., 2019 (10); and Armstrong et al., 2013 (17).

Figure 1

Flowchart of Study Inclusion Flowchart describing the systematic literature search in PubMed and the inclusion of relevant studies.

Figure 2

Replicated Genetic Variants Associated With Anthracycline-Induced Cardiomyopathy in Childhood Cancer Survivors and Their Cellular Functions Created with BioRender.com. A = anthracyclines; ABC = adenosine triphosphate binding cassette; ATP = adenosine triphosphate; CELF4 = CUGBP Elav-like family member 4; cTnT = cardiac troponin T; ETFB = electron transfer flavoprotein subunit beta; HAS3 = hyaluronan synthase 3; HNMT = histamine N-methyltransferase; RARG = retinoic acid receptor gamma; rs = reference single nucleotide polymorphism identification; SLC = solute carrier transporter; TOP2b = topoisomerase2b, TTNtv = titin truncating variant; UGT1A6 = UDP glucuronosyltransferase family 1 member A6.