Paediatric cardio-oncology: epidemiology, screening, prevention, and treatment

Abstract

With 5-year survival of children with cancer exceeding 80% in developed countries, premature cardiovascular disease is now a major cause of early morbidity and mortality. In addition to the acute and chronic cardiotoxic effects of anthracyclines, related chemotherapeutics, and radiation, a growing number of new molecular targeted agents may also have detrimental effects on the cardiovascular system. Survivors of childhood cancer also may have earlier development of conventional cardiovascular risk factors such as hypertension, dyslipidaemia, and diabetes, which further increase their risk of serious cardiovascular disease. This review will examine the epidemiology of acute and chronic cardiotoxicity relevant to paediatric cancer patients, including genetic risk factors. We will also provide an overview of current screening recommendations, including the evidence regarding both imaging (e.g. echocardiography and magnetic resonance imaging) and blood-based biomarkers. Various primary and secondary prevention strategies will also be discussed, primarily in relation to anthracycline-related cardiomyopathy. Finally, we review the available evidence related to the management of systolic and diastolic dysfunction in paediatric cancer patients and childhood cancer survivors.

Keywords: Anthracycline; Cardio-oncology; Cardiomyopathy; Paediatric; Prevention; Survivorship.

Figure 1

Event-free (A) and overall (B) survival according to the presence of LVSD, in the presence or absence of associated bloodstream infection, on COG trial AAML0531. Adapted from Getz et al.

Figure 2

Cumulative incidence of (A) congestive heart failure and (B) myocardial infarction among childhood cancer survivors since original cancer diagnosis (years). From Mulrooney et al.

Figure 3

Overview of cancer-related cardiomyopathy prevention strategies. From Armenian et al.

Figure 4

Relative risk of serious cardiovascular outcomes in long-term childhood cancer survivors (n = 10 724) in relation to cancer treatment exposures (ANTH, anthracycline; CRT, chest radiotherapy) and hypertension (HTN) status. Adapted from Armstrong et al. *P<0.01 vs. referent. ^†Relative excess risk due to interaction [RERI] = 24 (95% CI 12–40); RERI >0 indicates interaction was more than additive. ^‡RERI = 45 (95% CI 17–106).

Figure 5

Cumulative incidence of all-cause mortality according to quartiles of vigorous exercise at study entry. Adapted from Scott et al. MET, metabolic equivalent task.