Abstract
Background: Anthracyclines are widely used to treat childhood cancers; however, they cause cardiotoxicity. To address the paucity of clinical data from Asian populations, this study investigated the epidemiology of pediatric anthracycline-induced cardiotoxicity, during and after chemotherapy, in a multiethnic Asian population.Procedure: This was a single-center, retrospective analysis of 458 anthracycline-treated pediatric oncology patients at KK Women's and Children's Hospital, a tertiary children's hospital in Singapore from 2005 through 2015. We investigated cardiotoxicity (defined as left ventricular fractional shortening <28% on echocardiography) and its risk factors using univariate logistic regression as well as survival estimates through the Kaplan-Meier method to compare survival distribution between patients with and without cardiotoxicity.Results: Over a follow-up period of almost 4 years, we found that 7% (32/458) of the cohort developed cardiotoxicity, with 37.5% (12/32) of these manifesting as clinical heart failure, whilst the rest were asymptomatic. The cardiotoxic cohort demonstrated a significantly higher mortality rate compared to the non-cardiotoxic group at 46.9 vs. 19.2% (p < 0.001), of whom 3 (9.4%) died from end-stage heart failure. We found that traditional predictors such as female sex, age at diagnosis, and cumulative doxorubicin equivalent dose were not predictors of cardiotoxicity.Conclusion: Our study reaffirms that freedom from symptoms does not ensure normal heart function and suggests that children with abnormal ventricular systolic function have higher mortality risk compared to those with normal systolic function. The findings contribute to improved understanding of the Asian burden to aid development of measures to prevent or reduce the risk of cardiotoxicity.
Highlights
Pediatric cancer survival rates have risen significantly over the past few decades. [1] With contemporary therapies, over 80% of children diagnosed with cancer will become longterm survivors [2, 3]
We found that 7% of children treated with anthracyclines developed cardiotoxicity; the incidence of subclinical cardiotoxicity and anthracycline-related clinical heart failure were 4.4 and 2.6%, respectively
At a short follow-up duration of 3.9 years, 7% of our cohort were found to have reduced left ventricular (LV) systolic function (LV fractional shortening (FS)
Summary
Pediatric cancer survival rates have risen significantly over the past few decades. [1] With contemporary therapies, over 80% of children diagnosed with cancer will become longterm survivors [2, 3]. [4] anthracyclines have a well-known cardiotoxic effect, and observed frequencies vary between studies, up to 57% of patients treated with an anthracycline may develop echocardiographic abnormalities [5]. These abnormalities may be progressive in a significant proportion of patients [6,7,8,9]. Childhood cancer survivors (CCS) exposed to anthracyclines have a significantly higher risk of developing cardiac disease compared to their siblings or age-matched peers [10,11,12].
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