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  • Review Article
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Treatment-related cardiotoxicity in survivors of childhood cancer

Nature Reviews Clinical Oncology volume 10, pages 697–710 (2013)Cite this article

Subjects

Key Points

  • Advances in treatment have increased the number of childhood cancer survivors with late-occurring, treatment-related cardiovascular complications

  • Treatment-induced cardiovascular events associated with chemotherapy and radiotherapy include cardiomyopathy, conduction defects, myocardial infarction, hypertension, stroke, pulmonary oedema, dyspnoea, and exercise intolerance

  • The likelihood that subclinical damage will progress to clinically important events emphasizes the importance of reducing or eliminating this early damage

  • Protective strategies that have been partially tested include administering cardioprotective agents, using less-toxic anthracycline derivatives and correcting therapy-related endocrinopathies that affect cardiovascular disease development

  • Traditional cardiovascular risk factors, in addition to factors directly related to cancer treatments, can further increase the risk of cardiovascular complications in survivors

  • Cancer treatment protocols should be refined to minimize cardiovascular and other adverse effects while maintaining acceptable cancer treatment response rates

Abstract

Treatment advances and higher participation rates in clinical trials have rapidly increased the number of survivors of childhood cancer. However, chemotherapy and radiation treatments are cardiotoxic and can cause cardiomyopathy, conduction defects, myocardial infarction, hypertension, stroke, pulmonary oedema, dyspnoea and exercise intolerance later in life. These cardiotoxic effects are often progressive and irreversible, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Medical interventions, such as angiotensin-converting enzyme inhibitors, β-blockers, and growth hormone therapy, might be used to treat cardiotoxicity in childhood cancer survivors. Preventative strategies should include the use of dexrazoxane, which provides cardioprotection without reducing the oncological efficacy of doxorubicin chemotherapy; less-toxic anthracycline derivatives and the use of antioxidant nutritional supplements might also be beneficial. Continuous-infusion doxorubicin provides no benefit over bolus infusion in children. Identifying patient-related (for example, obesity and hypertension) and drug-related (for example, cumulative dose) risk factors for cardiotoxicity could help tailor treatments to individual patients. However, all survivors of childhood cancer are at increased risk of cardiotoxicity, suggesting that survivor screening recommendations for assessment of global risk of premature cardiovascular disease should apply to all survivors. Optimal, evidence-based monitoring strategies and multiagent preventative treatments still need to be identified.

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Figure 1: Progressive cardiac dysfunction after doxorubicin therapy in children treated for acute lymphoblastic leukaemia.
Figure 2: Stages in the course of paediatric ventricular dysfunction.
Figure 3: Potential opportunities for cardioprotection.
Figure 4: Differences in anthracycline cardiotoxic late effects experienced between adults and children attributable to common risk factors.39

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Acknowledgements

This article was supported in part by grants from the NIH (HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, HD80002), the Children's Cardiomyopathy Foundation, the Women's Cancer Association, the Lance Armstrong Foundation, the STOP Children's Cancer Foundation, the Scott Howard Fund and the Michael Garil Fund.

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  1. Department of Pediatrics, Wayne State University School of Medicine and Children's Hospital of Michigan, 3901 Beaubien Boulevard, Detroit, 48201, MI, USA

    Steven E. Lipshultz

  2. Department of Pediatrics, University of Miami Miller School of Medicine, Medical Campus-MCCD-D820, 1601 North West 12th Avenue, Miami, 33136, FL, USA

    Thomas R. Cochran, Vivian I. Franco & Tracie L. Miller

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S. E. Lipshultz and T. L. Miller researched data for the article. S. E. Lipshultz, T. R. Cochran, and V. I. Franco made a substantial contribution to discussion of the content and wrote the article, and all authors reviewed or edited the article before submission.

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Correspondence to Steven E. Lipshultz.

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Lipshultz, S., Cochran, T., Franco, V. et al. Treatment-related cardiotoxicity in survivors of childhood cancer. Nat Rev Clin Oncol 10, 697–710 (2013). https://doi.org/10.1038/nrclinonc.2013.195

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