Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review

Ann Oncol. 2002 Jun;13(6):819-29. doi: 10.1093/annonc/mdf167.


Background: The aim of this systematic review was to summarise and appraise the published evidence with regard to the frequency and risk factors of subclinical cardiotoxicity in apparently healthy survivors of childhood cancer after anthracycline therapy.

Patients and methods: A search was made in Medline for studies published between 1966 and May 2001 that included >50 children and reported on the frequency of measures of subclinical cardiotoxicity. Information about the studies was abstracted by two reviewers and a validity score was calculated for each study.

Results: The reported frequency of subclinical cardiotoxicity varied between 0% and 57% in the 25 studies included. Differences in outcome definitions of subclinical cardiotoxicity and differences in study patients with respect to the dose of anthracycline seemed to explain part of the wide variance of the frequency of subclinical cardiotoxicity. Fourteen of the 25 studies showed serious methodological limitations.

Conclusions: The reported frequency of subclinical cardiotoxicity shows a wide variation. Well designed studies with accurate and precise outcome measurements in well described groups of patients, after a sufficiently long follow-up period, are needed to obtain more insight into the frequency and importance of risk factors, and the clinical consequences of anthracycline-related subclinical cardiotoxicity.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / therapeutic use
  • Cardiomyopathies / chemically induced*
  • Cardiomyopathies / epidemiology*
  • Cardiomyopathies / physiopathology
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Male
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Netherlands / epidemiology
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Survival Rate


  • Antibiotics, Antineoplastic