Aerobic exercise and cardiopulmonary fitness in childhood cancer
survivors treated with a cardiotoxic agent: a meta-analysis
Scott A. Grandy
Melanie R. Keats
Received: 5 January 2018 / Accepted: 9 April 2018 / Published online: 18 April 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Purpose The main purpose of this review was to synthesize evidence from existing childhood cancer survivor studies that report
the effect of aerobic exercise on cardiopulmonary fitness (a marker of cardiovascular health), in survivors that were currently
receiving or had been treated with a cardiotoxic agent.
Methods Studies were identified for this review by searching both electronic databases of peer-reviewed articles, as well as
various sources of gray literature. Risk of bias was qualitatively assessed in these studies using the domains outlined in the
Cochrane Handbook for Systematic Reviews of Interventions. Data was analyzed quantitatively using random-effects meta-
analyses and subgroup analyses in RevMan Software.
Results Meta-analysis of pooled evidence from the nine included studies suggests that aerobic exercise has a statistically and
clinically significant positive effect on cardiopulmonary fitness (effect estimate = 6.92%, p value = 0.02). Findings from sub-
group analyses of clinical characteristics and exercise parameters were not significant.
Conclusions The findings from this review, although not directly demonstrating a cardioprotective effect, are a preliminary step
towards establishing the putative cardioprotective effect of aerobic exercise against the direct cardiotoxic impact of cancer
treatments. The significant positive effect estimate in favor of aerobic exercise is a small but important advancement towards
the standardization of aerobic exercise in childhood cancer survivors. Further studies are necessary.
Keywords Childhood cancer
The 5-year survival rate among childhood cancer survivors
(CCS) has increased from 30% to as high as 83% between
the early 1960s and 2013 . This significant increase in
survival rate is largely due to advances in antineoplastic ther-
apies . However, as the population of CCS steadily in-
creases, so too does our understanding of the adverse late
effects caused by cancer treatment. One of the most significant
late effects is cardiovascular disease (CVD) . Notably, the
incidence of cardiac mortality in CCS exceeds that in age-sex-
matched cohorts from the general population by as much as
eight times .
Two major contributors to the increased risk of CVD in
cancer survivors is chemotherapy (i.e., anthracycline) and ra-
diation therapy-induced damage to heart tissue (i.e.,
cardiotoxicity; CT) [5–8]. The most threatening manifestation
of CT is congestive heart failure, which may present as many
as 40 years after anthracycline treatment in childhood . The
severity of CT is dependent on a number of risk factors, in-
cluding but not limited to, total cumulative dose , age at
time of exposure , and time since initial exposure . As
a result of the latter two risk factors specifically, CCS are at a
high risk of developing CT-mediated CVD later in life .
The identification of cardioprotective strategies to mitigate
CT and reduce the risk of CVD in CCS has consequently
emerged as an important area of research . Currently, the
primary cardioprotective strategies against anthracycline-
induced CT are dose restriction  and dexrazoxane (a
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00520-018-4208-z) contains supplementary
material, which is available to authorized users.
* Melanie R. Keats
Northern Ontario School of Medicine, Laurentian University,
Sudbury, ON, Canada
School of Health and Human Performance, Dalhousie University
Halifax, 6230 South Street, Halifax, NS B3H 4R2, Canada
Supportive Care in Cancer (2018) 26:2113–2123