Cardiorespiratory Fitness in Childhood Cancer Survivors: A Systematic Review and Meta-Analysis

Kaitlyn Weinkauf; Emma Fyfe; Dean Hewitt; Jing Wang; Megan Kennedy; Edith Pituskin; Andre La Gerche; Stephen J Foulkes; Mark J Haykowsky

doi:10.1093/eurjpc/zwae317

Cardiorespiratory Fitness in Childhood Cancer Survivors: A Systematic Review and Meta-Analysis

Eur J Prev Cardiol. 2024 Oct 4:zwae317. doi: 10.1093/eurjpc/zwae317. Online ahead of print.

Authors

Kaitlyn Weinkauf¹, Emma Fyfe¹, Dean Hewitt¹, Jing Wang², Megan Kennedy³, Edith Pituskin¹, Andre La Gerche^{4

5}, Stephen J Foulkes^{1

4}, Mark J Haykowsky¹

Affiliations

¹ Integrated Cardiovascular Exercise Physiology and Rehabilitation Lab, Faculty of Nursing, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada.
² Division of Public Health, School of Medicine, University of Utah, Salt Lake City, Utah, USA.
³ University of Alberta Library, University of Alberta, Edmonton, Alberta, Canada.
⁴ Heart, Exercise and Research Trials Lab, St Vincent's Institute of Medical Research, Melbourne, Victoria, Australia.
⁵ Cardiology Department, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.

PMID: 39365168
DOI: 10.1093/eurjpc/zwae317

Abstract

Aims: Cardiovascular disease (CVD) is a leading cause of mortality in childhood cancer survivors (CCS) that may be related to the cardiotoxic effects of radiation or chemotherapy and concomitant reductions in cardiorespiratory fitness. Therefore, we sought to compare cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) between CCS and age-matched non-cancer controls (CON). Secondary outcomes included hemodynamics and resting cardiac function.

Methods: Embase, Scopus, MEDLINE, CINAHL and SPORTDiscus databases were searched from inception to June 2023 for eligible studies. Cross-sectional studies with V̇O2peak measured in CCS and CON were included. Differences in outcomes and pooled estimates for each outcome were estimated from a fixed effects meta-analysis and between group differences were reported as a weighted mean difference (WMD).

Results: Of 2026 studies identified, 18 reported V̇O2peak (CCS: n=786, 44% female, mean age: 16-years, time post-therapy: 5.8 years; CON: n=1379, 50% female, mean age: 16-years). V̇O2peak was lower in CCS (WMD: -7.08mL/kg/min, 95% CI: -7.75 to -6.42, I2: 79%, n=2,165) with no difference for peak exercise heart rate (WMD: -1.4bpm, 95% CI: -3.0 to 0.2, I2: 63%, n=741). Resting left-ventricular ejection fraction (WMD: -1.61%, 95% CI: -2.60 to -0.62, I2.: 49%, n=222) and systolic blood pressure were lower (WMD: -3.8mmHg, 95% CI: -5.7 to -1.9, I2: 25%, n=184) while resting heart rate was higher in CCS (WMD: 4.9bpm; 95% CI: 1.8 to 7.9, I2: 55%, n=262).

Conclusions: CCS have a marked reduction in cardiorespiratory fitness (7.1ml/kg/min lower than CON) that may have important prognostic implications for their future risk of CVD and mortality.

Keywords: Cardiotoxicity; cardiac reserve; exercise intolerance; peak oxygen uptake; pediatric malignancy.

Plain language summary

Childhood cancer survivors are at increased risk of developing cardiovascular disease, in particular, heart failure. This increased cardiovascular risk is partly due to cardiovascular damage from cancer treatment, but may also be due to reductions in cardiorespiratory fitness that accompany increased sedentary behavior prior to, during, or after cancer treatment. In this review, we assessed the degree of cardiorespiratory fitness impairment and cardiovascular function in childhood cancer survivors relative to their cancer-free peers. Key Findings: Whilst traditional markers of cardiovascular function appear normal, childhood cancer survivors have a marked reduction in cardiorespiratory fitness that may increase their risk of heart failure and cardiovascular mortality.Measuring cardiorespiratory fitness alongside traditional cardiovascular risk markers may help to identify cancer survivors at increased risk of cardiovascular disease.