Aims: Tumours are structurally and functionally abnormal. Tumour blood vessels are unevenly distributed and poorly developed, resulting in areas of hypoxia and heterogenous blood supply. Aerobic exercise may modulate tumour blood flow and normalise the tumour microenvironment to reduce hypoxia and improve chemotherapy delivery. This systematic review aims to evaluate the effects of aerobic exercise on tumour hypoxia, vascularisation and blood flow.
Methods: We searched Medline, EMBASE, Scopus and CINAHL through July 2020. Preclinical and clinical randomised controlled trials examining the effects of aerobic exercise (≥ 2 repeated bouts) on markers of hypoxia, vascularisation or blood flow in solid tumours were included (PROSPERO: Protocol number CRD42020159201). Two independent reviewers performed screening and data extraction.
Results: Fifteen preclinical studies and one clinical study met criteria. Nine studies assessed hypoxia, 15 studies assessed vascularisation and seven evaluated blood flow. There was large variability in the range of measures, cancer type and exercise interventions. Hypoxia showed little consistency with three studies demonstrating a decrease in hypoxia, five studies demonstrating no change and one study demonstrating an increase. Similarly, the effect on vascularisation was heterogenous with three studies demonstrating a decrease in vessel density, eight studies demonstrating no change and four studies demonstrating an increase. However, blood flow demonstrated a mostly positive effect across all the studies.
Conclusion: Most evidence of aerobic exercise effects on tumour blood flow is in animal models, with very limited evidence in humans. Despite wide variability in methodology, these findings suggest exercise has a positive effect on blood flow to solid tumours. However, evidence in inconsistent regarding effect on hypoxia and vascularisation. Further research is needed to extend this work in clinical trials and to investigate the potential for translation to intravenous chemotherapy delivery.