Impact of Physical Exercise on Growth and Progression of Cancer in Rodents—A Systematic Review and Meta-Analysis

Abstract

Background: Physical exercise is suspected to reduce cancer risk and mortality. So far, little is known about the underlying mechanisms. Although limited, murine models represent a promising attempt in order to gain knowledge in this field.Objective: A systematic review and meta-analysis examining various treatment protocols was conducted in order to determine the impact of exercise on tumor growth in rodents.Methods: PubMed, Google scholar and System for information on Gray literature in Europe were screened from inception to October 2017. Risk of bias within individual studies was assessed using the Office of Health Assessment and Translation risk of bias rating tool for human and animal trials. The effect of exercise on tumor growth over and above non-exercise control was pooled using random-effects model. Subgroup analyses were conducted to identify potential moderators.Results: The quality of the included 17 articles ranged between “probably low” and “high risk of bias.” A significant reduction in tumor growth in exercising animals compared to controls was detected (Hedges' g = −0.40; 95% CI −0.66 to −0.14, p < 0.01) with between-study heterogeneity (τ2 = 0.217, I2 = 70.28%, p < 0.001). The heterogeneity was partially explained by three moderators representing the in-between group differences of “maximum daily exercise” R2 = 33% (p < 0.01), “type of cancer administration” R2 = 28% (p < 0.05), and “training initiation” R2 = 27% (p < 0.05).Conclusion: This meta-analysis suggests that physical exercise leads to reduction of tumor size in rodents. Since “maximum daily exercise” was found to have at least modest impact on tumor growth, more clinical trials investigating dose-response relationships are needed.

Effect of post-implant exercise on tumour growth rate, perfusion and hypoxia in mice

“…Most preclinical studies that reported a statistical reduction in tumour growth rate with post-implantation exercise show only a marginal slowing of tumour growth [15,[31][32][33]. A recent systematic review and meta-analysis found a "small to moderate" effect size for exercise to reduce final tumour size [8]. However, of the 8 studies included that showed a statistically significant difference in tumour size, one of these showed an increase with exercise, one had a small effect size and four had a 'probably high' risk of bias [8].…”

“…A recent systematic review and meta-analysis found a "small to moderate" effect size for exercise to reduce final tumour size [8]. However, of the 8 studies included that showed a statistically significant difference in tumour size, one of these showed an increase with exercise, one had a small effect size and four had a 'probably high' risk of bias [8]. As there is little consistency between studies in terms of the effect of post-implantation exercise on tumour growth, it seems unlikely that exercise as a sole intervention (monotherapy) has a meaningful effect.…”

“…This is an important distinction, as pre-implantation exercise preconditions the animal and mimics the use of exercise as a preventative measure, while post-implantation exercise mimics the use of exercise in a therapeutic setting (post-diagnosis). When studies were grouped according to the timing of exercise initiation (pre-implant, post-implant or both pre-and post-implant), there was a significant difference between groups (p = 0.0284), with exercise starting before implant and continuing throughout moderately reducing final tumour size and exercise post-implant having only a small anti-tumour effect [8]. There was only one study investigating exercise pre-implant; which found a non-significant increase in tumour size with exercise [8].…”

“…When studies were grouped according to the timing of exercise initiation (pre-implant, post-implant or both pre-and post-implant), there was a significant difference between groups (p = 0.0284), with exercise starting before implant and continuing throughout moderately reducing final tumour size and exercise post-implant having only a small anti-tumour effect [8]. There was only one study investigating exercise pre-implant; which found a non-significant increase in tumour size with exercise [8]. This suggests that the biggest impact is seen when exercise begins prior to tumour implant and continues post-implant.…”

“…In preclinical studies, varying and conflicting data have been reported. Although there have been numerous reports of the effects of exercise on tumour progression in rodents [reviewed in 2, [6][7][8], only one systematic review includes a subgroup analysis to compare the effects of pre-vs post-implantation exercise [8]. This is an important distinction, as pre-implantation exercise preconditions the animal and mimics the use of exercise as a preventative measure, while post-implantation exercise mimics the use of exercise in a therapeutic setting (post-diagnosis).…”