Exercise Programming Modelling a Standard of Care Approach Improves Physical Health and Patient-Reported Outcomes in Individuals Living with Breast Cancer: A Pilot Study.

Controlled study designs widely report that exercise improves the health of individuals living with breast cancer. Still, many individuals living with breast cancer are not active enough to experience the benefits of exercise. The Activating Cancer Communities through an Exercise Strategy for Survivors study was developed to reach more individuals living with cancer. This report describes the effects of a 12-week individualized exercise program that models a standard-of-care approach on body composition, physical fitness, and patient-reported outcomes in individuals living with breast cancer. Individuals living with breast cancer were recruited for the study and completed an exercise program twice weekly overseen by a Clinical Exercise Physiologist. A total of 43 participants completed the exercise intervention, and 36 withdrew from the study. All participants had significantly improved aerobic fitness, waist circumference, hip circumference, lower body endurance, physical activity behaviour, health-related quality of life, emotional status, and fatigue levels after completing the program. Flexibility, balance, and sleep scores did not change. The results from the 12-week individualized exercise program largely align with the results from more controlled study designs. These results support future initiatives integrating exercise therapy into the standard of care for individuals living with breast cancer.

Use of Wearable Activity-Monitoring Technologies to Promote Physical Activity in Cancer Survivors: Challenges and Opportunities for Improved Cancer Care.

The aim of this review was to explore the acceptability, opportunities, and challenges associated with wearable activity-monitoring technology to increase physical activity (PA) behavior in cancer survivors. A search of Medline, Embase, CINAHL, and SportDiscus was conducted from 1 January 2011 through 3 October 2022. The search was limited to English language, and peer-reviewed original research. Studies were included if they reported the use of an activity monitor in adults (+18 years) with a history of cancer with the intent to motivate PA behavior. Our search identified 1832 published articles, of which 28 met inclusion/exclusion criteria. Eighteen of these studies included post-treatment cancer survivors, eight were on active cancer treatment, and two were long-term cancer survivor studies. ActiGraph accelerometers were the primary technology used to monitor PA behaviors, with Fitbit as the most commonly utilized self-monitoring wearable technology. Overall, wearable activity monitors were found to be an acceptable and useful tool in improving self-awareness, motivating behavioral change, and increasing PA levels. Self-monitoring wearable activity devices have a positive impact on short-term PA behaviors in cancer survivors, but the increase in PA gradually attenuated through the maintenance phase. Further study is needed to evaluate and increase the sustainability of the use of wearable technologies to support PA in cancer survivors.

The Impact of Exercise on Cardiotoxicity in Pediatric and Adolescent Cancer Survivors: A Scoping Review.

Childhood and adolescent cancer survivors are disproportionately more likely to develop cardiovascular diseases from the late effects of cardiotoxic therapies (e.g., anthracycline-based chemotherapy and chest-directed radiotherapy). Currently, dexrazoxane is the only approved drug for preventing cancer treatment-related cardiac damage. While animal models highlight the beneficial effects of exercise cancer treatment-related cardiac dysfunction, few clinical studies have been conducted. Thus, the objective of this scoping review was to explore the designs and impact of exercise-based interventions for managing cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors. Reviewers used Joanna Briggs Institute's methodology to identify relevant literature. Then, 4616 studies were screened, and three reviewers extracted relevant data from six reports. Reviewers found that exercise interventions to prevent cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors vary regarding frequency, intensity, time, and type of exercise intervention. Further, the review suggests that exercise promotes positive effects on managing cancer treatment-related cardiac dysfunction across numerous indices of heart health. However, the few clinical studies employing exercise interventions for childhood and adolescent cancer survivors highlight the necessity for more research in this area.

The Impact of Resistance Exercise on Muscle Mass in Glioblastoma in Survivors (RESIST): Protocol for a Randomized Controlled Trial.

BACKGROUND: Glioblastoma is the most common primary brain malignancy in adults, accounting for approximately 48% of all brain tumors. Standard treatment includes radiation and temozolomide chemotherapy. Glioblastomas are highly vascular and can cause vasogenic brain edema and mass effect, which can worsen the neurologic symptoms associated with the disease. The steroid dexamethasone (DEX) is the treatment of choice to reduce vasogenic edema and intracranial pressure associated with glioblastoma. However high-dose DEX or long-term use can result in muscle myopathy in 10%-60% of glioblastoma patients, significantly reducing functional fitness and quality of life (QOL). There is a wealth of evidence to support the use of exercise as an adjuvant therapy to improve functional ability as well as help manage treatment-related symptoms. Specifically, resistance training has been shown to increase muscle mass, strength, and functional fitness in aging adults and several cancer populations. Although studies are limited, research has shown that exercise is safe and feasible in glioblastoma populations. However, it is not clear whether resistance training can be successfully used in glioblastoma to prevent or mitigate steroid-induced muscle myopathy and associated loss of function. OBJECTIVE: The primary purpose of this study is to establish whether an individualized circuit-based program will reduce steroid-induced muscle myopathy, as indicated by maintained or improved functional fitness for patients on active treatment and receiving steroids. METHODS: This is a 2-armed, randomized controlled trial with repeated measures. We will recruit 38 adult (≥18 years) patients diagnosed with either primary or secondary glioblastoma who are scheduled to receive standard radiation and concurrent and adjuvant temozolomide chemotherapy postsurgical debulking and received any dose of DEX through the neurooncology clinic and the Nova Scotia Health Cancer Center. Patients will be randomly allocated to a standard of care waitlist control group or standard of care + circuit-based resistance training exercise group. The exercise group will receive a 12-week individualized, group and home-based exercise program. The control group will be advised to maintain an active lifestyle. The primary outcome, muscle myopathy (functional fitness), will be assessed using the Short Physical Performance Battery and hand grip strength. Secondary outcome measures will include body composition, cardiorespiratory fitness, physical activity, QOL, fatigue, and cognitive function. All measures will be assessed pre- and postintervention. Participant accrual, exercise adherence, and safety will be assessed throughout the study. RESULTS: This study has been funded by the Canadian Cancer Society Atlantic Cancer Research Grant and the J.D. Irving Limited-Excellence in Cancer Research Fund (grant number 707182). The protocol was approved by the Nova Scotia Health and Acadia University's Research Ethics Boards. Enrollment is anticipated to begin in March 2022. CONCLUSIONS: This study will inform how individualized circuit-based resistance training may improve functional independence and overall QOL of glioblastoma patients. TRIAL REGISTRATION: ClinicalTrails.gov NCT05116137; https://www.clinicaltrials.gov/ct2/show/NCT05116137. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37709.

Lifestyle factors and lung cancer risk among never smokers in the Canadian Partnership for Tomorrow's Health (CanPath).

BACKGROUND: Although smoking is the primary risk factor for lung cancer, 15-25% of lung cancers occur in never smokers. Emerging evidence suggests lifestyle factors are associated with lung cancer risk, but few studies among never smokers exist. METHODS: A case-control study of never smokers within the Canadian Partnership for Tomorrow's Health was conducted. At recruitment, participants provided data on lifestyle, health history and sociodemographic factors. Incident lung cancers were identified through linkage with administrative health records. Cases (n = 190) were matched to controls (n = 760) on age, sex, and follow-up time. Logistic regression analyses, adjusted for matching factors and annual income, were used to identify associations between lifestyle factors and lung cancer risk. RESULTS: Consumption of < 5 servings of fruits and vegetables/day was associated with higher risk of lung cancer (OR 1.50, 95% CI 1.03-2.17). Short or long sleep (≤ 6 or > 9 h/night) was also associated with increased risk of lung cancer (OR 1.52, 95% CI 1.01-2.29). No associations were observed for obesity measures, alcohol consumption, or physical activity. CONCLUSION: Our findings provide evidence of a potential role between sleep, fruits and vegetable consumption, and lung cancer risk in a pan-Canadian, non-smoking population. However, the sample size is modest, and further investigation is needed.

Aerobic Exercise Attenuates Frailty in Aging Male and Female C57Bl/6 Mice and Effects Systemic Cytokines Differentially by Sex.

Aerobic exercise is a promising intervention to attenuate frailty, but preclinical studies have used only male animals. We investigated the impact of voluntary aerobic exercise on frailty, biological age (FRailty Inferred Geriatric Health Timeline [FRIGHT] clock), predicted life expectancy (Analysis of FRAIlty and Death [AFRAID] clock), and mortality in both sexes and determined whether exercise was associated with changes in inflammation. Older (21-23 months) male (n = 12) and female (n = 22) C57Bl/6 mice matched for baseline frailty scores were randomized into exercise (running wheel) and sedentary (no wheel) groups. Frailty index scores were measured biweekly (13 weeks), and 23 serum cytokines were measured at midpoint and end point. Exercise levels varied between mice but not between the sexes. Exercise had no effect on mortality, but it attenuated the development of frailty in both sexes (female = 0.32 ± 0.04 vs 0.21 ± 0.01; p = .005; male = 0.30 ± 0.02 vs 0.22 ± 0.02; p = .042) and reduced frailty in older females after 10 weeks. FRIGHT scores were unaffected by exercise but increased with time in sedentary males indicating increased biological age. Exercise prevented the age-associated decline in AFRAID scores in older females such that exercised females had a longer life expectancy. We investigated whether aerobic exercise was associated with changes in systemic inflammation. Cytokine levels were not affected by exercise in males, but levels of pro-inflammatory cytokines were positively correlated with the frequency of exercise in females. Despite increases in systemic inflammation, exercise reduced frailty and increased life span in older females. Thus, voluntary aerobic exercise, even late in life, has beneficial effects on health in both sexes but may be especially helpful in older females.

Exercise to Reduce Anthracycline-Mediated Cardiovascular Complications in Breast Cancer Survivors.

While developments in cancer therapeutics have greatly reduced morbidity and mortality in females with breast cancer, it comes at a cost of an increased risk of cardiovascular complications. In particular, anthracyclines, like doxorubicin, which are a mainstay of current chemotherapy regimens, are associated with dose-dependent cardiotoxicity. Exercise has been widely accepted as an effective intervention in reducing cardiovascular risk in a variety of different clinical conditions. However, the benefits of exercise in anthracycline-mediated cardiotoxicity are not clearly understood. First, this review discusses the pre-clinical studies which have elucidated the cardioprotective mechanisms of aerobic and resistance exercise in improving cardiovascular function in the setting of anthracycline treatment. Next, it aims to summarize the results of aerobic and resistance exercise clinical trials conducted in females with breast cancer who received anthracycline-based chemotherapy. The review further discusses the current exercise guidelines for women undergoing chemotherapy and contraindications for exercise. Finally, the review addresses gaps in research, specifically the need for further clinical trials to establish a recommended exercise prescription within this patient population.

The association between mental health and shift work: Findings from the Atlantic PATH study.

We evaluated the relationship between mental health and shift work in the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. In a matched study with 12,413 participants, including 4155 shift workers and 8258 non-shift workers, we utilized general linear models and logistic regression models to assess the differences in depression, anxiety, and self-rated health. Shift workers reported higher levels of each of the mental health-related domains compared to non-shift workers. There was a significant increased risk of depression (OR = 1.13, 95% CI, 1.00-1.27) and poor self-rated health (OR = 1.13, 95% CI, 1.14-1.55) among shift workers compared to non-shift workers. Shift workers were more likely to have increased rates of depression and poor self-rated health, as well as depressive and anxiety symptom scores compared to non-shift workers. As a result, shift workers may be at increased risk of comorbidity, poor quality of life, missed work, and early retirement.

Burden of multimorbidity and polypharmacy among cancer survivors: a population-based nested case-control study.

PURPOSE: Individuals living with cancer have been shown to have a higher burden of comorbid disease and multimorbidity in comparison to their cancer-free counterparts consequently, leaving them at risk of polypharmacy (i.e., ≥ 5 medications) and its potential negative effects. The primary aim of the current study was to examine the self-reported prevalence of and association between multimorbidity and prescription medication use in a population-based sample of adult cancer survivors (CS). METHODS: This retrospective, nested case-control study drew participant data from the Atlantic Partnership for Tomorrow's Health cohort. CS (n = 1708) were matched to 4 non-cancer controls (n = 6832) by age and sex. Prevalence of polypharmacy by number of chronic conditions and age was estimated with 95% CI. Logistic regression was used to examine the association between multimorbidity and polypharmacy while adjusting for sociodemographic and lifestyle factors. The comorbidity-polypharmacy score was also calculated as an estimate of disease burden. RESULTS: Multimorbidity was common in both CS (53%) and non-cancer controls (43%); however, a significantly higher percentage of CS reported multimorbidity (p < 0.001). Prescription medication use was also found to be significantly higher among CS (2.3 ± 2.6) compared to non-cancer controls (1.8 ± 2.3; p < 0.0001). Exploratory comorbidity-polypharmacy score analyses indicated that CS had a significantly higher overall disease burden than the age/sex-matched non-cancer controls. CONCLUSIONS: As CS appear to be at a higher risk of multimorbidity and polypharmacy and by extension, increased healthcare burden, ongoing education on the prevention of medication-related harm, and interventions to reduce the occurrence of both co-morbid disease and unnecessary medications are warranted.

The association between physical activity and self-rated health in Atlantic Canadians.

The population of Atlantic Canada is aging rapidly and has among the highest rates of chronic disease in the country. This cross-sectional study drew data from the Atlantic Partnership for Tomorrow's Health (Atlantic PATH) study to investigate the association between physical activity and self-rated health among adults in this population. The results suggest that physical activity is associated with and may help to improve perceived health status of individuals with one or more chronic conditions. The findings support literature suggesting that physical activity can be beneficial for adults as they age with chronic disease.

Maladaptive Changes Associated With Cardiac Aging Are Sex-Specific and Graded by Frailty and Inflammation in C57BL/6 Mice.

We investigated whether late-life changes in cardiac structure and function were related to high levels of frailty and inflammation in male and female mice. Frailty (frailty index), ventricular structure/function (echocardiography), and serum cytokines (multiplex immunoassay) were measured in 16- and 23-month-old mice. Left ventricular (LV) mass and septal wall thickness increased with age in both sexes. Ejection fraction increased with age in males (60.4 ± 1.4 vs 68.9 ± 1.8%; p < .05) but not females (58.8 ± 2.5 vs 62.6 ± 2.4%). E/A ratios declined with age in males (1.6 ± 0.1 vs 1.3 ± 0.1; p < .05) but not females (1.4 ± 0.1 vs 1.3 ± 0.1) and this was accompanied by increased ventricular collagen levels in males. These changes in ejection fraction (r = 0.52; p = .01), septal wall thickness (r = 0.59; p = .002), E/A ratios (r = -0.49; p = .04), and fibrosis (r = 0.82; p = .002) were closely graded by frailty scores in males. Only septal wall thickness and LV mass increased with frailty in females. Serum cytokines changed modestly with age in both sexes. Nonetheless, in males, E/A ratios, LV mass, LV posterior wall thickness, and septal wall thickness increased as serum cytokines increased (eg, IL-6, IL-3, IL-1α, IL-1ß, tumor necrosis factor-α, eotaxin, and macrophage inflammatory protein-1α), while ejection fraction declined with increasing IL-3 and granulocyte-macrophage colony stimulating factor. Cardiac outcomes were not correlated with inflammatory cytokines in females. Thus, changes in cardiac structure and function in late life are closely graded by both frailty and markers of inflammation, but this occurs primarily in males. This suggests poor overall health and inflammation drive maladaptive changes in older male hearts, while older females may be resistant to these adverse effects of frailty.

Associations between Neighborhood Walkability, Physical Activity, and Chronic Disease in Nova Scotian Adults: An Atlantic PATH Cohort Study.

Background: While neighborhood walkability has been shown to positively influence health behaviors, less is known about its impact on chronic disease. Our aim was to examine the association between walkability and self-reported physical activity in relation to chronic health conditions in an Atlantic Canadian population. Methods: Using data from the Atlantic Partnership for Tomorrow's Health, a prospective cohort study, we employed both a cross-sectional and a prospective analytical approach to investigate associations of walkability and physical activity with five prevalent chronic diseases and multimorbidity. Results: The cross-sectional data show that participants with the lowest neighborhood walkability were more likely to have reported a pre-existing history of cancer and depression and least likely to report chronic respiratory conditions. Participants with low physical activity were more likely to have a pre-existing history of diabetes, chronic respiratory disease, and multimorbidity. Follow-up analyses showed no significant associations between walkability and chronic disease incidence. Low levels of physical activity were significantly associated with diabetes, cancer and multimorbidity. Conclusions: Our data provides evidence for the health protective benefits of higher levels of physical activity, and a reduction in prevalence of some chronic diseases in more walkable communities.

The relationship between anthropometric measures and cardiometabolic health in shift work: findings from the Atlantic PATH Cohort Study.

PURPOSE: To evaluate the relationship between anthropometric measures and cardiometabolic health in shift workers compared to non-shift workers. METHODS: A population health study was conducted with 4155 shift workers and 8258 non-shift workers from the Atlantic Partnership for Tomorrow's Health (PATH) cohort. Linear and logistic regression models were used to assess the differences in anthropometric measures (body adiposity) and self-reported cardiometabolic disease outcomes (obesity, diabetes, and cardiovascular disease) between shift workers and non-shift workers. RESULTS: There was a significant increased risk of cardiovascular disease, obesity, and diabetes among shift workers compared to matched controls despite higher levels of physical activity and lower levels of sedentary behaviour. Shift workers were 17% more likely to be obese (95% CI 7-27) and 27% more likely to have diabetes (95% CI 8-51). The strength of this association was demonstrated by also controlling for body mass index and fat mass index. CONCLUSIONS: Shift work is associated with obesity, cardiovascular disease, and diabetes despite higher levels of physical activity and lower levels of sedentary behaviour. The association between shift work and cardiometabolic health was independent of body mass index for cardiovascular disease and diabetes, and independent of fat mass index for diabetes.

Rural-Urban Disparities in Total Physical Activity, Body Composition, and Related Health Indicators: An Atlantic PATH Study.

PURPOSE: To describe and compare the sociodemographic and lifestyle characteristics of urban and rural residents in Atlantic Canada. METHODS: Cross-sectional analyses of baseline data from the Atlantic Partnership for Tomorrow's Health cohort were conducted. Specifically, 17,054 adults (35-69 years) who provided sociodemographic characteristics, measures of obesity, and a record of chronic disease and health behaviors were included in the analyses. Multiple linear regression and logistic regression models were used to calculate the multivariable-adjusted beta coefficients (ß), odds ratios (OR), and related 95% confidence intervals (CI). FINDINGS: After adjusting for age, sex, and province, when compared to urban participants, rural residents were significantly more likely to: be classified as very active (OR: 1.19, CI: 1.11-1.27), be obese (OR: 1.13, 1.05-1.21), to present with abdominal obesity (OR: 1.08, CI: 1.01-1.15), and have a higher body fat percentage (ß: 0.40, CI: 0.12-0.68) and fat mass index (ß: 0.32, CI: 0.19-0.46). Rural residents were significantly less likely to be regular or habitual drinkers (OR: 0.83, CI: 0.78-0.89). Significant differences remained after further adjustment for confounding sociodemographic, lifestyle, and health characteristics. No significant differences in smoking behavior, fruit and vegetable intake, multimorbidity, or waist circumference were found. CONCLUSIONS: As expected, obesity prevalence was higher in rural Atlantic Canadians. In contrast to much of the existing literature, we found that rural participants were more likely to report higher levels of total physical activity and lower alcohol consumption. Findings suggest that novel obesity prevention strategies may be needed for rural populations.

Short-term supplement of virgin coconut oil improves endothelial-dependent dilation but not exercise-mediated hyperemia in young adults.

Virgin coconut oil (VCO) is high in antioxidants, which reduce reactive oxygen species-induced conversion of vascular endothelial-derived nitric oxide (NO) to toxic peroxynitrite. As such, flow-mediated dilation (FMD, a surrogate marker of NO bioavailability) and exercise-mediated hyperemia may be enhanced following VCO treatment. Animal research supports these findings, but direct assessments of FMD after short-term VCO use in humans are unknown. We tested the hypotheses that a 4-week VCO supplement (30 mL·d-1) would improve popliteal artery (PA) FMD and the hyperemic response to aerobic exercise. Thirty-four young adults were divided into VCO (n = 19, 9 women, 22 ±â€¯2 years, 24 ±â€¯3 kg·m-2) and control (CON: n = 15, 7 women, 24 ±â€¯2 years, 24 ±â€¯3 kg·m-2) groups. PA-FMD and blood flow were assessed via high-resolution duplex ultrasonography (Vivid i, GE Healthcare, Mississauga, Ontario, Canada). PA blood flow was measured at rest and for 5 minutes following a 10-minute bout of moderate-intensity (60% heart rate reserve) cycling exercise. Total PA blood volume was calculated as the integral of the 5-minute postexercise PA blood flow response. After 4 weeks, PA-FMD increased (P = .04) following VCO supplementation (4.9% ±â€¯0.9% to 5.5% ±â€¯1.2%) with no change (P > .9) in the CON group (5.7% ±â€¯2.1% to 5.8% ±â€¯1.9%). There were no differences (both P > .28) in the postexercise total PA blood volume response in either group (VCO: 495 ±â€¯355 to 598 ±â€¯384 mL; CON: 562 ±â€¯362 to 488 ±â€¯229 mL). Short-term VCO supplementation does not alter aerobic exercise-mediated blood flow responses in young adults. However, the augmented popliteal FMD response observed in the VCO supplement group indicates that short-term VCO supplementation improves vascular endothelial function in young, healthy adults.

A Murine Frailty Index Based on Clinical and Laboratory Measurements: Links Between Frailty and Pro-inflammatory Cytokines Differ in a Sex-Specific Manner.

A frailty index (FI) based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI-Clinical scores, and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 and 23 months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) based on deviation from reference values in younger adults (12 months), which showed similar characteristics to a human FI-Lab tool. Interestingly, while FI-Clinical scores were higher in females, the opposite was true for FI-Lab scores and there was no sex difference in FI-Combined scores. All three FI tools revealed a positive correlation between pro-inflammatory cytokine levels and frailty in aging mice that differed between the sexes. Elevated levels of the pro-inflammatory cytokines interleukin (IL)-6, IL-9, and interferon-γ were associated with higher FI scores in aging females, while levels of IL-12p40 rose as FI scores increased in older males. Thus, an FI tool based on common laboratory tests can quantify frailty in mice; the positive correlation between inflammation and frailty scores in naturally aging mice differs between the sexes.

Chronic Treatment With the ACE Inhibitor Enalapril Attenuates the Development of Frailty and Differentially Modifies Pro- and Anti-inflammatory Cytokines in Aging Male and Female C57BL/6 Mice.

Studies on interventions that can delay or treat frailty in humans are limited. There is evidence of beneficial effects of angiotensin converting enzyme (ACE) inhibitors on aspects related to frailty, such as physical function, even in those without cardiovascular disease. This study aimed to longitudinally investigate the effect of an ACE inhibitor on frailty in aging male and female mice. Frailty was assessed with a clinical frailty index (FI) which quantifies health-related deficits in middle-aged (9-13 months) and older (16-25 months) mice. Chronic treatment with enalapril (30 mg/kg/day in feed) attenuated frailty in middle-aged and older female mice, and older male mice, without a long-term effect on blood pressure. Enalapril treatment resulted in a reduction in the proinflammatory cytokines interleukin (IL)-1α, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1a in older female mice, and an increase in the anti-inflammatory cytokine IL-10 in older male mice compared with control animals. These sex-specific effects on inflammation may contribute to the protective effects of enalapril against frailty. This is the first study to examine the longitudinal effect of an intervention on the FI in mice, and provides preclinical evidence that enalapril may delay the onset of frailty, even when started later in life.

Aerobic exercise and cardiopulmonary fitness in childhood cancer survivors treated with a cardiotoxic agent: a meta-analysis.

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 subgroup 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.