Measurement of Cognitive Function in Exercise Oncology Studies in Patients Treated With Chemotherapy: A Scoping Review.

Cancer-associated cognitive deficits following chemotherapy have received increased attention in clinical research. Exercise has been shown to preserve cognitive function in cancer patients, though the overall effect is mixed. Here we present a scoping review of the published literature summarizing methods used to assess cognitive function in exercise oncology trials. Methods: PubMed, PsycINFO and CINAHL databases were searched using keywords "cognition," "cancer" OR "neoplasm" OR "tumor," "chemotherapy" and "exercise" OR "physical activity." Studies eligible for inclusion include prospective studies that were published in English in peer-reviewed journals that include a method of assessing cognitive function in adult cancer patients, in which an exercise modality or method of quantifying exercise habits was evident. Studies were excluded if they included a pediatric population, patients that were not diagnosed with cancer, or were systematic/narrative/scoping reviews, protocol papers or dissertation/theses. Results: A total of 29 studies met the inclusion criteria. In total, 29 unique assessments were used to evaluate cognitive function, including patient-reported outcomes (PROs; n = 8) and objective (n = 21) methods. More than half (n = 17) of included studies relied on PROs while 12 studies utilized objective measures of cognitive function Cognitive domains of the PROs were limited in scope, focusing on memory and attention/concentration while the objective measures were broader and inclusive of multiple domains. Conclusion: The results of this review indicate that mixed approaches to evaluating cognitive function in cancer patients pose a major limitation to understanding the role of exercise as an integrative approach. The evidence demonstrates a need for more uniform assessment of cognitive function in exercise oncology trials.

Effects of high-intensity interval training on cardiometabolic biomarkers in patients with prostate cancer undergoing active surveillance: a randomized controlled trial.

PURPOSE: To report the effects of a 12-week high-intensity interval training (HIIT) program on cardiometabolic biomarkers in patients with prostate cancer on active surveillance (AS) from the Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial. METHODS: Fifty-two men with prostate cancer on AS were randomized to either an exercise (HIIT; n = 26) or usual care (UC; n = 26) group. The HIIT intervention consisted of progressive, supervised, aerobic HIIT at an intensity of 85 to 95% VO2peak for 28 to 40 min per session performed three times/week for 12 weeks. Blood samples were collected at baseline and postintervention to analyze cardiometabolic biomarkers. Analysis of covariance was used to examine between-group mean differences. RESULTS: Blood data were obtained from 49/52 (94%) participants at postintervention. Participants were aged 63.4 ± 7.1 years and 40% were obese. The HIIT group attended 96% of the planned exercise sessions. No significant between-group changes in weight were observed after the intervention. Compared to UC, HIIT significantly improved total cholesterol (-0.40 mmol/L; 95% confidence interval[CI], -0.70 to -0.10; p = 0.011), non-high-density lipoprotein-c (-0.35 mmol/L; 95% CI, -0.60 to -0.11; p = 0.006), insulin (-13.6 pmol/L; 95% CI, -25.3 to -1.8; p = 0.025), insulin-like growth factor (IGF)-1 (-15.0 ng/mL; 95% CI, -29.9 to -0.1; p = 0.048), and IGF binding protein (IGFBP)-3 (152.3 ng/mL; 95% CI, 12.6 to 292.1; p = 0.033). No significant differences were observed for fasting glucose, HbA1c, other lipid markers, IGFBP-1, adiponectin, and leptin. CONCLUSIONS: The ERASE Trial showed that a 12-week aerobic HIIT program improved several cardiometabolic biomarkers in patients with prostate cancer on AS that may contribute to cardiovascular health benefits and potentially influence signaling pathways in the progression of prostate cancer. Further research is needed to confirm the effects of exercise on cardiometabolic markers in men with prostate cancer on AS and determine if these effects are associated with improved long-term clinical outcomes.

Perceived stress and associations between physical activity, sedentary time, and interstitial glucose in healthy adolescents.

BACKGROUND: Less moderate to vigorous physical activity (MVPA), more sedentary time (ST), and higher perceived stress are related to type 2 diabetes mellitus (T2DM) occurrence, but observational evidence addressing the interaction of these factors is lacking in youth. This pilot study investigated momentary stress as a moderator in the acute associations of MVPA and ST with subsequent glucose in healthy adolescents. METHODS: Participants (N=15, Mage=13.1±1.0 years, 10 girls, 5 with overweight/obesity) simultaneously wore a continuous glucose monitor (CGM), thigh-mounted accelerometer, and reported momentary stress via random ecological momentary assessments (EMA; Time T) for 7-14 days. MVPA and ST (min) were calculated for 60- and 120-minute time windows before each EMA prompt (Time T-1). Mean CGM-measured interstitial glucose (mg/dL) was calculated after each prompt (Mmin=120.0±25.4; Time T+1). Multilevel models assessed whether within-subject MVPA and ST (Time T-1) predicted mean glucose (Time T+1), with momentary stress as a moderator (Time T). RESULTS: There were 513 time-matched EMA reports of stress, accelerometer, and CGM data. Momentary stress moderated the effects of MVPA 60 (ß=-0.22, p=.001) and 120 min (ß=-0.08, p=.02) before the prompt on subsequent glucose levels. When youth spent more time in MVPA than their average and when momentary stress was higher than their average, subsequent glucose was lower. Stress did not moderate associations of ST with glucose (p>.05). CONCLUSIONS: Higher momentary stress may interact with higher MVPA to lower subsequent glucose in youth. Accelerometers, EMA, and CGMs can be integrated in future studies to further understand these associations in free-living environments.

Resistance Exercise and Skeletal Muscle-Related Outcomes in Patients with Cancer: A Systematic Review.

BACKGROUND: Skeletal muscle loss is prevalent throughout the cancer continuum and correlates with morbidity and mortality. Resistance exercise has been trialed to mitigate skeletal muscle loss. This systematic review summarizes and qualitatively synthesizes the effects of resistance exercise on muscle-related outcomes in adult cancer populations, including skeletal muscle mass, performance and muscle-related biomarkers. METHODS: The systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). We searched electronic databases including AMED, CENTRAL, CINAHL, CIRRIE, EMBASE, MEDLINE, PEDro, REHABDATA, Scopus, and SPORTDiscus (from inception to December 2021).We included randomized controlled trials that investigated the effects of resistance exercise on muscle-related outcomes in adult cancer populations. Interventions that involved any resistance exercise were included. Muscle-related outcomes were categorized as skeletal muscle mass (e.g., lean mass, appendicular muscle mass), muscle performance (e.g., muscle strength, physical function), and muscle-related biomarkers (e.g., muscle cells, metabolic/inflammatory markers). Risk of bias (RoB) was assessed using the Cochrane ROB tool. RESULTS: 02 studies from 101 randomized controlled trials were included. The majority of studies focused on breast cancer (46%) and those who completed treatment (43%). Resistance exercise interventions were largely 3-4 months long (48%), combined with aerobic exercise (56%), at a vigorous intensity (25%), and in-person/supervised settings (57%). Among the studies that assessed muscle mass, performance, and biomarkers (n = 42, 83, and 22, respectively), resistance exercise interventions improved upper/lower body or appendicular muscle mass (67-100%), muscle strength (61-68%), and physical function (74-100%). Most biomarkers did not show significant changes (75-100%) or showed inconsistent results. CONCLUSIONS: Generally, resistance exercise had positive effects on skeletal muscle mass and performance with an absence of negative effects compared to controls. Our findings demonstrated that resistance exercise may be an effective strategy to attenuate deterioration or exert improvements in muscle mass and performance outcomes.

Low physical function following cancer diagnosis is associated with higher mortality risk in postmenopausal women.

BACKGROUND: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. METHODS: This prospective cohort study included 8068 postmenopausal women enrolled in the Women's Health Initiative with a cancer diagnosis and who had physical function assessed within 1 year of that diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the 36-Item Short Form Health Survey. Cause of death was determined by medical record review, with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022. RESULTS: Over a median follow-up of 7.7 years from cancer diagnosis, 3316 (41.1%) women died. Our results showed that for every 10% difference in the physical function score after cancer diagnosis versus pre-diagnosis, all-cause mortality and cancer-specific mortality were reduced by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [95% CI] = 0.87 to 0.89 and HR = 0.88, 95% CI = 0.86 to 0.91, respectively). Further categorical analyses showed a significant dose-response relationship between postdiagnosis physical function categories and mortality outcomes (P < .001 for trend), where the median survival time for women in the lowest physical function quartile was 9.1 years (Interquartile range [IQR] = 8.6-10.6 years) compared with 18.4 years (IQR = 15.8-22.0 years) for women in the highest physical function quartile. CONCLUSION: Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.

Exercise and Nutrition Interventions for Prehabilitation in Hepato-Pancreato-Biliary Cancers: A Narrative Review.

Gastrointestinal (GI) cancers constitute over 25% of global cancer cases annually, with hepato-pancreato-biliary (HPB) cancers presenting particularly poor prognosis and challenging surgical treatments. While advancements in clinical care have improved post-operative outcomes over time, surgery for HPB cancers remains associated with high morbidity and mortality rates. Patients with HPB cancer are often older, diagnosed at later stages, and have a higher prevalence of co-morbid conditions, leading to reduced life expectancy, suboptimal post-operative recovery, and increased recurrence risk. Exercise and nutrition interventions have emerged as safe non-pharmacological strategies to enhance clinical outcomes among cancer survivors, but their potential in the pre-operative period for patients with HPB cancer remains underexplored. This narrative review evaluates existing evidence on exercise and nutritional interventions during pre-operative prehabilitation for HPB cancer populations, focusing on clinically relevant post-operative outcomes related to frailty and malnutrition. We conducted a literature search in PubMed and Google Scholar databases to identify studies utilizing a prehabilitation intervention in HPB cancer populations with exercise and nutritional components. The currently available evidence suggests that incorporating exercise and nutrition into prehabilitation programs offers a critical opportunity to enhance post-operative outcomes, mitigate the risk of comorbidities, and support overall survivorship among HPB cancer populations. This review underscores the need for further research to optimize the timing, duration, and components of pre-operative prehabilitation programs, emphasizing patient-centered, multidisciplinary approaches in this evolving field.

Incorporating Exercise Training into Cardio-Oncology Care: Current Evidence and Opportunities: JACC: CardioOncology State-of-the-Art Review.

Cancer treatment-induced cardiotoxicities are an ongoing concern throughout the cancer care continuum from treatment initiation to survivorship. Several "standard-of-care" primary, secondary, and tertiary prevention strategies are available to prevent the development or further progression of cancer treatment-induced cardiotoxicities and their risk factors. Despite exercise's established benefits on the cardiovascular system, it has not been widely adopted as a nonpharmacologic cardioprotective strategy within cardio-oncology care. In this state-of-the-art review, the authors discuss cancer treatment-induced cardiotoxicities, review the existing evidence supporting the role of exercise in preventing and managing these sequelae in at-risk and affected individuals living after cancer diagnoses, and propose considerations for implementing exercise-based services in cardio-oncology practice.

Exercise as Medicine in Cardio-Oncology: Reducing Health Disparities in Hispanic and Latina Breast Cancer Survivors.

PURPOSE OF REVIEW: This review aims to access the current state of the evidence in exercise as medicine for cardio-oncology in Hispanic and Latina breast cancer survivors and to provide our preliminary data on the effects of supervised aerobic and resistance training on cardiovascular disease (CVD) risk in this population. RECENT FINDINGS: Breast cancer survivors have a higher risk of CVD; particularly Hispanic and Latina breast cancer survivors have a higher burden than their White counterparts. Exercise has been shown to reduce CVD risk in breast cancer survivors; however, evidence in Hispanic and Latina breast cancer survivors is scarce. Our review highlights a clear need for exercise oncology clinical trials in Hispanic and Latina breast cancer survivors targeting CVD risk factors. Moreover, our exploratory results highlight that 16 weeks of aerobic and resistance training may reduce the 10-year risk of developing CVD by 15% in Hispanic and Latina breast cancer survivors.

Physical activity and physical fitness assessments in adolescents and young adults diagnosed with cancer: a scoping review.

PURPOSE: This scoping review describes the assessment methodologies for physical activity (PA) and physical fitness assessments used in studies focusing on adolescents and young adults (AYAs) diagnosed with cancer. METHODS: A search of the literature was conducted in PubMed, CINAHL, Web of Science, and Cochrane Library following the PRISMA-ScR statement. A total of 34 studies were included in this review. RESULTS: PA was primarily assessed via self-reported questionnaires (30/34) either completed in-person (n = 17) or online (n = 13) at different time points and different stages along the cancer trajectory (i.e., from diagnosis onward). A total of 9 studies conducted a physical fitness assessment. CONCLUSIONS: PA and physical fitness measurements are key when trying to describe outcomes, assess for associations, track changes, measure intervention adherence, and test intervention efficacy and effectiveness. Considerable heterogeneity across studies was reported limiting the generation of formal recommendations or guidance for researchers, healthcare providers, and policy makers.

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

Obesity Risk of Pediatric Central Nervous System Tumor Survivors: A Cross-Sectional Study.

Adult survivors of pediatric central nervous system (CNS) tumors are at the highest risk for morbidity and late mortality among all childhood cancers due to a high burden of chronic conditions, and environmental and lifestyle factors. This study aims to epidemiologically characterize young adult survivors of pediatric CNS tumors using body mass index (BMI) to assess risk factors for obesity. Using a cross-sectional design, young adults (18-39 years) previously treated for pediatric CNS tumors and followed in a survivorship clinic during 2016-2021 were examined. Demographic, BMI, and diagnosis information were extracted from medical records of the most recent clinic visit. Data were assessed using a two-sample t-test, Fisher's exact test, and multivariable logistical regression. 198 survivors (53% female, 84.3% White) with a BMI status of underweight (4.0%), healthy weight (40.9%), overweight (26.8%), obesity (20.2%), and severe obesity (8.1%) were examined. Male sex (OR, 2.414; 95% CI, 1.321 to 4.414), older age at follow-up (OR, 1.103; 95% CI, 1.037 to 1.173), and craniopharyngioma diagnosis (OR, 5.764; 95% CI, 1.197 to 27.751) were identified as significant (p < 0.05) obesity-related (≥25.0 kg/m2) risk factors. The majority of patients were overweight or obese. As such, universal screening efforts with more precise determinants of body composition than BMI, risk stratification, and targeted lifestyle interventions are warranted during survivorship care.

Pharmacokinetics of cancer therapeutics and energy balance: the role of diet intake, energy expenditure, and body composition.

Energy balance accounts for an individual's energy intake, expenditure, and storage. Each aspect of energy balance has implications for the pharmacokinetics of cancer treatments and may impact an individual's drug exposure and subsequently its tolerance and efficacy. However, the integrated effects of diet, physical activity, and body composition on drug absorption, metabolism, distribution, and excretion are not yet fully understood. This review examines the existing literature on energy balance, specifically the role of dietary intake and nutritional status, physical activity and energy expenditure, and body composition on the pharmacokinetics of cancer therapeutics. As energy balance and pharmacokinetic factors can be influenced by age-related states of metabolism and comorbidities, this review also explores the age-related impact of body composition and physiologic changes on pharmacokinetics among pediatric and older adult populations with cancer.

Improving Cognitive Function Through High-Intensity Interval Training in Breast Cancer Patients Undergoing Chemotherapy: Protocol for a Randomized Controlled Trial.

BACKGROUND: More than 75% of patients with breast cancer treated with chemotherapy experience cognitive impairments (eg, memory and attention problems), commonly known as chemo-brain. Exercise, especially aerobic high-intensity interval training (HIIT), is associated with better cognitive function in healthy populations. However, clinical trials testing the impact of exercise interventions on chemotherapy-induced cognitive decline in patients with cancer are lacking, and the mechanisms through which exercise could improve cognitive function are unclear. OBJECTIVE: The objective of the Improving Cognitive Function Through High-Intensity Interval Training in Breast Cancer Patients Undergoing Chemotherapy trial is to examine the effects of HIIT on cognitive function in patients with breast cancer undergoing chemotherapy. METHODS: This 2-arm, single-center, pilot randomized controlled trial will randomize 50 patients with breast cancer undergoing chemotherapy to HIIT or attention control. The HIIT group will perform a supervised 16-week, thrice-weekly intervention, with each session including a 5-minute warm-up at 10% maximal power output (POmax), 10 sets of alternating 1-minute high-intensity (90% POmax) and 1-minute recovery (10% POmax) intervals, and a 5-minute cooldown (10% POmax). The attention control group will receive a stretching program with no exercise components and be asked to maintain their exercise levels for 16 weeks. The primary outcomes of the study are executive function and memory measured using the National Institutes of Health toolbox and resting-state connectivity and diffusion tensor imaging microstructure evaluated using magnetic resonance imaging. The secondary and tertiary outcomes include cardiorespiratory fitness, body composition, physical fitness, and psychosocial health. The study has been approved by the institutional review board of the Dana-Farber Cancer Institute (20-222). RESULTS: The trial was funded in January 2019, with recruitment started in June 2021. As of May 2022, a total of 4 patients have consented and been randomized (n=2, 50% to exercise; n=1, 25% to control; and n=1, 25% nonrandomized). Trial completion is expected in January 2024. CONCLUSIONS: This first-of-its-kind study incorporates a novel exercise intervention (ie, HIIT) and comprehensive cognitive measures. If positive, our findings will establish the pilot efficacy of HIIT on chemotherapy-induced cognitive function in patients with breast cancer, providing the foundation for future larger phase-II and phase-III trials to confirm the findings and potentially establish HIIT as a standard of care for women undergoing chemotherapy for breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT04724499; https://clinicaltrials.gov/ct2/show/NCT04724499. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39740.

Benefits and Barriers of Technology for Home Function and Mobility Assessment: Perspectives of Older Patients With Blood Cancers, Caregivers, and Clinicians.

PURPOSE: Advances in digital health technology can overcome barriers to measurement of function and mobility for older adults with blood cancers, but little is known about how older adults perceive such technology for use in their homes. METHODS: To characterize potential benefits and barriers associated with using technology for home functional assessment, we conducted three semistructured focus groups (FGs) in January 2022. Eligible patients came from the Older Adult Hematologic Malignancies Program at Dana-Farber Cancer Institute (DFCI), which includes adults 73 years and older enrolled during their initial consult with their oncologist. Eligible caregivers were 18 years and older and identified by enrolled patients as their primary caregiver. Eligible clinicians were practicing DFCI hematologic oncologists, nurse practitioners, or physician assistants with ≥2 years of clinical experience. A qualitative researcher led thematic analysis of FG transcripts to identify key themes. RESULTS: Twenty-three participants attended the three FGs: eight patients, seven caregivers, and eight oncology clinicians. All participants valued function and mobility assessments and felt that technology could overcome barriers to their measurement. We identified three themes related to potential benefits: making it easier for oncology teams to consider function and mobility; providing standardized, objective data; and facilitating longitudinal data. We also identified four themes related to barriers to home functional assessment: concerns related to privacy and confidentiality, burden of measuring additional patient data, challenges in operating new technology, and concerns related to data improving care. CONCLUSION: These data suggest that specific concerns raised by older patients, caregivers, and oncology clinicians must be addressed to improve acceptability and uptake of technology used to measure function and mobility in the home.

High-intensity interval training improves metabolic syndrome in women with breast cancer receiving Anthracyclines.

INTRODUCTION: Anthracycline chemotherapy is a frequent treatment for breast cancer, whereas it can increase risk of physiologic side-effects, such as metabolic syndrome (MetS). Exercise has been used as a non-pharmacological strategy to decrease MetS. Specifically, high-intensity interval training (HIIT) has been shown to improve MetS in patients with diabetes or cardiac rehabilitation patients; however, the effects of HIIT on MetS and associated biomarkers in patients with breast cancer receiving anthracycline chemotherapy have not been previously explored. Therefore, we purposed to determine the effects of HIIT on MetS in breast cancer patients undergoing anthracycline chemotherapy. METHODS: In total, 30 patients with breast cancer were recruited prior to initiating treatment and randomized into HIIT (n = 15) or control (n = 15). The HIIT group attended supervised cycling sessions 3 days/week for 8 weeks. MetS was assessed by waist circumference, blood pressure, fasting levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose. Circulating levels of MetS-related biomarkers were also measured (total cholesterol, insulin, HbA1c, leptin, adiponectin, and c-reactive protein). RESULTS: After 8 weeks, MetS z-score was significantly improved in the HIIT group compared with controls (-7.60, 95% CI: -9.08 to -6.13, p < 0.001). MetS variables (HDL-C, glucose, and triglycerides) and circulating levels of MetS-related biomarkers were significantly improved in the HIIT group compared with controls (p < 0.001). Non-significant differences were found in body composition outcomes at the end of the study. CONCLUSIONS: HIIT may be an effective strategy to improve MetS in breast cancer patients undergoing anthracycline chemotherapy. Furthermore, changes in MetS were independent of changes in body composition.

Impact of exercise on physical health status in bladder cancer patients.

INTRODUCTION: There is a scarcity of data on the impact of behavioral habits, such as exercise, on physical health in patients with bladder cancer. We investigated the association of exercise on self-reported physical health status and examined the prevalence of bladder cancer patients with sedentary lifestyle. METHODS: We examined cross-sectional data of participants diagnosed with bladder cancer within the Behavioral Risk Factor Surveillance System (BRFSS) from 2016-2020. Patient health status was surveyed using self-reported measures, such as the total days per month when their "physical health is not good." The primary outcome was patient-reported poor physical health for more than 14 days within a one-month period. RESULTS: Out of 2 193 981 survey participants, we identified 936 with a history of bladder cancer. Nearly one in three bladder cancer patients reported being sedentary within the last month, as a total of 307 (32.8%) patients reported no exercise within the last 30 days. The remaining 628 (67.2%) reported exercising for at least one day within the last month. In multivariable logistic regression model analysis, we found that exercise is protective for self-reported poor physical health status (odds ratio 0.37, 95% confidence interval 0.25-0.56, p<0.001). Patients that exercised were less likely to report bad physical health. CONCLUSIONS: Approximately one in three bladder cancer patients report no exercise within 30 days, suggesting a sedentary lifestyle. Patients that are active are less likely to self-report poor physical health status. Implementation of exercise programs for bladder cancer patients could be promising in improving health status.

Efficacy of resistive exercise on skeletal muscle-related outcomes in cancer survivors: a systematic review protocol.

BACKGROUND: Symptom burden and adverse treatment effects can negatively impact physical function, health-related outcomes, and quality of life in cancer survivors. Resistive exercise that improves skeletal muscle function can ameliorate these complications, but the central role of the skeletal muscle in mediating improvements in patient-related outcomes has not been explored. This protocol describes the rationale and methods for a systematic review that aims to determine the effects of resistive exercise on the skeletal muscle hypertrophy, muscle performance, and muscle-related biomarkers in cancer survivors. METHODS: A systematic review will be conducted on peer-reviewed randomized controlled trials (RCTs) that employ resistive exercise interventions for cancer survivors. The following electronic databases will be searched: AMED, CENTRAL, CINAHL, CIRRIE, EMBASE, MEDLINE, PEDro, REHABDATA, Scopus, and SPORTDiscus. Studies will be considered for inclusion if they present quantitative data in adult cancer survivors on skeletal muscle characteristics (e.g., muscle mass), muscle performance (e.g., strength), or skeletal muscle-related biomarkers (e.g., myocellular satellite cells). Secondary outcomes will be physical function (e.g., stair climb) and patient-reported outcomes (e.g., fatigue). Data will be reported through a narrative that describes study design, participants, interventions, and outcome characteristics. DISCUSSION: This systematic review will help clarify the influence of resistive exercise on factors relating to the skeletal muscle in adult cancer survivors. Findings may provide insight into optimal exercise selection for evidence-based practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: #277791 [under review].

A bench to bedside perspective on anthracycline chemotherapy-mediated cardiovascular dysfunction: challenges and opportunities. A symposium review.

Cardiovascular diseases (CVD) are the leading cause of death worldwide and the risk of developing CVD is markedly increased following anthracycline chemotherapy treatment. Anthracyclines are an essential component of the cancer treatment regimen used for common forms of cancer in male and female children, adolescents, young adults, and older adults. Increased CVD risk with anthracyclines occurs, in part, due to vascular dysfunction-impaired endothelial function and arterial stiffening. These features of vascular dysfunction also play a major role in other common disorders observed following anthracycline treatment, including chronic kidney disease, dementia, and exercise intolerance. However, the mechanisms by which anthracycline chemotherapy induces and sustains vascular dysfunction are incompletely understood. This budding area of biomedical research is termed cardio-oncology, which presents the unique opportunity for collaboration between physicians and basic scientists. This symposium, presented at Experimental Biology 2022, provided a timely update on this important biomedical research topic. The speakers presented observations made at levels from cells to mice to humans treated with anthracycline chemotherapeutic agents using an array of translational research approaches. The speaker panel included a diverse mix of female and male investigators and unique insight from a cardio-oncology physician-scientist. Particular emphasis was placed on challenges and opportunities in this field as well as mechanisms that could be viewed as therapeutic targets leading to novel treatment strategies.

Effect of exercise on tumor markers - Is exercise anti-tumorigenic in humans?: A scoping review of preliminary clinical investigations.

It has been increasingly conceptualized that exercise may be able to suppress cancer progression itself based on the preclinical evidence suggesting various mechanisms. The challenges exist in investigating the effects of exercise on tumor progression in human settings. Circulating or tissue-driven tumor markers can be a useful and cost-effective tool in monitoring the progression of some cancers. This scoping review summarized the current evidence on the use of tumor markers in clinical exercise oncology trials. A total of 14 studies were identified, and tumor markers included prostate-specific antigen for prostate cancer, carcinoembryonic antigen and circulating tumor cells for colorectal cancer, and Ki-67 for breast cancer. Treatment settings and exercise prescriptions were highly heterogeneous, while most studies did not find significant exercise-mediated effects on tumor markers. Nevertheless, we provide an insight into the utility and considerations in using tumor markers in clinical exercise oncology research.

Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer Survivors (The AIM Trial): Rationale, Design, and Methods.

Background: Obesity is a significant contributor to breast cancer recurrence and mortality. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise interventions to target chronic inflammation has a potential to improve obesity- and breast cancer-related outcomes; however, no studies have investigated the roles of exercise in modulating adipose tissue inflammation in breast cancer survivors. Also, it is unclear which exercise prescription would be optimal to maximize the outcomes. Therefore, we designed a randomized controlled trial (Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors [AIM] Trial) to examine the mechanisms by which different modalities of exercise impact chronic inflammation as a biomarker of breast cancer prognosis. Methods: The AIM trial is a prospective, three-armed, phase II randomized controlled trial investigating the effects of a 16-week supervised circuit aerobic and resistance exercise (CARE) program versus a traditional aerobic and resistance exercise (TARE) program and attention control (AC) on adipose tissue inflammation in breast cancer survivors. 276 patients who are diagnosed with stage 0-III breast cancer, post-treatment, sedentary, and centrally obese are randomized to one of the three groups. The CARE and TARE groups participate in thrice-weekly supervised exercise sessions for 16 weeks. The AC group are offered the CARE program after the intervention period. The primary endpoint is adipose tissue inflammation assessed by core biopsy and blood draw. The secondary and tertiary endpoints are sarcopenic obesity, physical fitness and function, and patient reported outcomes. The exploratory outcomes are long-term breast cancer outcomes. Discussion: This is the first randomized controlled trial examining the effects of exercise on adipose tissue inflammation in obese, breast cancer survivors. Our findings are anticipated to contribute to a better understanding of exercise modalities and mechanisms on adipose tissue inflammation that can potentially improve breast cancer prognosis. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03091842 identifier [NCT#03091842].