The effect of exercise intensity on the inflammatory profile of cancer survivors: A randomised crossover study.

BACKGROUND: Systemic inflammation has been clearly linked to poorer health outcomes from cancer diagnosis through to survivorship. There is accumulating evidence that exercise can reduce inflammation. However, the optimal intensity of exercise to reduce systemic inflammation is unknown. AIMS: The aim of this randomised crossover study was to identify the difference between high- and low-intensity aerobic exercise on the inflammatory profile of cancer survivors after a single exercise session (acute) and a short training period (six sessions over 2 weeks). METHOD: Participants (n = 20) were randomised to either low- or high-intensity exercise. They underwent 2 weeks of stationary cycling at their assigned intensity and then underwent a 6-week washout period of no exercise before returning to complete 2 weeks of exercise at the remaining intensity. RESULTS: Twenty participants with a mean age of 56.4 (±9.4) years were enrolled and completed the intervention. There was no effect of exercise intensity after a single exercise session. After 2 weeks of training, there was a significant effect of intensity on chemokines CCL2 (mean difference ± SEM; 13.2 pg/mL ± 5.0, p = .04) and CXCL12 (150.3 pg/mL ± 51.8, p = .02), where CCL2 was decreased after low-intensity exercise and CXCL12 decreased after high-intensity exercise. DISCUSSION: Our data suggest that while exercise intensity may impact different cell types in the circulation, both low- and high-intensity exercise can positively modulate inflammatory markers. CONCLUSION: The potential to scale up low-intensity exercise over time is likely to be more broadly applicable and achievable for cancer survivor cohorts while still eliciting beneficial effects on systemic inflammation.

Efficacy of exercise interventions for women during and after gynaecological cancer treatment - a systematic scoping review.

PURPOSE: To systematically synthesise evidence of exercise intervention efficacy for physical/psychosocial outcomes that matter to women during/following treatment for gynaecological cancer. METHODS: Five databases were searched (PubMed, EMBASE, CINAHL, PsychInfo, Scopus). Exercise-only intervention studies that included women during/ following treatment for any gynaecological cancer, with/ without control comparison, on any physical or psychosocial outcome(s), were included and qualitatively appraised using the Revised Cochrane Risk of Bias tool and a modified Newcastle-Ottawa Scale. RESULTS: Seven randomised controlled trials (RCTs), three single-arm pre-post studies, and one prospective cohort study satisfied were included (11 studies). Most studies were completed following treatment (91%), included combined (aerobic and resistance; 36%) and aerobic (36%) training, were fully/mostly (63%) unsupervised, and had a moderate-to-high risk of bias. Overall, 33 outcomes (64% objectively-measured) were assessed. Improvements were observed in aerobic capacity (V̇O2 Peak +1.6 mL/kg/min, 6-minute walk distance +20-27 m), lower- (30-second sit-to-stand +2-4 repetitions) and upper-limb strength (30-second arm curl +5 repetitions; 1RM grip strength/chest press +2.4-3.1 kg), and agility (timed up-and-go -0.6 seconds). However, changes in quality of life, anthropometry/body composition, balance and flexibility were inconsistent. There was no evidence to support worsening of outcomes. CONCLUSION: Preliminary research into the role of exercise post-gynaecological cancer suggests an improvement in exercise capacity, muscular strength, and agility which, in the absence of exercise, typically decline following gynaecological cancer. Future exercise trials involving larger and more diverse gynaecological cancer samples will improve understanding of the potential and magnitude of effect of guideline-recommended exercise on outcomes that matter to patients.

Irradiation-Induced Dysbiosis: The Compounding Effect of High-Fat Diet on Metabolic and Immune Functions in Mice.

The negative impact of irradiation or diet on the metabolic and immune profiles of cancer survivors have been previously demonstrated. The gut microbiota plays a critical role in regulating these functions and is highly sensitive to cancer therapies. The aim of this study was to investigate the effect of irradiation and diet on the gut microbiota and metabolic or immune functions. We exposed C57Bl/6J mice to a single dose of 6 Gy radiation and after 5 weeks, fed them a chow or high-fat diet (HFD) for 12 weeks. We characterised their faecal microbiota, metabolic (whole body and adipose tissue) functions, and systemic (multiplex cytokine, chemokine assay, and immune cell profiling) and adipose tissue inflammatory profiles (immune cell profiling). At the end of the study, we observed a compounding effect of irradiation and diet on the metabolic and immune profiles of adipose tissue, with exposed mice fed a HFD displaying a greater inflammatory signature and impaired metabolism. Mice fed a HFD also showed altered microbiota, irrespective of irradiation status. An altered diet may exacerbate the detrimental effects of irradiation on both the metabolic and inflammatory profiles. This could have implications for the diagnosis and prevention of metabolic complications in cancer survivors exposed to radiation.

Ballet after breast cancer: investigating the feasibility and acceptability of a novel 16-week classical ballet intervention for breast cancer survivors.

PURPOSE: The "Ballet after breast cancer" study sought to investigate the feasibility and acceptability of a 16-week classical ballet intervention for breast cancer survivors, delivered face-to-face and/or online. METHODS: Breast cancer survivors were recruited to take part in 2 × 1-h ballet classes per week for 16 weeks. Primary outcomes of feasibility and acceptability were assessed according to rates of enrolment and attendance and participant feedback via questionnaire. Secondary outcomes included quality of life (QOL), upper-body disability, shoulder range of motion (ROM), muscular strength, aerobic capacity, and physical activity levels. Associations between rate of attendance and changes in secondary measures were explored. RESULTS: Thirty-one participants (62% of eligible individuals) enrolled in the program. Twenty-nine women commenced the intervention [53.3 ± 10.8 years (Mean ± SD)], attending 77.6% [67.6, 87.5] (Mean [95% CI]) of sessions. Based on these rates of enrolment and attendance, and participant feedback, the program was deemed feasible and acceptable to participants. Significant improvements in shoulder ROM and reductions in sedentary behaviour were achieved. Participants also reported improvements in physical capacity and psychological, social, and cognitive wellbeing. CONCLUSIONS: The "Ballet after breast cancer" program, delivered face-to-face and/or online, was feasible and acceptable to breast cancer survivors. Improvements in shoulder ROM achieved doing ballet were pertinent given the adverse effects of upper-body morbidity on breast cancer survivor QOL. Improvements in physical activity behaviour and perceived benefits to wellbeing also support the use of ballet to mitigate QOL impairment after treatment. IMPLICATIONS FOR CANCER SURVIVORS: The physical demands and the fun, creative, and social characteristics of ballet promote improvement across multiple domains of health and wellbeing. Ballet shows promise as an activity to improve QOL and increase long-term engagement in health-promoting physical activity after breast cancer.

If exercise is medicine, why don't we know the dose? An overview of systematic reviews assessing reporting quality of exercise interventions in health and disease.

OBJECTIVE: To determine how well exercise interventions are reported in trials in health and disease. DESIGN: Overview of systematic reviews. DATA SOURCES: PubMed, EMBASE, CINAHL, SPORTDiscus and PsycINFO from inception until June 2021. ELIGIBILITY CRITERIA: Reviews of any health condition were included if they primarily assessed quality of exercise intervention reporting using the Consensus on Exercise Reporting Template (CERT) or the Template for Intervention Description and Replication (TIDieR). We assessed review quality using a modified version of A MeaSurement Tool to Assess systematic Reviews. RESULTS: We identified 7804 studies and included 28 systematic reviews. The median (IQR) percentage of CERT and TIDieR items appropriately reported was 24% (19%) and 49% (33%), respectively. TIDieR items 1, Brief name (median=100%, IQR 4) and 2, Why (median=98%, IQR 6), as well as CERT item 4, Supervision and delivery (median=68%, IQR 89), were the best reported. For replication of exercise interventions, TIDieR item 8, When and how much, was moderately well reported (median=62%, IQR 68) although CERT item 8, Description of each exercise to enable replication (median=23%, IQR 44) and item 13, Detailed description of the exercise intervention (median=24%, IQR 66) were poorly reported. Quality of systematic reviews ranged from moderate to critically low quality. CONCLUSION: Exercise interventions are poorly reported across a range of health conditions. If exercise is medicine, then how it is prescribed and delivered is unclear, potentially limiting its translation from research to practice. PROSPERO REGISTRATION NUMBER: CRD42021261285; Open Science Framework: osf.io/my3ec/.

Barriers and facilitators of exercise experienced by cancer survivors: a mixed methods systematic review.

PURPOSE: Exercise has been shown to improve the health and well-being of people who have survived cancer. Yet, less than 40% of cancer survivors in Australia meet the recommended 150 min of moderate-intensity physical activity per week. Our objective was to systematically review the literature regarding barriers, facilitators and preferences for exercise for survivors of cancer. METHOD: MEDLINE, EMBASE, CINAHL, PsycINFO and Scopus were searched for qualitative and quantitative articles addressing barriers, facilitators and preferences for exercise in cancer survivors. Quality assessment was performed by two independent reviewers using the Mixed Methods Appraisal Tool. Thomas and Harden's method of thematic synthesis was used to amalgamate qualitative data while descriptive statistics were used to collate quantitative data. RESULTS: Nineteen studies were included (9 qualitative and 10 quantitative). Persisting treatment-related side effects was the most commonly reported barrier to initiating or maintaining exercise, followed by lack of time and fatigue. The most common facilitators of exercise were gaining a feeling of control over their health as well as managing emotions and mental well-being, while the preferred method of exercise was walking. We also identified a lack of useful information provided to survivors regarding exercise. CONCLUSION: Treatment-related side effects, lack of time and fatigue were key barriers to exercise for survivors of varied cancer types. Insufficient patient education may contribute to the belief that exercise is not helpful when experiencing side effects of treatment, including fatigue. Identifying barriers and facilitators leads to improved support and education from health professionals which is required to provide safe and effective exercise recommendations for survivors.

Exercise Snacks and Other Forms of Intermittent Physical Activity for Improving Health in Adults and Older Adults: A Scoping Review of Epidemiological, Experimental and Qualitative Studies.

Exercise snacks, including other variants of brief intermittent bouts, are an emerging approach for increasing physical activity, although their operationalisation is unstandardised and their health benefits remain unclear. This scoping review aimed to explore characterisations of exercise snacks and summarise their effects on health in adults and older adults. Clinical trial registers (clinicaltrials.gov and ANZCTR) and electronic databases (PubMed, CINAHL, CENTRAL, PsycINFO) were searched from inception to 1 June 2023, for ongoing and published studies of exercise snacks. Backwards and forwards citation tracking was also conducted to identify additional eligible studies. Studies were included if they investigated exercise snacks-brief intermittent bouts of physical activity spread across the day-in adults or older adults. We included epidemiological, experimental, quasi-experimental and qualitative studies that examined the effect of exercise snacks on any health outcomes or described barriers to and enablers of these approaches. Thirty-two studies were included (7 trial registers, 1 published protocol, 3 epidemiological studies and 20 trials reported across 21 studies). Three main terms were used to describe exercise snacks: exercise snack(ing), snacktivity and vigorous intermittent lifestyle physical activity (VILPA). Participants were predominantly physically inactive but otherwise healthy adults or older adults. Exercise snacks were feasible and appeared safe. Epidemiological studies showed steep, near-linear associations of VILPA with reduced all-cause, cardiovascular and cancer mortality as well as reduced incidence of major adverse cardiovascular events and cancer. The limited trial evidence showed exercise snacks had modest effects on improving cardiorespiratory fitness, whereas effects on physical function, mood, quality of life and other health outcomes were equivocal. In conclusion, exercise snacks appear feasible and safe for adults and older adults and may have promising health benefits, but this is mostly based on findings from a limited number of small quasi-experimental studies, small randomised trials or qualitative studies. More studies are needed in individuals with chronic disease. This emerging physical activity approach may have appeal for individuals who find structured exercise unfeasible.Registration https://osf.io/qhu24/.

Evaluating the effect of upper-body morbidity on quality of life following primary breast cancer treatment: a systematic review and meta-analysis.

PURPOSE: Improvements in breast cancer management continue to increase survival and life expectancy after treatment. Yet the adverse effects of treatment may persist long term, threatening physical, psychological, and social wellbeing, leading to impaired quality of life (QOL). Upper-body morbidity (UBM) such as pain, lymphoedema, restricted shoulder range of motion (ROM), and impaired function are widely reported after breast cancer treatment, but evidence demonstrating its impact on QOL is inconsistent. Therefore, the aim of the study was to conduct a systematic review and meta-analysis evaluating the effect of UBM on QOL following primary breast cancer treatment. METHODS: The study was prospectively registered on PROSPERO (CRD42020203445). CINAHL, Embase, Emcare, PsycInfo, PubMed/Medline, and SPORTDiscus databases were searched for studies reporting QOL in individuals with and without UBM following primary breast cancer treatment. Primary analysis determined the standardised mean difference (SMD) in physical, psychological, and social wellbeing scores between UBM + /UBM - groups. Secondary analyses identified differences in QOL scores between groups, according to questionnaire. RESULTS: Fifty-eight studies were included, with 39 conducive to meta-analysis. Types of UBM included pain, lymphoedema, restricted shoulder ROM, impaired upper-body function, and upper-body symptoms. UBM + groups reported poorer physical (SMD = - 0.99; 95%CI = - 1.26, - 0.71; p < 0.00001), psychological (SMD = - 0.43; 95%CI = - 0.60, - 0.27; p < 0.00001), and social wellbeing (SMD = - 0.62; 95%CI = - 0.83, - 0.40; p < 0.00001) than UBM - groups. Secondary analyses according to questionnaire showed that UBM + groups rated their QOL poorer or at equal to, UBM - groups across all domains. CONCLUSIONS: Findings demonstrate the significant, negative impact of UBM on QOL, pervading physical, psychological, and social domains. IMPLICATIONS FOR CANCER SURVIVORS: Efforts to assess and minimise the multidimensional impact of UBM are warranted to mitigate impaired QOL after breast cancer.

The Effect of Exercise on Pain in People with Cancer: A Systematic Review with Meta-analysis.

INTRODUCTION: Cancer-related pain is common and undertreated. Exercise is known to have a pain-relieving effect in non-cancer pain. OBJECTIVES: This systematic review aimed to evaluate (1) the effect of exercise on cancer-related pain in all cancers, and (2) whether the effect of exercise differed according to exercise mode, degree of supervision, intervention duration and timing (during or after cancer treatment), pain types, measurement tool and cancer type. METHODS: Electronic searches were undertaken in six databases to identify exercise studies evaluating pain in people with cancer, published prior to 11 January 2023. All stages of screening and data extraction were conducted independently by two authors. The Cochrane risk of bias tool for randomised trials (RoB 2) was used and overall strength of evidence was assessed using the GRADE approach. Meta-analyses were performed overall and by study design, exercise intervention and pain characteristics. RESULTS: In total, 71 studies reported in 74 papers were eligible for inclusion. The overall meta-analysis included 5877 participants and showed reductions in pain favouring exercise (standardised mean difference - 0.45; 95% confidence interval - 0.62, - 0.28). For most (> 82%) of the subgroup analyses, the direction of effect favoured exercise compared with usual care, with effect sizes ranging from small to large (median effect size - 0.35; range - 0.03 to - 1.17). The overall strength of evidence for the effect of exercise on cancer-related pain was very low. CONCLUSION: The findings provide support that exercise participation does not worsen cancer-related pain and that it may be beneficial. Better pain categorisation and inclusion of more diverse cancer populations in future research would improve understanding of the extent of benefit and to whom. PROSPERO REGISTRATION NUMBER: CRD42021266826.

Effects of a single exercise session on pain intensity in adults with chronic pain: a systematic review and meta-analysis.

BACKGROUND: Chronic pain is prevalent amongst society, making it necessary to find strategies to manage chronic pain. Regular exercise is efficacious; however, pain is a barrier to initiating exercise. A single exercise session is also believed to acutely reduce pain, however, the evidence for this is less robust. OBJECTIVES: This systematic review and meta-analysis aimed to identify the effect of a single exercise session on pain intensity in adults with chronic pain. METHODS: We searched eight databases and trial registries to identify randomised controlled trials evaluating the effect of a single exercise session on pain intensity in adults with chronic pain compared to a non-exercise control. Literature screening, data extraction, risk of bias (Cochrane 2.0) and quality assessment (GRADE) were conducted independently and in duplicate. Random-effects meta-analyses were performed using the metafor package in R. RESULTS: We included 17 trials (46 study arms with 664 adults [44% female]). There were no significant differences in pain intensity (mean difference on a 0-10 scale) immediately post-exercise -0.02 (95% CI = -0.06, 0.62; I2 = 77.1%) or up to 45-min post-exercise -0.17 (95% CI = -0.49, 0.16; I2 = 34.2%). All trials were at high risk of bias and the overall confidence in these findings was very low. CONCLUSION: A single exercise session did not reduce pain intensity up to 1-h post-exercise. Notably, increases in pain were not observed either, suggesting that while pain can be a barrier to initiating exercise, clinicians can educate patients on the unlikelihood of exercise acutely increasing pain intensity.

The Effect of Resistance Training in Healthy Adults on Body Fat Percentage, Fat Mass and Visceral Fat: A Systematic Review and Meta-Analysis.

BACKGROUND: Resistance training is the gold standard exercise mode for accrual of lean muscle mass, but the isolated effect of resistance training on body fat is unknown. OBJECTIVES: This systematic review and meta-analysis evaluated resistance training for body composition outcomes in healthy adults. Our primary outcome was body fat percentage; secondary outcomes were body fat mass and visceral fat. DESIGN: Systematic review with meta-analysis. DATA SOURCES: We searched five electronic databases up to January 2021. ELIGIBILITY CRITERIA: We included randomised trials that compared full-body resistance training for at least 4 weeks to no-exercise control in healthy adults. ANALYSIS: We assessed study quality with the TESTEX tool and conducted a random-effects meta-analysis, with a subgroup analysis based on measurement type (scan or non-scan) and sex (male or female), and a meta-regression for volume of resistance training and training components. RESULTS: From 11,981 records, we included 58 studies in the review, with 54 providing data for a meta-analysis. Mean study quality was 9/15 (range 6-15). Compared to the control, resistance training reduced body fat percentage by - 1.46% (95% confidence interval - 1.78 to - 1.14, p < 0.0001), body fat mass by - 0.55 kg (95% confidence interval - 0.75 to - 0.34, p < 0.0001) and visceral fat by a standardised mean difference of - 0.49 (95% confidence interval - 0.87 to - 0.11, p = 0.0114). Measurement type was a significant moderator in body fat percentage and body fat mass, but sex was not. Training volume and training components were not associated with effect size. Resistance training reduces body fat percentage, body fat mass and visceral fat in healthy adults. STUDY REGISTRATION: osf.io/hsk32.

The effect of exercise intensity on exercise-induced hypoalgesia in cancer survivors: A randomized crossover trial.

Pain is experienced by people with cancer during treatment and in survivorship. Exercise can have an acute hypoalgesic effect (exercise-induced hypoalgesia; EIH) in healthy individuals and some chronic pain states. However, EIH, and the moderating effect of exercise intensity, has not been investigated in cancer survivors. This study examined the effect of low- and high-intensity aerobic exercise on EIH in cancer survivors after a single exercise session as well as a brief period of exercise training (2-weeks, three exercise sessions per week). Participants (N = 19) were randomized to low- (30%-40% Heart Rate Reserve (HRR) or high- (60%-70% HRR) intensity stationary cycling for 15-20 min. Pressure pain thresholds (PPT) were assessed over the rectus femoris and biceps brachii before and after a single exercise session and again after a short training period at the assigned intensity. Then, following a 6-week washout period, the intervention was repeated at the other intensity. After the first exercise session, high-intensity exercise resulted in greater EIH over the rectus femoris than low intensity (mean difference ± SE: -0.51 kg/cm2  ± 0.15, Cohen's d = 0.78, p = 0.004). After a 2-week training period, we found no difference in EIH between intensities (0.01 kg/cm2  ± 0.25, d = 0.00 p = 0.99), with comparable moderate effect sizes for both low- and high-intensity exercise, indicative of EIH. No EIH was observed over the biceps brachii of the arm at either low or high intensity. Low-intensity exercise training may be a feasible option to increase pain thresholds in cancer survivors.

The Effect of Resistance Training on Body Composition During and After Cancer Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Changes in body composition during cancer treatments have been linked with poorer outcomes, and increased morbidity and mortality. The effect of resistance training (RT) on body composition in cancer cohorts is debated. OBJECTIVE: We conducted a systematic review and meta-analysis to determine the effect of RT on body composition during and after treatment. METHODS: We searched five electronic databases for articles up to 1 February 2021 and included randomized controlled trials that compared RT with a non-exercise control in adults with cancer. Risk of bias was assessed using the RoB 2 tool. Pairwise, random-effects meta-analysis was used to synthesize the available data. RESULTS: Overall, we included 15 studies (n = 1368). After treatment (11 studies), RT increased lean mass with moderate heterogeneity {0.41 kg [95% confidence interval (CI) 0.05, 0.76], p = 0.029; I2 = 47.1%, p = 0.02} and decreased fat mass with substantial heterogeneity (- 0.59 kg [95% CI - 1.05, - 0.12], p = 0.019; I2 = 69.1%, p < 0.001). During treatment (4 studies), RT did not increase lean mass (0.71 kg [95% CI - 0.04, 1.45], p = 0.05; I2 = 0.0%, p = 0.75) or reduce fat mass (0.00 kg [95% CI - 5.31, 5.30], p = 0.99; I2 = 0.0%, p = 0.62), both with no heterogeneity. CONCLUSION: Modest improvements in body composition were observed following RT after cancer treatment; however, no changes were observed during treatment. These adaptations are markedly lower than those observed in healthy cohorts but may be clinically meaningful for the cancer survivorship population. At present it is unclear if these diminished adaptations are due to ineffective exercise prescriptions in cancer cohorts or due to an innate anabolic resistance as a result of cancer and its treatments. STUDY REGISTRATION: Open Science Framework (osf.io/x6z72).

T cell epigenetic remodeling and accelerated epigenetic aging are linked to long-term immune alterations in childhood cancer survivors.

BACKGROUND: Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory diseases in cancer survivors. RESULTS: To test this hypothesis, we established the epigenetic and transcriptomic profiles of immune cells from 44 childhood cancer survivors (CCS, > 16 years old) on full remission (> 5 years) who had received chemotherapy alone or in combination with total body irradiation (TBI) and hematopoietic stem cell transplant (HSCT). We found that more than 10 years post-treatment, CCS treated with TBI/HSCT showed an altered DNA methylation signature in T cell, particularly at genes controlling immune and inflammatory processes and oxidative stress. DNA methylation remodeling in T cell was partially associated with chronic expression changes of nearby genes, increased frequency of type 1 cytokine-producing T cell, elevated systemic levels of these cytokines, and over-activation of related signaling pathways. Survivors exposed to TBI/HSCT were further characterized by an Epigenetic-Aging-Signature of T cell consistent with accelerated epigenetic aging. To investigate the potential contribution of irradiation to these changes, we established two cell culture models. We identified that radiation partially recapitulated the immune changes observed in survivors through a bystander effect that could be mediated by circulating factors. CONCLUSION: Cancer treatments, in particular TBI/HSCT, are associated with long-term immune disturbances. We propose that epigenetic remodeling of immune cells following cancer therapy augments inflammatory- and age-related diseases, including metabolic complications, in childhood cancer survivors.

Distance-delivered physical activity interventions for childhood cancer survivors: A systematic review and meta-analysis.

This review aimed to determine the feasibility of distance-delivered physical activity (PA) interventions in childhood cancer survivors (CCS), and assess the effect on PA levels, and physical, physiological and psychological outcomes. We searched electronic databases until May 2016, including studies following intensive treatment. Meta-analyses were conducted on randomized controlled trials. We calculated the effect of interventions on PA levels and physical, physiological and psychological health outcomes. Thirteen studies (n=270 participants) were included in the systematic review and four (n=102 participants) in the meta-analysis. Most studies used telephone to deliver interventions with contact (1/day-1/month), duration (2 weeks-1year) and timing (maintenance therapy->20years following intensive treatment) varying between interventions. Interventions yielded a mean recruitment rate=64%, retention rate=85% and adherence rate=88%. Interventions did not increase PA levels (p=0.092), but had a positive effect on physical function (p=0.008) and psychological outcomes (p=0.006). Distance-delivered PA interventions are feasible in CCS. Despite not increasing PA levels, participation may improve physical and psychological health; however, larger randomized controlled trials are warranted.