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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
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Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
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.
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Mediterranean Style Dietary Pattern with High Intensity Interval Training in Men with Prostate Cancer Treated with Androgen Deprivation Therapy: A Pilot Randomised Control Trial.
Baguley, BJ, Adlard, K, Jenkins, D, Wright, ORL, Skinner, TL
International journal of environmental research and public health. 2022;19(9)
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The use of androgen deprivation therapy (ADT) has coincided with improvements in disease control and improved overall survivorship in many men treated for prostate cancer. Exercise and nutrition interventions during and/or after ADT are strongly recommended to mitigate or improve body composition and reduce cardiometabolic side effects. The aim of this study was to examine the combined effects of a Mediterranean diet (MED-diet) and high intensity interval training (HIIT) on cardiorespiratory fitness, body composition and quality of life, compared to usual care, in men with prostate cancer treated with ADT. This study is a two-arm randomised controlled trial. Participants (n = 23) were randomly allocated to either an intervention or usual care group in a 1:1 ratio. Results show that for men with prostate cancer undergoing ADT, a MED-diet with HIIT compared to usual care at 20 weeks (i) significantly improved cardiorespiratory fitness relative; (ii) reduced body weight; (iii) maintained lean body mass despite achieving weight loss; (iv) significantly improved vitality and mental health composite, and clinical improvements were seen in prostate-cancer specific quality of life and cancer-related fatigue. Authors conclude that future larger-scale trials examining the MED-diet with HIIT on cardiorespiratory fitness, body composition and quality of life would help to extend the findings of their study.
Abstract
Background: Androgen deprivation therapy (ADT) in prostate cancer has been shown to deteriorate body composition (reduced lean mass and increased body and fat mass) and increase the risk of cardiovascular morbidity. The Mediterranean style dietary pattern (MED-diet) and high intensity interval training (HIIT) may synergistically alleviate these side effects and improve quality of life in men treated with ADT. Methods: Twenty-three men (65.9 ± 7.8 years; body mass index: 29.6 ± 2.7 kg/m2; ADT duration: 33.8 ± 35.6 months) receiving ADT for ≥3 months were randomly assigned (1:1) to 20 weeks of usual care or the MED-diet (10 nutrition consults) with HIIT (4 × 4 min 85−95% heart rate peak, 3× week, starting at 12 weeks). Results: The MED-diet with HIIT significantly improved cardiorespiratory fitness (+4.9 mL·kg−1·min, p < 0.001), and body mass (−3.3 kg, p < 0.001) compared to the usual care group at 20 weeks. Clinically meaningful (≥3 points) improvements were seen in quality of life and cancer-related fatigue after 20 weeks. Conclusions: The MED-diet with HIIT increased cardiorespiratory fitness and reduced body weight in men with prostate cancer treated with ADT. Larger trials determining whether the MED-diet with HIIT translates to cardiovascular benefits are warranted.
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Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial.
Mundell, NL, Owen, PJ, Dalla Via, J, Macpherson, H, Daly, RM, Livingston, PM, Rantalainen, T, Foulkes, S, Millar, J, Murphy, DG, et al
BMJ open. 2022;12(6):e060189
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Androgen deprivation therapy (ADT) for local and advanced prostate cancer (PCa) is effective at reducing androgens, and thus inhibiting tumour progression. However, testosterone reduces the production of a highly neurotoxic protein (amyloid beta peptide 40), which is linked with the development of dementia and Alzheimer’s disease. The aim of this study was to investigate the effects of a multi-component resistance-based exercise programme with daily protein, vitamin D and calcium supplementation on cognitive function compared with usual care in PCa survivors treated with ADT. This study is a secondary analysis of a 12-month single-blinded, two-arm randomised controlled trial. Participants (n = 70) were randomised (1:1 ratio) to either: (a) multi-component exercise intervention including progressive resistance training, body-weight impact and balance exercises, as well as a daily nutritional supplement containing whey protein, calcium and vitamin D, or (b) usual care control receiving 1000 IU vitamin D only. Results show that a multicomponent exercise training and nutritional supplementation intervention did not improve cognitive function in men treated with ADT for PCa compared with usual care. Authors conclude that cognitive decline associated with ADT may mechanistically differ to that of general age-related cognitive declines, thus it is important that future studies also examine other intervention modalities.
Abstract
OBJECTIVES The aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and vitamin D supplementation on cognition in men with prostate cancer treated with androgen deprivation therapy (ADT). DESIGN 12-month, two-arm, randomised controlled trial. SETTING University clinical exercise centre. PARTICIPANTS 70 ADT-treated men were randomised to exercise-training plus supplementation (Ex+ Suppl, n=34) or usual care (control, n=36). INTERVENTION Men allocated to Ex + Suppl undertook thrice weekly resistance training with weight-bearing exercise training plus daily whey protein (25 g), calcium (1200 mg) and vitamin D (2000 IU) supplementation. PRIMARY AND SECONDARY OUTCOME MEASURES Cognition was assessed at baseline, 6 and 12 months via a computerised battery (CogState), Trail-making test, Rey auditory-verbal learning test and Digit span. Data were analysed with linear mixed models and an intention-to-treat and prespecified per-protocol approach (exercise-training: ≥66%, nutritional supplement: ≥80%). RESULTS Sixty (86%) men completed the trial (Ex + Suppl, n=31; control, n=29). Five (7.1%) men were classified as having mild cognitive impairment at baseline. Median (IQR) adherence to the exercise and supplement was 56% (37%-82%) and 91% (66%-97%), respectively. Ex + Suppl had no effect on cognition at any time. CONCLUSIONS A 12-month multicomponent exercise training and supplementation intervention had no significant effect on cognition in men treated with ADT for prostate cancer compared with usual care. Exercise training adherence below recommended guidelines does not support cognitive health in men treated with ADT for prostate cancer. TRIAL REGISTRATION NUMBER Australian and New Zealand Clinical Trial Registry (ACTRN12614000317695, registered 25/03/2014) and acknowledged under the Therapeutic Goods Administration Clinical Trial Notification Scheme (CT-2015-CTN-03372-1 v1).
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Exercise Preserves Physical Function in Prostate Cancer Patients with Bone Metastases.
Galvão, DA, Taaffe, DR, Spry, N, Cormie, P, Joseph, D, Chambers, SK, Chee, R, Peddle-McIntyre, CJ, Hart, NH, Baumann, FT, et al
Medicine and science in sports and exercise. 2018;50(3):393-399
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Existing research indicates cancer patients with bone metastases should not participate in exercise due to potential risks to the skeletal system. However, current oncology guidelines suggest that all cancer patients should avoid inactivity, including those with bone metastases. The purpose of this study is to determine the safety and efficacy of exercise among 57 prostate cancer patients with bone metastases. Participants were randomised to either participate in exercise or receive usual care for three months. Exercise consisted of supervised aerobic activity, resistance training and stretching three days a week. Overall health status and physical function was measured by self-reported questionnaire. This study found self-reported physical functioning and lower muscle strength was improved significantly in the exercise group. There were no difference in bone pain between groups, and no adverse events occurred. Based on these results, the authors conclude exercise is safe and can help improve physical functioning among prostate cancer patients with bone metastasis.
Abstract
PURPOSE The presence of bone metastases has excluded participation of cancer patients in exercise interventions and is a relative contraindication to supervised exercise in the community setting because of concerns of fragility fracture. We examined the efficacy and safety of a modular multimodal exercise program in prostate cancer patients with bone metastases. METHODS Between 2012 and 2015, 57 prostate cancer patients (70.0 ± 8.4 yr; body mass index, 28.7 ± 4.0 kg·m) with bone metastases (pelvis, 75.4%; femur, 40.4%; rib/thoracic spine, 66.7%; lumbar spine, 43.9%; humerus, 24.6%; other sites, 70.2%) were randomized to multimodal supervised aerobic, resistance, and flexibility exercises undertaken thrice weekly (EX; n = 28) or usual care (CON; n = 29) for 3 months. Physical function subscale of the Medical Outcomes Study Short-Form 36 was the primary end point as an indicator of patient-rated physical functioning. Secondary end points included objective measures of physical function, lower body muscle strength, body composition, and fatigue. Safety was assessed by recording the incidence and severity of any adverse events, skeletal complications, and bone pain throughout the intervention. RESULTS There was a significant difference between groups for self-reported physical functioning (3.2 points; 95% confidence interval, 0.4-6.0 points; P = 0.028) and lower body muscle strength (6.6 kg; 95% confidence interval, 0.6-12.7; P = 0.033) at 3 months favoring EX. However, there was no difference between groups for lean mass (P = 0.584), fat mass (P = 0.598), or fatigue (P = 0.964). There were no exercise-related adverse events or skeletal fractures and no differences in bone pain between EX and CON (P = 0.507). CONCLUSIONS Multimodal modular exercise in prostate cancer patients with bone metastases led to self-reported improvements in physical function and objectively measured lower body muscle strength with no skeletal complications or increased bone pain. TRIAL REGISTRATION ACTRN12611001158954.
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Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Demark-Wahnefried, W, Nix, JW, Hunter, GR, Rais-Bahrami, S, Desmond, RA, Chacko, B, Morrow, CD, Azrad, M, Frugé, AD, Tsuruta, Y, et al
BMC cancer. 2016;16:61
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There is a strong body of evidence associating obesity and increased risk for more aggressive and progressive cancer. This paper aims to assess the feasibility of a presurgical diet and exercise weight loss intervention in men with newly-diagnosed prostate cancer who elected for prostatectomy. It also aims to explore the intervention’s effects on tumour proliferation rates and other biomarkers. The 3-weeks randomised controlled study included 40 overweight or obese men newly-diagnosed with prostate cancer. Participants in experimental arm were assigned to a healthy energy-restricted diet versus wait-list control arm. All feasibility endpoints were achieved with accrual completed within 2 years, retention of 85%, adherence of 95% and no adverse events. Biologic outcomes were not included in this paper, as biological testing was still ongoing. Authors concluded that this study’s methods and data on feasibility could provide useful framework for the design of future trials. They also highlighted the importance of presurgical trials as a feasible and safe means to assess the impacts of diet and exercise on tumour tissue.
Abstract
BACKGROUND Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION NCT01886677.