Effects of short- and long-term exercise training on cancer cells in vitro: Insights into the mechanistic associations.

Exercise is a therapeutic approach in cancer treatment, providing several benefits. Moreover, exercise is associated with a reduced risk for developing a range of cancers and for their recurrence, as well as with improving survival, even though the underlying mechanisms remain unclear. Preclinical and clinical evidence shows that the acute effects of a single exercise session can suppress the growth of various cancer cell lines in vitro. This suppression is potentially due to altered concentrations of hormones (e.g., insulin) and cytokines (e.g., tumor necrosis factor alpha and interleukin 6) after exercise. These factors, known to be involved in tumorigenesis, may explain why exercise is associated with reduced cancer incidence, recurrence, and mortality. However, the effects of short- (<8 weeks) and long-term (≥8 weeks) exercise programs on cancer cells have been reported with mixed results. Although more research is needed, it appears that interventions incorporating both exercise and diet seem to have greater inhibitory effects on cancer cell growth in both apparently healthy subjects as well as in cancer patients. Although speculative, these suppressive effects on cancer cells may be driven by changes in body weight and composition as well as by a reduction in low-grade inflammation often associated with sedentary behavior, low muscle mass, and excess fat mass in cancer patients. Taken together, such interventions could alter the systemic levels of suppressive circulating factors, leading to a less favorable environment for tumorigenesis. While regular exercise and a healthy diet may establish a more cancer-suppressive environment, each acute bout of exercise provides a further "dose" of anticancer medicine. Therefore, integrating regular exercise could potentially play a significant role in cancer management, highlighting the need for future investigations in this promising area of research.

Creatine supplementation does not add to resistance training effects in prostate cancer patients under androgen deprivation therapy: A double-blind randomized trial.

OBJECTIVES: Androgen deprivation therapy (ADT) leads to loss of lean mass (LM) and reduced strength and physical function. Resistance exercise alone can counteract these changes; however, it is unknown if the addition of creatine supplementation can further protect against these ADT-induced toxicities. We compared the effects of creatine supplementation with resistance exercise versus resistance exercise alone in patients with prostate cancer undergoing ADT on LM, muscle strength, and physical function. DESIGN: A 12-week randomized trial. METHODS: Men with prostate cancer receiving ADT (n = 30) were randomized to either resistance exercise + placebo (PLA) or resistance exercise + creatine (SUPP), with both groups undertaking supervised exercise 3 days per week. Outcomes included whole body and appendicular LM and fat mass (FM) assessed by dual-energy X-ray absorptiometry, as well as muscle strength (chest press, seated low, leg press), and physical function (timed up-and-go, chair rise, 400-m walk) assessed at baseline and following the intervention. RESULTS: Patients were aged 59-84 years with a BMI of 28.6 kg·m-2. PLA completed a mean of 30 sessions (83 %) and SUPP a mean of 33 sessions (92 %). Despite similar within-group improvements (p < 0.05) in whole-body LM (PLA +0.6 kg, SUPP +1.3 kg), appendicular LM (PLA +0.5 kg, SUPP +0.6 kg), muscle strength (PLA +8.8-49.3 kg, SUPP +9.4-40.4 kg) and physical function, there were no between group differences (p = 0.078-0.951). No adverse events were reported due to creatine supplementation or resistance exercise. CONCLUSIONS: A short-term program of resistance exercise alone results in meaningful improvements in LM, muscle strength and physical function, with no additional effects of creatine supplementation.

Immediate Versus Delayed Exercise on Health-related Quality of Life in Patients Initiating Androgen Deprivation Therapy: Results from a Year-long Randomised Trial.

BACKGROUND AND OBJECTIVE: An array of treatment-related toxicities result from androgen deprivation therapy (ADT) in patients with prostate cancer (PCa), compromising function and health-related quality of life (HRQoL). Exercise has been demonstrated to counter a number of these adverse effects including decreased HRQoL; however, when exercise should be initiated is less clear. This study aims to examine whether commencing exercise when ADT is initiated rather than later during treatment is more effective in countering adverse effects on HRQoL. METHODS: Men with PCa (48-84 yr) initiating ADT were randomised to immediate exercise (IMEX; n = 54) or delayed exercise (DEL; n = 48) for 12 mo. IMEX consisted of 6 mo of supervised resistance/aerobic/impact exercise commenced at the initiation of ADT with 6 mo of follow-up. DEL consisted of 6 mo of usual care followed by 6 mo of the same exercise programme. HRQoL was assessed using the Short Form-36 at baseline and 6 and 12 mo. Intention to treat was utilised for the analyses that included group × time repeated-measures analysis of variance using log transformed data. KEY FINDINGS AND LIMITATIONS: There were a significant group × time interaction for the physical functioning domain (p = 0.045) and physical component summary score (p = 0.005), and a significant time effect for bodily pain (p < 0.001) and vitality domains (p < 0.001), with HRQoL maintained in IMEX and declining in DEL at 6 mo. Exercise in DEL reversed declines in vitality and in the physical component summary score, with no differences at 12 mo compared with baseline. Limitations include treatment alterations during the intervention. CONCLUSIONS AND CLINICAL IMPLICATIONS: Concurrently initiating exercise and ADT in patients with PCa preserves HRQoL, whereas exercise initiated while on established ADT regimens reverses declines in some HRQoL domains. PATIENT SUMMARY: To avoid initial treatment-related adverse effects on health-related quality of life, exercise medicine should be initiated at the start of treatment.

Acute effects of eccentric versus concentric exercise on executive function and attention of older adults.

Cognitive function is improved acutely after aerobic and/or resistance exercise, but it is unclear if the types of muscle contraction can influence this effect. This study tested the hypothesis that undertaking an acute bout of exercise with eccentric than concentric contractions would be more beneficial for improving cognitive function post-exercise in older adults. Twenty healthy older adults (66-75y) performed descending stair walking (DSW), ascending stair walking (ASW), and resistance exercise of the knee extensors with eccentric-only (RE-ECC) or concentric-only contractions (RE-CON) for 20 minutes each with a week between exercises in a randomized order. The Stroop tests of color naming (STCN) and conflicting color words (STCC), symbol digit modalities test, digit span test (DST), and two types of the trail making test (TMT-A, TMT-B) were assessed before and after sitting for 20 minutes (control session), and each exercise. A significant (p<0.05) improvement in the baseline test scores was found from the control session to the fourth exercise session. Time to complete the tests was significantly (p<0.05) reduced from pre- to post-exercise as well as after sitting for 20 minutes for STCN (-5.9±7.4s, Cohen's d=0.79), STCC (-8.9±11.1s, d=0.80), TMT-A (-22.6±9.7s, d=2.34) and TMT-B (-23.1±13.7s, d=1.69) without significant difference among the four exercise conditions. A significant (p<0.05) improvement of DST score was found from pre- to post-exercise for DSW (9.0±17.6%, d=0.51) and RE-ECC (6.5±10.6%, d=0.61), but not for ASW and RE-CON. These results partially supported the hypothesis that eccentric exercise could affect acute changes in cognitive function greater than concentric exercise.

Assessing Sarcopenia in Advanced-Stage Ovarian Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Case Series.

OBJECTIVES: In ovarian and other cancers, low muscle mass and density are associated with poorer clinical outcomes. However, screening for cancer-related sarcopenia (typically defined as low muscle mass) is not routinely conducted. The European Working Group on Sarcopenia in Older People (EWGSOP) recommends an algorithm for sarcopenia screening and diagnosis in clinical settings, with sarcopenia based on muscle strength and mass, and severity on physical performance. We explored the application of the EWGSOP2 algorithm to assess sarcopenia in six ovarian cancer patients receiving neoadjuvant chemotherapy. METHODS: We assessed sarcopenia risk with the SARC-F screening questionnaire (at risk ≥4 points), muscle strength with a handgrip strength test (cut point <16 kg) and five times sit-to-stand test (cut point >15 s), muscle mass by skeletal muscle index (SMI in cm2/m2 from a single computed tomography [CT] image; cut point <38.5 cm2/m2), and physical performance with a 4-m gait speed test (cut point ≤0.8 m/s). RESULTS: Of six participants, none were identified as "at risk" for sarcopenia based on SARC-F scores. Two participants were severely sarcopenic based on EWGSOP2 criteria (had low muscle strength, mass, and physical performance), and five participants were sarcopenic based on muscle mass only. DISCUSSION: Ovarian cancer patients with low muscle mass during neoadjuvant chemotherapy may not be identified as sarcopenic based on the EWGSOP2 diagnostic algorithm. While lacking a universally accepted definition for cancer-related sarcopenia and cancer-specific recommendations for the screening, diagnosis, and treatment of sarcopenia, ovarian cancer clinicians should focus on the diagnosis and treatment of low muscle mass and density.

Unleashing anti-tumour immunity: dietary restriction and exercise interventions adjunct to chemotherapy for cancer patients.

Conventional chemotherapies can stimulate the immune system by increasing tumour antigenicity (e.g., neoantigen exposure to immune cells) and altering adjuvanticity in the tumour (e.g., danger associated molecular patterns and cytokines). These molecules promote the recruitment, activation, and maturation of dendritic cells, which in turn, prime and activate cytotoxic T cells against tumour cells. However, several factors can decrease the immunostimulatory efficacy of chemotherapeutic agents. These include reduced tumour cell antigenicity and adjuvanticity and compromised immune function at a local and systemic level. Findings from preclinical studies show that dietary restriction and exercise promote systemic changes that may help to restore immune system function through several mechanisms, including an enhanced infiltration and function of antitumoral immune cells and a decrease in immunosuppressive cells, leading to a reduction in tumour volume. In addition, dietary restriction and exercise training in mice have been shown to enhance the efficacy of chemotherapy. In human studies there is also emerging evidence that dietary restriction and exercise can impact the immune system towards a more antitumoral profile. In this review, we discuss the immunostimulatory effects of dietary restriction (caloric restriction and fasting) and exercise training in preclinical cancer models, and potential synergies with chemotherapy. We then review clinical studies assessing the effects of these interventions on immune-related endpoints and tumour responses. Finally, we propose that combining dietary restriction with exercise could be a promising strategy to increase chemotherapy efficacy.

Effects of a 6-month dual-task, power-based exercise program on cognitive function, neurological and inflammatory markers in older adults: secondary analysis of a cluster randomised controlled trial.

Functional power-based exercise training can improve physical performance in older adults and cognitive training can improve measures of cognition, but their combined effects on cognition and related risk factors (neurological and inflammatory markers) remains uncertain. This 6-month cluster randomised controlled trial evaluated the effectiveness of dual-task functional power training (DT-FPT) on cognition and circulating neurological and inflammatory markers in older adults at increased falls risk, and whether intervention responses varied by apolipoprotein-E (ApoE) and brain derived neurotrophic factor (BDNF) polymorphisms. Three hundred residents aged ≥ 65 years at increased falls risk residing in 22 independent-living retirement communities, were randomised by village, to DT-FPT (n = 156, 11 villages) involving a multi-component power-based training program performed simultaneously with cognitive and/or motor tasks (45-60 min, 2/week), or a usual care control (CON) group (n = 144, 11 villages). Cognition (computerized CogState battery), inflammatory cytokines, BDNF, insulin-like growth factor-1, vascular endothelial growth factor, amyloid ß (1-40) and (1-42) were assessed at baseline and 6-months. Overall, 233 (78%) participants completed the intervention and adherence averaged 50.1%. DT-FPT led to a net 0.18-0.20 SD benefit versus CON in psychomotor ability/attention and reaction time/attention (both P < 0.05). There were no significant intervention effects on circulating markers, except for a net 10.5% benefit in amyloid ß (1-40) in DT-FPT versus CON (P < 0.05). Responses were not influenced by APOE or BDNF genotype. In conclusion, DT-FPT in older adults at increased falls risk can provide some cognitive benefits, but these were not related to corresponding changes in inflammatory or neurological markers or influenced by genotype. Australian New Zealand Clinical Trials Registry (ACTRN12613001161718). http://www.anzctr.org.au/ This project was funded by a grant from the National Health and Medical Research Council (NHMRC) Project (APP1046267).

Enhancing circulatory myokines and extracellular vesicle uptake with targeted exercise in patients with prostate cancer (the MYEX trial): a single-group crossover study.

INTRODUCTION: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. METHODS: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. DISCUSSION: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. TRIAL REGISTRATION: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.

Exercise training mode effects on myokine expression in healthy adults: A systematic review with meta-analysis.

BACKGROUND: The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle-organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment. METHODS: A systematic search was undertaken in PubMed, MEDLINE, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on interleukin15 (IL-15), irisin, secreted protein acidic and rich in cysteine (SPARC), oncostatin M (OSM), and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change. RESULTS: Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn. CONCLUSION: Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

Suppressive effects of exercise-conditioned serum on cancer cells: A narrative review of the influence of exercise mode, volume, and intensity.

Cancer is a major cause of morbidity and mortality worldwide, and the incidence is increasing, highlighting the need for effective strategies to treat this disease. Exercise has emerged as fundamental therapeutic medicine in the management of cancer, associated with a lower risk of recurrence and increased survival. Several avenues of research demonstrate reduction in growth, proliferation, and increased apoptosis of cancer cells, including breast, prostate, colorectal, and lung cancer, when cultured by serum collected after exercise in vitro (i.e., the cultivation of cancer cell lines in an experimental setting, which simplifies the biological system and provides mechanistic insight into cell responses). The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors, such as skeletal muscle-induced cytokines (i.e., myokines) and hormones. However, exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated, constraining more precise application of exercise medicine within clinical oncology. To date, it remains unclear what role different training modes (i.e., resistance and aerobic training) as well as volume and intensity have on exercise-conditioned serum and its effects on cancer cells. Nevertheless, the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects, while for chronic training interventions, exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode. Insights for future research investigating training modes, volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.

What are the most effective exercise, physical activity and dietary interventions to improve body composition in women diagnosed with or at high-risk of breast cancer? A systematic review and network meta-analysis.

BACKGROUND: Obesity has been recognized as a risk factor in the development and recurrence of breast cancer and is also associated with poor prognostic outcomes. This systematic review and network meta-analysis aimed to identify the most effective exercise, physical activity, and dietary interventions to reduce fat mass, body fat percentage and body weight as well as potentially increase lean mass in women diagnosed with or at high risk of breast cancer. METHODS: A systematic search of databases was performed up to May 2022. Eligible randomized controlled trials examined the effects of exercise, physical activity and/or dietary interventions on fat mass and lean mass in women diagnosed with or at high risk of breast cancer. A random-effects network meta-analysis was conducted to determine the effects of different interventions across outcomes when sufficient studies were available. RESULTS: Eighty-four studies (n = 6428) were included in this review. Caloric restriction and combined exercise + caloric restriction significantly reduced fat mass (range, -3.9 to -3.7 kg) and body weight (range, -5.3 to -4.7 kg), whereas physical activity + caloric restriction significantly reduced body fat percentage (-2.4%; 95% confidence interval [CI], -3.4% to -13%) and body mass index (-2.2 kg × m-2 ; 95% CI, -3.0 to -1.4 kg × m-2 ) in breast cancer patients. Resistance exercise was the most effective intervention to increase lean mass (0.7 kg; 95% CI, 0.5-1.0 kg) in breast cancer patients. CONCLUSION: Multimodal exercise and diet programs were the most effective interventions to reduce fat mass, body fat percentage, and body weight and increase and/or preserve lean mass.

Prehabilitative versus rehabilitative exercise in prostate cancer patients undergoing prostatectomy.

PURPOSE: The study compared the efficacy of commencing supervised exercise in men with prostate cancer before and after prostatectomy on objective and patient-reported outcomes, hospital length of stay, and urinary incontinence. METHODS: Forty-one men were randomised to a 6-week prehabilitation or rehabilitation exercise programme. Prehabilitation involved resistance and aerobic exercise thrice weekly pre-surgery, while rehabilitation comprised the same commencing 6-weeks post-surgery. Assessments included strength, function (chair rise, stair climb, 400-m, 6-m usual, fast, and backwards walk), body composition, fatigue and quality of life, undertaken at pre-surgery, early post-surgery and late post-surgery phase, with urinary incontinence (24-h pad test) assessed at 2, 6, and 12-weeks post-surgery. Intention-to-treat and sensitivity analyses were undertaken. RESULTS: Of thirty-eight men (48-73 years), 29 completed all assessments with most undergoing robotic-assisted laparoscopic prostatectomy (92.1%). In the pre-surgery phase, prehabilitation improved muscle strength (leg press: 17.2 kg; chest press: 2.9 kg; p ≤ 0.001), 400-m, chair rise, 6-m fast and backward walk tests (p ≤ 0.001-0.028). Strength and function declines in the early post-surgery phase were maintained late post-surgery. Rehabilitation showed declines of these outcomes after surgery with improvement late post-surgery (leg press: 14.6 kg, p < 0.001; chest press: 6.8 kg, p < 0.001; 400-m walk: -12.0 s, p = 0.005), resulting in no difference between groups at 12 weeks. There were no significant differences between groups for patient-reported outcomes, hospital length of stay or urinary incontinence. CONCLUSION: Pre-surgical exercise enhanced strength and function, protecting against post-surgery declines. Although exercise post-surgery is beneficial for recouping strength and function, where possible men undergoing prostatectomy are encouraged to exercise pre-surgery. TRIAL REGISTRATION: ACTRN12617001115325 registered 31 July 2017.

Time to consider the potential role of alternative resistance training methods in cancer management?

Exercise has emerged as fundamental therapeutic medicine in the management of cancer. Exercise improves health-related outcomes, including quality of life, neuromuscular strength, physical function, and body composition, and it is associated with a lower risk of disease recurrence and increased survival. Moreover, exercise during or post cancer treatments is safe, can ameliorate treatment-related side effects, and may enhance the effectiveness of chemotherapy and radiation therapy. To date, traditional resistance training (RT) is the most used RT modality in exercise oncology. However, alternative training modes, such as eccentric, cluster set, and blood flow restriction are gaining increased attention. These training modalities have been extensively investigated in both athletic and clinical populations (e.g., age-related frailty, cardiovascular disease, type 2 diabetes), showing considerable benefits in terms of neuromuscular strength, hypertrophy, body composition, and physical function. However, these training modes have only been partially or not at all investigated in cancer populations. Thus, this study outlines the benefits of these alternative RT methods in patients with cancer. Where evidence in cancer populations is sparse, we provide a robust rationale for the possible implementation of certain RT methods that have shown positive results in other clinical populations. Finally, we provide clinical insights for research that may guide future RT investigations in patients with cancer and suggest clear practical applications for targeted cancer populations and related benefits.

Exercise Mediates Myokine Release and Tumor Suppression in Prostate Cancer Independent of Androgen Signaling.

A prominent toxicity of androgen suppression in patients with prostate cancer (PCa) is loss of skeletal muscle. Exercise may induce tumor suppression through the endocrinal function of skeletal muscle; however, this is currently unknown. In this review, we summarize our work demonstrating the acute and chronic myokine response to exercise and the tumor-suppressive effect of circulatory milieu alteration in PCa patients.

Moderators of resistance-based exercise programs' effect on sarcopenia-related measures in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis.

INTRODUCTION: Older men with prostate cancer are commonly affected by reductions in lean mass and physical function following androgen deprivation therapy (ADT). Resistance-based exercise programs are critical to counteract the musculoskeletal toxicities derived from prostate cancer treatment and aging. However, there is significant variability in the effects of exercise interventions. Examining demographic and clinical moderators of exercise effects in this patient group can assist in identifying which subgroups of patients benefit most. Therefore, we examined the effects and moderators of resistance-based exercise programs on sarcopenia-related outcomes that included lean mass, skeletal muscle index, physical function, and muscle strength in older men with prostate cancer. MATERIALS AND METHODS: Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. For the present study, we included data from trials that examined the effects of supervised resistance-based exercise interventions on lean mass outcomes, muscle strength, and physical function in patients with prostate cancer previously or currently treated with ADT. Linear mixed models were undertaken to analyse the effects of resistance-based exercise programs considering the clustering of patients within studies. Effects were evaluated by regressing the study group on the post-intervention value of the outcome adjusted for the baseline value, while potential moderators were examined by adding the moderator and its interaction term into the regression model. RESULTS: A total of 560 patients with prostate cancer (age: 69.5 ± 7.8 yrs.; body mass index: 28.6 ± 4.0 kg.m-2) previously or currently treated with ADT were included. Resistance-based exercise programs resulted in significant effects on whole-body and appendicular lean mass and the skeletal muscle index (P < 0.05), with improvements observed across different characteristics. Improvements were also observed in 400-m walk and 6-m backwards tandem walk (P < 0.05), with patients presenting with lower baseline levels deriving greater exercise effects on 400-m walk (-19.4 s, 95% confidence interval [CI]: -36.6 to -2.3) and 6-m backwards tandem walk tests (-3.0 s, 95% CI: -5.7 to -0.3). For relative muscle strength, significant exercise effects were observed, with greater effects in younger patients (0.35 kg.kg-1, 95% CI: 0.22 to 0.48). DISCUSSION: Resistance-based exercise programs effectively improve well-known markers of sarcopenia in men with prostate cancer, with specific subgroups of patients, such as those younger and presenting with lower baseline levels of physical function, deriving greater effects on muscle strength and physical function, respectively.

Skeletal muscle morphology in patients receiving primary versus interval cytoreductive surgery for advanced high-grade serous ovarian cancer.

OBJECTIVE: Our primary aim was to compare muscle morphology (skeletal muscle mass and density) between patients who underwent primary cytoreductive surgery versus interval cytoreductive surgery for advanced high-grade serous ovarian cancer. Secondarily, we explored the associations of muscle morphology with survival outcomes. METHODS: We retrospectively analysed computed tomography (CT) images for 88 ovarian cancer patients (aged 38-89 years) to calculate skeletal muscle index (cm2/m2) and skeletal muscle density (Hounsfield units (HU)). A skeletal muscle index of <38.5 cm2/m2 and skeletal muscle density of <33.7 HU were classified as low. Analyses included repeated measures analysis of covariance and multivariable Cox proportional hazards regression. RESULTS: At baseline, 44.3% of patients had low skeletal muscle index and 50.6% had low skeletal muscle density, with interval surgery patients having significantly lower mean skeletal muscle density than primary surgery patients (32.2±8.9 vs 37.3±8.6 HU, p=0.014). Although both groups had similar reductions in skeletal muscle index following treatment (p=0.49), primary surgery patients had a greater reduction in skeletal muscle density compared with interval surgery patients (-2.4 HU, 95% CI -4.3 to -0.5, p=0.016). Patients who experienced skeletal muscle density loss >2% during treatment (HR 5.16, 95% CI 1.33 to 20.02) and had low skeletal muscle density post-treatment (HR 58.87, 95% CI 3.70 to 935.68) had significantly worse overall survival. CONCLUSION: Low skeletal muscle index and skeletal muscle density were prevalent at ovarian cancer diagnosis. While both groups experienced muscle mass loss, greater reductions in skeletal muscle density occurred in patients undergoing primary surgery. In addition, skeletal muscle density loss during treatment and low skeletal muscle density post-treatment were associated with poorer overall survival. Supportive care involving resistance exercise targeting muscle hypertrophic drive, and nutrition counseling during and after ovarian cancer treatment may help preserve/enhance muscle mass and density.

Feasibility of supervised telehealth exercise for patients with advanced melanoma receiving checkpoint inhibitor therapy.

PURPOSE: To determine the feasibility, safety and preliminary efficacy of a telehealth supervised exercise programme in patients with advanced melanoma receiving checkpoint inhibitor therapy. METHODS: A 8-week non-randomised feasibility pilot trial utilising a telehealth delivered multimodal exercise programme undertaken thrice weekly with assessments at baseline and post-intervention. The study was considered feasible if there were no severe or life-threatening adverse events as a result of exercise, and three or more of the following criteria were met: the recruitment rate was >50%, completion rate was >80%, median programme attendance was >75%, median exercise compliance >75%, and average tolerance was >70%. Preliminary efficacy was assessed for objective measures of physical function (2-min step test, repeated chair stand test, 30-s push-up test, and a modified static balance test) and quality of life (QoL), fatigue and other patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. RESULTS: Eleven patients (32-80 years) were included in the study (6 female, 5 male). The recruitment rate was 48%, completion rate 91%, programme attendance 88%, median exercise compliance 82.1% and 84.9% for resistance and aerobic exercise, respectively, and tolerance 88%, with no severe or life-threatening adverse events as a result of exercise. In terms of preliminary efficacy, physical function significantly improved while QoL was maintained following the intervention. CONCLUSION: An 8-week telehealth exercise intervention is feasible and safe for patients with advanced melanoma and appears to improve physical function while preserving QoL during checkpoint inhibitor therapy.

Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis.

PURPOSE: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. METHODS: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. RESULTS: Minimal significant beneficial exercise effects on self-reported CF (ß=-0.09 [-0.16; -0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, ß=-0.13 [-0.24; -0.02]), and no significant effect during cancer treatment (n=1,162, ß=-0.08 [-0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (ß=-0.14 [-0.25; -0.04]) or 24 weeks or longer (ß=-0.18 [-0.32; -0.02]), whereas no effects were observed in interventions of 12-24 weeks (ß=0.01 [-0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (ß=-0.10 [-0.19; -0.02]) or after completion of treatment in patients with cognitive problems (ß=-0.19 [-0.31; -0.06]). No other significant moderators were identified. CONCLUSIONS: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. IMPLICATIONS FOR CANCER SURVIVORS: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors.

Supervised resistance exercise for women with ovarian cancer who have completed first-line treatment: a pragmatic study.

OBJECTIVES: In ovarian cancer (OC), suboptimal muscle morphology (i.e., low muscle mass and density) is associated with poor clinical outcomes, yet little is known about the effect of interventions aimed at improving these measures. We investigated the effect of resistance exercise after first-line treatment on muscle mass and density, muscle strength and physical function, health-related quality of life (QoL), and pelvic-floor function in advanced-stage OC survivors. METHODS: Fifteen OC survivors participated in supervised resistance exercise twice weekly for 12 weeks (in-clinic or by telehealth). Assessments included muscle mass and density (dual-energy X-ray absorptiometry, peripheral quantitative computed tomography), muscle strength (1-repetition maximum [1RM] chest press, 5RM leg press, handgrip strength), physical function (400-m walk, timed up-and-go [TUG]), QoL (QLQ-C30 questionnaire), and self-reported pelvic floor function (Australian Pelvic Floor Questionnaire). RESULTS: The median age was 64 (range 33-72) years, 10 women underwent neoadjuvant chemotherapy and five underwent adjuvant chemotherapy. All participants completed the intervention (median attendance = 92%; range 79-100%). Post-intervention improvements were observed for whole-body lean mass (1.0 ± 1.4 kg, p = 0.015), appendicular lean mass (0.6 ± 0.9 kg, p = 0.013), muscle density (p = 0.011), upper and lower body strength (p ≤ 0.001), 400-m walk (p = 0.001), TUG (p = 0.005), and social and cognitive QoL domains (p = 0.002 and 0.007), with no change to pelvic floor symptoms (p > 0.05). CONCLUSION: In this study, supervised resistance exercise effectively improved muscle mass and density, muscle strength, and physical functioning without deleterious effects on the pelvic floor. Considering the prognostic value of these outcomes, larger studies are needed to confirm the benefits of resistance exercise in OC supportive care.