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.

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.

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.

Prostate Cancer Survivorship Essentials for men with prostate cancer on androgen deprivation therapy: protocol for a randomised controlled trial of a tele-based nurse-led survivorship care intervention (PCEssentials Hormone Therapy Study).

INTRODUCTION: Androgen deprivation therapy (ADT) is commonly used to treat men with locally advanced or metastatic prostate cancer. Men receiving ADT experience numerous side effects and frequently report unmet supportive care needs. An essential part of quality cancer care is survivorship care. To date, an optimal effective approach to survivorship care for men with prostate cancer on ADT has not been described. This protocol describes a randomised trial of tele-based nurse-led survivorship that addresses this knowledge gap: (1) determine the effectiveness of a nurse-led survivorship care intervention (PCEssentials), relative to usual care, for improving health-related quality of life (HR-QoL) in men with prostate cancer undergoing ADT and (2) evaluate PCEssentials implementation strategies and outcomes, including cost-effectiveness, compared with usual care. METHODS AND ANALYSIS: This is an effectiveness-implementation hybrid (type 1) trial with participants randomised to one of two arms: (1) minimally enhanced usual care and (2) nurse-led prostate cancer survivorship essentials (PCEssentials) delivered over four tele-based sessions, with a booster session 5 months after session 1. Eligible participants are Australian men with prostate cancer commencing ADT and expected to be on ADT for a minimum of 12 months. Participants are followed up at 3, 6 and 12 months postrecruitment. Primary outcomes are HR-QoL and self-efficacy. Secondary outcomes are psychological distress, insomnia, fatigue and physical activity. A concurrent process evaluation with participants and study stakeholders will be undertaken to determine effectiveness of delivery of PCEssentials. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Metro South Health HREC (HREC/2021/QMS/79429). All participants are required to provide written informed consent. Outcomes of this trial will be published in peer-reviewed journals. The findings will be presented at conferences and meetings, local hospital departments, participating organisations/clinical services, and university seminars, and communicated at community and consumer-led forums. TRIAL REGISTRATION NUMBER: ACTRN12622000025730.

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.

Assessment of Ground Contact Time in the Field: Evaluation of Validity and Reliability.

ABSTRACT: Weber, JA, Hart, NH, Rantalainen, T, Connick, M, and Newton, RU. Assessment of ground contact time in the field: evaluation of validity and reliability. J Strength Cond Res 38(1): e34-e39, 2024-The capacity to measure the kinetic and kinematic components of running has been extensively investigated in laboratory settings. Many authors have produced work that is of high value to practitioners within sporting environments; however, the lack of field-based technology to assess features of running gait validly and reliably has prevented the application of these valuable works. This paper examines the validity and reliability of a practical field-based methodology for using commercial inertial measurement units (IMUs) to assess ground contact time (GCT). Validity was examined in the comparison of GCT measured from ground reaction force by a force plate and that determined by a lumbar mounted commercial IMU and analyzed using a commercially available system (SPEEDSIG). Reliability was assessed by a field-based examination of within and between-session variability in GCT measured using a commercially available system (SPEEDSIG). Significance was set at p ≤ 0.05. Results for validity (intraclass correlation [ICC] 0.83) and reliability (ICC 0.91) confirm that the described field-based methodology is qualified for use to determine GCT in a practical setting. The implications of this study are important as they offer sport practitioners (S&C coaches, rehab specialists, and physios) a scalable method to assess GCT in the field to develop greater understanding of their athletes and improve performance, injury prevention, and rehabilitation interventions. Furthermore, these results provide the foundation for further work that could provide greater detail describing individual running gait in the field.

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.

Declaración de consenso de la organización ejercicio y ciencias del deporte - Australia: el ejercicio como medicina en el manejo del cáncer / The Exercise and Sports Science Australia position statement: Exercise medicine in cancer management / Declaração de consenso da Organização de Ciências do Exercício e do Esporte - Austrália: Exercício como medicamento no tratamento do câncer

Resumen Desde la primera publicación de la declaración de consenso sobre pautas de ejercicio para personas con cáncer, de la asociación Ejercicio y Ciencias del Deporte - Australia (ESSA, Exercise and Sports Science Australia), ha ocurrido un crecimiento exponencial en las investigaciones que evalúan el papel del ejercicio antes, durante y después del tratamiento del cáncer. El propósito de este reporte es utilizar la evidencia científica actual, junto a la experiencia clínica y los principios de las ciencias del ejercicio, para poner al día la declaración de consenso de ESSA sobre la prescripción de ejercicio específica para el cáncer. En esta declaración de consenso se reporta un resumen de los beneficios alcanzados mediante el ejercicio luego de un diagnóstico de cáncer, así como las fortalezas y limitaciones de la evidencia acumulada. Se propone, entonces, un marco de prescripción del ejercicio para permitir la aplicación de consideraciones específicas para el cáncer en la individualización, especificidad, seguridad, factibilidad y progresión del ejercicio para toda clase de pacientes. Se ofrecen consideraciones adicionales específicas para la prescripción del ejercicio cuando hay presencia de enfermedades hematológicas, osteomusculares, sistémicas, cardiovasculares, linfáticas, gastrointestinales, genitourinarias y neurológicas y preocupaciones relacionadas con su tratamiento, así como la presencia crónica de comorbilidades. Además, se identifican y comentan temas prácticos específicos y barreras que deben tomarse en cuenta para la prescripción del ejercicio. Si bien es cierto que el ejercicio multimodal de intensidad moderada a intensa será apropiado para la mayoría, no hay una prescripción establecida ni una dosificación semanal, que se puedan considerar basadas en la evidencia, para todos los pacientes de cáncer. Es necesaria una prescripción del ejercicio dirigida específicamente a esta población, que asegure el mayor beneficio (conforme lo defina cada paciente) a corto y largo plazo, con un bajo riesgo de perjuicio.

Abstract Objectives: Since Exercise and Sports Science Australia (ESSA) first published its position statement on exercise guidelines for people with cancer, there has been exponential growth in research evaluating the role of exercise pre-, during and post-cancer treatment. Design and Methods: The purpose of this report is to use the current scientific evidence, alongside clinical experience and exercise science principles to update ESSA's position statement on cancer-specific exercise prescription. Results: Reported in this position statement is a summary of the benefits accrued through exercise following a cancer diagnosis and the strengths and limitations of this evidence-base. An exercise prescription framework is then proposed to enable the application of cancer-specific considerations for individualisation, specificity, safety, feasibility and progression of exercise for all patients. Additional specific exercise prescription considerations are provided for the presence of haematological, musculoskeletal, systemic, cardiovascular, lymphatic, gastrointestinal, genitourinary and neurological disease- and treatment-related concerns, as well as presence of co-morbid chronic disease. Further, we also identify and discuss cancer-specific pragmatic issues and barriers requiring consideration for exercise prescription. Conclusions: While for the majority, multimodal, moderate to high intensity exercise will be appropriate, there is no set prescription and total weekly dosage that would be considered evidence-based for all cancer patients. Targeted exercise prescription, which includes the provision of behaviour change advice and support, is needed to ensure greatest benefit (as defined by the patient) in the short and longer term, with low risk of harm.

Resumo Desde a primeira publicação da declaração de consenso da Organização de Ciências do Exercício e do Esporte - Austrália ((ESSA, Exercise and Sports Science Australia) sobre diretrizes de exercícios para pessoas com câncer, tem ocorrido um crescimento exponencial nas pesquisas que avaliam o papel dos exercícios antes, durante e depois do tratamento do câncer. O objetivo deste relatório é usar as evidências científicas atuais com a experiência clínica e os princípios da ciência do exercício, para atualizar a declaração de consenso da ESSA sobre a prescrição de exercícios específica para o câncer. Esta declaração de consenso relata um resumo dos benefícios obtidos por meio de exercícios após o diagnóstico de câncer, bem como os pontos fortes e as limitações da evidência acumulada. Assim, propõe-se uma estrutura de prescrição de exercícios para permitir a aplicação de considerações específicas para o câncer na individualização, especificidade, segurança, viabilidade e progressão do exercício para todas as classes de pacientes. Considerações adicionais específicas para a prescrição de exercícios são fornecidas quando há doenças hematológicas, osteomusculares, sistêmicas, cardiovasculares, linfáticas, gastrointestinais, geniturinárias, neurológicas e preocupações relacionadas ao seu tratamento, bem como a presença crônica de comorbidades. Além disso, questões práticas específicas e barreiras à prescrição de exercícios são identificadas e discutidas. Embora seja verdade que o exercício multimodal de intensidade moderada a vigorosa seja apropriado para a maioria, não há uma prescrição definida ou dosagem semanal que possa ser considerada baseada em evidências para todos os pacientes com câncer. Há uma necessidade de prescrição de exercícios especificamente direcionada a essa população, garantindo o maior benefício (conforme definido pelo paciente individual) em curto e longo prazos, com baixo risco de danos.

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.

Associations of physical activity and quality of life in parapneumonic effusion patients.

Introduction: Little is known about activity behaviours and quality of life (QoL) of patients with parapneumonic pleural effusions (PPE) after hospital discharge. This study is a secondary analysis of a randomised trial (dexamethasone versus placebo) for hospitalised patients with PPE. We: 1) described the patients' activity behaviour patterns and QoL measured at discharge and at 30 days post-discharge; and 2) examined the association between activity behaviours and QoL scores. Methods: Activity behaviour (7-day accelerometry; Actigraph GT3X+) and QoL (Medical Outcomes Study Short-Form 36) were assessed. Repeated measures analysis of covariance controlling for baseline values and a series of linear regression models were undertaken. Results: 36 out of 53 eligible participants completed accelerometry assessments. Despite modest increases in light physical activity (+7.5%) and some domains of QoL (>2 points) from discharge to 30 days post-discharge, patients had persistently high levels of sedentary behaviour (>65% of waking wear time) and poor QoL (≤50 out of 100 points) irrespective of treatment group (p=0.135-0.903). Increasing moderate-to-vigorous physical activity was associated with higher scores on most QoL domains (p=0.006-0.037). Linear regression indicates that a clinically important difference of 5 points in physical composite QoL score can be achieved by reallocating 16.1 min·day-1 of sedentary time to moderate-to-vigorous physical activity. Conclusion: Patients with PPE had low levels of physical activity and QoL at discharge and 30 days post-discharge irrespective of treatment. Moderate-to-vigorous physical activity participation was associated with higher QoL scores. Increasing moderate-to-vigorous physical activity following discharge from the hospital may be associated with improvements in QoL.

Testing campaign slogans designed to motivate older people to be more physically active.

Objectives and importance of study: Being physically active is critical for healthy ageing, yet many older people do not meet physical activity guidelines. The aim of this study was to test the relative effectiveness of five previously identified campaign slogans designed to encourage older people to be more physically active: 'Be active 30-60 minutes a day to stay fit and well'; 'Move more, live longer'; 'Stay fit to stay functional'; 'This is your time - enjoy being strong and active'; and 'Use it or lose it'. STUDY TYPE: Online experiment Methods: A total of 1200 Australians aged 50 years and older (50% female, mean age 65 years) were recruited to complete an online survey, with respondents randomised to answer a series of questions on a video featuring one of the five slogan conditions. One-way ANOVAs with Tukey's post-hoc tests were used to identify differences in outcomes between slogans. RESULTS: Overall, the slogans were assessed favourably, suggesting older adults may be receptive to messages about increasing their physical activity. 'Use it or lose it 'performed best across the outcome measures of internal and external motivation, perceived effectiveness, liking, believability, and personal relevance. CONCLUSION: Efforts to encourage physical activity among older Australians could use the slogan 'Use it or lose it' as an evidence-based tagline.

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.

A feasibility, safety, and efficacy evaluation of supervised aerobic and resistance exercise for patients with glioblastoma undertaking adjuvant chemoradiotherapy.

Background: While therapeutically effective, chemoradiotherapy treatment for high-grade glioma (glioblastoma) is often accompanied by side effects. Exercise has been demonstrated to alleviate the adverse effects of such treatments in other cancers. We aimed to evaluate the feasibility and preliminary efficacy of supervised exercise incorporating autoregulation. Methods: Thirty glioblastoma patients were recruited, five declined exercise and 25 were provided with a multimodal exercise intervention for the duration of their chemoradiotherapy treatment. Patient recruitment, retention, adherence to training sessions and safety were evaluated throughout the study. Physical function, body composition, fatigue, sleep quality, and quality of life were evaluated before and after the exercise intervention. Results: Eight of the 25 participants commencing exercise withdrew prior to completion of the study (32%). Seventeen patients (68%) demonstrated low to high adherence (33%-100%) and exercise dosage compliance (24%-83%). There were no reported adverse events. Significant improvements were observed for all trained exercises and lower limb muscle strength and function with no significant changes observed for any other physical function, body composition, fatigue, sleep, or quality of life outcomes. Conclusions: Only half of glioblastoma patients recruited were willing or able to commence, complete or meet minimum dose compliance for the exercise intervention during chemoradiotherapy indicating the intervention evaluated may not be feasible for part of this patient cohort. For those who were able to complete the exercise program, supervised, autoregulated, multimodal exercise was safe and significantly improved strength and function and may have prevented deterioration in body composition and quality of life.

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.

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.

Effects and moderators of exercise medicine on cardiometabolic outcomes in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis.

PURPOSE: To examine the effects and moderators of exercise effects on cardiometabolic outcomes in men with prostate cancer previously or currently undergoing androgen deprivation therapy (ADT). RESULTS: Seven trials including 560 patients were examined. Exercise resulted in significant effects on whole-body and regional fat mass (P ≤ 0.001). For whole-body fat mass, significant exercise effects were observed in patients who were unmarried (-1.4 kg, P < 0.05) and who presented with higher fat mass levels (-1.0 kg, P < 0.05). For diastolic blood pressure and low-density lipoprotein (LDL), younger (-4.7 mmHg, P < 0.05) and older patients (-0.2 mmol.l-1, P < 0.10) achieved greater effects, respectively. Regarding high-density lipoprotein (HDL), patients undertaking ADT + prostatectomy + radiotherapy derived significant exercise effects (0.3 mmol.l-1, P < 0.05). CONCLUSIONS: Exercise effectively reduces fat mass across subgroups of men undergoing or following ADT with different characteristics. For diastolic blood pressure, HDL and LDL, groups based on age and treatment history could be specifically targeted with exercise medicine.