Technical and Biological Reliability of pQCT Measured Bone and Muscle Tissue Quality Across the Age-Span.

INTRODUCTION: Reliable peripheral quantitative computed tomography (pQCT) assessment is essential to the accurate longitudinal reporting of bone and muscle quality. However, the between-day reliability of pQCT and the influence of age on outcome reliability is currently unknown. OBJECTIVE: To quantify the same- and between-day reliability of morphological pQCT at proximal and distal segments of the forearm, shank, and thigh, and explore the influence of participant body size, age, and sex on outcome reliability. METHODS: Men and women (49 % female, 18-85 years, n=72-86) completed two consecutive-day pQCT testing sessions, where repeat measurements were conducted on day-one for technical error, and between-day for biological error quantification. Testing was undertaken following best practice body composition testing guidance, including standardized presentation and consistent time-of-day. RESULTS: All measurements of bone were classified as having 'good' to 'excellent' reliability [intraclass correlation coefficient (r=0.786- 0.999], as were measurements of muscle area (ICC r=0.991-0.999) and total fat (r=0.996-0.999). However, between- and same-day muscle density measurements at the thigh and forearm were classified as 'poor' (r=0.476) and 'moderate' (r=0.622), respectively. Likewise, intramuscular fat area at the thigh was classified as 'moderate' (r=0.737) for between-day measurement. Biological error was inflated compared to technical error by an average of 0.4 % for most measurements. Error values tended to increase proportionally with the amount of tissue quantified and males had significantly greater biological error for measurement of distal tibial bone (p<0.002) and trabecular area (p<0.002). Biological error was inflated among older adults for measurement of forearm muscle density (p<0.002). CONCLUSIONS: Most pQCT outcomes can be implemented with confidence, especially outcomes that assess bone area and density at any of the radial, tibial, and femoral sites investigated herein. However, it is important to account for the influence of biological measurement error in further studies, especially for muscle and intramuscular fat outcomes derived by pQCT.

Association between change in cardiorespiratory fitness and prostate cancer incidence and mortality in 57 652 Swedish men.

OBJECTIVES: To examine the associations between changes in cardiorespiratory fitness (CRF) in adulthood and prostate cancer incidence and mortality. METHODS: In this prospective study, men who completed an occupational health profile assessment including at least two valid submaximal CRF tests, performed on a cycle ergometer, were included in the study. Data on prostate cancer incidence and mortality were derived from national registers. HRs and CIs were calculated using Cox proportional hazard regression with inverse probability treatment weights of time-varying covariates. RESULTS: During a mean follow-up time of 6.7 years (SD 4.9), 592 (1%) of the 57 652 men were diagnosed with prostate cancer, and 46 (0.08%) died with prostate cancer as the primary cause of death. An increase in absolute CRF (as % of L/min) was associated with a reduced risk of prostate cancer incidence (HR 0.98, 95% CI 0.96 to 0.99) but not mortality, in the fully adjusted model. When participants were grouped as having increased (+3%), stable (±3%) or decreased (-3%) CRF, those with increased fitness also had a reduced risk of prostate cancer incidence compared with those with decreased fitness (HR 0.65, 95% CI 0.49 to 0.86), in the fully adjusted model. CONCLUSION: In this study of employed Swedish men, change in CRF was inversely associated with risk of prostate cancer incidence, but not mortality. Change in CRF appears to be important for reducing the risk of prostate cancer.

The effects of exercise on the bone health of people with cancer: a systematic review and meta-analysis.

PURPOSE: To determine the pooled effect of exercise on the bone health of people diagnosed with cancer. METHODS: Four electronic databases were systematically searched. Controlled trials that assessed the effect of exercise on the bone mineral density (BMD) or content (BMC) measured by dual-energy x-ray absorptiometry or peripheral quantitative computed tomography in people who had been diagnosed with cancer were included in the study. Random-effect meta-analyses of effect size (ES) were conducted. Sub-group analyses were performed to explore the influence of intervention duration, prescription and participant characteristics. RESULTS: Of 66 full-text articles screened, 22 studies, from 21 interventions, were included (primarily breast/prostate cancer, sample range n = 36-498). When all interventions were grouped, a significant pooled ES was observed for exercise on hip (ES = 0.112, 95% CI: 0.026 to 0.198; p = 0.011) and lumbar spine BMD (ES = 0.269, 95% CI: 0.036 to 0.501; p = 0.024) compared to control. There was also an influence of sex, where females had greater improvements in hip (ES = 0.120, 95% CI: 0.017 to 0.223; p = 0.022) and spine BMD (ES = 0.415, 95% CI: 0.056 to 0.774; p = 0.23) compared to males. CONCLUSION: Overall, exercise regimens of studies included in this review appear to improve bone health at the hip and spine in people diagnosed with cancer. Sub-analyses suggest some influence of sex, where females had greater improvements in BMD compared to males. It is essential that future studies evaluate the dose-response of exercise training on bone health and create exercise protocols that better align with the laws of bone modelling to enhance osteogenic potential.

Effects of Exercise on Chemotherapy Completion and Hospitalization Rates: The OptiTrain Breast Cancer Trial.

BACKGROUND: Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. Despite this, few randomized controlled exercise trials have reported on such clinical endpoints. From the OptiTrain trial we previously showed positive effects on physiological and health-related outcomes after 16 weeks of supervised exercise in patients with breast cancer undergoing chemotherapy. Here, we examined the effects of exercise on rates of chemotherapy completion and hospitalization, as well as on blood cell concentrations during chemotherapy. PATIENTS AND METHODS: Two hundred forty women scheduled for chemotherapy were randomized to 16 weeks of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). Outcomes included chemotherapy completion, hospitalization, hemoglobin, lymphocyte, thrombocyte, and neutrophil concentrations during chemotherapy. RESULTS: No significant between-groups differences were found in the proportion of participants who required dose reductions (RT-HIIT vs. UC: odds ratio [OR], 1.08; AT-HIIT vs. UC: OR, 1.39), or average relative dose intensity of chemotherapy between groups (RT-HIIT vs. UC: effect size [ES], 0.08; AT-HIIT vs. UC: ES, -0.07). A significantly lower proportion of participants in the RT-HIIT group (3%) were hospitalized during chemotherapy compared with UC (15%; OR, 0.20). A significantly lower incidence of thrombocytopenia was found for both RT-HIIT (11%) and AT-HIIT (10%) versus UC (30%; OR, 0.27; OR, 0.27). CONCLUSION: No beneficial effects of either RT-HIIT or AT-HIIT on chemotherapy completion rates were found. However, combined resistance training and high-intensity interval training were effective to reduce hospitalization rates, and both exercise groups had a positive effect on thrombocytopenia. These are important findings with potential positive implications for the health of women with breast cancer and costs associated with treatment-related complications. IMPLICATIONS FOR PRACTICE: Completing the prescribed chemotherapy regimen is strongly associated with a good prognosis for patients with primary breast cancer. Despite this, treatment-induced side effects make it necessary to reduce or alter the treatment regimen and can also lead to hospitalization. Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. This study showed that combined resistance and high-intensity interval training during chemotherapy resulted in lower hospitalization rates and a lower incidence of thrombocytopenia in women with breast cancer undergoing chemotherapy. However, no beneficial effects of either exercise program on chemotherapy completion rates were found, which is in contrast to previous findings in this population. The findings reported in the current article have positive implications for the health of women with breast cancer and costs associated with treatment-related complications.

Sense of coherence and its relationship to participation, cancer-related fatigue, symptom burden, and quality of life in women with breast cancer participating in the OptiTrain exercise trial.

PURPOSE: This study examined the Sense of Coherence (SOC) of patients participating in the randomized controlled 'Optimal Training for Women with Breast Cancer' (OptiTrain) study and assessed how patient characteristics were associated with SOC. Secondary aims were to assess the association between SOC and patients' participation in this study and to determine whether SOC moderates the effect of the 16-week exercise intervention on fatigue, quality of life (QoL), and symptom burden in women with breast cancer undergoing chemotherapy. METHODS: Modified Poisson regression analyses were conducted to determine the relative risk of weak-normal SOC versus strong SOC in terms of exercise session attendance, study and intervention dropout, and long absence rates. Analyses of covariance were performed to assess whether SOC moderated the effect of the exercise intervention (pinteraction ≤ 0.10). RESULTS: Two hundred and forty women with early breast cancer (mean age 53 ± 10) participated in the OptiTrain study. Women with strong SOC reported less fatigue, lower symptom burden, and higher QoL. Women with weak-normal SOC were significantly more likely to drop out from the OptiTrain study and tended to have slightly poorer exercise session attendance. Women with breast cancer and weaker SOC benefitted as much from the exercise intervention, in terms of fatigue and QoL, as those with stronger SOC (pinteraction > 0.10). CONCLUSIONS: Strong SOC appears to be associated with a more positive subjective state of health. Women with weak-normal SOC may need additional support to encourage participation and adherence in exercise trials. Assessing SOC may assist clinicians to identify and provide extra support for participants with weak SOC, who may be less inclined to participate in exercise programs.

Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss.

PURPOSE OF REVIEW: The aim of this narrative review is to summarise recent literature on the effects of exercise and nutrition interventions alone or in combination on muscle and bone loss in people with cancer. RECENT FINDINGS: There is emerging evidence to support the inclusion of targeted exercise and nutrition strategies to counter loss of muscle and bone associated with cancer treatments. Although research in this field is advancing, the optimal exercise and nutrition prescription to combat cancer-related bone and muscle loss remain unknown. This review identifies specific components of nutrition and exercise interventions that are promising although require further exploration through studies designed to determine the effect on muscle and bone. A focused research effort is required to elucidate the full potential of exercise and nutrition intervention for people with cancer at risk of bone and muscle loss.

The non-linear relationship between sum of 7 skinfolds and fat and lean mass in elite swimmers.

Body composition can substantially impact elite swimming performance. In practice, changes in fat and lean mass of elite swimmers are estimated using body mass, sum of seven skinfolds (∑7) and lean mass index (LMI). However, LMI may be insufficiently accurate to detect small changes in body composition which could meaningfully impact swimming performance. This study developed equations which estimate dual-energy x-ray absorptiometry (DXA)-derived lean and fat mass using body mass and ∑7 data. Elite Australian swimmers (n = 44; 18 male, 26 female) completed a DXA scan and standardised body mass and ∑7 measurements. Equations to estimate DXA-derived lean and fat mass based on body mass, ∑7 and sex were developed. The relationships between ∑7, body mass and DXA-derived lean and fat mass were non-linear. Fat mass (Adjusted R2 = 0.91; standard error = 1.0 kg) and lean mass (Adjusted R2 = 0.99; standard error = 1.0 kg) equations were considered sufficiently accurate. Lean mass estimates outperformed the LMI in identifying the correct direction of change in lean mass (82% correct; LMI 71%). Using the accurate estimations produced by these equations will enhance the prescription and evaluation of programmes to optimise the body composition and subsequent performance in swimmers.

Two-year follow-up of the OptiTrain randomised controlled exercise trial.

PURPOSE: The aim of this study was to determine if there were any differences in health-related outcomes and physical activity (PA) between the two OptiTrain exercise groups and usual care (UC), 2 years post-baseline. METHODS: The OptiTrain study was a three-arm randomised controlled trial comparing 16 weeks of concurrent aerobic high-intensity interval training (HIIT) and progressive resistance exercise (RT-HIIT) or concurrent HIIT and continuous moderate-intensity aerobic exercise (AT-HIIT) to UC in 206 patients with breast cancer undergoing chemotherapy. Eligible participants were approached 2 years following baseline to assess cancer-related fatigue, quality of life, symptoms, muscle strength, cardiorespiratory fitness, body mass, PA, sedentary behaviour, and sick leave. RESULTS: The RT-HIIT group reported lower total cancer-related fatigue, (- 1.37, 95% CI - 2.70, - 0.04, ES = - 0.06) and cognitive cancer-related fatigue (- 1.47, 95% CI - 2.75, - 0.18, ES = - 0.28), and had higher lower limb muscle strength (12.09, 95% CI 3.77, 20.40, ES = 0.52) than UC at 2 years. The AT-HIIT group reported lower total symptoms (- 0.23, 95% CI - 0.42, - 0.03, ES = - 0.15), symptom burden (- 0.30, 95% CI - 0.60, - 0.01, ES = - 0.19), and body mass - 2.15 (- 3.71, - 0.60, ES = - 0.28) than UC at 2 years. CONCLUSION: At 2 years, the exercise groups were generally experiencing positive differences in cancer-related fatigue (RT-HIIT), symptoms (AT-HIIT), and muscle strength (RT-HIIT) to UC. The findings provide novel evidence that being involved in an exercise program during chemotherapy can have long-term benefits for women with breast cancer, but that strategies are needed to create better pathways to support patients to maintain physical activity levels. TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT02522260. Trial registered on 9 June 2015. https://clinicaltrials.gov/ct2/show/NCT02522260 . Retrospectively registered.

Peer support for the maintenance of physical activity and health in cancer survivors: the PEER trial - a study protocol of a randomised controlled trial.

BACKGROUND: Despite an overwhelming body of evidence showing the benefits of physical activity (PA) and exercise for cancer survivors, few survivors meet the exercise oncology guidelines. Moreover, initiating, let alone maintaining exercise programs with cancer survivors continues to have limited success. The aim of this trial is to evaluate the influence of peer support on moderate-to-vigorous PA (MVPA) and various markers of health 12 months following a brief supervised exercise intervention in cancer survivors. METHODS: Men and women previously diagnosed with histologically-confirmed breast, colorectal or prostate cancer (n = 226), who are >1-month post-treatment, will be invited to participate in this trial. Once enrolled, participants will complete 4 weeks (12 sessions) of supervised high intensity interval training (HIIT). On completion of the supervised phase, both groups will be provided with written recommendations and verbally encouraged to achieve three HIIT sessions per week, or equivalent exercise that meets the exercise oncology guidelines. Participants will be randomly assigned to receive 12 months of peer support, or no peer support (control). Primary and secondary outcomes will be assessed at baseline, after the 4-week supervised HIIT phase and at 3-, 6- and 12-months. Primary outcomes will include accelerometry-derived MVPA and prescribed HIIT session adherence; whilst secondary outcomes will include cardiorespiratory fitness ([Formula: see text]), body composition, quality of life and select cytokines, myokines and inflammatory markers. Random effects mixed modelling will be used to compare mean changes in outcomes between groups at each time point. A group x time interaction will be used to formally test for differences between groups (alpha =0.05); utilising intention-to-treat analyses. DISCUSSION: If successful, peer support may be proposed, adopted and implemented as a strategy to encourage cancer survivors to maintain exercise beyond the duration of a short-term, supervised intervention. A peer support-exercise model has the long-term potential to reduce comorbidities, improve physical and mental wellbeing, and significantly reduce the burden of disease in cancer survivors. ETHICS: Human Research Ethics Committee of Bellberry Ltd. (#2015-12-840). TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry 12618001855213 . Retrospectively registered 14 November 2018. Trial registration includes all components of the WHO Trial Registration Data Set, as recommended by the ICMJE.

Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer: the OptiTrain randomized controlled trial.

PURPOSE: Exercise training is an effective and safe way to counteract cancer-related fatigue (CRF) and to improve health-related quality of life (HRQoL). High-intensity interval training has proven beneficial for the health of clinical populations. The aim of this randomized controlled trial was to compare the effects of resistance and high-intensity interval training (RT-HIIT), and moderate-intensity aerobic and high-intensity interval training (AT-HIIT) to usual care (UC) in women with breast cancer undergoing chemotherapy. The primary endpoint was CRF and the secondary endpoints were HRQoL and cancer treatment-related symptoms. METHODS: Two hundred and forty women planned to undergo chemotherapy were randomized to supervised RT-HIIT, AT-HIIT, or UC. Measurements were performed at baseline and at 16 weeks. Questionnaires included Piper Fatigue Scale, EORTC-QLQ-C30, and Memorial Symptom Assessment Scale. RESULTS: The RT-HIIT group was superior to UC for CRF: total CRF (p = 0.02), behavior/daily life (p = 0.01), and sensory/physical (p = 0.03) CRF. Role functioning significantly improved while cognitive functioning was unchanged for RT-HIIT compared to declines shown in the UC group (p = 0.04). AT-HIIT significantly improved emotional functioning versus UC (p = 0.01) and was superior to UC for pain symptoms (p = 0.03). RT-HIIT reported a reduced symptom burden, while AT-HIIT remained stable compared to deteriorations shown by UC (p < 0.01). Only RT-HIIT was superior to UC for total symptoms (p < 0.01). CONCLUSIONS: 16 weeks of resistance and HIIT was effective in preventing increases in CRF and in reducing symptom burden for patients during chemotherapy for breast cancer. These findings add to a growing body of evidence supporting the inclusion of structured exercise prescriptions, including HIIT, as a vital component of cancer rehabilitation. TRIAL REGISTRATION: Clinicaltrials.gov Registration Number: NCT02522260.

Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial.

BACKGROUND: Advanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy. METHODS: Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT-HIIT, or UC. OUTCOMES: cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold. RESULTS: Pre- to post-intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs. UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT-HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = - 0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT (trapezius: ES = 0.30). CONCLUSION: Sixteen weeks of RT-HIIT significantly improved muscle strength and reduced pain sensitivity. Both exercise programs were well tolerated and were equally efficient in preventing increases in body mass and in preventing declines in cardiorespiratory fitness. These results highlight the importance of implementing a combination of resistance and high-intensity interval training during chemotherapy for women with breast cancer.

The Osteogenic Effect of Impact-Loading and Resistance Exercise on Bone Mineral Density in Middle-Aged and Older Men: A Pilot Study.

BACKGROUND: Regular exercise has been recommended as a potential strategy to counteract the age-related bone loss experienced by men; however, the optimal exercise prescription is not known. OBJECTIVE: To perform a pilot study to examine the osteogenic effect, safety and feasibility of a combined program of upper body resistance exercise and two doses of impact-loading exercise on bone mineral density (BMD) of middle-aged and older men. METHODS: Forty-two community-dwelling men aged 50-74 years were randomly assigned to either an exercise program of combined upper body resistance exercise and either high-dose impact-loading (HI; 80 jumps per session) or moderate-dose impact-loading (MOD; 40 jumps per session) or a control (CON) group. The 9-month intervention involved 4 sessions each week: 2 supervised clinic-based and 2 home-based. BMD of the lumbar spine, femoral neck, total hip, trochanter and whole body as well as lean and fat mass were assessed at baseline and 9 months by dual-energy X-ray absorptiometry. Bone turnover markers, hormone levels, physical function and muscle strength were also assessed. RESULTS: Following 9 months of training, significant differences in BMD among groups were found at the total hip (p = 0.010) and trochanter (p = 0.047) with BMD in the MOD group decreasing relative to the HI group. Although not significant, the HI group consistently preserved BMD, whereas BMD of the MOD and CON groups declined at the hip sites. Mean change for all groups at all skeletal sites was approximately within ±1%. There was no change in bone turnover markers. There were no adverse events as a result of the intervention; however, overall attendance for the HI and MOD groups was 53% (clinic: 68%, home: 38%) and 65% (clinic: 74%, home: 55%), respectively. CONCLUSIONS: This study indicates that while impact-loading exercise can be safely undertaken in middle-aged and older men, the current combined program did not elicit significant improvements in BMD.

Concurrent and predictive validity of physical activity measurement items commonly used in clinical settings--data from SCAPIS pilot study.

BACKGROUND: As the understanding of how different aspects of the physical activity (PA) pattern relate to health and disease, proper assessment is increasingly important. In clinical care, self-reports are the most commonly used assessment technique. However, systematic comparisons between questions regarding concurrent or criterion validity are rare, as are measures of predictive validity. The aim of the study was to examine the concurrent (using accelerometry as reference) and predictive validity (for metabolic syndrome) of five PA questions. METHODS: A sample of 948 middle-aged Swedish men and women reported their PA patterns via five different questions and wore an accelerometer (Actigraph GT3X) for a minimum of 4 days. Concurrent validity was assessed as correlations and ROC-analyses. Predictive validity was assessed using logistic regression, controlling for potential confounders. RESULTS: Concurrent validity was low-to-moderate (r <0.35 and ROC AUC <0.7) with large misclassifications regarding time spent sitting/sedentary and in moderate-to vigorous PA. The predictive validity of the questions was good, and one question (PHAS) showed an 80 % decreased odds-ratio of having metabolic syndrome, after taking potential confounders into consideration. DISCUSSION: In this mixed sample of adults, both concurrent and predictive validity vaired between items and between measures of the physical activity pattern. The PHAS and WALK items are proposed for assessment of adherence to PA recommendations. CONCLUSION: Assessing PA patterns using self-report measures results in methodological problems when trying to predict individual risk for the metabolic syndrome, as the concurrent validity generally was low. However, several of the investigated questions may be useful for assessing risk at a group level, showing better predictive validity.

Distance-based delivery of exercise for people treated for breast, prostate or colorectal cancer: a study protocol for a randomised controlled trial of EX-MED Cancer Sweden.

BACKGROUND: Regular exercise has been shown to have beneficial health effects in cancer survivors, including improving quality of life and other important health outcomes. However, providing people with cancer with easily accessible, high-quality exercise support and programs is a challenge. Therefore, there is a need to develop easily accessible exercise programs that draw upon the current evidence. Supervised, distance-based exercise programs have the benefit of reaching out to many people whilst providing the support of an exercise professional. The aim of the EX-MED Cancer Sweden trial is to examine the effectiveness of a supervised, distance-based exercise program, in people previously treated for breast, prostate, or colorectal cancer, on health-related quality of life (HRQoL), as well as other physiological and patient-reported health outcomes. METHODS: The EX-MED Cancer Sweden trial is a prospective randomised controlled trial including 200 people that have completed curative treatment for breast, prostate, or colorectal cancer. Participants are randomly allocated to an exercise group or a routine care control group. The exercise group will participate in a supervised, distanced-based exercise program delivered by a personal trainer who has undertaken specialised exercise oncology education modules. The intervention consists of a combination of resistance and aerobic exercises with participants completing two 60-min sessions per week for 12 weeks. The primary outcome is HRQoL (EORTC QLQ-C30) assessed at baseline, 3- (end of intervention and primary endpoint) and 6-months post-baseline. Secondary outcomes are physiological (cardiorespiratory fitness, muscle strength, physical function, body composition) and patient-reported outcomes (cancer-related symptoms, fatigue, self-reported physical activity), and self-efficacy of exercise. Furthermore, the trial will explore and describe the experiences of participation in the exercise intervention. DISCUSSION: The EX-MED Cancer Sweden trial will provide evidence regarding the effectiveness of a supervised, distance-based exercise program for survivors of breast, prostate, and colorectal cancer. If successful, it will contribute to the implementation of flexible and effective exercise programs as part of the standard of care for people following cancer treatment, which is likely to contribute to a reduction in the burden of cancer on the individual, health care system and society. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05064670. Registered on October 1, 2021.

Association Between Cardiorespiratory Fitness and Cancer Incidence and Cancer-Specific Mortality of Colon, Lung, and Prostate Cancer Among Swedish Men.

Importance: Cardiorespiratory fitness (CRF) levels appear to be an important risk factor for cancer incidence and death. Objectives: To examine CRF and prostate, colon, and lung cancer incidence and mortality in Swedish men, and to assess whether age moderated any associations between CRF and cancer. Design, Setting, and Participants: A prospective cohort study was conducted in a population of men who completed an occupational health profile assessment between October 1982 and December 2019 in Sweden. Data analysis was performed from June 22, 2022, to May 11, 2023. Exposure: Cardiorespiratory fitness was assessed as maximal oxygen consumption, estimated using a submaximal cycle ergometer test. Main Outcomes and Measures: Data on prostate, colon, and lung cancer incidence and mortality were derived from national registers. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression. Results: Data on 177 709 men (age range, 18-75 years; mean [SD] age, 42 [11] years; mean [SD] body mass index, 26 [3.8]) were analyzed. During a mean (SD) follow-up time of 9.6 (5.5) years, a total of 499 incident cases of colon, 283 of lung, and 1918 of prostate cancer occurred, as well as 152 deaths due to colon cancer, 207 due to lung cancer, and 141 deaths due to prostate cancer. Higher levels of CRF (maximal oxygen consumption as milliliters per minute per kilogram) were associated with a significantly lower risk of colon (HR, 0.98, 95% CI, 0.96-0.98) and lung cancer (HR, 0.98; 95% CI, 0.96-0.99) incidence, and a higher risk of prostate cancer incidence (HR, 1.01; 95% CI, 1.00-1.01). Higher CRF was associated with a lower risk of death due to colon (HR, 0.98; 95% CI, 0.96-1.00), lung (HR, 0.97; 95% CI, 0.95-0.99), and prostate (HR, 0.95; 95% CI, 0.93-0.97) cancer. After stratification into 4 groups and in fully adjusted models, the associations remained for moderate (>35-45 mL/min/kg), 0.72 (0.53-0.96) and high (>45 mL/min/kg), 0.63 (0.41-0.98) levels of CRF, compared with very low (<25 mL/min/kg) CRF for colon cancer incidence. For prostate cancer mortality, associations remained for low (HR, 0.67; 95% CI, 0.45-1.00), moderate (HR, 0.57; 95% CI, 0.34-0.97), and high (HR, 0.29; 95% CI, 0.10-0.86) CRF. For lung cancer mortality, only high CRF (HR, 0.41; 95% CI, 0.17-0.99) was significant. Age modified the associations for lung (HR, 0.99; 95% CI, 0.99-0.99) and prostate (HR, 1.00; 95% CI, 1.00-1.00; P < .001) cancer incidence, and for death due to lung cancer (HR, 0.99; 95% CI, 0.99-0.99; P = .04). Conclusions and Relevance: In this cohort of Swedish men, moderate and high CRF were associated with a lower risk of colon cancer. Low, moderate, and high CRF were associated with lower risk of death due to prostate cancer, while only high CRF was associated with lower risk of death due to lung cancer. If evidence for causality is established, interventions to improve CRF in individuals with low CRF should be prioritized.

Harms of exercise training in patients with cancer undergoing systemic treatment: a systematic review and meta-analysis of published and unpublished controlled trials.

Background: Exercise is recommended for people with cancer. The aim of this study was to evaluate the harms of exercise in patients with cancer undergoing systemic treatment. Methods: This systematic review and meta-analysis included published and unpublished controlled trials comparing exercise interventions versus controls in adults with cancer scheduled to undergo systemic treatment. The primary outcomes were adverse events, health-care utilization, and treatment tolerability and response. Eleven electronic databases and trial registries were systematically searched with no date or language restrictions. The latest searches were performed on April 26, 2022. The risk of bias was judged using RoB2 and ROBINS-I, and the certainty of evidence for primary outcomes was assessed using GRADE. Data were statistically synthesised using pre-specified random-effect meta-analyses. The protocol for this study was registered in the PROESPERO database (ID: CRD42021266882). Findings: 129 controlled trials including 12,044 participants were eligible. Primary meta-analyses revealed evidence of a higher risk of some harms, including serious adverse events (risk ratio [95% CI]: 1.87 [1.47-2.39], I2 = 0%, n = 1722, k = 10), thromboses (risk ratio [95% CI]: 1.67 [1.11-2.51], I2 = 0%, n = 934, k = 6), and fractures (risk ratio [95% CI]: 3.07 [3.03-3.11], I2 = 0%, n = 203, k = 2) in intervention versus control. In contrast, we found evidence of a lower risk of fever (risk ratio [95% CI]: 0.69 [0.55-0.87], I2 = 0% n = 1109, k = 7) and a higher relative dose intensity of systemic treatment (difference in means [95% CI]: 1.50% [0.14-2.85], I2 = 0% n = 1110, k = 13) in intervention versus control. For all outcomes, we downgraded the certainty of evidence due to imprecision, risk of bias, and indirectness, resulting in very low certainty of evidence. Interpretation: The harms of exercise in patients with cancer undergoing systemic treatment are uncertain, and there is currently insufficient data on harms to make evidence-based risk-benefits assessments of the application of structured exercise in this population. Funding: There was no funding for this study.

Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial.

INTRODUCTION: In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT. METHOD: The Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582). EXPECTED RESULTS: If Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources.

Exercise Recommendation for People With Bone Metastases: Expert Consensus for Health Care Providers and Exercise Professionals.

PURPOSE: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. METHODS: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. RESULTS: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment-related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. CONCLUSION: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases.

Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life: the EFFECT study.

BACKGROUND: Many patients with metastatic breast cancer experience cancer- and treatment-related side effects that impair activities of daily living and negatively affect the quality of life. There is a need for interventions that improve quality of life by alleviating fatigue and other side effects during palliative cancer treatment. Beneficial effects of exercise have been observed in the curative setting, but, to date, comparable evidence in patients with metastatic breast cancer is lacking. The aim of this study is to assess the effects of a structured and individualized 9-month exercise intervention in patients with metastatic breast cancer on quality of life, fatigue, and other cancer- and treatment-related side effects. METHODS: The EFFECT study is a multinational, randomized controlled trial including 350 patients with metastatic breast cancer. Participants are randomly allocated (1:1) to an exercise or control group. The exercise group participates in a 9-month multimodal exercise program, starting with a 6-month period where participants exercise twice a week under the supervision of an exercise professional. After completing this 6-month period, one supervised session is replaced by one unsupervised session for 3 months. In addition, participants are instructed to be physically active for ≥30 min/day on all remaining days of the week, while being supported by an activity tracker and exercise app. Participants allocated to the control group receive standard medical care, general written physical activity advice, and an activity tracker, but no structured exercise program. The primary outcomes are quality of life (EORTC QLQ-C30, summary score) and fatigue (EORTC QLQ-FA12), assessed at baseline, 3, 6 (primary endpoint), and 9 months post-baseline. Secondary outcomes include physical fitness, physical performance, physical activity, anxiety, depression, pain, sleep problems, anthropometric data, body composition, and blood markers. Exploratory outcomes include quality of working life, muscle thickness, urinary incontinence, disease progression, and survival. Additionally, the cost-effectiveness of the exercise program is assessed. Adherence and safety are monitored throughout the intervention period. DISCUSSION: This large randomized controlled trial will provide evidence regarding the (cost-) effectiveness of exercise during treatment of metastatic breast cancer. If proven (cost-)effective, exercise should be offered to patients with metastatic breast cancer as part of standard care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04120298 . Registered on October 9, 2019.

High intensity exercise during breast cancer chemotherapy - effects on long-term myocardial damage and physical capacity - data from the OptiTrain RCT.

BACKGROUND: Adjuvant systemic breast cancer treatment improves disease specific outcomes, but also presents with cardiac toxicity. In this post-hoc exploratory analysis of the OptiTrain trial, the effects of exercise on cardiotoxicity were monitored by assessing fitness and biomarkers over the intervention and into survivorship. Methods; Women starting chemotherapy were randomized to 16-weeks of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). Outcome measures included plasma troponin-T (cTnT), Nt-pro-BNP and peak oxygen uptake (VO2peak), assessed at baseline, post-intervention, and at 1- and 2-years. RESULTS: For this per-protocol analysis, 88 women met criteria for inclusion. Plasma cTnT increased in all groups post-intervention. At the 1-year follow-up, Nt-pro-BNP was lower in the exercise groups compared to UC. At 2-years there was a drop in VO2peak for patients with high cTnT and Nt-pro-BNP. Fewer patients in the RT-HIIT group fulfilled biomarker risk criteria compared to UC (OR 0.200; 95% CI = 0.055-0.734). CONCLUSIONS: In this cohort, high-intensity exercise was associated with lower levels of NT-proBNP 1-year post-baseline, but not with cTnT directly after treatment completion. This may, together with the preserved VO2peak in patients with low levels of biomarkers, indicate a long-term cardioprotective effect of exercise. TRIAL REGISTRATION: Clinicaltrials. govNCT02522260 , Registered 13th of august 2015 - Retrospectively Registered.