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Natural killer (NK) cells are a population of innate immune cells known to play a pivotal role against tumor spread. In multiple murine models, it was shown that physical exercise had the potential to increase NK cell antitumor activity through their mobilization and tissue redistribution in an interleukin (IL)‐6 and epinephrine‐dependent manner. The translation of this finding to patients is unclear. In this randomized pilot trial, we analyzed blood samples of patients with resectable breast or colon cancer who were randomized into an evidence‐based moderate‐high intensity resistance and aerobic exercise intervention (n = 8) or a control group (n = 6) during the first 9–12 weeks of (neo)adjuvant chemotherapy. In this pilot, we did not solely focus on statistical significance, but also explored whether average between‐group differences reached 10%. NK cell degranulation was preserved in the exercise group whereas it decreased in the control group resulting in a between‐group difference of 11.4% CD107a+ degranulated NK cells (95%CI = 0.57;22.3, p = 0.04) in the presence and 13.8% (95%CI = −2.5;30.0, p = 0.09) in the absence of an anti‐epidermal growth factor receptor monoclonal antibody (EGFR‐mAb). In line, the between‐group difference of tumor cell lysis was 7.4% (95%CI = −9.1;23.9, p = 0.34), and 13.7% (95%CI = −10.1;37.5, p = 0.23) in favor of the exercise group in the presence or absence of EGFR mAb, respectively. Current explorative analyses showed that exercise during (neo)adjuvant chemotherapy may benefit NK cell activity. Future studies with a larger sample size are needed to confirm this finding and to establish its clinical potential. Trial registration: Dutch trial register number NTR4105. [ABSTRACT FROM AUTHOR]

Exercise during cancer treatment improves cancer‐related fatigue (CRF), but the importance of exercise intensity for CRF is unclear. We compared the effects of high‐ vs low‐to‐moderate‐intensity exercise with or without additional behavior change support (BCS) on CRF in patients undergoing (neo‐)adjuvant cancer treatment. This was a multicenter, 2x2 factorial design randomized controlled trial (Clinical Trials NCT02473003) in Sweden. Participants recently diagnosed with breast (n = 457), prostate (n = 97) or colorectal (n = 23) cancer undergoing (neo‐)adjuvant treatment were randomized to high intensity (n = 144), low‐to‐moderate intensity (n = 144), high intensity with BCS (n = 144) or low‐to‐moderate intensity with BCS (n = 145). The 6‐month exercise intervention included supervised resistance training and home‐based endurance training. CRF was assessed by Multidimensional Fatigue Inventory (MFI, five subscales score range 4‐20), and Functional Assessment of Chronic Illness Therapy‐Fatigue scale (FACIT‐F, score range 0‐52). Multiple linear regression for main factorial effects was performed according to intention‐to‐treat, with post‐intervention CRF as primary endpoint. Overall, 577 participants (mean age 58.7 years) were randomized. Participants randomized to high‐ vs low‐to‐moderate‐intensity exercise had lower physical fatigue (MFI Physical Fatigue subscale; mean difference −1.05 [95% CI: −1.85, −0.25]), but the difference was not clinically important (ie <2). We found no differences in other CRF dimensions and no effect of additional BCS. There were few minor adverse events. For CRF, patients undergoing (neo‐)adjuvant treatment for breast, prostate or colorectal cancer can safely exercise at high‐ or low‐to‐moderate intensity, according to their own preferences. Additional BCS does not provide extra benefit for CRF in supervised, well‐controlled exercise interventions. [ABSTRACT FROM AUTHOR]

Background: This pilot trial explores the feasibility of measuring muscle contractile properties in patients with cancer, effects of exercise during chemotherapy on muscle contractile properties and the association between changes in contractile muscle properties and perceived fatigue. Method: Patients who received (neo)adjuvant chemotherapy for breast or colon cancer were randomized to a 9‐12 week exercise intervention or a waitlist‐control group. At baseline and follow‐up, we measured knee extensor strength using maximal voluntary contraction (MVC), contractile muscle properties of the quadriceps muscle using electrical stimulation, and perceived fatigue using the Multidimensional Fatigue Inventory. Feasibility was assessed by the proportion of patients who successfully completed measurements of contractile muscle properties. Exercise effects on muscle contractile properties were explored using linear regression analyses. Between‐group differences >10% were considered potentially relevant. Pearson correlation (rp) of changes in contractile muscle properties and changes in perceived fatigue was calculated. Results: Twenty two of 30 patients completed baseline and follow‐up assessments. Measurements of contractile properties were feasible except for muscle fatigability. We found a potentially relevant between‐group difference in the rate of force development favoring the intervention group (1192 N/s, 95% CI = −335; 2739). Change in rate of force development was negatively correlated with change in perceived general (rp = −0.54, P =.04) and physical (rp = −0.59, P =.02) fatigue. Conclusion: Chemotherapy induces a decrease in the rate of force development, which may reflect a larger loss in type II muscle fibers. This may be attenuated with (resistance) exercise. The increase in the rate of force development was related to a decrease in perceived fatigue. [ABSTRACT FROM AUTHOR]

The aims of the present systematic review and meta‐analysis were to investigate the effect of exercise on maximal oxygen uptake (V˙O2max) and to investigate whether exercise frequency, intensity, duration, and volume are associated with changes in V˙O2max among adult patients with cancer undergoing treatment. Medline and Embase through OvidSP were searched to identify randomized controlled trials. Two reviewers extracted data and assessed the risk of bias. The overall effect size and differences in effects for different intensities and frequencies were calculated on change scores and post‐intervention V˙O2max data, and the meta‐regression of exercise duration and volumes was analyzed using the Comprehensive Meta‐Analysis software. Fourteen randomized controlled trials were included in the systematic review, comprising 1332 patients with various cancer types receiving (neo‐)adjuvant chemo‐, radio‐, and/or hormone therapy. Exercise induced beneficial changes in V˙O2max compared to usual care (effect size = 0.46, 95% Confidence Interval = 0.23‐0.69). Longer session duration (P = 0.020), and weekly duration (P = 0.010), larger weekly volume (P < 0.001), and shorter intervention duration (P = 0.005) were significantly associated with more beneficial changes in V˙O2max. No differences in effects between subgroups with respect to frequency and intensity were found. In conclusion, exercise has beneficial effects on V˙O2max in patients with cancer undergoing (neo‐)adjuvant treatment. As interventions with larger exercise volumes and longer session durations resulted in larger beneficial changes in V˙O2max, exercise frequency, intensity, and duration should be considered carefully for sufficient exercise volume to induce changes in V˙O2max for this patient group. [ABSTRACT FROM AUTHOR]

Objectives: To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year‐long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. Patients and Methods: In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short‐term) or 18 months (long‐term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6‐month home‐based maintenance programme, or to printed physical activity educational material for 12 months across 13 university‐affiliated exercise clinics in Australia and New Zealand. The participants were long‐term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X‐ray absorptiometry. Data were analysed using generalized estimating equations. Results: Time on ADT significantly moderated the exercise effects on chair rise (βinteraction = −1.3 s, 95% confidence interval [CI] −2.6 to 0.0), whole‐body lean mass (βinteraction = 1194 g, 95% CI 234 to 2153) and ASM mass (βinteraction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (βinteraction = −1107 g, 95% CI −2346 to 132), with greater benefits for men previously on long‐term ADT. At 6 months, the intervention effects on chair rise time −1.5 s (95% CI −2.5 to −0.5), whole‐body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass −1377 g (95% CI −2156 to −598) were significant for men previously on long‐term ADT, but not for men on short‐term ADT. At 12 months, the intervention effects for men on long‐term ADT remained significant for the chair rise, with improved performance (−2.0 s, 95% CI −3.0 to −1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. Conclusions: Men with PCa previously treated long‐term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short‐term ADT exposure. As a result, men who were formerly on long‐term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment‐related adverse effects. [ABSTRACT FROM AUTHOR]

Background Cancer-related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF. Methods A total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-fatigue questionnaire (cut-off for fatigue <34). Multiple linear regression analyses were conducted to study the association between SMI and CRF adjusting for relevant confounders. Results In this group of patients with advanced cancer, the median fatigue score was 36 (interquartile range 26-44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B − 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy-fatigue score was found ( n = 82). Conclusions The association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: Only between 25% and 50% of patients invited to participate in clinical trial-based physical exercise programs during cancer treatment agree to do so. The purpose of this study was to identify factors associated significantly with the decision (not) to participate in a randomized controlled trial of physical exercise during adjuvant chemotherapy for breast cancer.Methods: Based on questionnaire data, we compared trial participants and non-participants on a range of sociodemographic, clinical health-related, practical, behavioral, and attitudinal variables.Results: Two hundred thirty of 524 patients agreed to participate in the trial (44%). The 294 (56%) non-participants indicated that they wanted to exercise on their own or that they did not wish to exercise in the context of a trial. Those who preferred to exercise on their own were relatively similar to trial participants but were more likely to be in the maintenance exercise stage. Those non-participants who did not wish to exercise had a significantly lower level of education, were less likely to be working, reported more fatigue and lower health-related quality of life, had lower sense of self-efficacy, more negative attitudes towards exercise, less social support, and perceived fewer benefits and more barriers to exercising during treatment than trial participants.Conclusion: Minimizing practical barriers to participation, providing educational materials on the potential benefits of exercise, and giving adequate professional and social network encouragement may increase the number of patients willing to exercise during treatment and to participate in such studies. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND The current study examined effects, moderators (for whom), and mediators (working mechanisms) of 12 months of exercise on health-related quality of life (HRQoL) in older long-term survivors of prostate cancer. METHODS In total, 100 men aged 71.7 years (standard deviation, 6.4 years) were randomly assigned to 6 months of supervised aerobic and resistance exercise followed by 6 months of a home-based exercise maintenance program (EX group) or printed education material regarding physical activity for 12 months (PA group). Assessments took place at baseline and after 6 and 12 months. Generalized estimating equations were used to study the effects of EX versus PA on HRQoL at 6 and 12 months, adjusting for baseline HRQoL. The authors examined potential sociodemographic and clinical moderators by adding interaction terms, and potential physical and psychological mediators using the product-of-coefficients test. RESULTS At 6 months, significant beneficial effects were found for global QoL, physical function, and social function in the EX group compared with the PA group. For physical function, beneficial effects were sustained at 12 months. Moderation analyses demonstrated larger effects of EX versus PA for patients who were married, started exercising sooner after their diagnosis, and previously used bisphosphonates. Changes in lower body functional performance significantly mediated the effect of EX on global QoL, physical function, and social function. No mediating effects on HRQoL were found for aerobic fitness, physical activity, fatigue, distress, or falls self-efficacy. CONCLUSIONS Aerobic and resistance exercise appears to have beneficial effects on HRQoL among older, long-term survivors of prostate cancer. Effects were moderated by marital status, time since diagnosis, and use of bisphosphonates, and were mediated by lower body functional performance. Cancer 2015;121:2821-2830. © 2015 American Cancer Society [ABSTRACT FROM AUTHOR]

BACKGROUND The objective of the current study was to identify mediators of the effects of a combined resistance and aerobic exercise program on perceived physical and general health in men undergoing androgen deprivation therapy for prostate cancer. METHODS In total, 57 patients with prostate cancer undergoing androgen deprivation therapy were randomly assigned to 12 weeks of resistance and aerobic exercise or usual care. The outcome measures of physical and general health were assessed by standardized questionnaires. Linear regression analyses were conducted on the residual change scores of the variables. The mediating effects of fatigue, muscle strength, and functional performance on the intervention's effect on physical and general health were examined using the product of coefficients method. Bootstrapping was used to calculate the 95% confidence intervals (95% CIs). RESULTS The exercise intervention was found to significantly improve physical (beta, 5.03; 95% CI, 1.01-9.04) and general health (beta, 12.89; 95% CI, 2.24-23.54). Upper body muscle strength and walking speed significantly mediated the intervention effect on physical health (beta, 2.65; 95% CI, 0.64-5.54), accounting for 53% of the total effect. Walking speed and fatigue were found to be mediators in the intervention effect on general health (beta, 7.52; 95% CI, 2.16-16.92), accounting for 51% of the total effect. CONCLUSIONS The intervention effects on physical and general health were explained by different mediating mechanisms. Walking speed mediated the intervention effect on both physical and general health. The intervention effect on physical health was further mediated by upper body strength, whereas the effect on general health was mediated by fatigue. Cancer 2014;120:294-301. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

This study aimed to describe participation and health-related quality of life (HRQoL) in adolescents and young adults with myelomeningocele and to explore their relationships with lifestyle-related factors. Fifty-one individuals with a mean age of 21 years 1 month (SD 4y 6mo) years participated (26 males, 25 females; 82% hydrocephalus, 55% wheelchair-dependent). Participation was assessed using the Life Habits Questionnaire, and HRQoL was assessed using the Medical Outcomes Study 36-item Short-form Health Survey. Physical activity was measured using an accelerometry-based activity monitor, fitness (peak oxygen uptake) was measured during a maximal exercise test, and the sum of four skin-folds was assessed to indicate body fat. Relationships were studied using logistic regression analyses. Of the participants, 63% had difficulties in daily activities and 59% in social roles. Participants perceived lower physical HRQoL than a Dutch reference population. Participants with higher levels of physical activity and fitness had fewer difficulties in participating in daily activities (odds ratio [OR]=8.8, p=0.02 and OR=29.7, p=0.02 respectively) and a higher physical HRQoL (OR=4.8, p=0.02 and OR=30.2, p=0.006 respectively), but not mental HRQoL. Body fat was not related to participation or HRQoL. In conclusion, a large proportion of individuals with myelomeningocele had difficulties in participation and perceived low physical HRQoL. Higher levels of physical activity and fitness were related to fewer difficulties in participation and higher physical HRQoL. [ABSTRACT FROM AUTHOR]