Supervised, structured and individualized exercise in metastatic breast cancer: a randomized controlled trial.

Physical exercise both during and after curative cancer treatment has been shown to reduce side effects. Evidence in the metastatic cancer setting is scarce, and interventions that improve health-related quality of life (HRQOL) are much needed for patients with metastatic breast cancer (MBC). The multinational randomized controlled PREFERABLE-EFFECT trial assessed the effects of exercise on fatigue and HRQOL in patients with MBC. In total, 357 patients with MBC and a life expectancy of ≥6 months but without unstable bone metastases were recruited at eight study centers across five European countries and Australia. Participants were randomly assigned (1:1) to usual care (control group, n = 179) or a 9-month supervised exercise program (exercise group, n = 178). Intervention effects on physical fatigue (European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-FA12 scale) and HRQOL (EORTC QLQ-C30 summary score) were determined by comparing the change from baseline to 3, 6 (primary timepoint) and 9 months between groups using mixed models for repeated measures, adjusted for baseline values of the outcome, line of treatment (first or second versus third or higher) and study center. Exercise resulted in significant positive effects on both primary outcomes. Physical fatigue was significantly lower (-5.3 (95% confidence interval (CI), -10.0 to -0.6), Bonferroni-Holm-adjusted P = 0.027; Cohen's effect size, 0.22) and HRQOL significantly higher (4.8 (95% CI, 2.2-7.4), Bonferroni-Holm-adjusted P = 0.0003; effect size, 0.33) in the exercise group than in the control group at 6 months. Two serious adverse events occurred (that is, fractures), but both were not related to bone metastases. These results demonstrate that supervised exercise has positive effects on physical fatigue and HRQOL in patients with MBC and should be recommended as part of supportive care.ClinicalTrials.gov Identifier: NCT04120298 .

Effects of Exercise-Induced Changes in Myokine Expression on the Tumor Microenvironment.

In this narrative review, we summarize the direct and indirect effects that myokines have on the tumor microenvironment. We took studies of various cancer types and species into account. Systematic reviews and meta-analyses that matched the search terms were also considered. We searched databases for six months. As a narrative approach was chosen, no data was analyzed or reanalyzed. The goal of this narrative review is to create an overview on the topic to identify research gaps and answer the questions as to whether myokine expression may be relevant in cancer research in regard to the tumor microenvironment. Six commonly known myokines were chosen. We found strong links between the influence exercise has on interleukin-6, oncostatin M, secreted protein acidic and rich in cysteine, and irisin in the context of tumor progression and inhibition via interactions with the tumor microenvironment. It became clear that the effects of myokines on the tumor microenvironment can vary and contribute to disease progression or regression. Interactions among myokines and immune cells must also be considered and require further investigation. To date, no study has shown a clear connection, while multiple studies suggest further investigation of the topic, similar to the effects of exercise on myokine expression.

Perspectives of patients with metastatic breast cancer on physical exercise programs: results from a survey in five European countries.

BACKGROUND: To successfully implement exercise programs for patients with metastatic breast cancer (MBC), services and patient education should consider patients' knowledge, preferences, values, and goals. Hence, gaining insight into their perspectives on exercise and exercise programming is important. METHOD: In this cross-sectional survey, we recruited patients with MBC from the Netherlands, Germany, Poland, Spain, and Sweden. We collected data on patients' knowledge and skills about exercise and outcome expectations. We identified barriers to and facilitators of participation in exercise programs, and patients' preferences for program content and modes of exercise delivery. RESULTS: A total of 420 patients participated in the survey. Respondents were, on average, 56.5 years old (SD 10.8) and 70% had bone metastases. Sixty-eight percent reported sufficient skills to engage in aerobic exercise, but only 35% did so for resistance exercise. Respondents expected exercise to have multiple physical benefits, but a few patients expected exercise to worsen their pain (5%). Not having access to an exercise program for cancer patients (27%), feeling too tired (23%), and/or weak (23%) were the most often reported barriers. Facilitators for exercising regularly were previous positive physical (72%) and emotional (68%) experiences with exercising, and receiving personalized advice from a physiotherapist or sport/fitness instructor (62%). Patients were most interested in walking and preferred exercising at a public gym, although there were differences by country. Fifty-seven percent did not know whether their insurance company reimburses exercise programs and only 9% would be willing to pay more than €50 per month to participate. CONCLUSION: A large percentage of patients with MBC lack the skills to engage in regular exercise as recommended by exercise guidelines for people with cancer. Patients may benefit from personalized advice and appropriate training facilities to overcome barriers. When implementing exercise interventions, attention should be given to reimbursement and the relatively low willingness-to-pay.

Distinct distribution patterns of exercise-induced natural killer cell mobilization into the circulation and tumor tissue of patients with prostate cancer.

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti-oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune-responsive tumor entities.

Short- and Long-Term Stroboscopic Training Effects on Visuomotor Performance in Elite Youth Sports. Part 1: Reaction and Behavior.

PURPOSE: Recent research suggests that stroboscopic training is an effective tool to improve visual and visuomotor performance. However, many studies were limited by small samples, short training interventions, inexperienced athletes, and an exclusive focus on short-term effects. This first part of the study evaluates the short- and long-term effects of stroboscopic training on visuomotor reaction speed in elite athletes. METHODS: Forty-five young elite badminton athletes participated in this study, of which 32 (13.7 yr) were included in the final data analysis. Participants were assigned to an intervention (stroboscopic vision) or control group (normal vision). Both groups performed identical badminton-specific training drills implemented into the regular training schedule. Before and after a 10-wk training period and after a 6-wk retention interval, athletes performed a laboratory reaction test to determine EMG onset and visuomotor reaction time (VMRT). In addition, a field test investigated stroboscopic training effects on the quality of ball-racquet contact and net drop performance. RESULTS: VMRT decreased immediately after stroboscopic training (pre, 251 ms; post, 238 ms; P = 0.005, d = 0.63), and reactions remained significantly faster after the retention interval (retention, 241 ms; P = 0.041, d = 0.50). Analyses on EMG onset data suggested these adaptations were attributable to the premotor rather than the motor time. VMRT remained unchanged in the control group (pre, 252 ms; post, 256; retention, 253 ms; P > 0.99). Field test performance improvements were observed for the quality of ball-racquet contact and net drop performance; however, changes were not different between groups. CONCLUSIONS: Stroboscopic training induced short- and long-term accelerations of visuomotor reaction speed in elite badminton players. Stroboscopic eyewear may be an effective training tool to accelerate visuomotor reactions in highly skilled athletes.

Short- and Long-Term Stroboscopic Training Effects on Visuomotor Performance in Elite Youth Sports. Part 2: Brain-Behavior Mechanisms.

PURPOSE: Stroboscopic training has repeatedly been shown to improve visuomotor abilities. However, although performance improvements were attributed to visual processes, information on the neurophysiological mechanisms is missing. Part 2 of this study investigated the effects of stroboscopic training on neural visual and motor functions and its contribution to training-induced changes in visuomotor reaction time. METHODS: Forty-five young elite badminton athletes participated in this study, of which 32 (age, 13.7 yr) were included in the final data analysis. Participants were assigned to an intervention (stroboscopic vision) or control group (normal vision). Before and after a 10-wk training and after a 6-wk retention period, participants performed visual perception and reaction tasks in response to visual motion stimuli. The N2 and N2-r motion onset visual-evoked potentials, its linear combination (Vlc), and the BA6 negativity potential were determined using a 64-channel EEG. RESULTS: A significant TIME-GROUP effect was observed for the Vlc score (P = 0.019, ηp2 = 0.18), indicating a lower Vlc in the intervention group. However, post hoc tests did not reach significance. Within-subject correlation analyses revealed that changes in reaction speed were related to latency changes in N2 (r = 0.59, P < 0.001), N2-r (r = -0.64, P < 0.001), and the combined Vlc (r = 0.68, P < 0.001). Regression analyses across participants including multiple (N2/N2-r) or single (Vlc) predictors provided an explained variance of >60% (N2/N2-r, r2 = 0.62; Vlc, r2 = 0.64). No training effects or correlations were observed for the BA6 negativity. CONCLUSIONS: The results indicate that faster visuomotor reactions after stroboscopic training are accompanied by accelerated visual perception and processing, whereas motor processes seemed to be unaffected. Stroboscopic training may be promising to specifically address the visual system in visuomotor-demanding sports.