Health and performance effects of 12 weeks of small-sided street football training compared to grass football training in habitually active young men.

PURPOSE: The purpose of the present study was to investigate the health and exercise performance effects of street football training on very small pitches surrounded by boards in young habitually active men in comparison to small-sided football training on grass. METHODS: Thirty-nine habitually active men (30.7 ± 6.7 years, 90.9 ± 16.6 kg, 183.8 ± 4.5 cm, 39.6 ± 6.0 mL/min/kg) were randomly assigned to a street football training group (ST) or grass football group (GR) playing small-sided games for 70 min, 1.5 and 1.7 times per week for 12 weeks, respectively, or an inactive control group (CO). Intensity during training was measured using heart rate (HR) and GPS units. Pre- and post-intervention, a test battery was completed. RESULTS: Mean HR (87.1 ± 5.0 vs. 84.0 ± 5.3%HRmax; P > 0.05) and percentage of training time above 90%HRmax (44 ± 28 vs. 34 ± 24%; P > 0.05) were not different between ST and GR. VO2max increased (P < 0.001) by 3.6[95% CI 1.8;5.4]mL/min/kg in GR with no significant change in ST or CO. HR during running at 8 km/h decreased (P < 0.001) by 14[10;17]bpm in ST and by 12[6;19]bpm in GR, with no change in CO. No changes were observed in blood pressure, resting HR, total body mass, lean body mass, whole-body bone mineral density, fasting blood glucose, HbA1c, plasma insulin, total cholesterol(C), LDL-C or HDL-C. Moreover, no changes were observed in Yo-Yo IE2 performance, 30-m sprint time, jump length or postural balance. CONCLUSION: Small-sided street football training for 12 weeks with 1-2 weekly sessions led to improvements in submaximal exercise capacity only, whereas recreational grass football training confirmed previous positive effects on submaximal exercise capacity as well as cardiorespiratory fitness.

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training in patients with cancer undergoing systemic treatment: a systematic review and meta-analysis of published and unpublished controlled trials.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 Methods: This systematic review and meta-analysis included published and unpublished controlled trials comparing exercise interventions versus controls in adults with cancer scheduled to undergo systemic treatment.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.

Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer.

BACKGROUND: Chemotherapy efficacy is largely dependent on treatment adherence, defined by the relative dose intensity (RDI). Identification of new modifiable risk factors associated with low RDI might improve chemotherapy delivery. Here, we evaluated the association between low RDI and pre-chemotherapy factors, including patient- and treatment-related characteristics and markers of inflammation. METHODS: This exploratory analysis assessed data from 267 patients with early-stage breast cancer scheduled to undergo (neo-)adjuvant chemotherapy included in the Physical training and Cancer (Phys-Can) trial. The association between low RDI, defined as < 85%, patient-related (age, body mass index, co-morbid condition, body surface area) and treatment-related factors (cancer stage, receptor status, chemotherapy duration, chemotherapy dose, granulocyte colony-stimulating factor) was investigated. Analyses further included the association between RDI and pre-chemotherapy levels of interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) in 172 patients with available blood samples. RESULTS: An RDI of < 85% occurred in 31 patients (12%). Univariable analysis revealed a significant association with a chemotherapy duration above 20 weeks (p < 0.001), chemotherapy dose (p = 0.006), pre-chemotherapy IL-8 (OR 1.61; 95% CI (1.01; 2.58); p = 0.040) and TNF-α (OR 2.2 (1.17; 4.53); p = 0.019). In multivariable analyses, inflammatory cytokines were significant association with low RDI for IL-8 (OR: 1.65 [0.99; 2.69]; p = 0.044) and TNF-α (OR 2.95 [1.41; 7.19]; p = 0.007). CONCLUSIONS: This exploratory analysis highlights the association of pre-chemotherapy IL-8 and TNF-α with low RDI of chemotherapy for breast cancer. IL-8 and TNF-α may therefore potentially help to identify patients at risk for experiencing dose reductions. Clinical trial number NCT02473003 (registration: June 16, 2015).

Assessment of sarcopenia in patients with upper gastrointestinal tumors: Prevalence and agreement between computed tomography and dual-energy x-ray absorptiometry.

BACKGROUND & AIMS: Sarcopenia is associated with an increased risk of complications to treatment and lower survival rates in patients with cancer, but there is a lack of agreement on cut-off values and assessment methods. We aimed to investigate the prevalence of sarcopenia assessed by dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) as well as the agreement between the methods for identification of sarcopenia. METHODS: This cross-sectional study pooled data from two studies including patients scheduled for surgery for gastrointestinal tumors. We assessed sarcopenia using two different cut-off values derived from healthy young adults for DXA and two for CT. Additionally, we used one of the most widely applied cut-off values for CT assessed sarcopenia derived from obese cancer patients. The agreement between DXA and CT was evaluated using Cohen's kappa. The mean difference and range of agreement between DXA and CT for estimating total and appendicular lean soft tissue were assessed using Bland-Altman plots. RESULTS: In total, 131 patients were included. With DXA the prevalence of sarcopenia was 11.5% and 19.1%. Using CT, the prevalence of sarcopenia was 3.8% and 26.7% using cut-off values from healthy young adults and 64.1% using the widely applied cut-off value. The agreement between DXA and CT in identifying sarcopenia was poor, with Cohen's kappa values ranging from 0.05 to 0.39. The mean difference for estimated total lean soft tissue was 1.4 kg, with 95% limits of agreement from -8.6 to 11.5 kg. For appendicular lean soft tissue, the ratio between DXA and CT was 1.15, with 95% limits of agreement from 0.92 to 1.44. CONCLUSIONS: The prevalence of sarcopenia defined using DXA and CT varied substantially, and the agreement between the two modalities is poor.

Exercise intensity and markers of inflammation during and after (neo-) adjuvant cancer treatment.

Exercise training has been hypothesized to lower the inflammatory burden for patients with cancer, but the role of exercise intensity is unknown. To this end, we compared the effects of high-intensity (HI) and low-to-moderate intensity (LMI) exercise on markers of inflammation in patients with curable breast, prostate and colorectal cancer undergoing primary adjuvant cancer treatment in a secondary analysis of the Phys-Can randomized trial (NCT02473003). Sub-group analyses focused on patients with breast cancer undergoing chemotherapy. Patients performed 6 months of combined aerobic and resistance exercise on either HI or LMI during and after primary adjuvant cancer treatment. Plasma taken at baseline, immediately post-treatment and post-intervention was analyzed for levels of interleukin 1 beta (IL1B), IL6, IL8, IL10, tumor-necrosis factor alpha (TNFA) and C-reactive protein (CRP). Intention-to-treat analyses of 394 participants revealed no significant between-group differences. Regardless of exercise intensity, significant increases of IL6, IL8, IL10 and TNFA post-treatment followed by significant declines, except for IL8, until post-intervention were observed with no difference for CRP or IL1B. Subgroup analyses of 154 patients with breast cancer undergoing chemotherapy revealed that CRP (estimated mean difference (95% CI): 0.59 (0.33; 1.06); P = 0.101) and TNFA (EMD (95% CI): 0.88 (0.77; 1); P = 0.053) increased less with HI exercise post-treatment compared to LMI. Exploratory cytokine co-regulation analysis revealed no difference between the groups. In patients with breast cancer undergoing chemotherapy, HI exercise resulted in a lesser increase of CRP and TNFA immediately post-treatment compared to LMI, potentially protecting against chemotherapy-related inflammation.

[Exercise training as preoperative optimisation in patients with cancer].

This review summarises the current knowledge of exercise training, which is increasingly used to rehabilitate patients with cancer after anti-cancer treatment, aiming to manage acute and long-term side effects and physical limitations. However, exercise training may also play a critical role in the early preoperative management of patients with cancer. In this period, preoperative exercise training may ensure, that patients reach the curative tumour resection by preventing tumour progression, reducing complications to neoadjuvant treatment and lessening physical deterioration, all leading to improved surgical outcome and enhanced long-term survival. †) Pernille Højman died 6 April 2019, after she had written a major part of the script.

Interval Walking Improves Glycemic Control and Body Composition After Cancer Treatment: A Randomized Controlled Trial.

CONTEXT: Patients with colorectal cancer have increased risk of metabolic diseases including diabetes. Exercise training may counteract metabolic dysregulation, but the impact of exercise training on glycemic control, including postprandial glycemia, has never been explored in patients with colorectal cancer. OBJECTIVE: To examine the effects of home-based interval walking on aerobic and metabolic fitness and quality of life in patients with colorectal cancer. DESIGN: Randomized controlled trial. SETTING: Clinical research center. PARTICIPANTS: Thirty-nine sedentary (<150 minutes moderate-intensity exercise per week) patients with stage I to III colorectal cancer who had completed primary treatment. INTERVENTION: Home-based interval walking 150 min/wk or usual care for 12 weeks. MAIN OUTCOME MEASURES: Changes from baseline to week 12 in maximum oxygen uptake (VO2peak) by cardiopulmonary exercise test, glycemic control by oral glucose tolerance test (OGTT), body composition by dual-energy x-ray absorptiometry scan, blood biochemistry, and quality of life. RESULTS: Compared with control, interval walking had no effect on VO2peak [mean between-group difference: -0.32 mL O2 · kg-1 · min-1 (-2.09 to 1.45); P = 0.721] but significantly improved postprandial glycemic control with lower glucose OGTT area under the curve [-126 mM · min (-219 to -33); P = 0.009], 2-hour glucose concentration [-1.1 mM (-2.2 to 0.0); P = 0.056], and improved Matsuda index [1.94 (0.34; 3.54); P = 0.01]. Also, interval walking counteracted an increase in fat mass in the control group [-1.47 kg (-2.74 to -0.19); P = 0.025]. CONCLUSION: A home-based interval-walking program led to substantial improvements in postprandial glycemic control and counteracted fat gain in posttreatment patients with colorectal cancer, possibly providing an effective strategy for prevention of secondary metabolic diseases.

Exercise-mediated improvement of depression in patients with gastro-esophageal junction cancer is linked to kynurenine metabolism.

Background: Exercise may improve depression in cancer patients, yet the molecular mechanism behind this protection is poorly understood. Here, we aimed to explore the link between exercise and regulation of kynurenine (Kyn) metabolism and inflammation in patients with operable gastro-esophageal junction (GEJ) cancer patients, who improved significantly in depression score with exercise training. Material and Methods: Fifty GEJ cancer patients were allocated to 12 weeks of supervised training twice weekly including interval-based aerobic exercise and resistance training, or standard care. Depression score was evaluated by HADS, and blood samples and muscle biopsies were collected for determination of Kyn metabolism and inflammation across the intervention. Results: Depression scores decreased by -1.3 points in the exercise group (p < 0.01), whereas no changes were observed in the control group. Plasma 3-hydroxykynurenine (HK), a Kyn metabolite giving rise to other neurotoxic metabolites, increased by 48% (p <0.001) in the control group, while exercise training attenuated this accumulation. The production of HK is induced by inflammation, and while we observed no differences in systemic pro-inflammatory cytokines, exercise training ameliorated the treatment-induced intramuscular inflammation. Moreover, exercise has been suggested to convert Kyn to the neuroprotective metabolite, kynurenic acid (KA), but despite marked functional and muscular exercise-mediated adaptations, we did not observe any enhancement of KA production and related enzyme expression in the muscles of GEJ cancer patients. Conclusion: Exercise training reduced symptoms of depression in patients with GEJ cancer, and this effect was associated with an exercise-dependent attenuation of the inflammation-induced conversion of Kyn to neurotoxic metabolites.

Effects of 3 months of full-court and half-court street basketball training on health profile in untrained men.

PURPOSE: The aim of the present study was to investigate whether street basketball organized as 3 v 3 on either a half court (HC) with 1 basket or a full court (FC) with 2 baskets could improve fitness and health profiles of untrained men after 3 months of supervised training. METHODS: Thirty-five untrained men (aged 20-42 years) completed the pre- and post-intervention testing (FC: n = 13, HC: n = 12, CO (control): n = 10). The training attendance was 2.0 ± 0.4 and 1.9 ± 0.3 times per week in FC and HC, respectively. Mean heart rate (HR) was 83.8 ± 6.0 percent of maximal heart rate (%HRmax) and 84.5 ± 2.9 %HRmax in FC and HC, respectively. RESULTS: The 3 months of street basketball training on an FC with 2 baskets increased maximal oxygen uptake (2.4 mL/min/kg (95% confidence interval (CI): 1.0-3.9)), time to exhaustion (47 s (95%CI: 26-67)), lean body mass (0.8 kg (95%CI: 0.1-1.5)), and bone mineral density (0.021 g/cm2 (95%CI: 0.011-0.031)), whereas mean arterial pressure (-5.6 mmHg (95%CI: -7.5 to 3.7)), body fat percentage (-1.6%, (95%CI: -2.5 to -0.7)), heart rate (-18 bpm (95%CI: -24 to -12)), and blood lactate (median: -1.4 mmol/L (interquartile range: -1.5 to -0.6)) during submaximal running were lowered. The changes were less pronounced after the training period when playing on an HC with 1 basket, but increases in maximal oxygen uptake (1.6 mL/min/kg (95%CI: -0.1 to 3.3)), time to exhaustion (28 s (95%CI: 9-47)), lean body mass (1.3 kg (95%CI: 0.3-2.4)), and lower body fat percentage (-0.9% (95%CI: -1.9 to -0.1)) were observed in this group. CONCLUSION: Three months of 3 v 3 street basketball training improved fitness and led to broad-spectrum improvements in variables related to overall health profile, with the most marked effects observed when playing on an FC with 2 baskets.

Testing physical function in children undergoing intense cancer treatment-a RESPECT feasibility study.

BACKGROUND: The physical function of children with cancer is reduced during treatment, which can compromise the quality of life and increase the risk of chronic medical conditions. The study, "REhabilitation, including Social and Physical activity and Education in Children and Teenagers with cancer" (Clinicaltrials.gov: NCT01772862) examines the efficacy of multimodal rehabilitation strategies introduced at cancer diagnosis. This article addresses the feasibility of and obstacles to testing physical function in children with cancer. METHODS: The intervention group comprised 46 males and 29 females aged 6-18 years (mean ± SD: 11.3 ± 3.1 years) diagnosed with cancer from January 2013 to April 2016. Testing at diagnosis and after 3 months included timed-up-and-go, sit-to-stand, flamingo balance, handgrip strength, and the bicycle ergometer cardiopulmonary exercise test (CPET). RESULTS: Of the 75 children, 92% completed a minimum of one test; two children declined testing and four were later included. Completion was low for CPET (38/150, 25%) but was high for handgrip strength (122/150, 81%). Tumor location, treatment-related side effects, and proximity to chemotherapy administration were primary obstacles for testing physical function. Children with extracranial solid tumors and central nervous system tumors completed significantly fewer tests than those with leukemia and lymphoma. Children with leukemia demonstrated reduced lower extremity function, that is, 24% reduction at 3 months testing in timed-up-and-go (P = 0.005) and sit-to-stand (P = 0.002), in contrast with no reductions observed in the other diagnostic groups. CONCLUSION: Children with cancer are generally motivated to participate in physical function tests. Future studies should address diagnosis specific obstacles and design testing modalities that facilitate physical function tests in this target group.

The "Interval Walking in Colorectal Cancer" (I-WALK-CRC) study: Design, methods and recruitment results of a randomized controlled feasibility trial.

BACKGROUND: Low physical activity level is associated with poor prognosis in patients with colorectal cancer (CRC). To increase physical activity, technology-based platforms are emerging and provide intriguing opportunities to prescribe and monitor active lifestyle interventions. The "Interval Walking in Colorectal Cancer"(I-WALK-CRC) study explores the feasibility and efficacy a home-based interval-walking intervention delivered by a smart-phone application in order to improve cardio-metabolic health profile among CRC survivors. The aim of the present report is to describe the design, methods and recruitment results of the I-WALK-CRC study.Methods/Results: The I-WALK-CRC study is a randomized controlled trial designed to evaluate the feasibility and efficacy of a home-based interval walking intervention compared to a waiting-list control group for physiological and patient-reported outcomes. Patients who had completed surgery for local stage disease and patients who had completed surgery and any adjuvant chemotherapy for locally advanced stage disease were eligible for inclusion. Between October 1st, 2015, and February 1st, 2017, 136 inquiries were recorded; 83 patients were eligible for enrollment, and 42 patients accepted participation. Age and employment status were associated with participation, as participants were significantly younger (60.5 vs 70.8 years, P < 0.001) and more likely to be working (OR 5.04; 95%CI 1.96-12.98, P < 0.001) than non-participants. CONCLUSION: In the present study, recruitment of CRC survivors was feasible but we aim to better the recruitment rate in future studies. Further, the study clearly favored younger participants. The I-WALK-CRC study will provide important information regarding feasibility and efficacy of a home-based walking exercise program in CRC survivors.

Sarcopenia and Postoperative Complication Risk in Gastrointestinal Surgical Oncology: A Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate sarcopenia as a predictor of postoperative risk of major and total complications after surgery for gastrointestinal cancer. BACKGROUND: Sarcopenia is associated with poor survival in gastrointestinal cancer patients, but the role of sarcopenia as prognostic tool in surgical oncology has not been established, and no consensus exists regarding assessment and management of sarcopenic patients. METHODS: We performed a systematic search for citations in EMBASE, Web of Science, and PubMed from 2004 to January 31, 2017. Random effects meta-analyses were used to estimate the pooled risk ratio for postoperative complications by Clavien-Dindo grade (total complications: grade ≥2; major complications: grade ≥3) in patients with sarcopenia versus patients without sarcopenia. Stratified analyses were performed by sarcopenia criteria, cutoff level, assessment methods, study quality, cancer diagnosis, and "Enhanced Recovery After Surgery" care. RESULTS: Twenty-nine studies (n = 7176) were included with sarcopenia prevalence ranging between 12% and 78%. Preoperative incidence of sarcopenia was associated with increased risk of major complications (risk ratio 1.40; 95% confidence interval, 1.20-1.64; P < 0.001; I = 52%) and total complications (risk ratio 1.35; 95% confidence interval, 1.12-1.61; P = 0.001; I = 60%). Moderate heterogeneity was found for both meta-analyses. Subgroup analyses showed that sarcopenia remained a consistent risk factor across stratification by sarcopenia criteria, assessment methods, study quality, and diagnoses. CONCLUSIONS: Sarcopenia was associated with an increased risk of complications after gastrointestinal tumor resection, but lack of methodological consensus hampers the interpretation and clinical utilization of these findings. Combining assessment of muscle mass with measures of physical function may increase the prognostic value and accuracy in preoperative risk stratification.

Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment.

The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the status of the current molecular understanding of the effect of exercise on cancer. We propose that exercise has a role in controlling cancer progression through a direct effect on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of anti-cancer treatment efficacy. These findings have wide-ranging societal implications, as this understanding may lead to changes in cancer treatment strategies.

Exercise-Induced Catecholamines Activate the Hippo Tumor Suppressor Pathway to Reduce Risks of Breast Cancer Development.

Strong epidemiologic evidence documents the protective effect of physical activity on breast cancer risk, recurrence, and mortality, but the underlying mechanisms remain to be identified. Using human exercise-conditioned serum for breast cancer cell incubation studies and murine exercise interventions, we aimed to identify exercise factors and signaling pathways involved in the exercise-dependent suppression of breast cancer. Exercise-conditioned serum from both women with breast cancer (n = 20) and healthy women (n = 7) decreased MCF-7 (hormone-sensitive) and MDA-MB-231 (hormone-insensitive) breast cancer cell viability in vitro by 11% to 19% and reduced tumorigenesis by 50% when preincubated MCF-7 breast cancer cells were inoculated into NMRI-Foxn1nu mice. This exercise-mediated suppression of cell viability and tumor formation was completely blunted by blockade of ß-adrenergic signaling in MCF-7 cells, indicating that catecholamines were the responsible exercise factors. Both epinephrine (EPI) and norepinephrine (NE) could directly inhibit breast cancer cell viability, as well as tumor growth in vivo EPI and NE activate the tumor suppressor Hippo signaling pathway, and the suppressive effect of exercise-conditioned serum was found to be mediated through phosphorylation and cytoplasmic retention of YAP and reduced expression of downstream target genes, for example, ANKRD1 and CTGF. In parallel, tumor-bearing mice with access to running wheels showed reduced growth of MCF-7 (-36%, P < 0.05) and MDA-MB-231 (-66%, P < 0.01) tumors and, for the MCF-7 tumor, increased regulation of the Hippo signaling pathway. Taken together, our findings offer a mechanistic explanation for exercise-dependent suppression of breast cancer cell growth. Cancer Res; 77(18); 4894-904. ©2017 AACR.

Football training in men with prostate cancer undergoing androgen deprivation therapy: activity profile and short-term skeletal and postural balance adaptations.

PURPOSE: To investigate the activity profile of football training and its short-term effects on bone mass, bone turnover markers (BTMs) and postural balance in men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). METHODS: This was a randomised 12-week study in which men with PCa undergoing ADT were assigned to a football intervention group [FTG, n = 29, 67 ± 7 (±SD) years] training 2‒3 times per week for 45‒60 min or to a control group (n = 28, 66 ± 5 years). The activity profile was measured using a 5-Hz GPS. The outcomes were total body and leg bone mineral content (BMC) and density, BTMs and postural balance. RESULTS: In the last part of the 12 weeks, FTG performed 194 ± 41 accelerations and 296 ± 65 decelerations at >0.6 m/s/s and covered a distance of 905 ± 297 m at speeds >6 km/h and 2646 ± 705 m per training session. Analysis of baseline-to-12-week change scores showed between-group differences in favour of FTG in total body BMC [26.4 g, 95 % confidence interval (CI): 5.8-46.9 g, p = 0.013], leg BMC (13.8 g, 95 % CI: 7.0‒20.5 g, p < 0.001) and markers of bone formation: P1NP (36.6 µg/L, 95 % CI: 10.4‒62.8 µg/L, p = 0.008) and osteocalcin (8.6 µg/L, 95 % CI: 3.3‒13.8 µg/L, p < 0.01). The number of decelerations correlated to the increase in leg BMC (r = 0.65, p = 0.012). No between-group differences were observed for the remaining outcomes. CONCLUSION: Football training involves numerous runs, accelerations and decelerations, which may be linked to marked increases in bone formation markers and preserved bone mass in middle-aged and elderly men with PCa undergoing ADT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01711892.

A framework for prescription in exercise-oncology research.

The field of exercise-oncology has increased dramatically over the past two decades, with close to 100 published studies investigating the efficacy of structured exercise training interventions in patients with cancer. Of interest, despite considerable differences in study population and primary study end point, the vast majority of studies have tested the efficacy of an exercise prescription that adhered to traditional guidelines consisting of either supervised or home-based endurance (aerobic) training or endurance training combined with resistance training, prescribed at a moderate intensity (50-75% of a predetermined physiological parameter, typically age-predicted heart rate maximum or reserve), for two to three sessions per week, for 10 to 60 min per exercise session, for 12 to 15 weeks. The use of generic exercise prescriptions may, however, be masking the full therapeutic potential of exercise treatment in the oncology setting. Against this background, this opinion paper provides an overview of the fundamental tenets of human exercise physiology known as the principles of training, with specific application of these principles in the design and conduct of clinical trials in exercise-oncology research. We contend that the application of these guidelines will ensure continued progress in the field while optimizing the safety and efficacy of exercise treatment following a cancer diagnosis.

Treatment-related cardiovascular late effects and exercise training countermeasures in testicular germ cell cancer survivorship.

BACKGROUND: Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent cancer-specific survival comes at considerable costs, as individuals with a history of germ cell cancer experience serious long-term complications, including markedly increased risk of cardiovascular morbidities and premature cardiovascular death. The factors responsible, as well as their mode of action, are not fully understood and there is a lack of knowledge concerning optimal evidence-based long-term follow-up strategies. RESULTS: Here, we present the growing body of evidence suggesting that germ cell cancer patients as a consequence of the different treatment components, are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple-hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment-induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting. CONCLUSION: As exercise training may have the potential to ameliorate and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise oncology research in this setting, in order to provide exercise recommendations for optimal germ cell cancer survivorship.

The Yo-Yo IE2 test: physiological response for untrained men versus trained soccer players.

PURPOSE: This study aimed to examine the physical capacity and physiological response to the Yo-Yo Intermittent Endurance level 2 test (IE2) for untrained individuals (UTR) and trained male soccer players (TR) and to investigate the determinants of intense intermittent exercise performance. METHODS: Thirty-four healthy UTR males and 15 age-matched TR performed a maximal incremental treadmill test and a Yo-Yo IE2 test. Muscle biopsies and blood samples were obtained, and heart rate (HR) was measured before, during, and after tests. RESULTS: UTR had a 67% lower (P < 0.01) Yo-Yo IE2 performance (665 ± 271 vs 2027 ± 298 m; effect size (ES), 4.8), 34% lower V˙O2max (P < 0.01), and 19% lower resting muscle glycogen (P < 0.05) than those of TR. Blood lactate concentration and HR during the first 560 m of the Yo-Yo IE2 test were higher (P < 0.01) in UTR than those in TR (560 m, 7.4 ± 2.8 vs 2.4 ± 0.8 mM; ES, 1.7-2.8; 188 ± 11 vs 173 ± 8 bpm; ES, 0.9-1.5), with no differences at exhaustion. Time >95% HRmax was lower (P < 0.01) in UTR than that in TR (1.0 ± 1.1 vs 6.3 ± 2.9 min; ES, 3.1). Mean rates of muscle creatine phosphate utilization (16.5 ± 9.5 vs 4.3 ± 2.7 mmol·kg d.w·min), muscle lactate accumulation (16.8 ± 9.1 vs 4.2 ± 2.9 mmol·kg d.w.·min), and glycogen breakdown (29.6 ± 14.2 vs 7.7 ± 5.4 mmol·kg d.w.·min) were fourfold higher (P < 0.01; ES, 1.4-1.7) in UTR than those in TR. For UTR, correlations (P < 0.01) were observed between Yo-Yo IE2 performance and V˙O2max (r = 0.77), incremental treadmill test performance (r = 0.79), and muscle citrate synthase activity (r = 0.57) but not for TR (r = -0.12 to 0.50; P > 0.05). CONCLUSIONS: The Yo-Yo IE2 test was shown to possess high construct validity by showing large differences in performance, HR, and anaerobic metabolism between UTR and TR. In addition, V˙O2max seemed to be important for intermittent exercise performance in UTR but not for TR.

Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice.

Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P < 0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P < 0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P < 0.001), maintained lean body mass (P < 0.001) and muscle strength (P < 0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.