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Motor learning requires practice over a period of time and depends on brain plasticity, yet even for relatively simple movements, there are multiple practice strategies that can be used for skill acquisition. We investigated the role of intracortical inhibition in the primary motor cortex (M1) during motor skill learning. Event-related transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability and inhibition thought to involve synaptic and extrasynaptic γ-aminobutyric acid (GABA). Short intracortical inhibition (SICI) was assessed using 1- and 2.5-ms interstimulus intervals (ISIs). Participants learned a novel, sequential pinch-grip task on a computer in either a repetitive or interleaved practice structure. Both practice structures showed equivalent levels of motor performance at the end of acquisition and at retention 1 wk later. There was a novel task-related modulation of 1-ms SICI. Repetitive practice elicited a greater reduction of 1- and 2.5-ms SICI, i.e., disinhibition, between rest and task acquisition, compared with interleaved practice. These novel findings support the use of a repetitive practice structure for motor learning because the associated effects within M1 have relevance for motor rehabilitation. [ABSTRACT FROM AUTHOR]

Purpose: All patients living with cancer, including those with metastatic cancer, are encouraged to be physically active. This paper examines the secondary endpoints of an aerobic exercise intervention for men with metastatic prostate cancer. Methods: ExPeCT (Exercise, Prostate Cancer and Circulating Tumour Cells), was a multi-centre randomised control trial with a 6-month aerobic exercise intervention arm or a standard care control arm. Exercise adherence data was collected via heart rate monitors. Quality of life (FACT-P) and physical activity (self-administered questionnaire) assessments were completed at baseline, at 3 months and at 6 months. Results: A total of 61 patients were included (69.4 ± 7.3 yr, body mass index 29.2 ± 5.8 kg/m2). The median time since diagnosis was 34 months (IQR 7–54). A total of 35 (55%) of participants had > 1 region affected by metastatic disease. No adverse events were reported by participants. There was no effect of exercise on quality of life (Cohen’s d = − 0.082). Overall adherence to the supervised sessions was 83% (329 out of 396 possible sessions attended by participants). Overall adherence to the non-supervised home exercise sessions was 72% (months 1–3) and 67% (months 3–6). Modelling results for overall physical activity scores showed no significant main effect for the group (p-value = 0.25) or for time (p-value = 0.24). Conclusion: In a group of patients with a high burden of metastatic prostate cancer, a 6-month aerobic exercise intervention did not lead to change in quality of life. Further exercise studies examining the role of exercise for people living with metastatic prostate cancer are needed. Trial Registration: The trial was registered at clinicaltrials.gov (NCT02453139) on May 25th 2015. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) are drugs which treat cancer by manipulating the immune system. Exercise also influences the immune system and helps to reduce symptoms in people with cancer, particularly fatigue. However, the effect of combining exercise with ICIs has not been well established. We hypothesise that the combined approach will produce beneficial outcomes for people with cancer (such as fewer side effects from ICIs and better killing of cancer cells). To determine the need for, and design of, future studies which address this hypothesis, we first need to understand what previous research has already shown. We aim to identify previous studies which have investigated this topic. Subsequently, by summarising their findings, we aim to communicate the key gaps in current understanding and provide informed recommendations about the direction, and design, of future research addressing the role of exercise during ICI treatment for people with cancer. The impact of using exercise as a non-pharmacological intervention in patients with cancer receiving immune checkpoint inhibitors (ICIs) is not well known. Our objective was to determine the extent of, and identify gaps within, available literature addressing the effect of exercise on (a) oncological outcomes and (b) quality of life (QoL) in patients with cancer receiving ICIs, and (c) the underlying biological mechanisms for such effects. We conducted searches across EMBASE, APA PsycInfo and Ovid MEDLINE(R). Studies were eligible if they addressed at least one aspect of the objective and were available in the English language. Results were synthesised using a narrative approach and subsequently discussed with multidisciplinary stakeholders. As of the final search on 5 April 2022, 11 eligible studies were identified, of which 8 were preclinical and 3 were clinical. Clinical studies only focused on QoL-related outcomes. When studies were grouped by whether they addressed oncological outcomes (n = 7), QoL (n = 5) or biological mechanisms (n = 7), they were found to be heterogeneous in methodology and findings. Additional evidence, particularly in the clinical setting, is required before robust recommendations about whether, and how, to include exercise alongside ICI treatment can be made. [ABSTRACT FROM AUTHOR]

Purpose: Existing research indicates that physical activity (PA) is beneficial to men with prostate cancer (PCa). We examined the potential of a single-contact peer-support-based behavioural intervention to promote PA engagement in men treated for PCa. Methods: A mixed methods design was employed, comprising a two-arm pragmatic trial and semi-structured interviews. The intervention was a 10-min PA-based presentation by a former patient, delivered in group seminars that are provided for patients as standard care. Seminars were alternately allocated to (a) cancer exercise specialist talk + patient speaker talk or (b) cancer exercise specialist talk only. Self-reported PA, exercise motivation, quality of life, fatigue and clinical and demographic characteristics were obtained from n = 148 (intervention: n = 69; control: n = 79) patients immediately prior to the seminar, and at follow-up ≈ 100 days later. Data were analysed using ANCOVA models and χ2 tests. Fourteen semi-structured interviews with intervention participants, which explored how the intervention was experienced, were analysed using a grounded theory-style approach. Results: The intervention had no significant effect on quantitatively self-reported PA (p = 0.4). However, the intervention was statistically and clinically beneficial for fatigue (p = 0.04) and quality of life (p = 0.01). Qualitative analysis showed that the intervention was beneficial to psychological wellbeing and some participants had increased intention to engage in PA as a result of the intervention. Conclusions: A brief one-off PA-based presentation for men with PCa, delivered by a former patient alongside cancer exercise specialist advice, may result in clinically significant benefits to quality of life and may influence PA intention in certain individuals. [ABSTRACT FROM AUTHOR]

Background: Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer. Methods: Participants (n = 61) were randomised into either standard care (control) or exercise arms. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking. CTC data was correlated with clinico-pathological information. Results: Changes in CTC number were observed within group over time, however no significant difference in CTC number was observed between groups over time. Platelet cloaking was identified in 29.5% of participants. A positive correlation between CTC number and white cell count (WCC) was observed (p = 0.0001), in addition to a positive relationship between CTC clusters and PSA levels (p = 0.0393). Conclusion: The presence of platelet cloaking has been observed in this patient population for the first time, in addition to a significant correlation between CTC number and WCC. Trial registration: ClincalTrials.gov identifier NCT02453139. [ABSTRACT FROM AUTHOR]

Objectives: The main objective of this study is to determine the feasibility of recruiting and retaining patients recently diagnosed with thoracic cancer to a trial of short-term integrated rehabilitation; evaluate uptake of theoretically informed components targeting physical function, symptom self-management and participation; estimate sample size requirements for an efficacy trial. Design: Parallel group randomized controlled feasibility trial. Setting: Three U.K. hospitals. Participants: Patients ⩽eight weeks of thoracic cancer diagnosis, Eastern Cooperative Oncology Group Performance Status 0–3, any cancer stage and treatment plan. Interventions: Participants randomly allocated (1:1) to short-term integrated rehabilitation and standard care or standard care alone over 30 days. Main measures: Primary: participant recruitment and retention, targeting ⩾30% of eligible patients enrolling and ⩾50% of participants reporting outcomes at 30 days. Secondary: intervention fidelity; missing data and performance of outcome measures for self-efficacy, symptoms, physical activity and health-related quality of life. Results: Of 159 eligible patients approached, 54 (34%) were recruited. A total of 44 (82%) and 39 (72%) participants reported outcomes at 30 and 60 days, respectively. Intervention fidelity was high. Rehabilitation was delivered across 3 (1–3) sessions over 32 (22–45) days (median (range)). Changes in clinical outcomes were modest but most apparent at 60 days for health-related quality of life: Functional Assessment of Cancer Therapy Lung Cancer score median (interquartile range) change 9.7 (−12.0 to 16.0) rehabilitation versus 2.3 (−15.0 to 14.5) standard care. Conclusion: A trial to examine efficacy of short-term integrated rehabilitation for people newly diagnosed with thoracic cancer is feasible. A sample of 336 participants could detect a meaningful effect on health-related quality of life as the primary outcome. [ABSTRACT FROM AUTHOR]

Objective: Existing research indicates that moderate-to-vigorous physical activity (PA) alleviates treatment side effects and is associated with survival in men with prostate cancer. We aimed to ascertain the state of research investigating barriers and facilitators to PA in men with prostate cancer and synthesise existing qualitative research on this topic.Methods: A systematic review of qualitative and quantitative studies was conducted. MEDLINE, Embase, PsycINFO, Web of Knowledge, CINAHL, PEDro, OATD, and WorldCat were searched to June 2019 for quantitative studies investigating causes or predictors of PA or qualitative studies describing patient-reported barriers/facilitators to PA, amongst men with prostate cancer of any stage. Thirty-two studies (n = 17 quantitative; n = 15 qualitative) were included from 3698 screened articles.Results: Heterogeneity and unsystematic reporting of quantitative study methods prohibited a quantitative data synthesis. Thematic synthesis of qualitative studies produced five analytical themes: individual needs by treatment pathway, self-determination and its relationship with prostate cancer-related events, co-ordination and support of the clinical care team, individual preferences in discrete aspects of PA engagement style, and the potential for a bidirectional facilitative relationship between structured group PA and spontaneous peer support. Both qualitative and quantitative studies indicated incontinence as a barrier.Conclusions: Unsystematic reporting of interventions hinders a robust quantitative understanding of behavioural intervention research in this subject area. Good co-ordination of multidisciplinary care personnel could facilitate PA, by enabling a more comprehensive approach to targeting social cognitive processes. Well-timed intervention and access to highly individualised PA support, including optional group PA classes, seem to also be important facilitators. [ABSTRACT FROM AUTHOR]

Background: Access to rehabilitation to prevent disability and optimise function is recommended for patients with cancer, including following cancer diagnosis. Models to integrate rehabilitation within oncology services as cancer treatment commences are required, but must be informed by those they are intended to support. We aimed to identify views of patients, carers and clinicians to develop and refine a rehabilitation model to be tested in a feasibility trial for people newly diagnosed with lung cancer or mesothelioma. Methods: We conducted a focus group study with people affected by lung cancer or mesothelioma, their carers and clinicians providing their care to identify priorities for rehabilitation in this period. We sought views on core intervention components, processes and outcomes and integration with oncology services. Data were analysed using thematic analysis. Results: Fifteen clinicians (oncologists, nurse specialists, physiotherapists and occupational therapists), nine patients and five carers participated. A proposed outline rehabilitation model was perceived as highly relevant for this population. Participants recommended prompt and brief rehabilitation input, delivered whilst people attend for hospital appointments or at home to maximise accessibility and acceptability. Participants recognised variation in need and all prioritised tailored support for symptom self-management, daily activities and the involvement of carers. Clinicians also prioritised achieving fitness for oncology treatment. Patients and carers prioritised a sensitive manner of approach, positivity and giving hope for the future. Participant's recommendations for outcome measurement related to confidence in usual daily activities, symptom control and oncology treatment completion rates over objective measures of cardiorespiratory fitness. Conclusion: The importance of providing tailored rehabilitation around the time of diagnosis for people with lung cancer or mesothelioma was affirmed by all participants. The refined model of rehabilitation recommended for testing in a feasibility trial is flexible, tailored and short-term. It aims to support people to self-manage symptoms, tolerate cancer treatments and to remain active and independent in daily life. It is delivered alongside scheduled hospital appointments or at home by an expert practitioner sensitive to the psycho-social sequelae that follow a diagnosis of thoracic cancer. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity and subsequently decrease poor cancer-specific outcomes in this patient population. This study will assess the feasibility and safety of introducing a structured aerobic exercise intervention to an advanced cancer population. This study will also examine if the evasion of immune editing by circulating tumour cells (CTCs) is an exercise-modifiable mechanism in obese men with prostate cancer.Methods: This international multicentre prospective study will recruit men with metastatic prostate cancer. Participants will be recruited from centres in Dublin (Ireland) and London (UK). Participants will be divided into exposed and non-exposed groups based on body mass index (BMI) ≥ 25 kg/m2 and randomised to intervention and control groups. The exercise group will undertake a regular supervised aerobic exercise programme, whereas the control group will not. Exercise intensity will be prescribed based on a target heart rate monitored by a polar heart rate monitor. Blood samples will be taken at recruitment and at 3 and 6 months to examine the primary endpoint of platelet cloaking of CTCs. Participants will complete a detailed questionnaire to assess quality of life (QoL) and other parameters at each visit.Discussion: The overall aim of the ExPeCT trial is to examine the relationship between PrCa, exercise, obesity, and systemic inflammation, and to improve the overall QoL in men with advanced disease. Results will inform future work in this area examining biological markers of prognosis in advanced prostate cancer.Trial Registration: Clinicaltrials.gov NLM identifier: NCT02453139 . Registered on 12 May 2015. This document contains excerpts from the ExPeCT trial protocol Version 1.5, 28 July 2016. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells (CTCs) can be found in the bloodstream in men with advanced prostate cancer. Blood platelets, which normally help the blood to clot, may help the cancer cells to spread throughout the body by preventing the body's immune system from finding and destroying them while they are in the bloodstream. Blood samples were taken from men with prostate cancer who were involved in the ExPeCT clinical trial, some of whom were taking part in a regular exercise programme. The numbers of CTCs, platelets and immune system cells were counted and compared. Blood samples with more CTCs had higher numbers of platelets and higher numbers of some types of immune system cells. Some differences were also found in men involved in the exercise programme. This study helps to show that CTCs numbers are related to platelet and immune cell numbers in the blood. Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples (n = 29). CTC count positively correlated with absolute total lymphocyte count (r2 = 0.1709, p = 0.0258) and NK-cell count (r2 = 0.49, p < 0.0001). There was also a positive correlation between platelet count and CTC count (r2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group (n = 123, p < 0.0001), the non-exercise group (n = 79, p = 0.001) and blood draw samples lacking platelet cloaking (n = 128, p < 0.0001). By flow cytometry, blood samples from the exercise group (n = 15) had a higher proportion of CD3+ T-lymphocytes (p = 0.0003) and lower proportions of B-lymphocytes (p = 0.0264) and NK-cells (p = 0.015) than the non-exercise group (n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis. [ABSTRACT FROM AUTHOR]