International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

From Theory to Practice: An International Approach to Establishing Prehabilitation Programmes.

Purpose: This article focuses on the following:The importance of prehabilitation in people with cancer and the known and hypothesised benefits.Exploration of the principles that can be used when developing services in the absence of a single accepted model of how these services could be established or configured.Description of approaches and learning in the development and implementation of prehabilitation across three different countries: Canada, the Netherlands and the United Kingdom, based on the authors' experiences and perspectives. Recent Findings: Practical tips and suggestions are shared by the authors to assist others when implementing prehabilitation programmes. These include experience from three different approaches with similar lessons.Important elements include the following: (i) starting with a small identified clinical group of patients to refine and test the delivery model and demonstrate proof of concept; (ii) systematic data collection with clearly identified target outcomes from the outset; (iii) collaboration with a wide range of stakeholders including those who will be designing, developing, delivering, funding and using the prehabilitation services; (iv) adapting the model to fit local situations; (v) project leaders who can bring together and motivate a team; (vi) recognition and acknowledgement of the value that each member of a diverse multidisciplinary team brings; (vii) involvement of the whole team in prehabilitation prescription including identification of patients' levels of risk through appropriate assessment and need-based interventions; (viii) persistence and determination in the development of the business case for sustainable funding; (ix) working with patients ambassadors to develop and advocate for the case for support; and (x) working closely with commissioners of healthcare. Summary: Principles for the implementation of prehabilitation have been set out by sharing the experiences across three countries. These principles should be considered a framework for those wishing to design and develop prehabilitation services in their own areas to maximise success, effectiveness and sustainability.

Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer.

Multiple organizations around the world have issued evidence-based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health-related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home-based or community-based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Recruitment to the "Breast-Activity and Healthy Eating After Diagnosis" (B-AHEAD) Randomized Controlled Trial.

Excess weight at breast cancer diagnosis and weight gain during treatment are linked to increased breast cancer specific and all-cause mortality. The Breast-Activity and Healthy Eating After Diagnosis (B-AHEAD) trial tested 2 weight loss diet and exercise programmes versus a control receiving standard written advice during adjuvant treatment. This article identifies differences in characteristics between patients recruited from the main trial site to those of the whole population from that site during the recruitment period and identifies barriers to recruitment. A total of 409 patients with operable breast cancer were recruited within 12 weeks of surgery. We compared demographic and treatment factors between women recruited from the main trial coordinating site (n = 300) to the whole breast cancer population in the center (n = 532). Uptake at the coordinating site was 42%, comparable to treatment trials in the unit (47%). Women recruited were younger (55.9 vs 61.2 years, P < .001), more likely to live in least deprived postcode areas (41.7% vs 31.6%, P = .004), and more likely to have screen-detected cancers (55.3% vs 48.7%, P = .026) than the whole breast cancer population. The good uptake highlights the interest in lifestyle change around the time of diagnosis, a challenging time in the patient pathway, and shows that recruitment at this time is feasible. Barriers to uptake among older women and women with a lower socioeconomic status should be understood and overcome in order to improve recruitment to future lifestyle intervention programs.

Effects of supervised exercise on motivational outcomes in breast cancer survivors at 5-year follow-up.

PURPOSE: Short-term physical activity (PA) has beneficial effects on symptom management and quality of life, however, longer-term adherence is likely needed for improved disease outcomes in breast cancer survivors (BCS). This study examined the effects of a supervised group exercise program on motivational outcomes and PA among BCS at 5-year follow-up. METHODS: The original study was a two-armed, randomized controlled trial comparing a 12-week supervised group exercise program to usual care among 203 BCS. BCS for this follow-up study were contacted at 60 months postintervention and asked to complete assessments of motivational outcomes from the Theory of Planned Behavior and PA behavior using the Scottish Physical Activity Questionnaire. RESULTS: Overall, 87 participants provided 5-year follow-up data with no differences in participation by group. Analyses of covariance (ANCOVAs) revealed that supervised exercise had a significant positive effect on descriptive norm at 5-year follow-up (mean = +0.6; 95% CI = +0.1 to +1.1; d = +0.48; p = 0.021). Small positive effects were also noted for perceived behavioral control (d = +0.18), instrumental attitude (d = +0.26), and injunctive norm (d = +0.35), although they were not statistically significant. Moreover, BCS who were more active at 5-year follow-up also reported more favorable perceived behavioral control (d = +0.16), instrumental attitude (d = +0.28), injunctive norm (d = +0.24), and descriptive norm (d = +0.31), although these differences were not statistically significant. CONCLUSIONS: This trial provides suggestive evidence that a supervised exercise program has positive effects on motivational outcomes even after 5 years. Additional intervention strategies during follow-up may further improve long-term adherence and health outcomes in BCS.

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.

INTRODUCTION: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS: More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS: The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS: With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

Astrocyte proliferation is regulated by the OGF-OGFr axis in vitro and in experimental autoimmune encephalomyelitis.

Astrocytes become activated and proliferate in response to autoimmune diseases involving the CNS. In many cases, elevated numbers of astrocytes may compound inflammatory responses and exacerbate neuronal degeneration. The regulation of astrocytes in disease states has been shown as an important corollary to disease progression and recovery. This study explores the role of the opioid growth factor (OGF)-OGF receptor (OGFr) axis in the proliferation of primary cultures of mouse cerebral astrocytes, as well as in spinal cord astrocytes of mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. OGF was found to inhibit purified cultures of cortical astrocytes in a dose-related, receptor-mediated, and reversible manner. Examination of a number of endogenous opioid peptides supported that OGF was the most effective inhibitor of astrocyte proliferation and that endogenous production of this peptide was neutralized by OGF antibodies. The specificity and requirement for OGFr to be present and functional was indicated by studies using siRNA technology to knockdown the classical µ, δ, and κ opioid receptors, as well as OGFr. Only knockdown of OGFr resulted in changes in astrocyte cell number with OGF rendered ineffective without the presence of OGFr. Astrocyte migration as studied by a scratch model, as well as apoptosis and necrosis pathways, were not altered by OGF treatment. However, BrdU incorporation during DNA synthesis phases of the cell cycle was significantly repressed in activated cultured astrocytes by OGF exposure. Overall activation of the astrocytes measured by nitric oxide levels was reduced, but proportional to the reduction in cell number. Examination of spinal cord tissues from mice with EAE revealed fewer astrocytes within 10 days of OGF treatment, with the mechanism of cell number reduction being repression of DNA synthesis. In conclusion, these studies delineate a novel role for OGF in the proliferation of mouse cortical astrocytes in vitro and spinal cord astrocytes in vivo, and support the use of OGF as a therapy to inhibit astrogliosis within a broad spectrum of autoimmune diseases.

Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial.

OBJECTIVES: To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up. DESIGN: Pragmatic randomised controlled prospective open trial. SETTING: Three National Health Service oncology clinics in Scotland and community exercise facilities. PARTICIPANTS: 203 women entered the study; 177 completed the six month follow-up. INTERVENTIONS: Supervised 12 week group exercise programme in addition to usual care, compared with usual care. MAIN OUTCOME MEASURES: Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility. RESULTS: Mixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95% confidence interval 83 to 176) for metres walked in 12 minutes, 182 (75 to 289) for minutes of moderate intensity activity reported in a week, 2.6 (1.6 to 3.7) for shoulder mobility, 2.5 (1.0 to 3.9) for breast cancer specific subscale of quality of life, and 4.0 (1.8 to 6.3) for positive mood. No significant effect was seen for general quality of life (FACT-G), which was the primary outcome. At the six month follow-up, most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged. No adverse effects were noted. CONCLUSION: Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later. Clinicians should encourage activity for their patients. Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services. Trial registration Current controlled trials ISRCTN12587864 [controlled-trials.com].