Evaluating a Remotely Delivered Cardio-Oncology Rehabilitation Intervention for Patients With Breast Cancer (REMOTE-COR-B): Protocol for a Single-Arm Feasibility Trial.

BACKGROUND: Exercise rehabilitation is a promising strategy for reducing cardiovascular disease risk among patients with breast cancer. However, the evidence is primarily derived from programs based at exercise centers with in-person supervised delivery. Conversely, most patients report a preference for home-based rehabilitation. As such, there is a clear need to explore strategies that can provide real-time supervision and coaching while addressing consumer preferences. Evidence from cardiac rehabilitation has demonstrated the noninferiority of a smartphone-based telerehabilitation approach (REMOTE-CR) to improve cardiorespiratory fitness in people with cardiovascular disease compared to a center-based program. OBJECTIVE: This study aims to assess the feasibility, safety, and preliminary efficacy of the REMOTE-CR program adapted for patients with breast cancer at risk of cardiotoxicity (REMOTE-COR-B). We will also assess the satisfaction and usability of REMOTE-COR-B. METHODS: We will conduct a single-arm feasibility study of the REMOTE-COR-B program among patients with stage I-III breast cancer who are at risk of cardiotoxicity (taking treatment type and dose, as well as other common cardiovascular disease risk factors into account) and who are within 24 months of completing primary definitive treatment. Participants (target sample size of 40) will receive an 8-week smartphone-based telerehabilitation exercise program involving remotely delivered real-time supervision and behavior change support. The platform comprises a smartphone and wearable heart rate monitor, as well as a custom-built smartphone app and web application. Participants will be able to attend remotely monitored exercise sessions during set operating hours each week, scheduled in both the morning and evening. Adherence is the primary outcome of the trial, assessed through the number of remotely monitored exercise sessions attended compared to the trial target (ie, 3 sessions per week). Secondary outcomes include additional trial feasibility indicators (eg, recruitment and retention), safety, satisfaction, and usability, and objective and patient-reported efficacy outcomes (cardiovascular fitness, quality of life, fatigue, self-reported exercise, self-efficacy, habit strength, and motivation). Adherence, feasibility, and safety outcomes will be assessed during the intervention period; intervention satisfaction and usability will be assessed post intervention; and objective and patient-reported efficacy outcomes will be assessed at baseline, post intervention (2-month postbaseline assessment), and at follow-up (5-month postbaseline assessment). RESULTS: Recruitment for this trial commenced in March 2023, and 7 participants had been recruited as of the submission of the manuscript. The estimated completion date for the project is October 2024, with results expected to be published in mid-2025. CONCLUSIONS: The REMOTE-COR-B intervention is a novel and promising approach to providing exercise therapy to patients with breast cancer at risk of cardiotoxicity who have unique needs and heightened safety risks. This project will provide important information on the extent to which this approach is satisfactory to patients with breast cancer, safe, and potentially effective, which is necessary before larger-scale research or clinical projects. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621001557820; www.anzctr.org.au/ACTRN12621001557820.aspx. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53301.

Pre-post feasibility trial of a telephone-delivered exercise intervention for patients during chemotherapy for recurrent ovarian cancer: the ECHO-R trial protocol.

INTRODUCTION: The benefits of exercise in reducing treatment-related morbidity and improving quality of life following a primary diagnosis of cancer have been well documented and have led to exercise being recommended by oncology societies for all people with a cancer diagnosis. However, these recommendations are derived from research typically involving cohorts with more common cancers and relatively good prognosis, such as breast and prostate. Evidence from these cancers may not apply to women with recurrent ovarian cancer. Therefore, the primary objective of this trial is to evaluate the feasibility and safety of a home-based, telephone-delivered exercise intervention for women undergoing chemotherapy for recurrent ovarian cancer. METHODS AND ANALYSIS: The Exercise During Chemotherapy for Recurrent Ovarian Cancer (ECHO-R) trial is a single-arm, phase II, pre/postintervention trial of a 6-month, telephone-delivered exercise intervention (consistent with recommended exercise oncology prescription). The target sample size is 80 women who are currently undergoing (or are scheduled to receive) chemotherapy for recurrent ovarian cancer. Recruitment is through participating hospital sites in Queensland, Australia, or via self-referral. The exercise intervention comprises 12 telephone sessions over a 6-month period delivered by trial-trained exercise professionals and supplemented (where feasible) by five sessions face to face. Exercise prescription is individualised and works towards an overall goal of achieving a weekly target of 150 min of moderate-intensity, mixed-mode exercise. Assessments via self-administered survey and physical fitness and function tests occur at baseline and then at 6 and 9 months postbaseline. Data to inform feasibility and safety are recorded as case notes by the exercise professional during each session. ETHICS AND DISSEMINATION: Ethics approval for the ECHO-R trial was granted by the Metro North Human Research Ethics Committee (HREC/2020/QRBW/67223) on 6 November 2020. Findings from the trial are planned to be disseminated via peer-reviewed publications and both national and international exercise and oncology conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000042842.

Declaración de consenso de la organización ejercicio y ciencias del deporte - Australia: el ejercicio como medicina en el manejo del cáncer / The Exercise and Sports Science Australia position statement: Exercise medicine in cancer management / Declaração de consenso da Organização de Ciências do Exercício e do Esporte - Austrália: Exercício como medicamento no tratamento do câncer

Resumen Desde la primera publicación de la declaración de consenso sobre pautas de ejercicio para personas con cáncer, de la asociación Ejercicio y Ciencias del Deporte - Australia (ESSA, Exercise and Sports Science Australia), ha ocurrido un crecimiento exponencial en las investigaciones que evalúan el papel del ejercicio antes, durante y después del tratamiento del cáncer. El propósito de este reporte es utilizar la evidencia científica actual, junto a la experiencia clínica y los principios de las ciencias del ejercicio, para poner al día la declaración de consenso de ESSA sobre la prescripción de ejercicio específica para el cáncer. En esta declaración de consenso se reporta un resumen de los beneficios alcanzados mediante el ejercicio luego de un diagnóstico de cáncer, así como las fortalezas y limitaciones de la evidencia acumulada. Se propone, entonces, un marco de prescripción del ejercicio para permitir la aplicación de consideraciones específicas para el cáncer en la individualización, especificidad, seguridad, factibilidad y progresión del ejercicio para toda clase de pacientes. Se ofrecen consideraciones adicionales específicas para la prescripción del ejercicio cuando hay presencia de enfermedades hematológicas, osteomusculares, sistémicas, cardiovasculares, linfáticas, gastrointestinales, genitourinarias y neurológicas y preocupaciones relacionadas con su tratamiento, así como la presencia crónica de comorbilidades. Además, se identifican y comentan temas prácticos específicos y barreras que deben tomarse en cuenta para la prescripción del ejercicio. Si bien es cierto que el ejercicio multimodal de intensidad moderada a intensa será apropiado para la mayoría, no hay una prescripción establecida ni una dosificación semanal, que se puedan considerar basadas en la evidencia, para todos los pacientes de cáncer. Es necesaria una prescripción del ejercicio dirigida específicamente a esta población, que asegure el mayor beneficio (conforme lo defina cada paciente) a corto y largo plazo, con un bajo riesgo de perjuicio.

Abstract Objectives: Since Exercise and Sports Science Australia (ESSA) first published its position statement on exercise guidelines for people with cancer, there has been exponential growth in research evaluating the role of exercise pre-, during and post-cancer treatment. Design and Methods: The purpose of this report is to use the current scientific evidence, alongside clinical experience and exercise science principles to update ESSA's position statement on cancer-specific exercise prescription. Results: Reported in this position statement is a summary of the benefits accrued through exercise following a cancer diagnosis and the strengths and limitations of this evidence-base. An exercise prescription framework is then proposed to enable the application of cancer-specific considerations for individualisation, specificity, safety, feasibility and progression of exercise for all patients. Additional specific exercise prescription considerations are provided for the presence of haematological, musculoskeletal, systemic, cardiovascular, lymphatic, gastrointestinal, genitourinary and neurological disease- and treatment-related concerns, as well as presence of co-morbid chronic disease. Further, we also identify and discuss cancer-specific pragmatic issues and barriers requiring consideration for exercise prescription. Conclusions: While for the majority, multimodal, moderate to high intensity exercise will be appropriate, there is no set prescription and total weekly dosage that would be considered evidence-based for all cancer patients. Targeted exercise prescription, which includes the provision of behaviour change advice and support, is needed to ensure greatest benefit (as defined by the patient) in the short and longer term, with low risk of harm.

Resumo Desde a primeira publicação da declaração de consenso da Organização de Ciências do Exercício e do Esporte - Austrália ((ESSA, Exercise and Sports Science Australia) sobre diretrizes de exercícios para pessoas com câncer, tem ocorrido um crescimento exponencial nas pesquisas que avaliam o papel dos exercícios antes, durante e depois do tratamento do câncer. O objetivo deste relatório é usar as evidências científicas atuais com a experiência clínica e os princípios da ciência do exercício, para atualizar a declaração de consenso da ESSA sobre a prescrição de exercícios específica para o câncer. Esta declaração de consenso relata um resumo dos benefícios obtidos por meio de exercícios após o diagnóstico de câncer, bem como os pontos fortes e as limitações da evidência acumulada. Assim, propõe-se uma estrutura de prescrição de exercícios para permitir a aplicação de considerações específicas para o câncer na individualização, especificidade, segurança, viabilidade e progressão do exercício para todas as classes de pacientes. Considerações adicionais específicas para a prescrição de exercícios são fornecidas quando há doenças hematológicas, osteomusculares, sistêmicas, cardiovasculares, linfáticas, gastrointestinais, geniturinárias, neurológicas e preocupações relacionadas ao seu tratamento, bem como a presença crônica de comorbidades. Além disso, questões práticas específicas e barreiras à prescrição de exercícios são identificadas e discutidas. Embora seja verdade que o exercício multimodal de intensidade moderada a vigorosa seja apropriado para a maioria, não há uma prescrição definida ou dosagem semanal que possa ser considerada baseada em evidências para todos os pacientes com câncer. Há uma necessidade de prescrição de exercícios especificamente direcionada a essa população, garantindo o maior benefício (conforme definido pelo paciente individual) em curto e longo prazos, com baixo risco de danos.

Self-efficacy, motivation, and habits: psychological correlates of exercise among women with breast cancer.

PURPOSE: The purpose of this analysis was to explore associations between exercise behaviour among breast cancer survivors and three behavioural constructs from distinct theories: self-efficacy from social cognitive theory, motivation from self-determination theory, and habits from habit theory. METHODS: Breast cancer survivors (n = 204) completed a cross-sectional survey that collected demographic and disease characteristics, exercise levels, and self-efficacy, motivation, and habits. Multivariable linear regression models were used to identify constructs associated with total activity and resistance training. RESULTS: Participants were a mean (SD) age of 57.3 (10.8) years and most were diagnosed with early-stage disease (72%) and engaged in sufficient levels of total activity (94%), though only 45% completed ≥ 2 resistance training sessions/week. Identified motivation (ꞵ[95% CI] = 7.6 [3.9-11.3]) and habits (ꞵ[95% CI] = 4.4 [1.4-7.4]) were significantly associated with total activity (as were body mass index and disease stage), whilst identified motivation (ꞵ[95% CI] = 0.6 [0.3-0.9]) and coping self-efficacy (ꞵ[95% CI] = 0.02 [< 0.01-0.03]) were significantly associated with resistance training. The models explained 27% and 16% of variance in total activity and resistance training behaviour, respectively. CONCLUSION: Results suggest that incorporating strategies that support identified motivation, habits, and coping self-efficacy in future interventions could promote increased exercise behaviour among breast cancer populations. Future longitudinal research should examine associations with exercise in a more representative, population-based sample.

The safety, feasibility, and efficacy of an 18-week exercise intervention for adults with primary brain cancer - the BRACE study.

PURPOSE: To determine the safety, feasibility, and potential effect of an 18-week exercise intervention for adults with primary brain cancer. MATERIALS AND METHODS: Eligible patients were 12-26-weeks post-radiotherapy for brain cancer. The individually-prescribed weekly exercise was ≥150-minutes of moderate-intensity exercise, including two resistance-training sessions. The intervention was deemed "safe" if exercise-related, serious adverse events (SAE) were experienced by <10% of participants, and feasible if recruitment, retention, and adherence rates were ≥75%, and ≥75% compliance rates were achieved in ≥75% of weeks. Patient-reported and objectively-measured outcomes were assessed at baseline, mid-intervention, end-intervention, and 6-month follow-up, using generalized estimating equations. RESULTS: Twelve participants enrolled (51 ± 19.5 years, 5 females). There were no exercise-related SAEs. The intervention was feasible (recruitment:80%, retention:92%, adherence:83%). Participants completed a median of 172.8 (min:77.5, max:560.8) minutes of physical activity per week. 17% met the compliance outcome threshold for ≥75% of the intervention. Improvements in quality of life (mean change (95% CI): 7.9 units (1.9, 13.8)), functional well-being (4.3 units (1.4, 7.2)), depression (-2.0 units (-3.8, -0.2)), activity (112.8 min (42.1, 183.4)), fitness (56.4 meters (20.4, 92.5)), balance (4.9 s (0.9, 9.0)), and lower-body strength (15.2 kg (9.3, 21.1)) were observed end-intervention. CONCLUSION: Preliminary evidence support that exercise is safe and beneficial to the quality of life and functional outcomes for people with brain cancer.Registration: ACTRN12617001577303.

The BRAin Cancer and Exercise (BRACE) study highlights the need for regular monitoring of disease- and treatment-related side effects which may present as barriers to exercise.Exercise prescription should be modified according to the presence and severity of disease- and treatment-related barriers.Adverse events observed, such as dizziness, highlight the importance of supervised exercise for people with brain cancer.If supervision is not possible, then exercise modes with low risk of harm from falls are recommended (e.g., walking, machine-based resistance training).

Barriers, facilitators, perceptions and preferences influencing physical activity participation, and the similarities and differences between cancer types and treatment stages - A systematic rapid review.

The aim of this systematic rapid review was to explore barriers, facilitators, perceptions and preferences of physical activity for people diagnosed with cancer, by cancer type and treatment stage. The search strategy, implemented through four databases, included terms relating to cancer, physical activity, barriers, facilitators, perceptions and preferences, and relevant study designs. Studies reporting the outcomes of interests for adults diagnosed with cancer and living in Western countries were included and grouped according to the Social-Ecological Model and the Health Belief Model, and pragmatically. A total of 118 studies, involving 15 cancers were included. Outcomes were most commonly explored within samples involving mixed cancers (32 studies) and breast cancer (31 studies), and at the post-treatment phase (52 studies). Across all cancers and during- and post-treatment, treatment- and disease-related side-effects were the most commonly identified barrier, social support and guidance was the most commonly identified facilitator, and promoting health and recovery was the most commonly identified perception of benefit of physical activity. Notable differences were identified in barriers, facilitators and perceptions across cancer types and treatment stages, with specific examples including: comorbidities were inconsistently reported as a barrier across cancers; time pressure was more commonly reported as a barrier post-treatment; and women with breast cancer reported inaccessibility of appropriate services more commonly during-treatment than post-treatment. Preference findings varied widely across cancer types and treatment phases. These findings can be used to aid efforts to improve physical activity levels post-cancer by providing healthcare professionals with information to facilitate individualised advice and services.

Efficacy of exercise interventions for women during and after gynaecological cancer treatment - a systematic scoping review.

PURPOSE: To systematically synthesise evidence of exercise intervention efficacy for physical/psychosocial outcomes that matter to women during/following treatment for gynaecological cancer. METHODS: Five databases were searched (PubMed, EMBASE, CINAHL, PsychInfo, Scopus). Exercise-only intervention studies that included women during/ following treatment for any gynaecological cancer, with/ without control comparison, on any physical or psychosocial outcome(s), were included and qualitatively appraised using the Revised Cochrane Risk of Bias tool and a modified Newcastle-Ottawa Scale. RESULTS: Seven randomised controlled trials (RCTs), three single-arm pre-post studies, and one prospective cohort study satisfied were included (11 studies). Most studies were completed following treatment (91%), included combined (aerobic and resistance; 36%) and aerobic (36%) training, were fully/mostly (63%) unsupervised, and had a moderate-to-high risk of bias. Overall, 33 outcomes (64% objectively-measured) were assessed. Improvements were observed in aerobic capacity (V̇O2 Peak +1.6 mL/kg/min, 6-minute walk distance +20-27 m), lower- (30-second sit-to-stand +2-4 repetitions) and upper-limb strength (30-second arm curl +5 repetitions; 1RM grip strength/chest press +2.4-3.1 kg), and agility (timed up-and-go -0.6 seconds). However, changes in quality of life, anthropometry/body composition, balance and flexibility were inconsistent. There was no evidence to support worsening of outcomes. CONCLUSION: Preliminary research into the role of exercise post-gynaecological cancer suggests an improvement in exercise capacity, muscular strength, and agility which, in the absence of exercise, typically decline following gynaecological cancer. Future exercise trials involving larger and more diverse gynaecological cancer samples will improve understanding of the potential and magnitude of effect of guideline-recommended exercise on outcomes that matter to patients.

The Effect of Exercise on Pain in People with Cancer: A Systematic Review with Meta-analysis.

INTRODUCTION: Cancer-related pain is common and undertreated. Exercise is known to have a pain-relieving effect in non-cancer pain. OBJECTIVES: This systematic review aimed to evaluate (1) the effect of exercise on cancer-related pain in all cancers, and (2) whether the effect of exercise differed according to exercise mode, degree of supervision, intervention duration and timing (during or after cancer treatment), pain types, measurement tool and cancer type. METHODS: Electronic searches were undertaken in six databases to identify exercise studies evaluating pain in people with cancer, published prior to 11 January 2023. All stages of screening and data extraction were conducted independently by two authors. The Cochrane risk of bias tool for randomised trials (RoB 2) was used and overall strength of evidence was assessed using the GRADE approach. Meta-analyses were performed overall and by study design, exercise intervention and pain characteristics. RESULTS: In total, 71 studies reported in 74 papers were eligible for inclusion. The overall meta-analysis included 5877 participants and showed reductions in pain favouring exercise (standardised mean difference - 0.45; 95% confidence interval - 0.62, - 0.28). For most (> 82%) of the subgroup analyses, the direction of effect favoured exercise compared with usual care, with effect sizes ranging from small to large (median effect size - 0.35; range - 0.03 to - 1.17). The overall strength of evidence for the effect of exercise on cancer-related pain was very low. CONCLUSION: The findings provide support that exercise participation does not worsen cancer-related pain and that it may be beneficial. Better pain categorisation and inclusion of more diverse cancer populations in future research would improve understanding of the extent of benefit and to whom. PROSPERO REGISTRATION NUMBER: CRD42021266826.

Exercise during CHemotherapy for Ovarian cancer (ECHO) trial: design and implementation of a randomised controlled trial.

INTRODUCTION: Epidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. The Exercise during CHemotherapy for Ovarian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer. METHODS AND ANALYSIS: Participants (target sample size: n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either the exercise intervention (plus usual care) or usual care alone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage. ETHICS AND DISSEMINATION: Ethics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ANZCTRN12614001311640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367123&isReview=true).

Exploring women's experiences with persistent pain and pain management following breast cancer treatment: A qualitative study.

This qualitative study aimed to explore experiences of women with persistent pain following breast cancer treatment, including their perceptions about the cause of their pain, how they manage their pain and their interactions with healthcare providers related to their pain during and following breast cancer treatment. Fourteen women who experienced pain for more than 3 months following breast cancer treatment were recruited from the general breast cancer survivorship community. Focus groups and in-depth, semi-structured interviews were conducted by one interviewer, audio-recorded, and transcribed verbatim. Transcripts were coded and analysed using Framework Analysis. Three main descriptive themes emerged from the interview transcripts: (1) characteristics of pain, (2) interactions with healthcare providers and (3) pain management. Women had various types and degrees of persistent pain, all of which they believed were related to breast cancer treatment. Most felt like they were not given enough information pre- or post-treatment and believed their experience and ability to cope with pain would have been better if they were given accurate information and advice about (the possibility of) experiencing persistent pain. Pain management strategies ranged from trial and error approaches, to pharmacotherapy, and to 'just coping with the pain". These findings highlight the importance of the provision of empathetic supportive care before, during and after cancer treatment that can facilitate access to relevant information, multidisciplinary care teams (including allied health professionals) and consumer support.

Economic evaluation of exercise interventions for individuals with cancer: A systematic review.

While there is good evidence that exercise is an effective adjunct therapy to cancer care, little is known about its value for money. The aim of this systematic review is to explore the available evidence pertaining to the cost-effectiveness of exercise interventions following cancer. A search of eight online databases (CINAHL, the Cochrane Library (NHSEED), Econlit, Embase, PsycInfo, PubMed, Scopus, Web of science) was first conducted on 26 March 2021 and updated on 8 March 2022. Only economic evaluations with results in the form of incremental cost-effectiveness ratio (ICER) were included. The Consolidated Health Economics Evaluation Reporting Standards (CHEERS) was used to appraise the quality of reporting in the studies. The study protocol was registered in PROSPERO. Sixteen studies comprising seven (44%) cost-utility analyses (CUA), one (6%) cost-effectiveness analyses (CEA) and eight (50%) combined CUA and CEA were identified. These studies explored exercise in five cancer types (breast, colon, lung, prostate, and blood), with half (50%) in breast cancer. Seven studies (44%) adopted societal perspectives. Exercise interventions were found to be cost-effective in five of ten (50%) trial-based economic evaluations and in five of the six (83%) model-based economic evaluations. Most exercise interventions included were supervised, while close supervision and individualized exercise sessions incurred higher costs. Exercise interventions in cancer care are cost-effective for various cancer types despite considerable heterogeneity in exercise delivery and the type of analysis used for economic evaluation. There is clear value in using decision-analytic modelling to account for the long-term benefits of exercise in cancer care.

A cost-consequences analysis of the SAFE trial: a comparative, effectiveness trial evaluating high- versus low-supervision of an exercise intervention for women with breast cancer.

PURPOSE: The aim of this analysis was to compare the cost-consequences of a 12 week exercise intervention when delivered under high- versus low-level supervision conditions by an Exercise Professional (ExP) to women with breast cancer. METHODS: 60 women (50 ± 9 years) with stage II + breast cancer, who were insufficiently active, and reported ≥ 1 comorbidities or persistent treatment-related side-effects, were randomized to the high- or low-supervision group. The high-supervision group received 20 supervised sessions with an ExP over a 12 week period (reflecting a typical research model), whereas the low-supervision group received five sessions over the same period (replicating what is publicly funded within Australia). Health outcomes including health-related quality of life, and physical and psychosocial outcomes were assessed at baseline and post-intervention. To assess intervention consequences, composite effectiveness scores were created by calculating mean z-scores from raw data for all outcomes per participant. Total program costs were calculated including program development, staff training, program implementation, and equipment. RESULTS: 79.3% of the high- and 63.0% of the low-supervision group showed clinically relevant health improvements. Cost per improver was $1,814 for 23 improvers and $1,571 for 17 improvers in the high- and low-supervision groups, respectively. CONCLUSION: The SAFE exercise intervention, when delivered via high- or low-supervised conditions, represents good value with over 60% of women in both groups reporting health improvements. High-supervision levels resulted in a greater proportion of women experiencing health benefits, but future research will need to determine the longer term health impacts of these group differences.

Do Patient-Reported Upper-Body Symptoms Predict Breast Cancer-Related Lymphoedema: Results from a Population-Based, Longitudinal Breast Cancer Cohort Study.

The objectives of this work were to (i) describe upper-body symptoms post-breast cancer; (ii) explore the relationship between symptoms and upper-body function, breast cancer-related lymphoedema (BCRL), physical activity levels, and quality of life; and (iii) determine whether the presence of upper-body symptoms predicts BCRL. Nine symptoms, upper-body function, lymphoedema, physical activity, and quality of life were assessed in women with invasive breast cancer at baseline (2- to 9-months post-diagnosis; n = 2442), and at 2- and 7-years post-diagnosis. Mann−Whitney tests, unpaired t-tests, and chi-squared analyses were used to assess cross-sectional relationships, while regression analyses were used to assess the predictive relationships between symptoms at baseline, and BCRL at 2- and 7-years post-diagnosis. Symptoms are common post-breast cancer and persist at 2- and 7-years post-diagnosis. Approximately two in three women, and one in three women, reported >2 symptoms of at least mild severity, and of at least moderate severity, respectively. The presence of symptoms is associated with poorer upper-body function, and lower physical activity levels and quality of life. One or more symptoms of at least moderate severity increases the odds of developing BCRL by 2- and 7-years post-diagnosis (p < 0.05). Consequently, improved monitoring and management of symptoms following breast cancer have the potential to improve health outcomes.

The Lymphatic System, Lymphoedema, and Medical Curricula-Survey of Australian Medical Graduates.

The aim of this study was to survey the perceptions of recent (i.e., within the past 12 months) Australian medical graduates regarding (i) their understanding of the lymphatic system and lymphoedema, and (ii) the extent to which the lymphatic system and lymphoedema were covered as part of their medical degree. Medical graduates were invited to participate in a 17-item online survey that asked respondents to rate their level of agreement (using a 5-point Likert scale; higher scores = higher agreement) to statements that explored their understanding and comprehensiveness of their medical degree. Responses to each item were described using n (%). Subscale scores for understanding and medical degree were computed by summing scores of individual items, described using means (SD) and compared by participant characteristics. Medical graduates (n = 230) perceived their understanding of the lymphatic system and lymphoedema to be low, and comprehensiveness of medical curricula specific to the lymphatic system and lymphoedema to be lacking. Subscale scores did not differ by participant characteristics. Improvement of medical graduates understanding of lymphoedema may facilitate greater awareness of lymphoedema, thus optimizing the timeliness of diagnosis and access to treatment.

Burden of lymphedema in long-term breast cancer survivors by race and age.

BACKGROUND: Risk assessment for breast cancer-related lymphedema has emphasized upper-limb symptoms and treatment-related risk factors. This article examined breast cancer-related lymphedema after surgery, overall and in association with broader demographic and clinical features. METHODS: The Carolina Breast Cancer Study phase 3 followed participants for breast cancer-related lymphedema from baseline (on average, 5 months after breast cancer diagnosis) to 7 years after diagnosis. Among 2645 participants, 552 self-reported lymphedema cases were identified. Time-to-lymphedema curves and inverse probability weighted conditional Cox proportional hazards model were used to evaluate whether demographics and clinical features were associated with breast cancer-related lymphedema. RESULTS: Point prevalence of breast cancer-related lymphedema was 6.8% at baseline, and 19.9% and 23.8% at 2 and 7 years after diagnosis, respectively. Most cases had lymphedema in the arm (88%-93%), whereas 14% to 27% presented in the trunk and/or breast. Beginning approximately 10 months after diagnosis, younger Black women had the highest risk of breast cancer-related lymphedema and older non-Black women had the lowest risk. Positive lymph node status, larger tumor size (>5 cm), and estrogen receptor-negative breast cancer, as well as established risk factors such as higher body mass index, removal of more than five lymph nodes, mastectomy, chemotherapy, and radiation therapy, were significantly associated with increased hazard (1.5- to 3.5-fold) of lymphedema. CONCLUSIONS: Findings highlight that hazard of breast cancer-related lymphedema differs by demographic characteristics and clinical features. These factors could be used to identify those at greatest need of lymphedema prevention and early intervention. LAY SUMMARY: In this study, the aim was to investigate breast cancer-related lymphedema (BCRL) burden. This study found that risk of BCRL differs by race, age, and other characteristics.

The Effect of Exercise for the Prevention and Treatment of Cancer-Related Lymphedema: A Systematic Review with Meta-analysis.

INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the effects of exercise on (i) the prevention of cancer-related lymphedema (CRL) and (ii) the treatment of CRL, lymphedema-associated symptoms, and other health outcomes among individuals with CRL. METHODS: An electronic search was undertaken for exercise studies measuring lymphedema and involving individuals at risk of developing or with CRL. The Effective Public Health Practice Project Quality scale was used to assess study quality, and overall quality of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses were performed to evaluate effects of exercise on CRL incidence, existing CRL status, lymphedema-associated symptoms, and health outcomes. RESULTS: Twelve studies ( n = 1955; 75% moderate-high quality) and 36 studies ( n = 1741; 58% moderate-high quality) were included in the prevention and treatment aim, respectively. Relative risk of developing CRL for those in the exercise group compared with the nonexercise group was 0.90 (95% confidence interval (CI), 0.72 to 1.13) overall and 0.49 (95% CI, 0.28 to 0.85) for those with five or more lymph nodes removed. For those with CRL in the exercise group, the standardized mean difference (SMD) before to after exercise of CRL was -0.11 (95% CI, -0.22 to 0.01), and compared with usual care postintervention, the SMD was -0.10 (95% CI, -0.24 to 0.04). Improvements after intervention were observed for pain, upper-body function and strength, lower-body strength, fatigue, and quality of life for those in the exercise group (SMD, 0.3-0.8; P < 0.05). CONCLUSIONS: Findings support the application of exercise guidelines for the wider cancer population to those with or at risk of CRL. This includes promotion of aerobic and resistance exercise, and not just resistance exercise alone, as well as unsupervised exercise guided by symptom response.

A Randomised, Comparative, Effectiveness Trial Evaluating Low- versus High-Level Supervision of an Exercise Intervention for Women with Breast Cancer: The SAFE Trial.

The aim of this comparative, effectiveness trial was to evaluate the safety, feasibility and effect of an exercise intervention delivered via low-level versus high-level supervision. The target population were women who were diagnosed with ≥stage II breast cancer, had ≥ one comorbidity and/or persistent treatment-related side-effects, and were insufficiently physically active. Sixty women (50 ± 9 years) were randomized to the low-supervision group (n = 30) or high-supervision group (n = 30). The low-supervision group participated in a 12-week, individually-tailored exercise intervention supported by five supervised sessions with an exercise professional. The high-supervision group participated in the same exercise intervention but received 20 supervised sessions across the 12-week period. The target weekly dosage of 600 metabolic equivalent minutes of exercise per week (MET-mins/wk) and the session content, such as safety and behaviour change topics, were standardized between the groups. The primary outcomes were intervention safety, defined as the number, type, and severity of exercise-related adverse events (e.g., musculoskeletal injury or exacerbated treatment-related side effects), and feasibility, which was defined as compliance to target exercise dosage. The effect of the intervention on quality of life, physical activity, self-efficacy, fitness, and strength was also assessed (pre- and post-intervention, and at 12-week follow-up). The intervention was safe, with no exercise-related adverse events of grade 3 or above in either group. Both groups reported high compliance to the target exercise dosage (median MET-mins/wk: High = 817; Low = 663), suggesting the exercise intervention was feasible, irrespective of supervision level. Improvements in quality of life, physical activity and fitness were observed post-intervention and maintained at follow-up for both groups (p < 0.05). Only the high-supervision group showed clinically-relevant improvements in strength and self-efficacy at post-intervention (p < 0.05). Individually-targeted exercise delivered under high- or low-levels of supervision is safe, feasible and beneficial for women with stage II+ breast cancer. Future research needs to assess whether the greater gains observed in the group who received higher supervision may contribute to longer term maintenance of physical activity levels and overall health benefits. Australian and New Zealand Clinical Trials Registry: ACTRN12616000547448.

Allogeneic CD20-targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models.

OBJECTIVES: Autologous chimeric antigen receptor (CAR) αß T-cell therapies have demonstrated remarkable antitumor efficacy in patients with haematological malignancies; however, not all eligible cancer patients receive clinical benefit. Emerging strategies to improve patient access and clinical responses include using premanufactured products from healthy donors and alternative cytotoxic effectors possessing intrinsic tumoricidal activity as sources of CAR cell therapies. γδ T cells, which combine innate and adaptive mechanisms to recognise and kill malignant cells, are an attractive candidate platform for allogeneic CAR T-cell therapy. Here, we evaluated the manufacturability and functionality of allogeneic peripheral blood-derived CAR+ Vδ1 γδ T cells expressing a second-generation CAR targeting the B-cell-restricted CD20 antigen. METHODS: Donor-derived Vδ1 γδ T cells from peripheral blood were ex vivo-activated, expanded and engineered to express a novel anti-CD20 CAR. In vitro and in vivo assays were used to evaluate CAR-dependent and CAR-independent antitumor activities of CD20 CAR+ Vδ1 γδ T cells against B-cell tumors. RESULTS: Anti-CD20 CAR+ Vδ1 γδ T cells exhibited innate and adaptive antitumor activities, such as in vitro tumor cell killing and proinflammatory cytokine production, in addition to in vivo tumor growth inhibition of B-cell lymphoma xenografts in immunodeficient mice. Furthermore, CD20 CAR+ Vδ1 γδ T cells did not induce xenogeneic graft-versus-host disease in immunodeficient mice. CONCLUSION: These preclinical data support the clinical evaluation of ADI-001, an allogeneic CD20 CAR+ Vδ1 γδ T cell, and a phase 1 study has been initiated in patients with B-cell malignancies (NCT04735471).