Personalised exercise rehabilitation in cancer survivorship: the percs triage and referral system study protocol.

BACKGROUND: To effectively embed exercise rehabilitation in cancer survivorship care, a co-ordinated system of acute and community exercise rehabilitation services, forming a stepped model of care, is recommended. Patients can be directed to the exercise rehabilitation service which best meets their needs through a system of assessment, triage and referral. Triage and referral systems are not yet widely applied in cancer survivorship practice and need to be evaluated in real-world contexts. The PERCS (Personalised Exercise Rehabilitation in Cancer Survivorship) study aims to evaluate the real-world application of an exercise rehabilitation triage and referral system in cancer survivors treated during the COVID-19 pandemic. Secondary aims are to evaluate change in physical and psychosocial outcomes, and to qualitatively evaluate the impact of the system and patient experiences, at three months after application of the triage and referral system. METHODS: This study will assess the implementation of an exercise rehabilitation triage and referral system within the context of a physiotherapy-led cancer rehabilitation clinic for cancer survivors who received cancer treatment during the COVID-19 pandemic. The PERCS triage and referral system supports decision making in exercise rehabilitation referral by recommending one of three pathways: independent exercise; fitness professional referral; or health professional referral. Up to 100 adult cancer survivors treated during the COVID-19 pandemic who have completed treatment and have no signs of active disease will be recruited. We will assess participants' physical and psychosocial wellbeing and evaluate whether medical clearance for exercise is needed. Participants will then be triaged to a referral pathway and an exercise recommendation will be collaboratively decided. Reassessment will be after 12 weeks. Primary outcomes are implementation-related, guided by the RE-AIM framework. Secondary outcomes include physical function, psychosocial wellbeing and exercise levels. Qualitative analysis of semi-structured interviews guided by the Consolidated Framework for Implementation Research (CFIR) will provide insights on implementation and system impact. DISCUSSION: The PERCS study will investigate the real-world application of a cancer rehabilitation triage and referral system. This will provide proof of concept evidence for this triage approach and important insights on the implementation of a triage system in a specialist cancer centre. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, registration number: NCT05615285, date registered: 21st October 2022.

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PURPOSE: Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. METHODS: Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). RESULTS: Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). CONCLUSIONS: Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Sarcopenia: Prevalence, and Impact on Operative and Oncologic Outcomes in the Multimodal Management of Locally Advanced Esophageal Cancer.

OBJECTIVE: The aim of this article was to study the prevalence and significance of sarcopenia in the multimodal management of locally advanced esophageal cancer (LAEC), and to assess its independent impact on operative and oncologic outcomes. SUMMARY OF BACKGROUND DATA: Sarcopenia in cancer may confer negative outcomes, but its prevalence and impact on modern multimodal regimens for LAEC have not been systematically studied. METHODS: Two hundred fifty-two consecutive patients were studied. Lean body mass (LBM), skeletal muscle index (SMI), and fat mass (FM) were determined pre-treatment, preoperatively, and 1 year postoperatively. Sarcopenia was defined by computed tomography (CT) at L3 as SMI < 52.4 cm/m for males and SMI < 38.5 cm/m for females. All complications were recorded prospectively, including comprehensive complications index (CCI), Clavien-Dindo complication (CDC), and pulmonary complications (PPCs). Multivariable linear, logistic, and Cox regression analysis was performed. RESULTS: In-hospital mortality was 1%, and CCI was 21 ±â€Š19. Sarcopenia increased (P = 0.02) from 16% at diagnosis to 31% post-neoadjuvant therapy, with loss of LBM (-3.0 ±â€Š5.4 kg, P < 0.0001), but not FM (-0.3 ±â€Š2.7 kg, P= 0.31) during treatment. On multivariable analysis, preoperative sarcopenia was associated with CCI (P = 0.043), and CDC ≥IIIb (P = 0.003). PPCs occurred in 36% nonsarcopenic versus 55% sarcopenic patients (P = 0.01). Sarcopenia did not impact disease-specific (P = 0.14) or overall survival (P = 0.11) after resection. At 1 year, 35% had sarcopenia, significantly associated with pre-treatment BMI (P = 0.013) but not complications (P = 0.20). CONCLUSIONS: Sarcopenia increases through multimodal therapy, is associated with an increased risk of major postoperative complications, and is prevalent in survivorship. These data highlight a potentially modifiable marker of risk that should be assessed and targeted in modern multimodal care pathways.

Weight Loss, Satiety, and the Postprandial Gut Hormone Response After Esophagectomy: A Prospective Study.

OBJECTIVE: To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy. BACKGROUND: With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood. METHODS: In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires. RESULTS: Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1 ±â€Š2.3% (P < 0.001) and 16.3 ±â€Š2.2% (P < 0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P= 0.006), and diarrhea (P= 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4 ±â€Š0.2-fold increase, P < 0.01), and GLP-1 peak increased 3.8 ±â€Š0.6-, 4.7 ±â€Š0.8-, and 4.4 ±â€Š0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P < 0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R = 0.74), eating symptoms (P = 0.007, R = 0.54), and trouble enjoying meals (P = 0.0004, R = 0.73). CONCLUSIONS: After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life.

Effects of a multimodal rehabilitation programme on inflammation and oxidative stress in oesophageal cancer survivors: the ReStOre feasibility study.

PURPOSE: Physical, nutritional and quality-of-life compromises are known sequelae of oesophageal cancer (OC) treatment. Inflammation and oxidative stress may be relevant to adverse consequences. Multimodal rehabilitation involving exercise and diet prescription may attenuate some of the negative consequences and optimise survivorship, and this was assessed in this feasibility study in OC patients at least 1 year post-oesophagectomy. METHODS: The 12-week programme included supervised and home-based exercise, dietetic counselling to ensure energy balance and multidisciplinary education. Baseline and post-intervention assessments examined aerobic fitness, physical activity and body composition. Serum interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, IL-6 and IL-8 were measured via multiplex arrays. Lactate secretion, lipid peroxidation (4-HNE) and oxidative stress (8-iso-PGF2α) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Twelve patients (mean (SD) age 64(1.29) years) participated. IL-8 reduced significantly from pre- to post-intervention (percentage change -11.25 % (95 % CI -20.98 to -1.51 %), p = 0.03), and there was a non-significant trend towards lower expression patterns of other inflammatory mediators. At baseline, inflammatory status correlated inversely with sedentary behaviour (IL-6 rho = -0.74, IL-8 rho = -0.59, TNF-α rho = -0.69; p < 0.05). While energy metabolism did not change, post-intervention lactate concentration correlated strongly and inversely with aerobic fitness (rho = -0.68, p = 0.02). Body composition was maintained throughout the intervention. CONCLUSIONS: Results suggest that multimodal rehabilitation following OC treatment reduced inflammatory status without compromising body composition. Findings will be further examined in a larger randomised controlled trial.

A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers.

BACKGROUND: Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers. METHODS/DESIGN: Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. DISCUSSION: The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive of breast cancer occurrence.

The presentation of metabolic dysfunction and the relationship with energy output in breast cancer survivors: a cross-sectional study.

BACKGROUND: Breast cancer prognosis can be adversely influenced by obesity, physical inactivity and metabolic dysfunction. Interventions aimed at improving surrogate markers of breast cancer risk such as insulin resistance may result in improved breast cancer outcomes. The design of such interventions may be improved through increased understanding of metabolic presentation in this cohort. This cross-sectional study aimed to characterise the metabolic profile of breast cancer survivors relative to abdominal obesity and insulin resistance. A secondary aim was to compare measures of energy output across these groups. METHODS: Sixty-nine women (mean (SD) age 53.43 (9.39) years) who had completed adjuvant chemotherapy and radiotherapy for breast cancer were recruited. All measures were completed during one assessment conducted 3.1 (1.0) years post diagnosis. Body composition was measured by bioimpedance analysis and waist circumference (WC). Fasting (12 hour) blood samples were drawn to measure lipid profile, glucose, insulin, glycosylated haemoglobin A1c (HBA1c) and C-reactive protein (CRP). Insulin resistance was estimated by the homeostatic model assessment index (HOMA-IR)). Energy output was evaluated by resting metabolic rate (RMR) measured by indirect calorimetry and physical activity measured by accelerometry. Characteristics were compared across four groups (1. WC <80 cm, not insulin resistant; 2. WC 80-87.9 cm, not insulin resistant; 3. WC >88 cm, not insulin resistant; 4. WC >80 cm, insulin resistant) using ANOVA (p < 0.05). RESULTS: Group 4 was characterised by significant disturbances in measures of glucose metabolism (glucose, insulin, HOMA-IR and HBA1c) and raised CRP compared to other groups. Group 4 also displayed evidence of dyslipidemia and higher body composition values compared to Groups 1 and 2. Both absolute and adjusted RMR were significantly higher in the Group 4 versus all other groups. Physical activity levels were similar for all groups. CONCLUSIONS: The results from this study suggest that participants who were both centrally obese and insulin resistant showed evidence of dyslipidemia, low-grade inflammation and glucose dysregulation. Metabolic profiles of participants who were centrally obese only were not significantly different from lean participants. Consideration of baseline metabolic presentation may be useful when considering the therapeutic targets for future interventions in this cohort.

Adherence to physical activity recommendations and barriers to physical activity participation among adults with type 1 diabetes.

BACKGROUND: Physical activity (PA) is important for those with type 1 diabetes (T1DM); however, accurate information on PA in people with T1DM is limited. AIMS: This study assessed adherence to PA guidelines using both objective and subjective PA measures and evaluated the relationship between accelerometer-measured PA and cardiovascular disease (CVD) risk factors. Barriers to PA were also assessed. METHODS: Using an observational cross-sectional design, PA was measured objectively over 7 days in 72 participants (34 males) using an accelerometer (ActiGraph) and subjectively using the International Physical Activity Questionnaire (IPAQ). Perceived barriers to PA were assessed using the Barriers to Physical Activity in Diabetes (type 1) scale. Multiple linear regression models assessed the influence of PA on HbA1c and CVD risk factors. RESULTS: Mean age ± SD was 40.9 ± 12.9 years, diabetes duration was 18 ± 11.6 years, and HbA1c was 65 ± 14 mmol/mol /8.0 ± 1.3%. Twenty-three (32%) participants exercised according to PA recommendations as measured by an accelerometer. Sixty-nine (97%) participants reported meeting the recommendations as per the IPAQ. Those meeting recommendations (accelerometry) had a lower HbA1c (p = 0.001), BMI (p = 0.032), waist circumference (p = 0.006), and fat mass (p = 0.032) and a greater number of hypoglycaemic events (p = 0.004). Fear of hypoglycaemia was the strongest barrier to PA (mean 3.4 ± 2.0). CONCLUSION: The majority of participants failed to meet PA recommendations. Meeting the recommendations was associated with healthier CVD risk factor profiles. Individuals with T1DM possibly overestimate their PA using self-reported measures and require support and education to safely improve activity levels.

Associations Among Physical Activity, Skeletal Related Events, and Patient Reported Outcomes in Patients with Bone Metastases.

OBJECTIVES: Emerging evidence supports exercise as a therapeutic intervention for patients with bone metastases. However, exercise prescription in practice is limited by concerns regarding skeletal-related events (SREs). This study examined associations among habitual physical activity levels, history of SREs, and patient reported outcomes in patients with bone metastases. DATA SOURCES: A total of 58 patients with bone metastases (n = 45 breast cancer; n = 13 prostate cancer; mean time since cancer diagnosis 5.8 [4.7] years) were assessed. Habitual physical activity levels were collected by accelerometry. Standardized subjective assessment collected history of SREs, quality of life (EORTC-QLQ-C30 and EORTC-BM22), pain (Brief Pain Inventory), sleep quality (Pittsburgh Sleep Quality Questionnaire), and perceptions about exercise (Exercise Benefits/Barriers Scale). Participants spent a mean of 77.37% (standard deviation 14.3)% of waking hours sedentary and a mean of 20.14% (standard deviation 13.4)% of waking hours in light intensity activity. Almost half (n = 28) completed ≥150 min/wk moderate-to-vigorous intensity activity. Higher levels of moderate-to-vigorous intensity activity were associated with lower pain scores, better perceived physical function, lower functional interference scores, and better quality of life. Patients with a history of fracture since diagnosis spent more time sedentary and in light intensity activity in comparison to those with no fracture history (P < .05). CONCLUSION: Moderate-to-vigorous intensity physical activity may have multiple benefits for patients with bone metastases. Reducing sedentary behavior may be a key target for patients with a history of fracture. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses play a key role in providing education on the benefits of exercise, overcoming barriers to physical activity and timely referrals.

The Effectiveness of Nutrition Interventions Combined with Exercise in Upper Gastrointestinal Cancers: A Systematic Review.

Malnutrition and muscle wasting are associated with impaired physical functioning and quality of life in oncology patients. Patients diagnosed with upper gastrointestinal (GI) cancers are considered at high risk of malnutrition and impaired function. Due to continuous improvement in upper GI cancer survival rates, there has been an increased focus on multimodal interventions aimed at minimizing the adverse effects of cancer treatments and enhancing survivors' quality of life. The present study aimed to evaluate the effectiveness of combined nutritional and exercise interventions in improving muscle wasting, physical functioning, and quality of life in patients with upper GI cancer. A comprehensive search was conducted in MEDLINE, EMBASE, Web of Science, Cochrane Library, and CINHAL. Of the 4780 identified articles, 148 were selected for full-text review, of which 5 studies met the inclusion criteria. Whilst reviewed studies showed promising effects of multimodal interventions on physical functioning, no significant differences in postoperative complications and hospital stay were observed. Limited available evidence showed conflicting results regarding the effectiveness of these interventions on preserving muscle mass and improving health-related quality of life. Further studies examining the impact of nutrition and exercise interventions on upper GI patient outcomes are required and would benefit from reporting a core outcome set.

Effect of the Rehabilitation Program, ReStOre, on Serum Biomarkers in a Randomized Control Trial of Esophagogastric Cancer Survivors.

BACKGROUND: The Rehabilitation Strategies Following Esophagogastric cancer (ReStOre) randomized control trial demonstrated a significant improvement in cardiorespiratory fitness of esophagogastric cancer survivors. This follow-up, exploratory study analyzed the biological effect of exercise intervention on levels of 55 serum proteins, encompassing mediators of angiogenesis, inflammation, and vascular injury, from participants on the ReStOre trial. METHODS: Patients >6 months disease free from esophagogastric cancer were randomized to usual care or the 12-week ReStOre program (exercise training, dietary counselling, and multidisciplinary education). Serum was collected at baseline (T0), post-intervention (T1), and at 3-month follow up (T2). Serum biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-seven patients participated in this study; 17 in the control arm and 20 in the intervention arm. Exercise intervention resulted in significant alterations in the level of expression of serum IP-10 (mean difference (MD): 38.02 (95% CI: 0.69 to 75.35)), IL-27 (MD: 249.48 (95% CI: 22.43 to 476.53)), and the vascular injury biomarkers, ICAM-1 (MD: 1.05 (95% CI: 1.07 to 1.66)), and VCAM-1 (MD: 1.51 (95% CI: 1.04 to 2.14)) at T1. A significant increase in eotaxin-3 (MD: 2.59 (95% CI: 0.23 to 4.96)), IL-15 (MD: 0.27 (95% CI: 0 to 0.54)) and decrease in bFGF (MD: 1.62 (95% CI: -2.99 to 0.26)) expression was observed between control and intervention cohorts at T2 (p<0.05). CONCLUSIONS: Exercise intervention significantly altered the expression of a number of serum biomarkers in disease-free patients who had prior treatment for esophagogastric cancer. IMPACT: Exercise rehabilitation causes a significant biological effect on serum biomarkers in esophagogastric cancer survivors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03314311).

eHealth-based intervention to increase physical activity levels in people with cancer: protocol of a feasibility trial in an Irish acute hospital setting.

INTRODUCTION: Exercise and physical activity (PA) are established and effective treatment options for various side effects of cancer treatments such as surgery, chemotherapy and radiotherapy. The advent of eHealth brings new opportunities to influence healthy behaviours, using interactive and novel approaches. Influencing PA behaviours in people with cancer presents a potential application of this. The aim of this study is to evaluate the feasibility and preliminary efficacy of an intervention, using eHealth, for increasing PA in cancer survivors. METHODS AND ANALYSIS: This will be a single-arm pre-post feasibility study. We aim to recruit a heterogeneous sample of 60 participants from cancer clinics in St. James's Hospital, Dublin, Ireland. Eligibility criteria will include patients who have completed chemotherapy and/or radiotherapy with curative intent between 3 and 36 months prior to enrolment. The intervention will include the delivery of a 12-week PA programme. The eHealth aspect of the intervention will involve the provision of a Fitbit activity tracker, which will be used in conjunction with specific PA goals remotely prescribed and monitored by a physiotherapist. Primary outcomes will be feasibility measures related to the study (recruitment capability, data collection procedures, adherence and compliance, evaluation of the resources to implement the study and evaluation of participant responses to the intervention). Secondary measures will evaluate preliminary efficacy of the intervention in terms of clinical outcomes (body composition, PA (objective and self-report), quality of life and aerobic capacity). Primary and secondary outcomes will be assessed at baseline (as appropriate), at conclusion of the intervention and at a 6-month follow-up. ETHICS AND DISSEMINATION: Ethical approval has been granted by the St. James's Hospital/AMNCH Joint Ethics Committee (2016/05/02). Results from this study will be submitted for publication in peer-reviewed journals, as well as for presentation and dissemination at conferences in the field of oncology and survivorship. TRIAL REGISTRATION: NCT03036436; Pre-results.

Acute high-intensity aerobic exercise affects brain-derived neurotrophic factor in mild cognitive impairment: a randomised controlled study.

OBJECTIVE: To investigate the brain-derived neurotrophic factor (BDNF) and cognitive response to a short bout of high-intensity aerobic exercise in older adults with mild cognitive impairment (MCI). METHODS: Participants were randomised to one of two testing schedules, completing either a standardised exercise test (group A) or a resting control condition (group B). Blood sampling and cognitive measures (visuospatial learning and memory, sustained attention and executive function) were collected at baseline (T1) and postintervention (T2). An additional measurement of study outcomes was collected after exercise (T3) in group B only. RESULTS: 64 participants (female 53.2%, mean age 70.5±6.3 years) with MCI were recruited. From T1 to T2, serum BDNF (sBDNF) concentration increased in group A (n=35) (median (Md) 4564.61±IQR 5737.23 pg/mL to Md 5173.27±5997.54 pg/mL) and decreased in group B (Md 4593.74±9558.29 pg/mL to Md 3974.66±3668.22 pg/mL) (between-group difference p=0.024, effect size r=0.3). The control group made fewer errors on the sustained attention task compared with the exercise group (p=0.025). Measures of visuospatial learning and memory or executive function did not change significantly between groups. CONCLUSION: This study is the first to show that a short bout of high-intensity aerobic exercise increases peripheral sBDNF in a population with MCI. However, acute exercise did not improve cognitive performance.

Considerations for Exercise Prescription in Patients With Bone Metastases: A Comprehensive Narrative Review.

Metastatic disease is a frequent complication of advanced cancer, with bone representing one of the most common sites of metastatic occurrence. Patients with bone metastases receive long-term systemic treatments that have a significant attritional impact on muscle strength, fatigue, and physical functioning. Physical rehabilitation involving exercise and physical activity prescription has a considerable role in counteracting these changes; however, exercise is often perceived as a contraindication in the presence of bone metastases due to concerns about aggravating skeletal related events. This article examines the physical sequelae of bone metastases and outlines the factors for consideration with exercise prescription in metastatic bone disease, including bone health, pain levels, and oncologic treatment. This article includes a comprehensive review of the evidence from trials of exercise prescription in this population, including the efficacy and safety outcomes of exercise interventions. Exercise interventions for patients with bone metastases are associated with positive physical and self-reported outcomes. Studies reviewed reporting adverse events did not find a high fracture incidence with exercise in comparison with control participants, or an association between exercise and fracture risk. The need to individualize exercise prescription and adapt exercises to patient ability were reinforced in all papers reviewed. Exercise prescription to patients with bone metastases does involve complex decision making; however, a number of tools are available that may inform both the assessment of patients and the prescription of exercise. LEVEL OF EVIDENCE: NA.

Physical decline and its implications in the management of oesophageal and gastric cancer: a systematic review.

PURPOSE: The management of oesophageal and gastric cancer can cause significant physical decline, impacting on completion rates and outcomes. This systematic review aimed to (i) determine the impact of chemotherapy, chemoradiotherapy and surgery on physical function; (ii) identify associations between physical function and post-operative outcomes; and (iii) examine the effects of rehabilitation on physical function. METHODS: We included randomised controlled trials (RCT), non-RCTs of interventions and cohort studies that measured physical function by objective means in patients with oesophageal or gastric cancer. EMBASE, PubMed, CINAHL, Cochrane Library, SCOPUS, PEDro and the WHO Trial Registry were searched up to June 2016. Risk of bias assessment was performed using a suite of validated tools. RESULTS: Twenty-five studies involving 1897 participants were included. A meta-analysis was not indicated due to the heterogeneity of the literature. Significant reductions in physical function occur in patients undergoing neoadjuvant treatment and in the first 3 months post-resection. Lower pre-operative exercise capacity is associated with an increased risk of post-operative pulmonary complications (PPCs). Evidence to support exercise prehabilitation and rehabilitation in these treatment pathways is currently lacking. CONCLUSIONS: Chemotherapy, chemoradiation and surgery lead to reduced physical function in patients with oesophageal and gastric cancer. High quality evidence is lacking to prove the benefit of interventions that improve physical function through the treatment pathway and in recovery, and well-designed studies are required. This review was limited due to the heterogeneity of the literature, high risk of bias in some articles and the lack of high quality research encompassing sufficient time points in the patient journey. IMPLICATIONS FOR CANCER SURVIVORS: Curative treatment for oesophago-gastric cancer can negatively impact on physical function. Rehabilitation programmes have considerable potential to enhance physical function across the oesophago-gastric cancer journey.

Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4): a multicentre, randomised, controlled phase III study protocol.

INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. ETHICS AND DISSEMINATION: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation. TRIAL REGISTRATION NUMBER: NCT02730338.

The development of the metabolic syndrome and insulin resistance after adjuvant treatment for breast cancer.

BACKGROUND: Adjuvant breast cancer treatment is associated with a number of adverse physical changes, including weight gain, and therefore may represent a critical period for the development of metabolic disturbance. OBJECTIVE: The aim of this study was to evaluate changes in the presentation of the metabolic syndrome (MetSyn) and insulin resistance from breast cancer surgery to postcompletion of adjuvant treatment. METHODS: Sixty-one participants who had completed metabolic screening, including fasting blood samples and anthropometric measurements, on the morning of breast cancer surgery were recruited. Measures were repeated after completion of adjuvant treatment. Change in the proportion of participants presenting with the MetSyn was evaluated using the related-samples McNemar test, and changes in measures of glucose metabolism (fasting insulin, insulin resistance [homeostatic model assessment index], and glycosylated hemoglobin [HbA1c]) were analyzed using paired t tests. The Kruskal-Wallis test was used to compare differences in changes in metabolic parameters across clinical and lifestyle characteristics. RESULTS: There was a significant (P < .001) increase in fasting insulin (mean [SE] change, 2.73 [0.57] mU/L), homeostatic model assessment index (0.58 [0.14]), and HbA1c level (4.49 [5.63] mmol/mol) from baseline to follow-up along with an increase in the proportion diagnosed with the MetSyn (P = .03). Those with the MetSyn at diagnosis experienced a greater increase in insulin resistance. Premenopausal women experienced greatest increases in HbA1c level. CONCLUSIONS: Results demonstrate the development of significant metabolic dysfunction, characterized by glucose dysmetabolism and MetSyn, after adjuvant treatment for breast cancer. IMPLICATIONS FOR PRACTICE: Interventions to improve the metabolic profile of breast cancer survivors are warranted.