ArticleLiterature Review

# Exercise intolerance in cancer and the role of exercise therapy to reverse dysfunction

Authors:
• University of British Columbia
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## Abstract

Exercise tolerance reflects the integrative capacity of components in the oxygen cascade to supply adequate oxygen for ATP resynthesis. Conventional cancer therapies can simultaneously affect one or more components of this cascade and reduce the body's ability to deliver or utilise oxygen and substrate, leading to exercise intolerance. We propose that molecularly-targeted therapy is associated with a further, more subtle, negative effect on the components that regulate exercise limitation. We outline possible causes of exercise intolerance in patients with cancer and the role of exercise therapy to mitigate or prevent dysfunction. We also discuss possible implications for exercise-regulated gene expression for cancer biology and treatment efficacy. A better understanding of these issues might lead to more effective integration of exercise therapy to optimise the treatment and management of patients with cancer.

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... Cancer survivors are exposed to a variety of direct (local/regional therapy, systemic therapy, and supportive care) and indirect factors (modifiable and nonmodifiable risk factors) that may lead to adverse effects on pulmonary, cardiovascular, hematologic, and musculoskeletal components [4]. Oxygen consumption in cancer patients may be adversely affected by aging, deconditioning, existing comorbidities, cancer pathophysiology, and cancer therapies (surgery, radiation, chemotherapy, and hormone therapy) [5]. Each class of cytotoxic chemotherapy used in cancer treatment can cause short-or long-term cardiovascular complications. ...
... In addition, chemotherapy is known to impact hemoglobin concentration [7]. The decrease in hemoglobin concentration results in lower arterial oxygen saturation and reduced oxygen consumption [5]. This impairment in oxygen consumption can lead to reduced exercise capacity in cancer and consequent complications such as exercise intolerance, fatigue, muscle weakness, and pain in cancer survivors [8]. ...
... Neoadjuvant chemoradiotherapy significantly reduces muscle mitochondrial function and physical fitness objectively evaluated with CPET [25,26]. Surgical treatment of malignant diseases other than lung cancer does not directly affect the structural integrity of the components in the oxygen cascade, but indirect factors such as functional limitations, longterm bed rest and immobility, deconditioning, and pain can reduce physical fitness [5]. The results of CPET showed that CRC survivors had poorer cardiorespiratory fitness compared to healthy individuals. ...
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Article
Purpose This study aimed to evaluate respiratory muscle strength and endurance, maximal oxygen consumption, and fatigue of colorectal cancer (CRC) survivors and compare them with healthy individuals. Methods Demographic and clinical characteristics were recorded. Respiratory muscle strength (maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP)) was measured using an electronic mouth pressure device, and respiratory muscle endurance was assessed using a constant workload protocol with linear workload device. Peak oxygen consumption (VO2peak) was measured using the cardiopulmonary exercise test (CPET) with modified Bruce protocol. Fatigue was assessed using the Brief Fatigue Inventory (BFI). Results The patients had similar demographic characteristics (p > 0.05). MEP (cmH2O and %predicted) were lower in the CRC group than in healthy controls (p < 0.05). MIP (cmH2O and %predicted) and test duration did not differ between the groups (p > 0.05). VO2peak (ml/min and %predicted) and VO2peak/kg (%predicted) were significantly lower in the CRC group (p < 0.05). BFI score differed significantly in the CRC and control groups (p < 0.05). Conclusion Respiratory muscle strength, maximal exercise capacity, and fatigue are adversely affected in CRC survivors. Cancer treatment may cause loss of muscle strength and impair energy metabolism and oxygen transmission. These changes can result in decreased exercise capacity and respiratory muscle strength and increased fatigue. Studies examining the effects of different exercise training programs in CRC survivors are needed.
... These findings are of major concern given that low CRF is an important risk factor for cardiopulmonary disease and mortality in both healthy individuals and patients with cancer [8,9]. SufficientV O 2 max is related to fewer toxic effects of radiotherapy, chemotherapy, and endocrine therapy on the cardiovascular system, respiratory system, and skeletal muscles [10][11][12][13][14][15], and higher physical activity level and daily functioning in patients with cancer [16]. ...
... Unfortunately, studies including self-reports of PA levels among patients with cancer, have shown that patients reduce their PA levels from prior to diagnosis to start of adjuvant treatment [22], and that PA levels decrease significantly during adjuvant therapy [16]. In addition, similar to healthy adults, patients with cancer are subject to the effects of ageing and age-related deconditioning that adversely affect components of the oxygen cascade and lead to reduced tolerance for exercise [13]. However, in patients with cancer, these consequences are compounded by the effects of cancer therapies leading to reductions in exercise tolerance [13]. ...
... In addition, similar to healthy adults, patients with cancer are subject to the effects of ageing and age-related deconditioning that adversely affect components of the oxygen cascade and lead to reduced tolerance for exercise [13]. However, in patients with cancer, these consequences are compounded by the effects of cancer therapies leading to reductions in exercise tolerance [13]. ...
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Article
Background Adjuvant therapy may cause multiple sideeffects on long term health, including reduced cardiorespiratory fitness (CRF) in patients with breast cancer (1, 2). However, there is currently limited knowledge regarding the effect of different types of adjuvant cancer treatment on CRF in other cancer populations. The primary objective of the present study was to assess whether previously known correlates (age, diagnosis, initial CRF, physical activity level), type of adjuvant treatment and cancer-related fatigue were associated with changes in V̇O2max\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{O}_2\mathit{\max}$$\end{document} in patients with breast, prostate or colorectal cancer. Methods Prospective study with two time points of assessment, 85 patients scheduled for adjuvant cancer treatment were included. Cardiorespiratory fitness was assessed by V̇O2max\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{\ V}{O}_2\mathit{\max}$$\end{document} during a maximal incremental exercise test on a treadmill before start of adjuvant therapy and again six months later. Physical activity level was recorded with a physical activity monitor (Sense Wear™ Mini) at baseline as average minutes of moderate-to-vigorous intensity physical activity (MVPA) per day. Physical fatigue at baseline was reported using the Multidimensional Fatigue Inventory-20 questionaire. Results In multivariate linear regression analysis, 30 min higher daily MVPA at baseline was associated with a 5% higher V̇O2max\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{O}_2\mathit{\max}$$\end{document} at six months follow up when adjusted for adjuvant treatment (P = 0.010). Patients receiving adjuvant chemotherapy had a mean decline in V̇O2max\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{O}_2\mathit{\max}$$\end{document} of 10% (− 19, − 1; 95% confidence interval) compared to patients receiving adjuvant endocrine treatment (P = 0.028). Adjuvant radiotherapy, fatigue, age and diagnosis were not significantly associated with changes in V̇O2max\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{O}_2\mathit{\max}$$\end{document}. Conclusion The results of the present study indicate that adjuvant chemotherapy is associated with a subsequent reduction in V̇O2max\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{O}_2\mathit{\max}$$\end{document} in patients with cancer whereas MVPA before start of adjuvant treatment is positively associated with a higher V̇O2max\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{O}_2\mathit{\max}$$\end{document} after end of adjuvant treatment.
... Numerous intervention studies have shown that exercise training has beneficial effects in patients with cancer [19]. Documented effects include reduction of symptoms and side effects, improved physical capacity and functioning, increased muscular strength, and improvements in quality of life (QoL) [20][21][22][23][24][25]. These improvements have been demonstrated both during and after anti-cancer treatment, and across several cancers, disease stages and treatment regimens [19][20][21][22][23]. ...
... Documented effects include reduction of symptoms and side effects, improved physical capacity and functioning, increased muscular strength, and improvements in quality of life (QoL) [20][21][22][23][24][25]. These improvements have been demonstrated both during and after anti-cancer treatment, and across several cancers, disease stages and treatment regimens [19][20][21][22][23]. There is also growing epidemiological evidence that a physical active lifestyle is associated with lower risk of several cancers [26], most clearly elucidated in colon [27], breast [28] and endometrial cancer [29]. ...
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Article
Background The increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer. Methods HI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO 2 max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes. Discussion To our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy. Trial registration The study was prospectively registered at ClinicalTrials.gov on February 10 th 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT04263467
... Age or disease treatments may affect processes related to oxygen supply. It could result in exercise intolerance or limited exercise capacity 58 . Structured aerobic exercise has been proposed to try to mitigate this exercise intolerance 58 . ...
... It could result in exercise intolerance or limited exercise capacity 58 . Structured aerobic exercise has been proposed to try to mitigate this exercise intolerance 58 . ...
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Article
... Physical activity (PA) has been proposed as a nonpharmacologic intervention to combat these effects of treatment in cancer survivors [14,15]. It is a pleiotropic therapeutic strategy with the capacity to act across multiple organ systems to facilitate attenuation and/or prevention of cancer therapyassociated morbidity as well as improve clinical outcomes in cancer survivors so, it has been the focus of many studies [16,17]. ...
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Preprint
Purpose Survival rates for many forms of thoracic malignancies have improved over the past few decades, however, many survivors are coping with the side effects of cancer treatment for longer. Physical activity has been proposed as a therapeutic strategy to act across multiple organ systems and improve clinical outcomes and eHealth could be a good way to encourage patients. The aim of this systematic review was to explore the effects of eHealth in the promotion of PA among thoracic malignancies. Methods Suitable articles were searched using PubMed, Web of Science and Scopus databases using a combination of medical subject headings. Articles were screened by two independent reviewers and were included if they presented an eHealth intervention to improve PA in thoracic malignancies. Results In total, 4781 articles were identified, of which ten met eligibility criteria. Different eHealth interventions were described in these studies: mobile application (app) (n=3), website (n=2), email (n=2), web and mobile application (n=1), telephone counseling (n=1) and online sheet (n=1). All studies reported improvements in PA, with 8/10 studies reporting statistically significant changes. Conclusion Meta-analysis revealed eHealth is a good way to improve PA in thoracic malignancies survivors, compared to no intervention, conventional treatment or a diet approach. Future studies are needed to clarify the specific intervention to improve these patients’ recovery.
... It is well-known that exercise therapy has an impact on improving cardiorespiratory fitness and vital capacity. Also, physical exercise reduces tumor growth, and it has a significant benefit of the patient s quality of life (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). This review used different exercises like aerobic exercise, anaerobic exercise, resistance exercise, high-intensity interval training, and moderate-intensity interval training. ...
Article
Introduction: Cancer is one of the leading causes of death worldwide. However, if diagnosed in an operable stage, it is treated as a chronic disease. As such, long-term results and quality of life requirements imposed a comprehensive approach. Prehabilitation programs encompassing nutritional, physical, and psychological components improved the recovery and minimized the complication rate after surgery. We will focus on physiotherapy as part of prehabilitation in this review. Methods: For systematic search, we used the MEDLINE/PubMed (National Library of medicine), Cochrane Central Register of Controlled Trials (Wiley), Embase (Elsevier, Web of Science, and Cochrane database of systematic reviews. The last search update was on 15th December 2020. The search included randomized clinical trials or quasi-randomized clinical trials evaluating exercise or other non-pharmacological preoperative interventions in gastrointestinal cancers. Results: The ten trials included 1058 patients, 535 (50,6%) patients were in the experimental group, and 523 (49,4%) patients were in the control group. Bicycle exercise training was the best-ranked intervention with the standard mean difference (SMD) of 1,4077 (95% C.I. is 0,7018 – 2,1135) to improve vital functional capacity (s, VO˙ 2 at uˆ L). Short-term exercise affected inspiratory muscle strength, and SMD was 1,1819 (95% C.I.,2953 – 2,0684). Short- term intensity training program SMD was 0,8356 (95% C.I. 0,2042 - 1,4669), and short- term intensity program for muscle endurance 0,8156 (95% C.I. 0,2042 – 1,4669). improves respiratory muscle endurance. Small effect was shown on quality of life in high-intensity cycling interval training SMD 0,7439( 95%C.. 0,0856 – 1,4023), WHO performance status in bicycle exercise training SMD 0,7068( 95% C.I. 0,0547 – 1,3589), mean number of complication in high-intensity endurance training SMD 0,3606 (95% C.I. 0,0072 – 0,7141). Conclusion: Although exercise therapy has been shown to improve vital capacity and respiratory muscle strength, there was a lack of comparison between different exercises. Evidence from these indirect-comparisons studies indicated that physical activity should be encouraged during the preoperative period before oncologic surgery.
... For example, women treated with doxorubicin can develop cardiac complications and might not be able to exercise or might need to have specific monitoring and restrictions, which is why reconditioning should be done gradually ( 33). Regardless of this, exercise training has been shown to improve exercise capacity in cancer survivors without notable adverse events (34,35). Rehabilitation specialists and OT specialists should be aware of these aspects and should closely monitor the patient, due to reduced tolerance to exercise, altered baseline vital signs, and altered physiological responses to certain interventions: excessive fatigue, sweating, pallor changes with exercise or activity, and severe shortness of breath (36). ...
Article
Background. Most adult cancer survivors report a significant decrease of their quality of life and limitations in performing activities of daily living. Occupational therapy is a form of rehabilitation treatment that uses certain techniques and tools aimed at improving functional capacity, improve social participation and overall quality of life. Objective. The overall purpose of this narrative review is to provide a better understanding of the role that occupational therapy can play in the rehabilitation of cancer patients with a focus on the most important cancer-related aspects amenable and manageable by occupational therapy interventions and to increase awareness regarding this form of rehabilitation. Discussion. Given the fact that there is constant grow in the number of cancer survivors with complex needs, rehabilitation and occupational therapy strategies can increase functionality and health-related quality of life of patients with cancer at any point of the disease, but it remains underused, due to certain barriers. Conclusions. Occupational therapy, as part of cancer rehabilitation therapy, can lead to improvements in both short and long-term outcomes, while being cost-effective as goals are always set in collaboration with the patients and are aimed to identify and improve the activities most important and relevant for them.
... Therefore, even if adapted to cope with the imposed COVID-19 pandemic restrictions, nutrition and exercise interventions seem to be effective in improving cardiorespiratory fitness and thus may represent a useful tool to face with the new health challenges imposed by the COVID-19 lockdown [79] to BCS and BC patients. This assumes particular importance if considering the emerging evidence showing that adjuvant therapy can negatively affect cardiorespiratory fitness [80][81][82] and that cardiorespiratory fitness is usually lower in BC patients compared to healthy controls [83,84]. ...
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Article
This study aimed to evaluate the cardiometabolic effects of a home-based lifestyle intervention (LI) in breast cancer survivors (BCSs) during the COVID-19 lockdown. In total, 30 BCSs (women; stages 0–II; non-metastatic; aged 53.5 ± 7.6 years; non-physically active; normal left ventricular systolic function) with a risk factor for recurrence underwent a 3-month LI based on nutrition and exercise. Anthropometrics, Mediterranean diet adherence, physical activity level (PAL), cardiorespiratory fitness (VO2max), echocardiographic parameters, heart rate variability (average standard deviation of NN intervals (ASDNN/5 min) and 24 h very- (24 hVLF) and low-frequency (24 hLF)), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein (hs-CRP)) were evaluated before (T0) and after (T1) the LI. After the LI, there were improvements in: body mass index (kg/m2: T0 = 26.0 ± 5.0, T1 = 25.5 ± 4.7; p = 0.035); diet (Mediet score: T0 = 6.9 ± 2.3, T1 = 8.8 ± 2.2; p < 0.001); PAL (MET-min/week: T0 = 647 ± 547, T1 = 1043 ± 564; p < 0.001); VO2max (mL·min−1·kg−1: T0 = 30.5 ± 5.8, T1 = 33.4 ± 6.8; p < 0.001); signs of diastolic dysfunction (participants: T0 = 15, T1 = 10; p = 0.007); AS-DNN/5 min (ms: T0 = 50.6 ± 14.4, T1 = 55.3 ± 16.7; p = 0.032); 24 hLF (ms2: T0 = 589 ± 391, T1 = 732 ± 542; p = 0.014); glycemia (mg/dL: T0 = 100.8 ± 11.4, T1 = 91.7 ± 11.0; p < 0.001); insulin resistance (HOMA-IR score: T0 = 2.07 ± 1.54, T1 = 1.53 ± 1.11; p = 0.005); testosterone (ng/mL: T0 = 0.34 ± 0.27, T1 = 0.24 ± 0.20; p = 0.003); hs-CRP (mg/L: T0 = 2.18 ± 2.14, T1 = 1.75 ± 1.74; p = 0.027). The other parameters did not change. Despite the home-confinement, LI based on exercise and nutrition improved cardiometabolic health in BCSs.
... De ese modo, el EF en caso de anemia sería efectivo, ya que estimula la producción de eritrocitos 9 . Concretamente el EA de intensidad moderada, como ocurre en población sana, aumenta el volumen sanguíneo por un aumento temprano del volumen plasmático, y uno posterior en el volumen eritrocitario, normalizando el hematocrito 10,79 . Esto no solo mejora el transporte de oxígeno (al aumentar la masa total de hemoglobina), sino que también mejora el gasto cardíaco por aumento de la precarga en diástole 10 , ambos fundamentales en la reducción de la FRC. ...
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Article
Introduction: Several publications have theorized about the triggers of cancer-related fatigue, one of the side effects of the disease and its treatments that most stress cancer survivors. On the other hand, physical exercise has been analyzed as a therapy to reduce the impact of this sequel, and several institutions support its inclusion within care programs for the oncological population. However, cancer fatigue and the role that exercise plays in its control has been exposed without an overall assessment that shows its complexity and why physical exercise is so valuable to reducing it. Objectives: The objective of this work was to review the existing evidence about triggers of fatigue in cancer, to expose how physical exercise acts on each of them to control their symptoms and achieve a comprehensive therapeutic effect. Material and method: Several bibliographic searches were carried out to find out which were the triggers of fatigue proposed by the research, how they develop and affect the oncological patient and, finally, to what extent physical exercise would be a viable tool to control its effects. Results: Exposed to more than twenty triggers and aggravating factors of cancer-related fatigue, we found that most of them could be prevented or at least controlled through physical exercise. Conclusions: It is impossible to isolate some triggers from others, and some of them are inevitable as they are part of the medical treatment of the disease. Understanding the relationships between triggers and knowing the positive effects of physical exercise on each one of them is clearly useful to control this side effect.
... As a result, cancer is now recognized as a chronic illness. 2 However, the adverse effects of many oncologic treatments (ie, cardiotoxicity), the presence of comorbidities, increasing age, and physical inactivity 3 are believed to contribute to the high rates of cardiovascular events and mortality among cancer survivors. 4 While treatment may improve survival, the side effects on physical and psychosocial well-being often reduce quality of life, 5 highlighting the importance of secondary prevention strategies for reducing mortality in the steadily growing number of cancer survivors. 6 Although the preventive role of physical activity has been well established both for the incidence and mortality of cancer, 7 the role of physical fitness, which is partly an objective physiological surrogate of physical activity, 8,9 is less characterized in cancer, particularly for clinical oncology settings. ...
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Article
Introduction: The inverse association between cardiorespiratory fitness and all-cause mortality in apparently healthy populations has been previously reported; however, the existence of this association among adults diagnosed with cancer is unclear. Aim: To determine the association between cardiorespiratory fitness and all-cause mortality in adults diagnosed with cancer. Methods: Medline, Embase, and SPORTDiscus databases were searched. Eligible prospective cohort studies that examined the association of cardiorespiratory fitness with all-cause mortality in adults diagnosed with cancer were included. Hazard ratios (HRs) with associated 95% confidence intervals (CIs) were extracted from studies for all-cause mortality. Random-effects inverse-variance model with the Hartung-Knapp-Sidik-Jonkman adjustment. Results: Data from 13 studies with 6,486 adults were included. Compared with lower levels of cardiorespiratory fitness, high levels were associated with a reduced risk of all-cause mortality among adults diagnosed with any cancer (HR=0.52; 95% CI, 0.35-0.77), lung cancer (HR=0.62; 95% CI, 0.46-0.83), and among those with cardiorespiratory fitness measurement via indirect calorimetry (HR=0.47; 95% CI, 0.27-0.80). Pooled HRs for the reduction in all-cause mortality risk per 1-MET increase were also statistically significant (HR=0.82; 95% CI, 0.69-0.99). Neither age at baseline nor the length of follow-up had a significant influence on the HR estimates for all-cause mortality risk. Conclusion: Cardiorespiratory fitness may confer an independent protective benefit against all-cause mortality in adults diagnosed with cancer. The use of cardiorespiratory fitness as a prognostic parameter might help determine risk for future adverse clinical events and optimise therapeutic management strategies to reduce long-term treatment-related effects in adults diagnosed with cancer.
... Exercise is found to be effective in preventing or reducing the symptoms of cancer and the side effects of cancer treatment [9]. Studies have shown that various exercise interventions (e.g. ...
... 22 In the specific case of cancer patients, this concern is justified by the weaknesses caused by radiotherapy or chemotherapy cytotoxicity, reducing cardiorespiratory capacity, muscle strength and mass, and physical activity levels, and affecting activities of daily life. 23 Considering that demographic and clinical data of the population with cancer may interfere in the differences among physically active groups, 24 we found a significant contrast in the quality of life scores regarding general and functional status between physically active and poorly active individuals after adjusting sample data for cancer type and age. ...
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Article
Introduction: Physical exercise has been considered an important non-pharmacological treatment for reducing tiredness, pain, low self-esteem and increases in body mass in individuals diagnosed with cancer. Objective: To verify the relationship between fatigue, quality of life and levels of physical activity in cancer patients undergoing chemotherapy. Methods: Observational, cross-sectional study. The sample consisted of 85 adult patients undergoing cancer treatment at a university hospital. Physical activity was assessed by the IPAQ, and fatigue and quality of life by the PFS and EORTC QLQ-C30 questionnaires, respectively. Student's t and the Fisher's Exact tests were used to identify differences between active and physically inactive patients for the variables fatigue and quality. Additionally, covariance analysis (ANCOVA) was used, in which simple (outcome and exposure) and adjusted models (age, time of diagnosis and type of cancer) were tested. Results: The study included 85 cancer patients, with a mean of 51.78 years of age (±11.72). Most were female and not physically active. Patients classified as physically inactive had higher scores for “total fatigue” (p=0.01), “behavioral” (p=0.01), “affective” (p=0.02) and psychological/sensory fatigue (p=0.04), compared to the physically active patients (p=0.01). Patients classified as physically not very active presented poorer quality of life in the dimensions: “overall” quality of life (p=0.05) and “functional” (p=0.04), “appetite” (p=0.02), “insomnia” (p=0.0 2), “diarrhea” (p=0.04), “fatigue” (p=0.01), “pain” (p=0.01) and “nausea” (p=0.03), when compared to the physically active patients in both analyses; simple and adjusted. Conclusion: The practice of physical activity during treatment can be a determining factor for increasing quality of life and reducing fatigue in cancer patients, minimizing the adverse effects of chemotherapy. Level of evidence II; retrospective study.
... Patients with lung cancer also develop sequelae because of anti-cancer treatment and inactivity [5]. Lung resection surgery has been related to persistent dyspnoea and lower functional outcomes [6], and coadjuvant treatments are associated with an additional impairment that affects all pathways involved in oxygen transport from the lungs to the working muscles [7]. ...
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Article
Purpose To assess the exercise intervention focused on high-intensity interval training (HIIT) in lung cancer survivors. Design We performed a literature search using PubMed, Web of Science, and Science Direct (last search March 2021). Quality assessment and risk of bias were assessed using the Downs and Black scale and the Cochrane tool. Participants A total of 305 patients of 8 studies were assessed, with their mean age ranging from 61 ± 6.3 to 66 ± 10 years in the exercise group and from 58.5 ± 8.2 to 68 ± 9 years in the control group. Methods A systematic review and meta-analysis of randomized controlled trials and pilot randomized controlled trials was performed. We included controlled trials testing the effect of HIIT in lung cancer survivors versus the usual care provided to these patients. The data were pooled and a meta-analysis was completed for cardiorespiratory fitness (VO2peak). Results We selected 8 studies, which included 305 patients with lung cancer: 6 studies were performed around surgical moment, one study during radiotherapy’s treatment, and other during target therapy. After pooling the data, exercise capacity was included in the analysis. Results showed significant differences in favour to HIIT when compared to usual care in cardiorespiratory fitness (standard mean difference = 2.62; 95% confidence interval = 1.55, 3.68; p < 0.00001). Conclusions and implications The findings indicated a beneficial effect of HIIT for improving cardiorespiratory fitness in lung cancer patients in early stages around oncological treatment moment. Nevertheless, this review has several limitations, the total number of studies was low, and the stage and subtype of lung cancer patients were heterogeneous that means that the conclusions of this review should be taken with caution. Review registration: PROSPERO Identifier: CRD42021231229
... Lung resection is a common treatment for lung cancer and is effective at improving survival rates in stage I and II lung cancer survivors by up to 75 % (Le Chevalier, 2010). In spite of this improvement in survival, overwhelmingly patients experience significant disease-and treatment-related reductions in pulmonary and physical function (Pompili et al., 2011;Wildgaard et al., 2011;Arbane et al., 2011;Brunelli et al., 2009;Jones et al., 2009). Patients who present with low pulmonary and physical function before surgery are at an even greater risk of premature death, and adverse treatment-and diseaserelated outcomes (Ha et al., 2016;Jones et al., 2008a). ...
Article
Lung cancer patients undergoing surgery are often left physically deconditioned and/or with functional deficits. Exercise interventions may improve pulmonary and physical function before and after lung resection. We conducted a systematic review of randomized-controlled trials (RCTs) testing the impact of pre-, post-, and combined pre-and-post surgery exercise interventions on physical and pulmonary function in lung cancer patients. Exercise pre-surgery seems to substantially improve physical and pulmonary function, which are factors associated with improved ability to undergo surgery while reducing post-surgery complications. Evidence is inconsistent for post-surgery interventions, reporting no or moderate effects. Results from pre-and-post surgery interventions are limited to one study. In conclusion, pre- and post-surgery exercise interventions, individually, have shown beneficial effects for lung cancer patients undergoing surgery. The impact of interventions combining both pre- and post-surgery exercise programs remains unknown. More evidence is needed on the ideal exercise setting, and timing across the lung cancer care continuum.
... Also, exercise has been shown to decrease oxidative stress or ROS (51) and improve the cardiometabolic risk profiles, in part by challenging the sarcopenic effects of cancer treatments (52). Specifically, exercise has been shown to increase cardiovascular reserve (50,53,54), such as by increasing peak oxygen consumption (VO 2peak ) through improved endothelial and autonomic function (55), as well as improved cardiac perfusion (56). Importantly, exercise has been shown to counteract the fall in VO 2peak that typically occurs with anthracycline treatment (57). ...
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Article
Anthracyclines are one of the most effective chemotherapy agents and have revolutionized cancer therapy. However, anthracyclines can induce cardiac injuries through ‘multiple-hits', a series of cardiovascular insults coupled with lifestyle risk factors, which increase the risk of developing short- and long-term cardiac dysfunction and cardiovascular disease that potentially lead to premature mortality following cancer remission. Therefore, the management of anthracycline-induced cardiotoxicity is a serious unmet clinical need. Exercise therapy, as a non-pharmacological intervention, stimulates numerous biochemical and physiologic adaptations, including cardioprotective effects, through the cardiovascular system and cardiac muscles, where exercise has been proposed to be an effective clinical approach that can protect or reverse the cardiotoxicity from anthracyclines. Many preclinical and clinical trials demonstrate the potential impacts of exercise on cardiotoxicity; however, the underlying mechanisms as well as how to implement exercise in clinical settings to improve or protect against long-term cardiovascular disease outcomes are not clearly defined. In this review, we summarize the current evidence in the field of “exercise cardio-oncology” and emphasize the utilization of exercise to prevent and manage anthracycline-induced cardiotoxicities across high-risk and vulnerable populations diagnosed with cancer.
... Despite overall low survival rates resulting in less than 20% of LC patients surviving five years or more from initial diagnosis, advances in screening and early detection are causing an increase in LC survivors. Tumours in the lungs directly impair the oxygen cascade leading to a decrease in pulmonary function, cardiorespiratory fitness and exercise capacity [2] which could be further aggravated due to anti-cancer therapies such as surgery as well as chemo radiotherapy. Moreover, LC patients are frequently older and have other concomitant diseases caused by tobacco smoking such as Chronic Obstructive Pulmonary Disease (COPD), which commonly lead to a worsening in symptoms like dyspnoea and fatigue [3]. ...
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Objective The aim of this systematic review was to examine the association between physical activity (PA) and Health-Related Quality of Life (HRQoL) as well as other Patient-Reported Outcome Measures (PROMs) in patients with lung cancer. Material and Methods A systematic search was conducted using the following databases: PUBMED, MEDLINE(Ovid), Cochrane Library Plus, Web Of Science (WOS), SCOPUS, SPORTDiscus and PEDro. The last search was conducted in October the 5th, 2021. Articles which explored the association between PA levels and Health-Related Quality of Life (HRQoL) and/or other PROMs were included. Risk of bias was assessed using the Johanna Briggs Institute Critical Appraisal Tools. When appropriate, a meta-analysis was performed to summarise the strength of the association between PA and each PROM. Results The electronic search yielded 1,000 records of which 23 were finally selected by two independent reviewers. Moderate associations were found between engaging in PA and global HRQoL (r = 0.41; 95% CI: 0.21 – 0.57; p < .0001) as well as depression (r = -0.33; 95% CI: -0.44, -0.19; p < .001). In addition, small assocaitions were also reported for fatigue (r = -0.23; 95% CI: -0.3, -0.17; p < .001) and dyspnoea (r = -0.25; 95% CI: -0.33, -0.16; p < .001). No significant associations were found for anxiety or sleep. Conclusions Although the majority of the studies included some risk of bias, engaging in regular PA seems to be associated with better overall HRQoL, mood and less symptom burden in patients with LC.
... Based on the convenience, security and efficiency, aerobic exercise is recommended as a non-pharmacological method to protect against DOX-induced cardiotoxicity [15]. Nevertheless, the physical endurance is obviously decreased in cancer patients due to cachexia, cardiopulmonary dysfunction or other complications [16]. Therefore, understanding the molecular basis and then artificially imitating the beneficial effects of exercise may provide novel insights to mitigate cardiac injury for DOX-treated cancer patients. ...
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Meteorin-like (METRNL) protein is a newly identified myokine that functions to modulate energy expenditure and inflammation in adipose tissue. Herein, we aim to investigate the potential role and molecular basis of METRNL in doxorubicin (DOX)-induced cardiotoxicity. METRNL was found to be abundantly expressed in cardiac muscle under physiological conditions that was decreased upon DOX exposure. Cardiac-specific overexpression of METRNL by adeno-associated virus serotype 9 markedly improved oxidative stress, apoptosis, cardiac dysfunction and survival status in DOX-treated mice. Conversely, knocking down endogenous METRNL by an intramyocardial injection of adenovirus exacerbated DOX-induced cardiotoxicity and death. Meanwhile, METRNL overexpression attenuated, while METRNL silence promoted oxidative damage and apoptosis in DOX-treated H9C2 cells. Systemic METRNL depletion by a neutralizing antibody aggravated DOX-related cardiac injury and dysfunction in vivo, which were notably alleviated by METRNL overexpression within the cardiomyocytes. Besides, we detected robust METRNL secretion from isolated rodent hearts and cardiomyocytes, but to a less extent in those with DOX treatment. And the beneficial effects of METRNL in H9C2 cells disappeared after the incubation with a METRNL neutralizing antibody. Mechanistically, METRNL activated SIRT1 via the cAMP/PKA pathway, and its antioxidant and antiapoptotic capacities were blocked by SIRT1 deficiency. More importantly, METRNL did not affect the tumor-killing action of DOX in 4T1 breast cancer cells and tumor-bearing mice. Collectively, cardiac-derived METRNL activates SIRT1 via cAMP/PKA signaling axis in an autocrine manner, which ultimately improves DOX-elicited oxidative stress, apoptosis and cardiac dysfunction. Targeting METRNL may provide a novel therapeutic strategy for the prevention of DOX-associated cardiotoxicity.
... In addition, it can be speculated that cluster sets may also offer benefit in other health-related settings (i.e. clinical) where muscular strength, power and mass are of importance but exercise capacity and tolerance are compromised (for examples see Gong et al. 2018 [81]; Jones et al. [82]). As a further example of potential application, the acute hemodynamic response appears to be lower in cluster compared to traditional set configurations [83,84]. ...
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Background The acute responses to cluster set resistance training (RT) have been demonstrated. However, as compared to traditional sets, the effect of cluster sets on muscular and neuromuscular adaptations remains unclear.Objective To compare the effects of RT programs implementing cluster and traditional set configurations on muscular and neuromuscular adaptations.Methods Systematic searches of Embase, Scopus, Medline and SPORTDiscus were conducted. Inclusion criteria were: (1) randomized or non-randomized comparative studies; (2) publication in English; (3) participants of all age groups; (4) participants free of any medical condition or injury; (5) cluster set intervention; (6) comparison intervention utilizing a traditional set configuration; (7) intervention length ≥ three weeks and (8) at least one measure of changes in strength/force/torque, power, velocity, hypertrophy or muscular endurance. Raw data (mean ± SD or range) were extracted from included studies. Hedges’ g effect sizes (ES) ± standard error of the mean (SEM) and 95% confidence intervals (95% CI) were calculated.ResultsTwenty-nine studies were included in the meta-analysis. No differences between cluster and traditional set configurations were found for strength (ES = − 0.05 ± 0.10, 95% CI − 0.21 to 0.11, p = 0.56), power output (ES = 0.02 ± 0.10, 95% CI − 0.17 to 0.20, p = 0.86), velocity (ES = 0.15 ± 0.13, 95% CI − 0.10 to 0.41, p = 0.24), hypertrophy (ES = − 0.05 ± 0.14, 95% CI − 0.32 to 0.23, p = 0.73) or endurance (ES = − 0.07 ± 0.18, 95% CI − 0.43 to 0.29, p = 0.70) adaptations. Moreover, no differences were observed when training volume, cluster set model, training status, body parts trained or exercise type were considered.Conclusion Collectively, both cluster and traditional set configurations demonstrate equal effectiveness to positively induce muscular and neuromuscular adaptation(s). However, cluster set configurations may achieve such adaptations with less fatigue development during RT which may be an important consideration across various exercise settings and stages of periodized RT programs.
... Cancer patients may exhibit a significant reduction in cardiorespiratory fitness as a result of anticancer therapy and physical inactivity. [51,52] In an exercise prescription, a sufficient training stimulus without overexertion is necessary to achieve favorable effects. This dose-response relationship between exercise intensity and favorable effects may be absent in cancer patients. ...
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Purpose of Review Chimeric antigen receptor (CAR) T-cell therapy is a relatively new, innovative treatment strategy to manage refractory hematological cancers, including some types of leukemia, lymphoma, and multiple myeloma. This article outlines the CAR T-cell therapy process, toxicity, and complications, along with an overview of the currently known short- and long-term physical and functional sequelae that will be helpful for general or oncology rehabilitation specialists caring for these patients. Recent Findings There is a dearth of literature on the topic of rehabilitation of patients receiving CAR T-cell therapy. Rehabilitation practices can be extrapolated from the limited functional information on patients who have completed treatment for lymphoma and multiple myeloma. Patients present with cognitive impairment, muscle weakness, reduced exercise capacity, neuropathy, and cancer-related fatigue. Physical activity and rehabilitation programs may be beneficial to address fatigue, psychological symptoms, and quality of life. Summary There is limited rehabilitation research in patients receiving CAR T-cell therapy. These patients may present with general deconditioning and neurological complications which translate to neuromuscular and cognitive impairment that benefit from multidisciplinary rehabilitation intervention prior to, during, and after treatment. Studies measuring the impairments at baseline and evaluation of the impact of rehabilitation practices are much needed to support this.
... Exercise interventions have been shown to be effective in preventing or relieving cancer symptoms and side effects from cancer treatment. 12 Furthermore, several studies including different exercise interventions (eg, aerobic exercise or resistance exercise) have shown improved physical and mental health, QoL, muscle strength, physical function and reduced fatigue in patients with cancer. [13][14][15] Nevertheless, very few trials have investigated the effect of exercise interventions in older women with breast cancer receiving chemotherapy or therapy for advanced/ metastatic disease. ...
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Introduction: Exercise interventions have been widely investigated in patients with cancer and demonstrate beneficial effects. However, intervention studies that include older women with breast cancer exercising during medical treatment are scarce. Hence, the aim of this study is to investigate the effect of a 12-week exercise-based intervention in older women (≥65 years) with breast cancer receiving (neo)adjuvant or first-line or second-line systemic therapy. Methods and analysis: This is a single-centre, two-armed randomised controlled trial. We anticipate including 100 patients, who will be randomised 1:1 to exercise-based intervention or control stratified by treatment setting ((neo)adjuvant or metastatic) and treatment (chemotherapy or endocrine therapy + cyclin-dependent kinase (CDK) 4/6 inhibitors). The intervention group will receive standard oncological treatment and a 12-week supervised exercise-based intervention comprising a progressive resistance exercise programme two times per week, a protein supplement after exercise and a home-based walking programme based on daily step counts. The control group will receive standard oncological treatment. Assessments will be performed at baseline and 6, 12 and 24 weeks after start of the intervention. Primary outcome is physical function, measured by the 30-second Chair Stand Test. Secondary outcomes are feasibility (compliance and adherence to intervention), objective and patient-reported functional measures (6-meter and 10-meter gait speed; 6-min Walk Test; Handgrip Strength; Stair Climb Test; Physical Activity Questionnaire), symptom burden and well-being (MD Anderson Symptom Inventory; Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and B23), body composition (dual-energy X-ray absorptiometry scan), side effects, inflammatory biomarkers, hospitalisation and survival. Ethics and dissemination: The protocol was reviewed and accepted by the Scientific Ethics Review Committee of the Capital Region of Denmark, 17 June 2018 (VEK ref.: H-18021013). Trial results will be submitted for publication in a peer-reviewed journal and presented on conferences, in oncology wards, exercise centres in municipalities and patient organisations, ensuring dissemination to relevant stakeholders. Trial registration number: https://clinicaltrials.gov/ on 3 September 2018. Identifier: NCT03656731.
... 20,22 Finally, reduction in serum estrogen and higher symptom burden associated with endocrine therapy-another of the factors associated with membership to this trajectory-may have deleterious physiologic consequences on multiple systems and interfere with exercise capacity and tolerance. 62,63 Whether behavioral changes occurring after diagnosis of BC can influence recurrence and cancer-related outcomes, including QOL, is the subject of vivid research. Lifestyle interventions proved safe, feasible, and effective for several outcomes in women with BC. 18,[64][65][66][67][68] For example, exercise training during and after completion of chemotherapy led to improvements in physiologic variables and psychosocial status, 69 with beneficial effects on QOL. ...
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Purpose: We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors. Methods: Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498) were included. Trajectories of QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 Summary Score) and associations with trajectory group membership were identified by iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively. Results: Four trajectory groups were identified (N = 4,131): excellent (51.7%), very good (31.7%), deteriorating (10.0%), and poor (6.6%) QOL. The deteriorating trajectory group reported fairly good baseline QOL (mean [95% CI], 78.3/100 [76.2 to 80.5]), which significantly worsened at year-1 (58.1/100 [56.4 to 59.9]) and never recovered to pretreatment values through year-4 (61.1/100 [59.0 to 63.3]) postdiagnosis. Healthy behaviors were associated with better performing trajectory groups. Obesity (adjusted odds ratio [aOR] v lean, 1.51 [95% CI, 1.28 to 1.79]; P < .0001) and current smoking (aOR v never, 1.52 [95% CI, 1.27 to 1.82]; P < .0001) at diagnosis were associated with membership to the deteriorating group, which was also characterized by a higher prevalence of patients with excess body weight and insufficient physical activity through year-4 and by frequent exposure to tobacco smoking during chemotherapy. Additional factors associated with membership to the deteriorating group included younger age (aOR, 1-year decrement 1.01 [95% CI, 1.01 to 1.02]; P = .043), comorbidities (aOR v no, 1.22 [95% CI, 1.06 to 1.40]; P = .005), lower income (aOR v wealthier households, 1.21 [95% CI, 1.07 to 1.37]; P = .002), and endocrine therapy (aOR v no, 1.14 [95% CI, 1.01 to 1.30]; P = .047). Conclusion: This latent-class analysis identified some patients with upfront poor QOL and a high-risk cluster with severe, persistent postchemotherapy QOL deterioration. Screening relevant patient-level characteristics may inform tailored interventions to mitigate the detrimental impact of chemotherapy and preserve QOL, including early addressal of behavioral concerns and provision of healthy lifestyle support programs.
... However, studies in non-metastatic breast cancer survivors provide support for the use of submaximal, HR-based tests in this population, with an example study nding a 90% VO 2 corresponds with 89.1% age-predicted maximum HR [22]. The ndings from this current study, alongside previous research, suggest HR can be used as a marker of more individualized intensity [16,19,35,36]. Additionally, quantifying intensity via an objective (HR) and subjective (RPE) measurement may provide a more balanced and clinically feasible approach to prescribing exercise, as done in the present study and supported by ndings that higher HR was accompanied by increased RPE. ...
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Background: Metastasis breast cancer commonly report physical and psychosocial side effects, which requires a supervised exercise prescription with an individualized assessment. This cross-sectional study examined the feasibility of energy system-based assessment, also generating descriptive values for assessment performance in this population. Methods: This cross-sectional study recruited 70 women diagnosed with metastatic breast cancer. After baseline assessment, participants attempted up to three energy system assessments: submaximal aerobic (multi-stage treadmill); anaerobic alactic (30-second sit-to-stand [30-STS]); and anaerobic lactic (adapted burpees). Heart rate and rating of perceived exertion (RPE) were recorded. Secondary outcomes included body composition, CRF and upper- and lower-limb functionality. Results: 64 and 70 of the participants performed the submaximal aerobic test and the 30-STS, respectively, and 5 completed the adapted burpees task. Heart rate and RPE specific to each task were correlated, reflecting increased intensity. Women reported low-moderate levels of CRF [3(2.1)] and moderate-high functionality levels [upper-limb: 65.8% (23.3); lower-limb: 63.7% (34.7)]. Conclusions: Using a combination of heart rate and RPE, as well as baseline assessment of each energy system, clinicians may improve ability to prescribe personalized exercise and give patients greater ability to self-monitor intensity and progress. Trial registration: ClinicalTrials.gov ID NCT03879096
... 8 Despite the importance of preserving physical function in patients with metastatic cancer, 9 few therapeutic options exist, and there is no standard of care. 10 The decline of physical function may result from the age-related and treatment-related impairments in aerobic capacity, 11 ambulatory activity, 12 13 and muscle strength and mass. 14 15 Randomised controlled trials of older adults without cancer demonstrate that structured physical activity preserves or prevents the deterioration of physical function. ...
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Objectives This study determined the feasibility of delivering a 12-week structured physical activity programme during chemotherapy to older adults recently diagnosed with metastatic gastrointestinal (GI) cancer. Methods This study used a single-cohort design. Older adults (aged ≥65 years) diagnosed with metastatic oesophageal, gastric, pancreatic or colorectal cancer who planned to initiate chemotherapy were enrolled. The physical activity programme included a combination of aerobic, flexibility, strength and balance modalities delivered by a certified cancer exercise trainer during chemotherapy infusion appointments, then translated and sustained at home by participants. The co-primary endpoints included: (1) accrual of 20 participants in 12 months and (2) physical activity adherence of ≥50%. Results Between March and October 2018, 29 participants were screened, and 20 were enrolled within 12 months (recruitment rate: 69% (90% CI: 55% to 83%); p<0.001), meeting the first co-primary endpoint. The median age of participants was 73.3 years (IQR: 69.3–77.2). At week 12, 67% (90% CI: 48% to 85%) of participants adhered to ≥50% of the prescribed physical activity (p=0.079 (statistically significant)), meeting the second co-primary endpoint. From baseline to week 12, accelerometer-measured light-intensity and moderate-intensity to vigorous-intensity physical activity increased by 307.4 (95% CI: 152.6 to 462.2; p<0.001) and 25.0 min per week (95% CI: 9.9 to 40.1; p=0.001), respectively. There were no serious or unexpected adverse events. The median overall survival was 16.2 months (8.4–22.4). Conclusion These results establish the feasibility of a larger scale randomised controlled trial that enrols older adults with metastatic GI cancer and delivers a structured physical activity programme during chemotherapy. Trial registration number NCT03331406 .
... The indirect impact of cancer and cancer treatment on CVD risk should also be considered. Exercise intolerance and subsequent sedentarism is one such sequelae of cancer that is common in survivors and can predispose to CVD [38,39]. Sedentarism is undoubtedly an important consideration in assessing cardiovascular risk, with a 2016 American Heart Association review suggesting a link between sedentary behaviour and not only CVD risk, but also cardiovascular morbidity and mortality [39]. ...
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Purpose of Review Cardiovascular disease is long-term complication of both cancer and anti-cancer treatment and can have significant ramifications for health-related quality of life and mortality. This narrative review explores the current evidence linking cardiovascular disease and cancer, as well as exploring strategies for the prevention and management of cardiovascular disease, and outlines future opportunities in the field of cardio-oncology. Recent Findings Cancer confers risk for various cardiovascular diseases including heart failure, cardiomyopathy, arrhythmia, coronary heart disease, stroke, venous thromboembolism, and valvular heart disease. Cancer treatment, in particular agents such as platinum-based chemotherapy, anthracyclines, hormonal treatments, and thoracic radiotherapy, further increases risk. While cardiovascular disease can be identified early and effectively managed in cancer survivors, cardiovascular screening and management does not typically feature in routine long-term cancer care of adult cancer survivors. Summary Cancer and cancer treatment can accelerate the development of cardiovascular disease. Further research into screening and management strategies for cardiovascular disease, along with evidence-based guidelines, is required to ensure adult cancer survivors receive appropriate long-term care.
... Exercise training also prolongs lifespan, but enhanced exercise performance is not a feature of calorie restriction Racette et al., 2017). When exercise intolerance occurs in the older population, its severity is augmented by chronic diseases, including heart failure (Del Buono et al., 2019), diabetes (Poitras et al., 2018), lung diseases (Vogiatzis and Zakynthinos, 2012) and cancer (Jones et al., 2009), which all share increased oxidative stress as a mechanism in their pathophysiology. For example, exercise intolerance in patients with heart failure is linked to increased mitochondrial ROS (Shirakawa et al., 2019), increased plasma lipid peroxidation (Keith et al., 1998;Sawyer, 2011), and increased plasma malondialdehyde (Nishiyama et al., 1998) and decreased SOD activity (Nishiyama et al., 1998). ...
Article
The progressive increase in lifespan over the past century carries with it some adversity related to the accompanying burden of debilitating diseases prevalent in the older population. This review focuses on oxidative stress as a major mechanism limiting longevity in general, and healthful aging, in particular. Accordingly, the first goal of this review is to discuss the role of oxidative stress in limiting longevity, and compare healthful aging and its mechanisms in different longevity models. Secondly, we discuss common signaling pathways involved in protection against oxidative stress in aging and in the associated diseases of aging, e.g., neurological, cardiovascular and metabolic diseases, and cancer. Much of the literature has focused on murine models of longevity, which will be discussed first, followed by a comparison with human models of longevity and their relationship to oxidative stress protection. Finally, we discuss the extent to which the different longevity models exhibit the healthful aging features through physiological protective mechanisms related to exercise tolerance and increased β-adrenergic signaling and also protection against diabetes and other metabolic diseases, obesity, cancer, neurological diseases, aging-induced cardiomyopathy, cardiac stress and osteoporosis.
... Although cancer itself in combination with surgery, radiotherapy, and endocrine treatment can impair CRF, the chemotherapy-induced toxicity caused by the generation of reactive oxygen species and the induction of cardiac myocyte apoptosis or necrosis is known to be the most harmful treatment, especially if the therapy is anthracycline-based (Chen et al., 2007;Shi et al., 2011;Suter and Ewer, 2013). There may be other mechanisms for why chemotherapy impairs CRF, for example, anemia, dehydration, and impairment of pathways within muscle cells which again impair the O 2 extraction from the blood to the muscles (Jones et al., 2009;Christensen et al., 2018). Consequently, it may be more physiologically difficult for younger women to gain the beneficial effect of HI vs. LMI exercise because more of them receive chemotherapy. ...
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IntroductionThe results from the physical training and cancer randomized controlled trial (Phys-Can RCT) indicate that high intensity (HI) strength and endurance training during (neo-)adjuvant cancer treatment is more beneficial for cardiorespiratory fitness (CRF, measured as peak oxygen uptake [VO2peak]) than low-to-moderate intensity (LMI) exercise. Adherence to the exercise intervention and demographic or clinical characteristics of patients with breast cancer undergoing adjuvant treatment may moderate the exercise intervention effect on VO2peak. In this study, the objective was to investigate whether baseline values of VO2peak, body mass index (BMI), time spent in moderate- to vigorous-intensity physical activity (MVPA), physical fatigue, age, chemotherapy treatment, and the adherence to the endurance training moderated the effect of HI vs. LMI exercise on VO2peak.Materials and Methods We used data collected from a subsample from the Phys-Can RCT; women who were diagnosed with breast cancer and had a valid baseline and post-intervention VO2peak test were included (n = 255). The exercise interventions from the RCT included strength and endurance training at either LMI, which was continuous endurance training at 40–50% of heart rate reserve (HRR), or at HI, which was interval training at 80–90% of HRR, with similar exercise volume in the two groups. Linear regression analyses were used to investigate moderating effects using a significance level of p < 0.10. Statistically significant interactions were examined further using the Johnson–Neyman (J-N) technique and regions of significance (for continuous variables) or box plots with adjusted means of post-intervention VO2peak (for binary variables).ResultsAge, as a continuous variable, and adherence, dichotomized into < or > 58% based on median, moderated the effect of HI vs. LMI on CRF (B = −0.08, 95% CI [−0.16, 0.01], pinteraction = 0.06, and B = 1.63, 95% CI [−0.12, 3.38], pinteraction = 0.07, respectively). The J-N technique and regions of significance indicated that the intervention effect (HI vs. LMI) was positive and statistically significant in participants aged 61 years or older. Baseline measurement of CRF, MVPA, BMI, physical fatigue, and chemotherapy treatment did not significantly moderate the intervention effect on CRF.Conclusion Women with breast cancer who are older and who have higher adherence to the exercise regimen may have larger effects of HI exercise during (neo-)adjuvant cancer treatment on CRF.
... In their study, Sanver et al. showed that expiratory muscle strength and maximal oxygen uptake were lower in patients undergoing surgery for colorectal cancer compared to healthy individuals [17]. The reduced mobility in the spine joints may also have been caused by the reduced physical activity of patients after the procedure, pain within the operated area and fatigue associated with treatment [18,19]. ...
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Article
The aim of this non-randomized study was to evaluate the impact of spine joint mobility and chest mobility on inhalation and exhalation, and to assess the abdominal muscle strength in patients undergoing surgery for colorectal cancer with one of the following methods: anterior resection, laparoscopic anterior resection or abdominoperineal resection. In patients who were successively admitted to the Department of Surgical Oncology at the Oncology Center in Bydgoszcz, the impact of spine joint mobility, muscle strength and chest mobility on inhalation and exhalation wasassessed three times, i.e., at their admission and three and six months after surgery. The analysis included 72 patients (18 undergoing abdominoperineal resection, the APR group; 23 undergoing laparoscopic anterior resection, the LAR group; and 31 undergoing anterior resection, the AR group). The study groups did not differ in terms of age, weight, height, BMIor hospitalization time (p > 0.05). Three months after surgery, reductions in spine joint mobility regarding flexion, extension and lateral flexion, as well asreductions in the strength of the rectus abdominis and oblique muscles, were noted in all study groups (p < 0.05). In comparison between the groups, the lowest values suggesting the greatest reduction in the range of mobility were recorded in the APR group. Surgical treatment and postoperative management in colorectal cancer patients caused a reduction in spine mobility, abdominal muscle strength and chest mobility. The patients who experienced those changes most rapidly and intensively werethose undergoing abdominoperineal resection.
... There is vast literature on neurological and oncological rehabilitation but relatively little on the rehabilitation of patients with brain tumors [24,34], although several randomized controlled trials are now underway to address this knowledge gap [35][36][37]. The functional status and condition of patients with brain tumors are often compared with those occurring in patients after stroke [34,[38][39][40][41][42][43][44][45] or craniocerebral injury [42,46,47]. ...
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Article
Repeat surgery is often required to treat brain tumor recurrences. Here, we compared the functional state and rehabilitation of patients undergoing initial and repeat surgery for brain tumors to establish their individual risks that might impact management. In total, 835 patients underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. The Karnofsky performance status, Barthel index, and the modified Rankin scale were used to assess functional status, and the gait index was used to assess gait efficiency. Motor skills, postoperative complications, and length of hospital stay were recorded. Patients were classified into two groups: first surgery (n = 103) and repeat surgery (n = 30). Eighteen percent of patients required reoperations, and these patients required prolonged postoperative rehabilitation as often as those operated on for the first time. Rehabilitation was more often complicated in the repeat surgery group (p = 0.047), and the complications were more severe and persistent. Reoperated patients had significantly worse motor function and independence in activities of daily living before surgery and at discharge, but the deterioration after surgery affected patients in the first surgery group to a greater extent according to all metrics (p < 0.001). The length of hospital stay was similar in both groups. These results will be useful for tailoring postoperative rehabilitation during a hospital stay on the neurosurgical ward as well as planning discharge requirements after leaving the hospital.
... As a consequence, DOX treatment is associated with skeletal muscle atrophy/wasting, as well as functional deficits [17][18][19][20][21][22][23][24][25] as characterized by reduced force production and increased susceptibility to skeletal muscle fatigue in pre-clinical animal models [26][27][28][29] . These data are consistent with clinical descriptions of exercise intolerance, a lesser capacity for activities of daily living and reduced quality of life in patients following chemotherapy treatment [30][31][32] . The functional benefits of SN co-supplementation on the skeletal muscular system in both rodents and humans is well documented, whereby enhanced NO bioavailability augments functional adaptations that lower the oxidative cost of exercise, subsequently improving fatigue resistance and exercise tolerance [33][34][35] . ...
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The purpose of this study was to determine whether (1) sodium nitrate (SN) treatment progressed or alleviated doxorubicin (DOX)-induced cachexia and muscle wasting; and (2) if a more-clinically relevant low-dose metronomic (LDM) DOX treatment regimen compared to the high dosage bolus commonly used in animal research, was sufficient to induce cachexia in mice. Six-week old male Balb/C mice (n = 16) were treated with three intraperitoneal injections of either vehicle (0.9% NaCl; VEH) or DOX (4 mg/kg) over one week. To test the hypothesis that sodium nitrate treatment could protect against DOX-induced symptomology, a group of mice (n = 8) were treated with 1 mM NaNO3 in drinking water during DOX (4 mg/kg) treatment (DOX + SN). Body composition indices were assessed using echoMRI scanning, whilst physical and metabolic activity were assessed via indirect calorimetry, before and after the treatment regimen. Skeletal and cardiac muscles were excised to investigate histological and molecular parameters. LDM DOX treatment induced cachexia with significant impacts on both body and lean mass, and fatigue/malaise (i.e. it reduced voluntary wheel running and energy expenditure) that was associated with oxidative/nitrostative stress sufficient to induce the molecular cytotoxic stress regulator, nuclear factor erythroid-2-related factor 2 (NRF-2). SN co-treatment afforded no therapeutic potential, nor did it promote the wasting of lean tissue. Our data re-affirm a cardioprotective effect for SN against DOX-induced collagen deposition. In our mouse model, SN protected against LDM DOX-induced cardiac fibrosis but had no effect on cachexia at the conclusion of the regimen.
... heart, lung, vascular, skeletal muscle), organs that enable the convective delivery of oxygen from the environment to the skeletal muscle mitochondria, termed the oxygen cascade. 48 To support the exercise response, other non-cardiovascular tissues organs play a central role including the brain (e.g. central nervous system control), liver (e.g. release of glucose), and adipose tissue (e.g. release of free fatty acids), adrenal glands (e.g. release of adrenaline and cortisol) and pancreas (e.g. release of glucagon). ...
Article
Unhealthful lifestyle factors, such as obesity, disrupt organismal homeostasis and accelerate cancer pathogenesis, partly through metabolic and immunological dysregulation. Exercise is a prototypical strategy that maintains and restores homeostasis at the organismal, tissue, cellular and molecular levels and can prevent or inhibit numerous disease conditions, including cancer. Here, we review unhealthful lifestyle factors that contribute to metabolic and immunological dysregulation and drive tumourigenesis, focusing on patient physiology (host)-tissue-tumour microenvironment interactions. We also discuss how exercise may influence distant tissue microenvironments, thereby improving tissue function through both metabolic and immunospecific pathways. Finally, we consider future directions that merit consideration in basic and clinical translational exercise studies.
... However, despite a great number of studies showing the positive effects of exercise interventions on many different health parameters (44)(45)(46); the literature also highlights the significant variability of patient adaptation to exercise programs (33,47,48). This variability appears to be accountable for the lack of tailored exercise interventions (49) and occurs due to the large number of parameters that influence the effects of exercise prescribed to patients: the type and stage of cancer, the type of treatment, and the physical status at the time of diagnosis. ...
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Background: Cancer cachexia and exacerbated fatigue represent two hallmarks in cancer patients, negatively impacting their exercise tolerance and ultimately their quality of life. However, the characterization of patients' physical status and exercise tolerance and, most importantly, their evolution throughout cancer treatment may represent the first step in efficiently counteracting their development with prescribed and tailored exercise training. In this context, the aim of the PROTECT-01 study will be to investigate the evolution of physical status, from diagnosis to the end of first-line treatment, of patients with one of the three most common cancers (i.e., lung, breast, and colorectal). Methods: The PROTECT-01 cohort study will include 300 patients equally divided between lung, breast and colorectal cancer. Patients will perform a series of assessments at three visits throughout the treatment: (1) between the date of diagnosis and the start of treatment, (2) 8 weeks after the start of treatment, and (3) after the completion of first-line treatment or at the 6-months mark, whichever occurs first. For each of the three visits, subjective and objective fatigue, maximal voluntary force, body composition, cachexia, physical activity level, quality of life, respiratory function, overall physical performance, and exercise tolerance will be assessed. Discussion: The present study is aimed at identifying the nature and severity of maladaptation related to exercise intolerance in the three most common cancers. Therefore, our results should contribute to the delineation of the needs of each group of patients and to the determination of the most valuable exercise interventions in order to counteract these maladaptations. This descriptive and comprehensive approach is a prerequisite in order to elaborate, through future interventional research projects, tailored exercise strategies to counteract specific symptoms that are potentially cancer type-dependent and, in fine, to improve the health and quality of life of cancer patients. Moreover, our concomitant focus on fatigue and cachexia will provide Mallard et al. The PROTECT-01 Cohort Study Protocol insightful information about two factors that may have substantial interaction but require further investigation. Trial registration: This prospective study has been registered at ClinicalTrials.gov (NCT03956641), May, 2019.
... Sufficient V O 2 max in patients is related to higher physical activity level 13 and daily functioning and fewer toxic effects of radiotherapy, chemotherapy, and androgen deprivation therapy on the cardiovascular system, respiratory system, and skeletal muscles. [14][15][16][17][18][19][20] Frequency, intensity, and duration determine the total exercise volume. To improve V O 2 max, the training principle of overload must be present by increasing frequency, intensity, or exercise duration above the initial physical exercise levels. ...
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Article
Résumé Depuis leur officialisation en cancérologie de l’adulte au travers de la circulaire DHOS du 22 février 2005 et de la mesure 42 du Plan cancer 2003–2007, les soins oncologiques de support se sont enrichis de nouvelles offres afin que toute personne puisse bénéficier d’un accompagnement global approprié tant à l’hôpital qu’à domicile. Un « panier de soins » à garantir aux patients et à leurs proches, a été défini en février 2017 suite à un travail mené par l’Afsos et l’INCa. Ce panier élargi, intègre des offres comme l’activité physique adaptée ou l’oncosexualité, à un socle constitué par la prise en charge de la douleur, diététique et nutritionnelle, psychologique et l’accompagnement social. La circulaire DHOS du 29 mars 2004 qui déterminait l’organisation propre des activités d’oncologie pédiatrique faisait état de l’offre de soins de support pour les jeunes patients, dont l’intégration aux soins oncologiques spécifiques a toujours reflété la prise en charge holistique classique dans cette population de patients. L’offre en soins de support à la population pédiatrique, adolescents et jeunes adultes et l’offre en soins de support aux adultes peuvent se compléter et s’inspirer l’une de l’autre afin d’améliorer l’accompagnement personnalisé des patients atteints de cancer.
Article
Reduced physical function, incorporating exercise intolerance, physical inactivity and dependency, is a common consequence of cancer and its treatment. Most guidelines for cancer survivors suggest that physical activity and exercise should be an integral and continuous part of care for all cancer survivors. However, the full potential of exercise will be only realized with careful and considered individual prescription. Strong evidence supports the promotion of physical activity and exercise for adult cancer patients before, during, and after cancer treatment, across all cancer types, and including patients with advanced disease. Combined aerobic and resistance exercise training, targeting fitness and muscle function, may be particularly relevant in patients with cachexia and other wasting related syndromes. Evidence for the added value of providing nutritional support alongside exercise is emerging. Patient, family and professional beliefs about the value and benefits of physical activity and exercise all influence patients’ attitudes and motivation to participate in programmes.
Article
Background Survival rates for many forms of thoracic malignancies have improved over the past few decades, however, many survivors are coping with the side effects of cancer treatment for longer. Physical activity (PA) has been proposed as a therapeutic strategy to combat the effects of treatment in cancer survivors and eHealth could be a good way to encourage patients to practice it. Objective To explore the effects of eHealth in the promotion of PA among thoracic malignancies. Methods Suitable articles were searched using PubMed, Web of Science and Scopus databases using a combination of medical subject headings. Results In total, 4781 articles were identified, of which ten met eligibility criteria. Different eHealth interventions were described in these studies: mobile application (app) (n = 3), website (n = 2), email (n = 2), web and mobile application (n = 1), telephone counseling (n = 1) and online sheet (n = 1). All studies reported improvements in PA, with 8/10 studies reporting statistically significant changes. Conclusion Our results show that eHealth programs are useful to promote PA in malignancy thoracic survivors, compared to no intervention, conventional treatment or a dietary approach. Moreover, the meta-analysis also revealed eHealth is a good way to improve the level of PA in thoracic malignancies survivors.
Article
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, and the increasing incidence of PDAC may be related to the prevalence of obesity. Physical activity (PA), a method known to mitigate obesity by increasing total energy expenditure, also modifies multiple cellular pathways associated with cancer hallmarks. Epidemiologic evidence has shown that PA can lower the risk of developing a variety of cancers, reduce some of the detrimental side effects of treatments, and improve patient's quality of life during cancer treatment. However, little is known about the pathways underlying the correlations observed between PA interventions and PDAC. Moreover, there is no standard dose of PA intervention that is ideal for PDAC prevention or as an adjuvant of cancer treatments. In this review, we summarize relevant literature showing how PDAC patients can benefit from PA, the potential of PA as an adjuvant treatment for PDAC, the studies using preclinical models of PDAC to study PA, and the clinical trials to date assessing the effects of PA in PDAC.
Thesis
Le cancer de la prostate est un fléau mondial et l’échec des traitements est un défi majeur pour combattre cette maladie. La pratique d’une activité physique chez des patients atteints d’un cancer est associée à une amélioration du pronostic et certains mécanismes biologiques sous-jacents à ces bénéfices ont été identifiés grâce à des modèles précliniques. Il est dès lors plausible que l’activité physique améliore l’efficacité des traitements utilisés contre le cancer. Toutefois, l’effet de l’activité physique sur l’efficacité de la radiothérapie reste méconnu. L’objectif a cette thèse est d’étudier l’impact de l’activité physique sur la croissance tumorale et la réponse à la radiothérapie dans différents modèles précliniques de cancer de la prostate. Notre travail montre (1) qu’un entrainement sur tapis roulant permet d’améliorer l’efficacité de la radiothérapie dans un modèle préclinique de cancer de la prostate PPC-1 en améliorant l’infiltration des cellules tueuses naturelles dans le tissu tumoral ; (2) qu’un modèle de roue volontaire ne permet pas d’obtenir ces effets chez des souris porteuses de tumeurs PC-3, ce qui semble être attribuable au sous-type de cancer plutôt qu’à la modalité d’activité physique ; et (3) que les processus épigénétiques au sein de la tumeur sont régulés par l’activité physique chez des rats porteurs de tumeurs AT1, le rôle de cet effet sur l’efficacité des traitements restant à explorer. Nos travaux suggèrent donc que l’activité physique pourrait sensibiliser les cellules cancéreuses prostatiques à la radiothérapie et souligne également la nécessité de programmes d’entrainement personnalisés pour les patients atteints de cancer pourrait améliorer l’efficacité de la radiothérapie.
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Purpose: The current study was conducted to evaluate the effect of aerobic exercise on cancer pain in patients with solid metastatic tumors receiving palliative radiotherapy. Methods: Thirty-six patients from both genders were included in this study. Their ages were ≥ 18 years. They were randomly divided into two groups equal in number (each 18 patients). Procedures: Group Ι (Study group) received the program of aerobic exercise using the bicycle ergometer (30 minute per session) 5 sessions per week for 2 weeks in parallel with the palliative radiotherapy and Group Ⅱ (control group) received the palliative radiotherapy protocol only. Pain was assessed by the Visual Analogue Scale (VAS) and the blood Cortisol level was assessed before and after the program (2 weeks). Results: Post treatment comparison between both groups revealed a significant reduction in cortisol level and VAS of the study group in comparison with that of the control group. There was a significant reduction in cortisol level and VAS post-treatment compared with that of pretreatment in the study group (p > 0.001). The correlation between VAS and cortisol level was a positive and statistically significant correlation (r = 0.68, p = 0.0001). Conclusion: Short term moderate intensity aerobic exercise led to a significant decrease in cancer pain and blood cortisol (stress hormone) level in solid metastatic tumors patients receiving palliative radiotherapy.
Article
Purpose To evaluate whether postoperative exercise training is effective in improving clinical outcomes such as the quality of life (QoL), exercise capacity and respiratory function of patients receiving pulmonary resection. Data sources The PubMed, EMBASE, Web of Science and PEDro electronic databases were comprehensively searched to identify eligible randomized controlled trials (RCTs). Methods The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. The primary outcome was postoperative QoL and secondary outcomes were exercise capacity and respiratory function. Results A total of eight studies involving 691 participants were enrolled in this systematic review and meta-analysis. For the postoperative QoL measured by 36-Item Short Form Health Survey (SF-36), the pooled results demonstrated that postoperative exercise training could significantly improve the SF-36 physical domain score [weighted mean difference (WMD)=5.87, 95% confidence interval (CI): 3.96 to 7.78, P＜0.001] and SF-36 mental domain score (WMD=8.15, 95% CI: 0.13 to 16.16, P=0.05). The results of further analysis for the eight dimensions of SF-36 were similar to the overall results. However, for secondary outcomes, no significant effects of postoperative exercise training on exercise capacity and respiratory function were observed. Conclusion Postoperative exercise training could significantly improve the QoL of patients undergoing lung surgery. However, more RCTs with large samples are still needed to verify the effects of postoperative exercise rehabilitation on clinical outcomes of patients who receive pulmonary resection.
Chapter
Cancers are largely diseases of ageing. There is a strong referral bias for more fit older adults to be seen in cancer clinical samples. Clinical decision‐making in cancer is complicated by marked under‐representation of participants over age 70 in cancer clinical trials. Geriatricians assess for frailty, which is a biological characteristic of decreased physiologic reserve and for functional status such as ADLs (the ability to care for oneself at home) and IADLs (the ability to live alone and manage one's own household affairs). If highly toxic or invasive surgical curative cancer treatment is contemplated, geriatric assessments should include determining the patient's decisional capacity: that is, whether the patient is cognizant of the risks and benefits of the alternative courses. The short‐term impact of chemotherapy on functional capacity should be monitored proactively and prospectively. The impact of exercise on functional status and disease management has been reported to be beneficial for managing age‐related frailty.
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Purpose To investigate breast cancer survivors’ inflammatory responses to typhoid vaccine as a window into their innate immune response to novel pathogens. Methods This double-blind crossover trial randomized 158 breast cancer survivors to either the vaccine/saline placebo or the placebo/vaccine sequence. The relative contributions of age, cardiorespiratory fitness (VO2peak), type of cancer treatment, central obesity, and depression to interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra), and WBC vaccine responses were assessed pre-injection and 1.5, 3, 4.5, 6, and 7.5 hours post-injection. Results The vaccine produced larger IL-6, IL-1Ra, and WBC responses than placebo, ps<.0001. Prior chemotherapy, higher central obesity, and lower VO2peak were associated with smaller vaccine responses after controlling for baseline inflammation. Vaccine response was summarized by the percent increase in area under the curve (IL-6, WBC) or average post-injection mean (IL-1Ra) for vaccine relative to placebo. Women who received chemotherapy had smaller vaccine responses than women who did not for both IL-6 (44% vs 78%, p<.001) and WBC (26% vs 40%, p<.001); IL-1ra response was not significantly moderated by chemotherapy. Women whose central adiposity was one standard deviation above the mean had smaller vaccine responses than women with average adiposity for IL-6 (33% vs 54%, p<.001), WBC (20% vs 30%, p<.001), and IL-1Ra (2.0% vs 3.2%, p<.001). Women with an average level of VO2peak had smaller vaccine responses than women whose VO2peak was one standard deviation above the mean for IL-6 (54% vs 73%, p<.001), WBC (30% vs 40%, p<.001), and IL-1Ra (3.2% vs. 4.1%, p=0.01). Age and depression did not significantly moderate vaccine responses. Conclusions This study provided novel data on chemotherapy’s longer-term adverse immune consequences. The data also have an important public health message: even relatively low levels of fitness can benefit the innate immune response to a vaccine.
Chapter
It is well established that people diagnosed with cancer should participate in physical activity and exercise to improve health outcomes and decrease mortality and secondary diagnosis. Even though the evidence is clear, many people diagnosed with cancer are still not moving enough. When prescribing exercise for this population much needs to be taken into consideration. Exercise guidelines remain somewhat generalized and exercise prescribers need to take the individual needs of the person into consideration. In the first instance, the best practice is to refer clients diagnosed with cancer to an Accredited Exercise Physiologist/Clinical Exercise Physiologist or Physiotherapist/Physical Therapist experienced in cancer care for the delivery of targeted exercise. These professions are best placed to identify the needs of the individual and any safety implications for exercise that may be apparent. This chapter provides an overview of cancer and its implications for those diagnosed as well as the current exercise guidelines and clinical considerations. This chapter also contains a specific section on lung cancer to assist the reader in the identification and understanding of the needs of these complex clients. The Exercise and Sports Science Australia (ESSA) and the American College of Sports Medicine (ACSM) have provided position statements and guidelines on exercise for working with individuals with cancer-based on the evidence that we have so far. This important information has been referred to and explained throughout this chapter. It is however extremely important that exercise prescribers work with the individual, taking their very important personal needs, goals, and safety requirements into consideration.
Article
Background: Surgical resection for early-stage non-small cell lung cancer (NSCLC) offers the best chance of cure, but it is associated with a risk of postoperative pulmonary complications. It is unclear if preoperative exercise training, and the potential resultant improvement in exercise capacity, may improve postoperative outcomes. This review updates our initial 2017 systematic review. Objectives: 1. To evaluate the benefits and harm of preoperative exercise training on postoperative outcomes, such as the risk of developing a postoperative pulmonary complication and the postoperative duration of intercostal catheter, in adults scheduled to undergo lung resection for NSCLC. 2. To determine the effect on length of hospital stay (and costs associated with postoperative hospital stay), fatigue, dyspnoea, exercise capacity, lung function and postoperative mortality. Search methods: We used standard, extensive Cochrane search methods. The latest search date was from 28 November 2016 to 23 November 2021. Selection criteria: We included randomised controlled trials (RCTs) in which study participants who were scheduled to undergo lung resection for NSCLC were allocated to receive either preoperative exercise training or no exercise training. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were 1. risk of developing a postoperative pulmonary complication; 2. postoperative duration of intercostal catheter and 3. Safety: Our secondary outcomes were 1. postoperative length of hospital stay; 2. postintervention fatigue; 3. postintervention dyspnoea; 4. postintervention and postoperative exercise capacity; 5. postintervention lung function and 6. postoperative mortality. We used GRADE to assess the certainty of evidence for each outcome. Main results: Along with the five RCTs included in the original version, we identified an additional five RCTs, resulting in 10 RCTs involving 636 participants. Preoperative exercise training results in a large reduction in the risk of developing a postoperative pulmonary complication compared to no preoperative exercise training (risk ratio (RR) 0.45, 95% CI 0.33 to 0.61; I2 = 0%; 9 studies, 573 participants; high-certainty evidence). The evidence is very uncertain about its effect on postoperative intercostal catheter duration (MD -2.07 days, 95% CI -4.64 to 0.49; I2 = 77%, 3 studies, 111 participants; very low-certainty evidence). Preoperative exercise training is likely safe as studies reported no adverse events. Preoperative exercise training likely results in a reduction in postoperative length of hospital stay (MD -2.24 days, 95% CI -3.64 to -0.85; I2 = 85%; 9 studies, 573 participants; moderate-certainty evidence). Preoperative exercise training likely increases postintervention exercise capacity measured by peak oxygen consumption (MD 3.36 mL/kg/minute, 95% CI 2.70 to 4.02; I2 = 0%; 2 studies, 191 participants; moderate-certainty evidence); but the evidence is very uncertain about its effect on postintervention exercise capacity measured by the 6-minute walk distance (MD 29.55 m, 95% CI 12.05 to 47.04; I2 = 90%; 6 studies, 474 participants; very low-certainty evidence). Preoperative exercise training may result in little to no effect on postintervention lung function (forced expiratory volume in one second: MD 5.87% predicted, 95% CI 4.46 to 7.28; I2 = 0%; 4 studies, 197 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Preoperative exercise training results in a large reduction in the risk of developing a postoperative pulmonary complication compared to no preoperative exercise training for people with NSCLC. It may also reduce postoperative length of hospital stay, and improve exercise capacity and lung function in people undergoing lung resection for NSCLC. The findings of this review should be interpreted with caution due to risk of bias. Research investigating the cost-effectiveness and long-term outcomes associated with preoperative exercise training in NSCLC is warranted.
Chapter
Engaging in exercise or physical activity has been found to be safe and strongly recommended, as well as beneficial, in patients with lung cancer at any stage of the disease and its treatment. Factors that may affect the exercise tolerance or capacity and functional Independence in patients with lung cancer include prediagnosis fitness level, normal aging, comorbidities, tumor burden, cancer-related, and treatment-related side effects. Tailoring cancer rehabilitation and exercise programs for this population may alleviate some of the current barriers including low adherence and high dropout rates. Optimized clinical and research collaboration between oncologists, cancer rehabilitation physicians, and exercise specialists may aid in creating these programs while emphasizing on specific considerations related to lung cancer and its treatments.
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The fully updated third edition of this popular handbook provides a concise summary of perioperative management of high-risk surgical patients. Written by an international group of senior clinicians, chapters retain the practical nature of previous editions, with concise text in a bulleted format offering rapid access to key facts and advice. Several new chapters cover topics including: anesthetic mortality; cardiopulmonary exercise testing; perioperative optimization; obstructive sleep apnea and obesity hypoventilation syndrome; smoking, alcohol and recreational drug abuse; intraoperative ventilatory management; the role of simulation in managing the high-risk patient; anesthesia, surgery and palliative care; anesthesia and cancer surgery; neurotrauma and other high-risk neuro cases; anesthesia for end-stage renal and liver disease; and transplant patients. Essential reading for trainee anesthesiologists managing seriously ill patients during surgery or studying for postgraduate examinations, this is also a valuable refresher for anesthesiologists and intensivists looking for an update on the latest evidence-based care.
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The fully updated third edition of this popular handbook provides a concise summary of perioperative management of high-risk surgical patients. Written by an international group of senior clinicians, chapters retain the practical nature of previous editions, with concise text in a bulleted format offering rapid access to key facts and advice. Several new chapters cover topics including: anesthetic mortality; cardiopulmonary exercise testing; perioperative optimization; obstructive sleep apnea and obesity hypoventilation syndrome; smoking, alcohol and recreational drug abuse; intraoperative ventilatory management; the role of simulation in managing the high-risk patient; anesthesia, surgery and palliative care; anesthesia and cancer surgery; neurotrauma and other high-risk neuro cases; anesthesia for end-stage renal and liver disease; and transplant patients. Essential reading for trainee anesthesiologists managing seriously ill patients during surgery or studying for postgraduate examinations, this is also a valuable refresher for anesthesiologists and intensivists looking for an update on the latest evidence-based care.
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Cardiovascular diseases (CVD) are the leading cause of death worldwide and risk for developing CVD is markedly increased following anthracycline chemotherapy treatment. Anthracyclines are an essential component of the cancer treatment regimen used for common forms of cancer in male and female children, adolescents, young adults and older adults. Increased CVD risk with anthracyclines occurs, in part, due to vascular dysfunction - impaired endothelial function and arterial stiffening. These features of vascular dysfunction also play a major role in other common disorders observed following anthracycline treatment, including chronic kidney disease, dementia and exercise intolerance. However, the mechanisms by which anthracycline chemotherapy induces and sustains vascular dysfunction are incompletely understood. This budding area of biomedical research is termed cardio-oncology, which presents the unique opportunity for collaboration between physicians and basic scientists. This symposium, presented at Experimental Biology 2022, provided a timely update of this important biomedical research topic. The speakers presented observations made at levels from cells to mice to humans treated with anthracycline chemotherapeutic agents using an array of translational research approaches. The speaker panel included a diverse mix of female and male investigators and unique insight from a cardio-oncology physician scientist. Particular emphasis was placed on challenges and opportunities in this field as well as mechanisms that could be viewed as therapeutic targets leading to novel treatment strategies.
Article
Purpose Many lung cancer patients are inactive due to their disease and underlying comorbidities, and activity levels can decline further during cancer therapy. Here we explore dosimetric predictors of activity decline in a cohort of patients who underwent continuous activity monitoring during definitive concurrent chemoradiotherapy (CRT) for locally advanced lung cancer. Methods and Materials We identified patients who participated in prospective clinical trials involving the use of a commercial fitness tracker throughout the course of CRT. For each subject, we applied linear regression to log-transformed daily step counts to compute the weekly rate of activity change from one week before radiotherapy [RT] initiation to two weeks after RT completion. Clinical and dosimetric factors were tested as predictors of activity change using linear regressions. Results Forty-six subjects met eligibility criteria. Median age was 66 years (range 38-90). Pre-treatment ECOG performance status [PS] was 0, 1 and 2 for 17%, 70% and 13% of the subjects, respectively. Mean lung dose ranged from 5.0 to 23.5 Gy, mean esophagus dose 1.1 to 39.6 Gy, and mean heart dose 0.6 to 31.5 Gy. Median daily step count average before RT was 5861 (IQR: 3540 to 8282) and two weeks following RT completion was 3422 (IQR: 2364 to 5395). Rate of activity change was not significantly associated with age, PS, or mean RT dose received by lungs or esophagus. In multivariate analysis, mean heart dose was significantly associated with rate of activity decline, with a 3.1% reduction in step count per week for every 10 Gy increase in mean heart dose (95% CI: 0.5 to 5.7, p=0.023). Conclusion Extent of cardiac irradiation is associated with the rate of physical activity decline during CRT for lung cancer. Our novel finding contributes to the growing body of evidence that adverse effects of cardiac irradiation may be manifested at early time points.
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In 1995 the American College of Sports Medicine and the Centers for Disease Control and Prevention published national guidelines on Physical Activity and Public Health. The Committee on Exercise and Cardiac Rehabilitation of the American Heart Association endorsed and supported these recommendations. The purpose of the present report is to update and clarify the 1995 recommendations on the types and amounts of physical activity needed by healthy adults to improve and maintain health. Development of this document was by an expert panel of scientists, including physicians, epidemiologists, exercise scientists, and public health specialists. This panel reviewed advances in pertinent physiologic, epidemiologic, and clinical scientific data, including primary research articles and reviews published since the original recommendation was issued in 1995. Issues considered by the panel included new scientific evidence relating physical activity to health, physical activity recommendations by various organizations in the interim, and communications issues. Key points related to updating the physical activity recommendation were outlined and writing groups were formed. A draft manuscript was prepared and circulated for review to the expert panel as well as to outside experts. Comments were integrated into the final recommendation. Primary recommendation: To promote and maintain health, all healthy adults aged 18 to 65 yr need moderate-intensity aerobic (endurance) physical activity for a minimum of 30 min on five days each week or vigorous-intensity aerobic physical activity for a minimum of 20 min on three days each week. [I (A)] Combinations of moderate- and vigorous-intensity activity can be performed to meet this recommendation. [IIa (B)] For example, a person can meet the recommendation by walking briskly for 30 min twice during the week and then jogging for 20 min on two other days. Moderate-intensity aerobic activity, which is generally equivalent to a brisk walk and noticeably accelerates the heart rate, can be accumulated toward the 30-min minimum by performing bouts each lasting 10 or more minutes. [I (B)] Vigorous-intensity activity is exemplified by jogging, and causes rapid breathing and a substantial increase in heart rate. In addition, every adult should perform activities that maintain or increase muscular strength and endurance a minimum of two days each week. [IIa (A)] Because of the dose-response relation between physical activity and health, persons who wish to further improve their personal fitness, reduce their risk for chronic diseases and disabilities or prevent unhealthy weight gain may benefit by exceeding the minimum recommended amounts of physical activity. [I (A)]
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Background: Aerobic power declines with age. The degree to which this decline is reversible remains unclear. In a 30-year longitudinal follow-up study, the cardiovascular adaptations to exercise training in 5 middle-aged men previously trained in 1966 were evaluated to assess the degree to which the age-associated decline in aerobic power is attributable to deconditioning and to gain insight into the specific mechanisms involved. Methods and Results-- The cardiovascular response to acute submaximal and maximal exercise were assessed before and after a 6-month endurance training program. On average, VO(2max) increased 14% (2.9 versus 3.3 L/min), achieving the level observed at the baseline evaluations 30 years before. Likewise, VO(2max) increased 16% when indexed to total body mass (31 versus 36 mL/kg per minute) or fat-free mass (44 versus 51 mL/kg fat-free mass per minute). Maximal heart rate declined (181 versus 171 beats/min) and maximal stroke volume increased (121 versus 129 mL) after training, with no change in maximal cardiac output (21.4 versus 21.7 L/min); submaximal heart rates also declined to a similar degree. Maximal AVDO(2) increased by 10% (13.8 versus 15.2 vol%) and accounted for the entire improvement of aerobic power associated with training. Conclusions: One hundred percent of the age-related decline in aerobic power among these 5 middle-aged men occurring over 30 years was reversed by a 6-month endurance training program. However, no subject achieved the same maximal VO(2) attained after training 30 years earlier, despite a similar relative training load. The improved aerobic power after training was primarily the result of peripheral adaptation, with no effective improvement in maximal oxygen delivery.
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Cancer survival varies widely between countries. The CONCORD study provides survival estimates for 1·9 million adults (aged 15–99 years) diagnosed with a first, primary, invasive cancer of the breast (women), colon, rectum, or prostate during 1990–94 and followed up to 1999, by use of individual tumour records from 101 population-based cancer registries in 31 countries on five continents. This is, to our knowledge, the first worldwide analysis of cancer survival, with standard quality-control procedures and identical analytic methods for all datasets.
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The insulin-like growth factor-I receptor (IGF-IR) was first cloned in 1986. Since then, intense work has defined classic phosphorelays activated via the IGF-IR, which regulate cell proliferation, apoptosis, motility, and fate. The understanding of the roles of hormones in cancer and the growth hormone-IGF-IGF-binding protein axis specifically has yield to a second wave of development: the design of specific inhibitors that interrupt the signaling associated with this axis. The ability to manipulate these pathways holds not only significant therapeutic implications but also increase the chance of deeper insight about the role of the axis in carcinogenesis and metastasis. Nowadays, >25 molecules with the same goal are at different stages of development. Here, we review the clinical and preclinical experience with the two most-investigated strategies, tyrosine kinase inhibitors and monoclonal antibodies, and the advantages and disadvantages of each strategy, as well as other alternatives and possible drug combinations. We also review the biomarkers explored in the first clinical trials, the strategies that have been explored thus far, and the clinical trials that are going to explore their role in cancer treatment.
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The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.
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Our purpose was to determine the relationship between habitual aerobic exercise status and the rate of decline in maximal aerobic capacity across the adult age range in women. A meta-analytic approach was used in which mean maximal oxygen consumption (VO2 max) values from female subject groups (ages 18-89 yr) were obtained from the published literature. A total of 239 subject groups from 109 studies involving 4,884 subjects met the inclusion criteria and were arbitrarily separated into sedentary (groups = 107; subjects = 2,256), active (groups = 69; subjects = 1, 717), and endurance-trained (groups = 63; subjects = 911) populations. VO2 max averaged 29.7 +/- 7.8, 38.7 +/- 9.2, and 52.0 +/- 10.5 ml . kg-1 . min-1, respectively, and was inversely related to age within each population (r = -0.82 to -0.87, all P < 0.0001). The rate of decline in VO2 max with increasing subject group age was lowest in sedentary women (-3.5 ml . kg-1 . min-1 . decade-1), greater in active women (-4.4 ml . kg-1 . min-1 . decade-1), and greatest in endurance-trained women (-6.2 ml . kg-1 . min-1 . decade-1) (all P < 0.001 vs. each other). When expressed as percent decrease from mean levels at age approximately 25 yr, the rates of decline in VO2 max were similar in the three populations (-10.0 to -10.9%/decade). There was no obvious relationship between aerobic exercise status and the rate of decline in maximal heart rate with age. The results of this cross-sectional study support the hypothesis that, in contrast to the prevailing view, the rate of decline in maximal aerobic capacity with age is greater, not smaller, in endurance-trained vs. sedentary women. The greater rate of decline in VO2 max in endurance-trained populations may be related to their higher values as young adults (baseline effect) and/or to greater age-related reductions in exercise volume; however, it does not appear to be related to a greater rate of decline in maximal heart rate with age.
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The role of androgens in producing cardiac hypertrophy by direct action on cardiac myocytes is uncertain. Accordingly, we tested the hypothesis that cardiac myocytes in adult men and women express an androgen receptor gene and that myocytes respond to androgens by a hypertrophic response. We used reverse transcription-polymerase chain reaction methods to demonstrate androgen receptor transcripts in multiple tissues and [3H]phenylalanine incorporation and atrial natriuretic peptide secretion as markers of hypertrophy in cultured rat myocytes. Messenger RNA encoding androgen receptors was detected in myocytes of male and female adult rats, neonatal rat myocytes, rat heart, dog heart, and infant and adult human heart. Both testosterone and dihydrotestosterone produced a robust receptor-specific hypertrophic response in myocytes, determined by indices of protein synthesis and atrial natriuretic peptide secretion. Androgen receptors are present in cardiac myocytes from multiple species, including normal men and women, in a context that permits androgens to modulate the cardiac phenotype and produce hypertrophy by direct, receptor-specific mechanisms. There are clinical implications for therapeutic or illicit use of androgens in humans.
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Exercise training in patients with chronic heart failure improves work capacity by enhancing endothelial function and skeletal muscle aerobic metabolism, but effects on central hemodynamic function are not well established. To evaluate the effects of exercise training on left ventricular (LV) function and hemodynamic response to exercise in patients with stable chronic heart failure. Prospective randomized trial conducted in 1994-1999. University department of cardiology/outpatient clinic in Germany. Consecutive sample of 73 men aged 70 years or younger with chronic heart failure (with LV ejection fraction of approximately 0.27). Patients were randomly assigned to 2 weeks of in-hospital ergometer exercise for 10 minutes 4 to 6 times per day, followed by 6 months of home-based ergometer exercise training for 20 minutes per day at 70% of peak oxygen uptake (n=36) or to no intervention (control group; n=37). Ergospirometry with measurement of central hemodynamics by thermodilution at rest and during exercise; echocardiographic determination of LV diameters and volumes, at baseline and 6-month follow-up, for the exercise training vs control groups. After 6 months, patients in the exercise training group had statistically significant improvements compared with controls in New York Heart Association functional class, maximal ventilation, exercise time, and exercise capacity as well as decreased resting heart rate and increased stroke volume at rest. In the exercise training group, an increase from baseline to 6-month follow-up was observed in mean (SD) resting LV ejection fraction (0.30 [0.08] vs 0.35 [0.09]; P=.003). Mean (SD) total peripheral resistance (TPR) during peak exercise was reduced by 157 (306) dyne/s/cm(-5) in the exercise training group vs an increase of 43 (148) dyne/s/cm(-5) in the control group (P=.003), with a concomitant increase in mean (SD) stroke volume of 14 (22) mL vs 1 (19) mL in the control group (P=.03). There was a small but significant reduction in mean (SD) LV end diastolic diameter of 4 (6) mm vs an increase of 1 (4) mm in the control group (P<.001). Changes from baseline in resting TPR for both groups were correlated with changes in stroke volume (r=-0.76; P<.001) and in LV end diastolic diameter (r=0.45; P<.001). In patients with stable chronic heart failure, exercise training is associated with reduction of peripheral resistance and results in small but significant improvements in stroke volume and reduction in cardiomegaly. JAMA. 2000.
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Physical exercise has been identified as a potential intervention to improve quality of life in women with breast cancer. We sought to summarize the available evidence concerning the effects of exercise on breast cancer patients and survivors. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsychINFO, CancerLit, PEDro and SportDiscus as well as conference proceedings, clinical practice guidelines and other unpublished literature resources. We included only randomized controlled trials that examined exercise interventions for breast cancer patients or survivors with quality of life, cardiorespiratory fitness or physical functioning as primary outcomes. We also extracted data on symptoms of fatigue, body composition and adverse effects. Of 136 studies identified, 14 met all the inclusion criteria. Despite significant heterogeneity and relatively small samples, the point estimates in terms of the benefits of exercise for all outcomes were positive even when statistical significance was not achieved. Exercise led to statistically significant improvements in quality of life as assessed by the Functional Assessment of Cancer Therapy-General (weighted mean difference [WMD] 4.58, 95% confidence interval [CI] 0.35 to 8.80) and Functional Assessment of Cancer Therapy-Breast (WMD 6.62, 95% CI 1.21 to 12.03). Exercise also led to significant improvements in physical functioning and peak oxygen consumption and in reducing symptoms of fatigue. Exercise is an effective intervention to improve quality of life, cardiorespiratory fitness, physical functioning and fatigue in breast cancer patients and survivors. Larger trials that have a greater focus on study quality and adverse effects and that examine the long-term benefits of exercise are needed for this patient group.
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Although malignant tumors occur at all ages, cancer disproportionately strikes individuals in the age group 65 years and older. Data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program for the most recent five-year period, 1998–2002, reveal that 56% of all newly diagnosed cancer patients and 71% of cancer deaths are in this age group. Median ages of cancer patients at death for the major tumors common to both males and females, all races (lung, colorectal, lymphoma, leukemia, pancreas, stomach, urinary bladder) range from 71 to 77 years. The median age for prostate cancer is 79 years; for ovarian and female breast cancer, the median age is 71 for each tumor. These cancer statistics when cast against the demographic changes occurring in the U.S. population take on urgency and importance for cancer treatment and care in our nation's health care system. The U.S. Census Bureau demographic projections indicate that the number of persons 65 years and older in the United States will double from the current estimate of 35 million persons to a projected 70 million by 2030. Barring any cancer prevention breakthroughs, the expansion of the aged population will likely increase the absolute number of older individuals diagnosed and treated for cancer in coming decades. The United States is not unique as an aging developed industrial nation with a high proportion of the cancer burden in the elderly. Other developed industrial countries have a potentiality for increased cancer incidence and mortality as their populations grow older. This paper, using U.S. Bureau of Census demographic projections and current age standardized death rates per 100,000 population (from World-wide Cancer Mortality Statistics, Cancer Mondial, WHO, and the International Association for Research on Cancer) compares cancer in the elderly in Italy and the United States. Italy is demographically ranked as the oldest nation in the world. Dimensions of the cancer burden challenge ahead are inferred in the context of two countries with aging populations to underscore the possible increase that demographic factors may have on the magnitude of the cancer problem for older persons in the next 25 years.
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Context Exercise training in patients with chronic heart failure improves work capacity by enhancing endothelial function and skeletal muscle aerobic metabolism, but effects on central hemodynamic function are not well established.Objective To evaluate the effects of exercise training on left ventricular (LV) function and hemodynamic response to exercise in patients with stable chronic heart failure.Design Prospective randomized trial conducted in 1994-1999.Setting University department of cardiology/outpatient clinic in Germany.Patients Consecutive sample of 73 men aged 70 years or younger with chronic heart failure (with LV ejection fraction of approximately 0.27).Intervention Patients were randomly assigned to 2 weeks of in-hospital ergometer exercise for 10 minutes 4 to 6 times per day, followed by 6 months of home-based ergometer exercise training for 20 minutes per day at 70% of peak oxygen uptake (n=36) or to no intervention (control group; n=37).Main Outcome Measures Ergospirometry with measurement of central hemodynamics by thermodilution at rest and during exercise; echocardiographic determination of LV diameters and volumes, at baseline and 6-month follow-up, for the exercise training vs control groups.Results After 6 months, patients in the exercise training group had statistically significant improvements compared with controls in New York Heart Association functional class, maximal ventilation, exercise time, and exercise capacity as well as decreased resting heart rate and increased stroke volume at rest. In the exercise training group, an increase from baseline to 6-month follow-up was observed in mean (SD) resting LV ejection fraction (0.30 [0.08] vs 0.35 [0.09]; P=.003). Mean (SD) total peripheral resistance (TPR) during peak exercise was reduced by 157 (306) dyne/s/cm−5 in the exercise training group vs an increase of 43 (148) dyne/s/cm−5 in the control group (P=.003), with a concomitant increase in mean (SD) stroke volume of 14 (22) mL vs 1 (19) mL in the control group (P=.03). There was a small but significant reduction in mean (SD) LV end diastolic diameter of 4 (6) mm vs an increase of 1 (4) mm in the control group (P<.001). Changes from baseline in resting TPR for both groups were correlated with changes in stroke volume (r=−0.76; P<.001) and in LV end diastolic diameter (r=0.45; P<.001).Conclusions In patients with stable chronic heart failure, exercise training is associated with reduction of peripheral resistance and results in small but significant improvements in stroke volume and reduction in cardiomegaly.
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Environmental oxygen is transported by the respiratory cascade to the site of oxidation in active tissues. Under conditions of heavy exercise, it is ultimately the working skeletal muscle cells that set the aerobic demand because over 90 % of energy is spent in muscle cells. The pathways for oxygen and substrates converge in muscle mitochondria. In mammals, a structural limitation of carbohydrate and lipid transfer from the microvascular system to the muscle cells is reached at a moderate work intensity (i.e. at 40-50 % of VO2max). At higher work rates, intracellular substrate stores must be used for oxidation. Because of the importance of these intracellular stores for aerobic work, we find larger intramyocellular substrate stores in 'athletic' species as well as in endurance-trained human athletes. The transfer limitations for carbohydrates and lipids at the level of the sarcolemma imply that the design of the respiratory cascade from lungs to muscle mitochondria reflects primarily oxygen demand. Comparative studies indicate that the oxidative capacity of skeletal muscle tissue, and hence maximal oxygen demand, is adjusted by varying mitochondrial content. At the level of microcirculatory oxygen supply, it is found that muscle tissue capillarity is adjusted to muscle oxygen demand but that the capillary erythrocyte volume also plays a role. Oxygen delivery by the heart has long been recognized to be a key link in the oxygen transport chain. In allometric variation it is heart rate and in adaptive variation it is essentially stroke volume, and hence heart size, that determines maximal cardiac output. Again, haematocrit is an important variable that allows the heart of athletic species to generate higher flux rates for oxygen. The pulmonary gas exchanger offers only a negligible resistance to oxygen flux to the periphery. However, in contrast to all other steps in the respiratory cascade, the lungs have only a minimal phenotypical plasticity and appear, therefore, to be built with considerable structural redundancy in all but the most athletic species. Because of the lack of malleability, the lungs may ultimately become limiting for VO2max when adaptive processes have maximized O2 flux through the malleable downstream elements of the respiratory system: the heart, microcirculation and muscle mitochondria.
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A feasibility study examining the effects of supervised aerobic exercise training on cardiopulmonary and quality of life (QOL) endpoints among postsurgical nonsmall cell lung cancer (NSCLC) patients was conducted. Using a single-group design, 20 patients with stage I-IIIB NSCLC performed 3 aerobic cycle ergometry sessions per week at 60% to 100% of peak workload for 14 weeks. Peak oxygen consumption (VO(2peak)) was assessed using an incremental exercise test. QOL and fatigue were assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale. Nineteen patients completed the study. Intention-to-treat analysis indicated that VO(2peak) increased 1.1 mL/kg(-1)/min(-1) (95% confidence interval [CI], -0.3-2.5; P = .109) and peak workload increased 9 W (95% CI, 3-14; P = .003), whereas FACT-L increased 10 points (95% CI, -1-22; P = .071) and fatigue decreased 7 points (95% CI; -1 to -17; P = .029) from baseline to postintervention. Per protocol analyses indicated greater improvements in cardiopulmonary and QOL endpoints among patients not receiving adjuvant chemotherapy. This pilot study provided proof of principle that supervised aerobic training is safe and feasible for postsurgical NSCLC patients. Aerobic exercise training is also associated with significant improvements in QOL and select cardiopulmonary endpoints, particularly among patients not receiving chemotherapy. Larger randomized trials are warranted.
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To describe the most relevant recent findings concerning the molecular mechanisms involved in both fat and muscle tissues in cachectic cancer patients. Relevant progress has been made in the mechanism of signalling protein metabolism in skeletal muscle. PI3K has a dual role inhibiting protein degradation by inhibition of Atrogin-1 and MuRF1 gene expression and facilitating AKT phosphorylation, leading to increased protein synthesis. Interestingly, Caspase-3 activity is intimately associated with myofibrillar protein degradation in muscle tissue. With respect to fat metabolism, increased lipolysis in human cancer cachexia seems to be directly connected to increased hormone-sensitive lipase activity. The results and findings described in this review represent important progress in wasting disease mechanisms and may provide hints for future therapeutic approaches in cancer cachexia.
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to the editor: Two comments. 1. It is extremely unlikely that all patients with COPD have the same major limitation ([1][1], [2][2], [4][3]). 2. As regards the three choices, I would choose none of the above. I do not understand the term dynamic hyperinflation. Hyperinflation refers to a large
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The use of exercise testing as an objective assessment of cardiorespiratory fitness in clinical oncology research has increased substantially over the past decade. However, its quality has not been assessed. We did a systematic review of studies of formal exercise testing for adults with cancer. Studies were assessed according to the American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations for exercise testing. Overall, the reporting of exercise-testing methods and data for adults with cancer suggests that the conduct of these tests does not comply with national and international quality guidelines. We give recommendations for exercise testing in clinical oncology research. The adoption of consistent, formal standards for methods and data reporting in exercise testing is needed to ensure high-quality research in clinical oncology. Overall, we present information for clinicians and exercise-oncology researchers who assess and care for patients with cancer.
Patients after pneumonectomy are severely limited upon exercise, but impairments in gas exchange are generally mild. One potential explanation of this observation is the existence of functional reserves of diffusing capacity (DLCO), which may be recruited during exercise, predominantly by increasing pulmonary blood flow (Qc). After pneumonectomy, DLCO reserves are recruited even at rest. To investigate if the pattern of recruitment of DLCO is altered and if reserves of DLCO are exhausted during exercise after pneumonectomy, DLCO, lung volume, and cardiac output were measured by the rebreathing method at rest and at multiple levels of steady-state exercise in eight subjects after pneumonectomy and in eight age- and sex-matched nonsmoking normal subjects. In patients after pneumonectomy, the slopes of increase in DLCO [ml.(min.mm Hg)-1.m-2] with respect to QC [ml.min-1.m-2] were normal (0.91 +/- 0.09 x 10(-3) in the pneumonectomy group, 1.16 +/- 0.12 x 10(-3) in the control group, mean +/- SE, p less than 0.05). Thus, the pattern of DLCO recruitment was not significantly affected by pneumonectomy. The ratio of DLCO/Qc fell more rapidly during exercise in patients after pneumonectomy, but the lowest value of the ratio achieved was relatively normal in all except one patient. Declines in arterial O2 saturation at exercise were mild and insufficient to explain the exercise limitation except in the patient whose DLCO/Qc fell below normal. There was no evidence that an upper limit of recruitment was approached. We conclude that the normal ability to recruit DLCO during exercise after pneumonectomy constitutes an important compensatory feature that prevents significant arterial O2 desaturation. In most patients, exercise is limited by a reduced maximal stroke index before reserves of diffusing capacity are exhausted.