Christina Andersen

Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial

Objective To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease. Design Randomised controlled trial. Setting Two university hospitals in Copenhagen, Denmark. Participants 269 patients with cancer; 73 men, 196 women, mean age 47 years (range 20-65) representing 21 diagnoses. Main exclusion criteria were brain or bone metastases. 235 patients completed follow-up. Intervention Supervised exercise comprising high intensity cardiovascular and resistance training, relaxation and body awareness training, massage, nine hours weekly for six weeks in addition to conventional care, compared with conventional care. Main outcome measures European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, muscular strength (one repetition maximum), maximum oxygen consumption (Vo2max). Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables. Results Adjusted for baseline score, disease, and demographic covariates, the intervention group showed an estimated improvement at six weeks for the primary outcome, fatigue, of −6.6 points (95% confidence interval −12.3 to −0.9, P=0.02; effect size=0.33, 0.04 to 0.61). Significant effects were seen on vitality (effect size 0.55, 95% CI 0.27 to 0.82), physical functioning (0.37, 0.09 to 0.65), role physical (0.37, 0.10 to 0.64), role emotional (0.32, 0.05 to 0.59), and mental health (0.28, 0.02 to 0.56) scores. Improvement was noted in physical capacity: estimated mean difference between groups for maximum oxygen consumption was 0.16 l/min (95% CI 0.1 to 0.2, P<0.0001) and for muscular strength (leg press) was 29.7 kg (23.4 to 34.9, P<0.0001). No significant effect was seen on global health status/quality of life. Conclusion A supervised multimodal exercise intervention including high and low intensity components was feasible and could safely be used in patients with various cancers who were receiving adjuvant chemotherapy or treatment for advanced disease. The intervention reduced fatigue and improved vitality, aerobic capacity, muscular strength, and physical and functional activity, and emotional wellbeing, but not quality of life. Trial registration Current Controlled trials ISRCTN05322922.

High‐intensity resistance and cardiovascular training improve physical capacity in cancer patients undergoing chemotherapy

The purpose of the study was to examine the effects of a supervised high‐ and low‐intensity structured training program in cancer patients concurrently undergoing chemotherapy. Seventy patients, in different stages of the disease and with different diagnoses (48 females, 22 males), between 18 and 65 years of age (mean age 42.8) participated in a 9‐h weekly training program over 6 weeks. The intervention involved physical exercise, relaxation, massage, and body‐awareness training. Physical capacity (one‐repetition maximum tests (1RM), VO2max) and body composition (weight, skin‐fold) were compared before and after the exercise intervention.

Self-reported physical activity behaviour; exercise motivation and information among Danish adult cancer patients undergoing chemotherapy

BACKGROUND Physical activity is considered an important and determining factor for the cancer patients physical well-being and quality of life. However, cancer treatment may disrupt the practice of physical activity, and the prevention of sedentary lifestyles in cancer survivors is imperative. PURPOSE The current study aimed at investigating self-reported physical activity behaviour, exercise motivation and information in cancer patients undergoing chemotherapy. METHODS AND SAMPLE Using a cross-sectional design, 451 patients (18-65 years) completed a questionnaire assessing pre-illness and present physical activity; motivation and information received. RESULTS Patients reported a significant decline in physical activity from pre-illness to the time in active treatment (p<0.001). Amongst the respondents, 68% answered that they believed exercise to be beneficial; and 78% claimed not exercising as much as desired. Exercise barriers included fatigue (74%) and physical discomfort (45%). Present physical activity behaviour was associated with pre-illness physical activity behaviour (p<0.001), exercise belief (p<0.001), and diagnosis (p<0.001). More patients <40 years than patients >40 years (OR 0.36, p<0.001); more men than women (OR 2.12, p<0.001); and more oncological than haematological patients (OR 0.41, p<0.001) stated being informed about physical activity. Moreover patients who claimed to have been informed about exercise were more in agreement with being able to exercise while undergoing chemotherapy (OR 1.69, p=0.023). CONCLUSIONS This study suggests that Danish adult cancer patients in chemotherapy experience a significant decline in physical activity behaviour. Results indicate a general positive interest in physical activity amongst the patients, which however may be only suboptimally exploited.

Struggling with cancer and treatment: young athletes recapture body control and identity through exercise: qualitative findings from a supervised group exercise program in cancer patients of mixed gender undergoing chemotherapy

Cancer and treatment can negatively affect the bodys performance and appearance. Exercise has been tested in a few studies for altered body image among middle‐aged women with breast cancer. The aim of the study was to explore how young pre‐cancer athletes of both genders experience disease‐ and treatment‐related physical fitness and appearance changes while undergoing chemotherapy and participating in a 6‐week group exercise intervention. A prospective, explorative study using semi‐structured interviews was conducted before and at termination of the intervention. The study included 22 cancer patients (median age 28 years). The young athletes experienced a change from a high level of physical activity, body satisfaction and a positive self‐identity to a low level of physical activity, body denial and a negative self‐identity. In the program, the patients experienced increased physical strength and recapture of certain aspects of their former positive body perception. Deterioation of muscle functions caused by chemotherapy was particularly painful to these patients, independent of gender and age. Young physically active patients are heavily dependent on their physical capacity, body satisfaction and self‐identity. This should be taken into account when designing programs to rehabilitate and encourage these patients through the often‐strenuous antineoplastic treatments.

Exercise may reduce depression but not anxiety in self-referred cancer patients undergoing chemotherapy. Post-hoc analysis of data from the ‘Body & Cancer’ trial

Abstract Background. The diagnosis and treatment of cancer may cause clinically significant and persistent psychological morbidity. The objective of this study was to determine the short-term effect of a six week exercise intervention on anxiety and depression in cancer patients undergoing chemotherapy (The ‘Body & Cancer’ trial). Methods. Two hundred and nine self-referred patients (52 males, 157 females, mean age 47 years) were randomised into an intervention group and a waiting-list control group. Anxiety and depression was measured by the Hospital Anxiety and Depression Scale. Results. At baseline, 23.5% and 11.5% of the population scored >8 on the HADS and were classified as suspicious or definite cases of anxiety and depression, respectively. Adjusted for baseline score, disease and demographic covariates the estimated intervention effect showed improvement at six weeks for depression of −0.7 points (95% confidence interval [CI] −1.27 to −0.14, p = 0.0153). No significant effect was seen on anxiety. Further subanalysis, including only suspicious or definite cases of depression, resulted in an estimated intervention effect of −2.53 points (95% CI, −0.64 to −0.42, p = 0.021). Conclusion. Anti-depressant effects could be caused by exercise in self-referred cancer patients undergoing chemotherapy. Dedicated trials and follow-up studies are needed to clarify the optimal duration and content of exercise interventions to meet the needs of clinically depressive or anxious patients.

Cancer survivors’ experience of exercise-based cancer rehabilitation – a meta-synthesis of qualitative research

Abstract Background. Evidence for the safety and benefits of exercise training as a therapeutic and rehabilitative intervention for cancer survivors is accumulating. However, whereas the evidence for the efficacy of exercise training has been established in several meta-analyses, synthesis of qualitative research is lacking. In order to extend healthcare professionals’ understanding of the meaningfulness of exercise in cancer survivorship care, this paper aims to identify, appraise and synthesize qualitative studies on cancer survivors’ experience of participation in exercise-based rehabilitation. Material and methods. Five electronic databases (PubMed, PsychINFO, EMBASE, Cinahl and Scopus) were searched systematically for articles published up to May 2014 using keywords and MeSH terms. To be included, studies had to contain primary data pertaining to patient experiences from participation in supervised, structured moderate to vigorous-intensity exercise. Results. In total 2447 abstracts were screened and 37 papers were read in full. Of these, 19 studies (n = 390) were selected for inclusion and critically appraised. Synthesis of data extracted from eight studies including in total 174 patients (77% women, age 28–76 years) exclusively reporting experiences of participation in structured, supervised exercise training resulted in nine themes condensed into three categories: 1) emergence of continuity; 2) preservation of health; and 3) reclaiming the body reflecting the benefits of exercise-based rehabilitation according to cancer survivors. Accordingly, the potential of rebuilding structure in everyday life, creating a normal context and enabling the individual to re-establish confidentiality and trust in their own body and physical potential constitute substantial qualities fundamental to the understanding of the meaningfulness of exercise-based rehabilitation from the perspective of patients. Conclusions. In addition to the accumulating evidence for the efficacy of exercise training in cancer rehabilitation, it is incumbent upon clinicians and policy-makers to acknowledge and promote the meaningfulness of exercise for the individual, and to use this knowledge to provide new solutions to current problems related to recruitment of underserved populations, long-term adherence and implementation.

At cancer diagnosis: a 'window of opportunity' for behavioural change towards physical activity. A randomised feasibility study in patients with colon and breast cancer.

Introduction Challenges exist in identifying, recruiting and motivating sedentary patients with cancer to initiate physical activity towards recommended levels. We hypothesise that the onset period of adjuvant chemotherapy can be ‘the open window of opportunity’ to identify and motivate sedentary patients with breast and colon cancers, at risk for developing coronary heart disease, to initiate and sustain lifestyle changes. Aims To investigate the feasibility of oncologists/nurses screening for physical inactivity, in order to identify and recruit an at-risk population of sedentary patients with breast or colon cancer at the onset of adjuvant chemotherapy. Furthermore, the study will examine the adherence to one of two multimodal exercise interventions lasting 12 weeks; (1) hospital-based, high intensity, group exercise intervention (2) home-based, low intensity, individual, pedometer intervention. Both arms will be compared with a control group. Methods and analyses All newly referred patients will be screened for sedentary behaviour, using national recommendations. Testing at baseline, 6, 12 and 39 weeks will include; (1) physiological testing (VO2-peak, one repetition maximum muscle strength and lung function (2) fasting full body dual-energy X-ray absorptiometry scan (3) fasting blood glucose, insulin, lipids and cholesterols, (4) psychometric questionnaires (general well-being, quality of life, anxiety and depression, motivational readiness). The randomised controlled trial feasibility design is selected in order to examine barriers for recruitment, programme adherence, safety aspects and potential efficacy to the interventions during adjuvant chemotherapy. Ethics and dissemination The Scientific Committee of the Capital Region (case No. H-1-2011-131) and the Danish Data Protection Agency (j. No. 2011-41-6349) approved the study. Data will be entered and locked into a database hosted by the Copenhagen Trial Unit, Rigshosptialet. Data will be available for analyses to project members and the trial statistician after the 45 included patients have completed the 12-week test. Results will be published in peer-reviewed scientific journals. Trial registration Current Controlled Trials ISRCTN24901641.

Exercise-Induced Catecholamines Activate the Hippo Tumor Suppressor Pathway to Reduce Risks of Breast Cancer Development

Strong epidemiologic evidence documents the protective effect of physical activity on breast cancer risk, recurrence, and mortality, but the underlying mechanisms remain to be identified. Using human exercise-conditioned serum for breast cancer cell incubation studies and murine exercise interventions, we aimed to identify exercise factors and signaling pathways involved in the exercise-dependent suppression of breast cancer. Exercise-conditioned serum from both women with breast cancer (n = 20) and healthy women (n = 7) decreased MCF-7 (hormone-sensitive) and MDA-MB-231 (hormone-insensitive) breast cancer cell viability in vitro by 11% to 19% and reduced tumorigenesis by 50% when preincubated MCF-7 breast cancer cells were inoculated into NMRI-Foxn1nu mice. This exercise-mediated suppression of cell viability and tumor formation was completely blunted by blockade of β-adrenergic signaling in MCF-7 cells, indicating that catecholamines were the responsible exercise factors. Both epinephrine (EPI) and norepinephrine (NE) could directly inhibit breast cancer cell viability, as well as tumor growth in vivo EPI and NE activate the tumor suppressor Hippo signaling pathway, and the suppressive effect of exercise-conditioned serum was found to be mediated through phosphorylation and cytoplasmic retention of YAP and reduced expression of downstream target genes, for example, ANKRD1 and CTGF. In parallel, tumor-bearing mice with access to running wheels showed reduced growth of MCF-7 (-36%, P < 0.05) and MDA-MB-231 (-66%, P < 0.01) tumors and, for the MCF-7 tumor, increased regulation of the Hippo signaling pathway. Taken together, our findings offer a mechanistic explanation for exercise-dependent suppression of breast cancer cell growth. Cancer Res; 77(18); 4894-904. ©2017 AACR.

Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction.

Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction.

The challenge of preserving cardiorespiratory fitness in physically inactive patients with colon or breast cancer during adjuvant chemotherapy: a randomised feasibility study

Introduction Anti-neoplastic treatment is synonymous with an inactive daily life for a substantial number of patients. It remains unclear what is the optimal setting, dosage and combination of exercise and health promoting components that best facilitate patient adherence and symptom management in order to support cardio-respiratory fitness and lifestyle changes in an at-risk population of pre-illness physically inactive cancer patients. Methods Patients with breast or colon cancer referred to adjuvant chemotherapy and by the oncologists pre-screening verified as physically inactive were eligible to enter a randomised three-armed feasibility study comparing a 12-week supervised hospital-based moderate to high intensity exercise intervention or alternate an instructive home-based12-week pedometer intervention, with usual care. Results Using a recommendation based physical activity screening instrument in order to correspond with cardio-respiratory fitness (VO2 peak) proved to be an applicable method to identify pre-illness physically inactive breast and colon cancer patients. The study demonstrated convincing recruitment (67%), safety and intervention adherence among breast cancer patients; while the attendance rate for colon cancer patients was notably lower (33%). VO2-peak declined on average 12% across study groups from baseline to 12 weeks though indices towards sustaining watt performance and reduce fat mass favoured the hospital-based intervention. Pedometer use was well adapted in both breast and colon cancer patients. Conclusions Despite a fair adherence and safety, the current study calls into question whether aerobic exercise, regardless of intensity, is able to increase VO2-peak during texane-based chemotherapy in combination with Neulasta in physically inactive breast cancer patients. Trial Registration: ISRCTN24901641