Design of a randomized controlled trial of physical training and cancer (Phys-Can) – the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome

Background: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life in persons undergoing adjuvant cancer treatment. In addition, to examine effects of exercise intensity on mood disturbance, adherence to oncological treatment, adverse effects from treatment, activities of daily living after treatment completion and return to work, and behaviour change techniques effect on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life. Methods/design: Six hundred newly diagnosed persons with breast, colorectal or prostate cancer undergoing adjuvant therapy will be randomized in a 2 × 2 factorial design to following conditions; A) individually tailored low-to-moderate intensity exercise with or without behaviour change techniques or B) individually tailored high intensity exercise with or without behaviour change techniques. The training consists of both resistance and endurance exercise sessions under the guidance of trained coaches. The primary outcomes, fatigue and health related quality of life, are measured by self-reports. Secondary outcomes include fitness, mood disturbance, adherence to the cancer treatment, adverse effects, return to activities of daily living after completed treatment, return to work as well as inflammatory markers, cytokines and gene expression. Discussion: The study will contribute to our understanding of the value of exercise and exercise intensity in reducing fatigue and improving health related quality of life and, potentially, clinical outcomes. The value of behaviour change techniques in terms of adherence to and maintenance of physical exercise behaviour in persons with cancer will be evaluated

Optitrain : a randomised controlled exercise trial for women with breast cancer undergoing chemotherapy.

BACKGROUND: Women with breast cancer undergoing chemotherapy suffer from a range of detrimental disease and treatment related side-effects. Exercise has shown to be able to counter some of these side-effects and improve physical function as well as quality of life. The primary aim of the study is to investigate and compare the effects of two different exercise regimens on the primary outcome cancer-related fatigue and the secondary outcomes muscle strength, function and structure, cardiovascular fitness, systemic inflammation, skeletal muscle gene activity, health related quality of life, pain, disease and treatment-related symptoms in women with breast cancer receiving chemotherapy. The second aim is to examine if any effects are sustained 1, 2, and 5 years following the completion of the intervention and to monitor return to work, recurrence and survival. The third aim of the study is to examine the effect of attendance and adherence rates on the effects of the exercise programme. METHODS: This study is a randomised controlled trial including 240 women with breast cancer receiving chemotherapy in Stockholm, Sweden. The participants are randomly allocated to either: group 1: Aerobic training, group 2: Combined resistance and aerobic training, or group 3: usual care (control group). During the 5-year follow-up period, participants in the exercise groups will receive a physical activity prescription. Measurements for endpoints will take place at baseline, after 16 weeks (end of intervention) as well as after 1, 2 and 5 years. DISCUSSION: This randomised controlled trial will generate substantial information regarding the effects of different types of exercise on the health of patients with breast cancer undergoing chemotherapy. We expect that dissemination of the knowledge gained from this study will contribute to developing effective long term strategies to improve the physical and psychosocial health of breast cancer survivors. TRIAL REGISTRATION: OptiTrain - Optimal Training Women with Breast Cancer (OptiTrain), NCT02522260 ; Registration: June 9, 2015, Last updated version Feb 29, 2016. Retrospectively registered

Possible utilization of salivary IFN‐γ/IL‐4 ratio as a marker of chronic stress in healthy individuals

INTRODUCTION: Several studies show that psychological stress reduces Th1/Th2 ratio in blood samples. However, evidence is scarce regarding the cytokine alterations during stress in saliva. We investigated the influence of chronic stress on Th1/Th2 ratio and cytokine profiles in the saliva of healthy individuals. Further, we examined the associations of the salivary cytokine levels with sleep and attention problems, which are closely related with psychological stress. METHODS: Salivary levels of 27 cytokines were measured by multiplex bead array assays in 31 healthy young individuals (health science students and hospital staff consisting of 11 men and 20 women, mean age [standard deviation] =21.5 [0.8] years). The Kessler Psychological Distress scale (K10) and Athens Insomnia Scale (AIS) were administered to assess subjective chronic psychological stress and sleep problems. Further, participants were asked to wear Actigraph GT3X accelerometers for 3 days to assess the total sleep time. Attention problems were assessed by administering the Integrated Visual and Auditory Continuous Performance Test (IVA‐CPT). RESULTS: Thirteen cytokines with >80% detectable results were included in the main analyses. The IFN‐γ/IL‐4 ratio, which is a commonly used index for Th1/Th2 ratio, showed significant negative correlations with the K10 and AIS scores. None of the cytokines were significantly associated with sex, body mass index, sleep index measured by Actigraph, or IVA‐CPT scores. CONCLUSION: Chronic stress may be associated with alterations of the Th1/Th2 balance in salivary cytokine production. IFN‐γ/IL‐4 ratio in saliva may serve as a potential biomarker of chronic stress in healthy individuals