Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

The potential therapeutic effects of creatine supplementation on body composition and muscle function in cancer.

Low muscle mass in individuals with cancer has a profound impact on quality of life and independence and is associated with greater treatment toxicity and poorer prognosis. Exercise interventions are regularly being investigated as a means to ameliorate treatment-related adverse effects, and nutritional/supplementation strategies to augment adaptations to exercise are highly valuable. Creatine (Cr) is a naturally-occurring substance in the human body that plays a critical role in energy provision during muscle contraction. Given the beneficial effects of Cr supplementation on lean body mass, strength, and physical function in a variety of clinical populations, there is therapeutic potential in individuals with cancer at heightened risk for muscle loss. Here, we provide an overview of Cr physiology, summarize the evidence on the use of Cr supplementation in various aging/clinical populations, explore mechanisms of action, and provide perspectives on the potential therapeutic role of Cr in the exercise oncology setting.

Effects of physical exercise on breast cancer-related secondary lymphedema: a systematic review.

PURPOSE: The aim of this systematic review is to assess the effect of different types of exercise on breast cancer-related lymphedema (BCRL) in order to elucidate the role of exercise in this patient group. METHODS: A systematic data search was performed using PubMed (December 2016). The review is focused on the rehabilitative aspect of BCRL and undertaken according to the PRISMA statement with Levels of Evidence (LoE) assessed. RESULTS: 11 randomized controlled trials (9 with LoE 1a and 2 with LoE 1b) that included 458 women with breast cancer in aftercare were included. The different types of exercise consisted of aqua lymph training, swimming, resistance exercise, yoga, aerobic, and gravity-resistive exercise. Four of the studies measured a significant reduction in BCRL status based on arm volume and seven studies reported significant subjective improvements. No study showed adverse effects of exercise on BCRL. CONCLUSION: The evidence indicates that exercise can improve subjective and objective parameters in BCRL patients, with dynamic, moderate, and high-frequency exercise appearing to provide the most positive effects.

The feasibility of a pragmatic distance-based intervention to increase physical activity in lung cancer survivors.

The purpose of this study was to investigate the feasibility and preliminary efficacy of a pragmatic distance-based intervention designed to increase physical activity (PA) participation in lung cancer survivors. Fourteen lung cancer survivors were recruited via invitation from the State Cancer Registry to join a 12-week PA intervention of print materials paired with brief telephone follow-up. Outcome measures of feasibility, PA participation and quality of life (QoL) were assessed at baseline, post-intervention and follow-up via telephone interview. Eligibility, recruitment and attrition rates were 16%, 58% and 29% respectively. No adverse events were reported; however, pain scores worsened following the intervention (median change -3.6, IQR -8.0, 0.0). Average intervention adherence was 91% with low median ratings of participation burden (i.e., all items 1/7) and high trial evaluation (i.e., all items 7/7). Post-intervention, median change in self-reported moderate and vigorous PA was 84 min (IQR -22, 188), and several domains of QoL improved. However, for both of these outcomes, improvements were not maintained at follow-up. Our findings suggest that this pragmatic distance-based intervention was safe, had good adherence rates, and indicate potential for improving short-term PA and QoL in lung cancer survivors. Additional strategies are needed to improve other indicators of feasibility, particularly recruitment, retention and long-term maintenance of improvements. Australian New Zealand Clinical Trials Registration: ACTRN12612000085875.

Men's help-seeking in the first year after diagnosis of localised prostate cancer.

This study describes sources of support utilised by men with localised prostate cancer in the first year after diagnosis and examines characteristics associated with help-seeking for men with unmet needs. A cross-sectional survey of 331 patients from a population-based sample who were in the first year after diagnosis (M = 9.6, SD = 1.9) was conducted to assess sources of support, unmet supportive care needs, domain-specific quality of life and psychological distress. Overall, 82% of men reported unmet supportive care needs. The top five needs were sexuality (58%); prostate cancer-specific (57%); psychological (47%); physical and daily living (41%); and health system and information (31%). Professional support was most often sought from doctors (51%). Across most domains, men who were older (Ps ≤ 0.03), less well educated (Ps ≤ 0.04) and more depressed (Ps ≤ 0.05) were less likely to seek help for unmet needs. Greater sexual help-seeking was related to better sexual function (P = 0.03), higher education (P ≤ 0.03) and less depression (P = 0.05). Unmet supportive care needs are highly prevalent after localised prostate cancer diagnosis with older age, lower education and higher depression apparent barriers to help-seeking. Interventions that link across medicine, nursing and community based peer support may be an accessible approach to meeting these needs. Clinical Trial Registry: Trial Registration: ACTRN12611000392965.

Associations between aerobic exercise levels and physical and mental health outcomes in men with bone metastatic prostate cancer: a cross-sectional investigation.

Cancer patients with bone metastases have previously been excluded from participation in physical activity programmes due to concerns of skeletal fractures. Our aim was to provide initial information on the association between physical activity levels and physical and mental health outcomes in prostate cancer patients with bone metastases. Between 2012 and 2015, 55 prostate cancer patients (mean age 69.7 ± 8.3; BMI 28.6 ± 4.0) with bone metastases (58.2% >2 regions affected) undertook assessments for self-reported physical activity, physical and mental health outcomes (SF-36), objective physical performance measures and body composition by DXA. Sixteen men (29%) met the current aerobic exercise guidelines for cancer survivors, while 39 (71%) reported lower aerobic exercise levels. Men not meeting aerobic exercise guidelines had lower physical functioning (p = .004), role functioning (physical and emotional) (p < .05), general health scores (p = .014) as well all lower measures of physical performance (p < .05). Lower levels of aerobic exercise are associated with reduced physical and mental health outcomes in prostate cancer patients with bone metastases. While previous research has focused primarily in those with non-metastatic disease, our initial results suggest that higher levels of aerobic exercise may preserve physical and mental health outcomes in prostate cancer patients with bone metastases. Clinical Trial Registry: Trial Registration: ACTRN12611001158954.

EFFECTS OF COMPRESSION ON LYMPHEDEMA DURING RESISTANCE EXERCISE IN WOMEN WITH BREAST CANCER-RELATED LYMPHEDEMA: A RANDOMIZED, CROSS-OVER TRIAL.

The use of compression garments during exercise is recommended for women with breast cancer-related lymphedema, but the evidence behind this clinical recommendation is unclear. The aim of this randomized, cross-over trial was to compare the acute effects of wearing versus not wearing compression during a single bout of moderate-load resistance exercise on lymphedema status and its associated symptoms in women with breast cancer-related lymphedema (BCRL). Twenty-five women with clinically diagnosed, stable unilateral breast cancer-related lymphedema completed two resistance exercise sessions, one with compression and one without, in a randomized order separated by a minimum 6 day wash-out period. The resistance exercise session consisted of six upper-body exercises, with each exercise performed for three sets at a moderate-load (10-12 repetition maximum). Primary outcome was lymphedema, assessed using bioimpedance spectroscopy (L-Dex score). Secondary outcomes were lymphedema as assessed by arm circumferences (percent inter-limb difference and sum-of-circumferences), and symptom severity for pain, heaviness and tightness, measured using visual analogue scales. Measurements were taken pre-, immediately post- and 24 hours post-exercise. There was no difference in lymphedema status (i.e., L-Dex scores) pre- and post-exercise sessions or between the compression and non-compression condition [Mean (SD) for compression pre-, immediately post- and 24 hours post-exercise: 17.7 (21.5), 12.7 (16.2) and 14.1 (16.7), respectively; no compression: 15.3 (18.3), 15.3 (17.8), and 13.4 (16.1), respectively]. Circumference values and symptom severity were stable across time and treatment condition. An acute bout of moderate-load, upper-body resistance exercise performed in the absence of compression does not exacerbate lymphedema in women with BCRL.

The relationship between BPAQ-derived physical activity and bone density of middle-aged and older men.

UNLABELLED: The bone-specific physical activity questionnaire (BPAQ) accounts for activities that affect bone but has not been used in studies with older adults. Relationships exist between the BPAQ-derived physical activity and bone density in healthy middle-aged and older men but not men with prostate cancer. Disease-related treatments detrimental to bone should be considered when administering the BPAQ. INTRODUCTION: The bone-specific physical activity questionnaire (BPAQ) was developed to account for bone-specific loading. In this retrospective study, we examined the relationship between BPAQ-derived physical activity and bone mineral density (BMD) in middle-aged and older men with and without prostate cancer. METHODS: Two groups, 36 healthy men and 69 men with prostate cancer receiving androgen suppression therapy (AST), completed the BPAQ and had whole body, total hip, femoral (FN) and lumbar spine BMD assessed by dual-energy X-ray absorptiometry. RESULTS: Past (pBPAQ), current (cBPAQ) and total BPAQ (tBPAQ) scores for the healthy men were related to FN BMD (pBPAQ r = 0.36, p = 0.030; cBPAQ r s = 0.35, p = 0.034; tBPAQ r = 0.41, p = 0.014), and pBPAQ and tBPAQ were related to total hip (r s = 0.35, p = 0.035 and r s = 0.36, p = 0.029, respectively) and whole body BMD (r s = 0.44, p = 0.007 and r s = 0.45, p = 0.006, respectively). In men with prostate cancer, the BPAQ was not significantly associated with BMD. In stepwise regression analyses, body mass and tBPAQ predicted 30 % of the variance in total hip BMD (p = 0.003), cBPAQ predicted 14 % of the variance in FN BMD (p = 0.002), and body mass, age and tBPAQ predicted 47% of the variance in whole body BMD (p < 0.001) in healthy men. In men with prostate cancer, the BPAQ was not an independent predictor of BMD. CONCLUSIONS: Although BPAQ-derived estimates of physical activity are related to bone status in healthy middle-aged and older men, the adverse effect of AST on bone appears to obscure this relationship in men with prostate cancer.

Evidence-based physical activity guidelines for cancer survivors: current guidelines, knowledge gaps and future research directions.

Physical activity during and after cancer treatment has beneficial effects on a number of physical and psychosocial outcomes. This paper aims to discuss the existing physical activity guidelines for cancer survivors and to describe future research directions to optimize prescriptions. Studies on physical activity during and after cancer treatment were searched in PubMed, Clinicaltrials.gov, Australian New Zealand Clinical Trials Registry, and Dutch Trial registry. Physical activity guidelines for cancer survivors suggest that physical activity should be an integral and continuous part of care for all cancer survivors. However, the development of these guidelines has been limited by the research conducted. To be able to develop more specific guidelines, future studies should focus on identifying clinical, personal, physical, psychosocial, and intervention moderators explaining 'for whom' or 'under what circumstances' interventions work. Further, more insight into the working mechanisms of exercise interventions on health outcomes in cancer survivors is needed to improve the efficacy and efficiency of interventions. Finally, existing programs should embrace interests and preferences of patients to facilitate optimal uptake of interventions. In conclusion, current physical activity guidelines for cancer survivors are generic, and research is needed to develop more personalized physical activity guidelines.

Safety and efficacy of resistance exercise in prostate cancer patients with bone metastases.

BACKGROUND: Due to concerns of fragility fracture, exercise is a perceived contraindication for prostate cancer patients with bone metastases. These patients experience significant functional impairment and muscle atrophy, which may lead to an increased likelihood of skeletal complicaTIOns (i.e., pathological fracture, bone pain) and/or falls. Safe resistance exercise prescription may counteract this effect. The aim of this feasibility trial was to determine the safety and efficacy of resistance exercise by prostate cancer survivors with bone metastatic disease. METHODS: Twenty men with established bone metastases secondary to prostate cancer were randomly assigned to a 12-week resistance exercise program in which exercise prescription was based on the location of bone lesions (n=10) or usual care (n=10). Outcomes included safety and tolerance of the exercise program, physical function, physical activity level, body composition, fatigue, quality of life and psychological distress. Outcomes were compared between groups using analysis of covariance adjusted for baseline values. RESULTS: Participants had significant disease load with 65% of participants presenting with two or more regions affected by bone metastases and an average Gleason score of 8.2±0.9. Five participants (exercise=2; usual care=3) did not complete the intervention, three of which were due to advancing disease (exercise=2; usual care=1). No adverse events or skeletal complications occurred during the supervised exercise sessions. The exercise program was well tolerated as evidenced by high attendance (83%) and compliance rates (93%), and the ability of the participants to exercise at an intensity within the target range for cancer survivors (rating of perceived exertion =13.8±1.5). The change in physical function (muscle strength ∼11%; submaximal aerobic exercise capacity ∼5% and ambulation ∼12%), physical activity level (∼24%) and lean mass (∼3%) differed significantly between groups following the intervention, with favorable changes in the exercise group compared with the usual care group. No significant between-group differences were observed for fatigue, quality of life or psychological distress. CONCLUSIONS: This initial evidence involving a small sample size suggests that appropriately designed and supervised resistance exercise may be safe and well tolerated by prostate cancer patients with bone metastatic disease and can lead to improvements in physical function, physical activity levels and lean mass. Future trials involving larger sample sizes are required to expand these preliminary findings.

Exercise maintains sexual activity in men undergoing androgen suppression for prostate cancer: a randomized controlled trial.

BACKGROUND: Previous research has shown exercise to be an effective method to mitigate many adverse treatment-related effects of androgen suppression therapy (AST) but the potential impact of exercise on sexual activity remains unknown. The purpose of this investigation was to report the effect of a 12-week exercise program on sexual activity in prostate cancer patients undergoing AST. METHODS: Fifty-seven prostate cancer patients undergoing AST were randomly assigned to an exercise program (resistance and aerobic modes; n=29) or usual care control (n=28). Sexual activity was assessed by the European Organization for Research and Treatment of Cancer prostate cancer-specific quality of life questionnaire (QLQ-PR25). RESULTS: QLQ-PR25 data were log transformed and analysis of covariance was used to compare sexual activity between groups following the intervention adjusted for baseline activity. No differences in sexual activity were observed between the exercise and control groups before the intervention. There was a significant (P=0.045) adjusted group difference in sexual activity following the 12-week intervention. Patients undergoing usual care decreased sexual activity while patients in the exercise program maintained their level of sexual activity. At baseline, 20.6 and 22.2% of participants in the exercise and control groups reported a major interest in sex (that is, high libido). Following the intervention, the exercise group had a significantly higher percentage of participants reporting a major interest in sex (exercise=17.2% vs control=0%; P=0.024). CONCLUSIONS: Participation in a short-term exercise program resulted in the maintenance of sexual activity in prostate cancer patients undergoing AST.

Long-term effects of intermittent androgen suppression therapy on lean and fat mass: a 33-month prospective study.

BACKGROUND: To examine changes to whole body and regional lean mass (LM) and fat mass (FM) over 33 months of intermittent androgen suppression therapy (IAST). METHODS: Phase II cohort study of 72 prostate cancer patients without metastatic bone disease. Patients received flutamide 250 mg tid and leuprolide 22.5 mg three monthly depot for the 9-month initial treatment phase (iTREAT), at which point patients ceased therapy providing PSA <4 ng ml(-1) with continued monitoring for further 2 years (POST). AST was recommenced when PSA exceeded pretreatment level or ≥ 20 ng ml(-1). Body composition was assessed using dual energy X-ray absorptiometry at baseline, completion of treatment phase, and 1 and 2 years post treatment phase (months 21 and 33). RESULTS: LM decreased by 1.3 kg and FM increased by 2.3 kg (P<0.001) following iTREAT. During the POST period, there were no further adverse effects on LM or FM, but also no recovery to pretreatment levels. Patients who failed to recover testosterone by month 33 experienced a significant increase in FM compared with those who recovered eugonadal levels of testosterone (10 nmol ml(-1); P = 0.019). Change in testosterone was moderately correlated to changes in % FM (r = -0.314, P<0.028) and LM (r = 0.300, P<0.036) during POST phase. Waist circumference progressively increased over time and by 2 years, POST had not recovered to baseline levels. CONCLUSIONS: Loss of LM and gain in FM during the 9-month iTREAT was not reversed during 2-year POST, although further deterioration was not observed. Subgroup analysis identified those recovering testosterone showed some body composition improvements. These findings suggest potential benefits of IAST, where testosterone levels are able to recover, to reduce the ongoing adverse effects on body composition, such as the acceleration of sarcopenia and risks associated with metabolic disease.

AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure.

Androgen suppression treatment (AST) for men with prostate cancer is associated with a number of treatment-related side effects including an accelerated rate of bone loss. This loss of bone is greatest within the first year of AST and increases the risk for fracture. Pharmaceutical treatment in the form of bisphosphonates is currently used to counter the effects of hormone suppression on bone but is costly and associated with potential adverse effects. Recently, exercise has been shown to be an important adjuvant therapy to manage a range of treatment-related toxicities and enhance aspects of quality of life for men receiving AST. We propose that physical exercise may also have an important role in not only attenuating the bone loss associated with AST but in improving bone health and reducing fracture risk. In this review, the rationale underlying exercise as a countermeasure to AST-induced bone loss is provided.

Cardiovascular and metabolic complications during androgen deprivation: exercise as a potential countermeasure.

Apart from the well-established adverse musculoskeletal and sexual health effects of androgen deprivation therapy (ADT), evidence is accumulating of substantial ADT-related cardiovascular and metabolic complications, which may impact quality of life and overall survival. In this brief review we discuss (1) the incidence of cardiovascular and metabolic complications during/following ADT from large cohort studies, (2) the increased risk factors for cardiovascular and metabolic disease from cross-sectional and prospective studies and (3) the use of physical exercise as a countermeasure in this new era of ADT-related toxicity. It is clear that exercise has the potential to provide a myriad of benefits to men undergoing ADT that may result in reduced morbidity and mortality, and subsequently improve quality of life.

Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation.

This study examined the effects of androgen suppression therapy (AST) on upper and lower body muscle strength and a range of direct measures of physical performance using a cross-sectional design with 118 men (48 men undertaking AST for prostate cancer and 70 healthy aged-matched controls) from a single tertiary center. Primary end points included muscle strength for the upper- and lower-body; functional performance--repeated chair rise, usual and fast 6-m walk, 6-m backwards walk and 400-m walk time; and dual-energy X-ray absorptiometry assessment--whole body, regional soft tissue composition and bone mineral density (BMD). Men on AST had significantly reduced muscle strength for the upper- and lower-body and impaired functional performance compared to controls (P<0.05). As expected, AST patients had significantly lower whole-body and hip BMD and higher percent of body fat than controls (P<0.05), and tended to have lower whole-body lean mass (-2.3 kg, P=0.077). Appendicular skeletal muscle was positively associated with upper-body (r=0.400-0.606, P<0.001) and lower-body (r=0.549-0.588, P<0.001) muscle strength, and strength was related to functional performance. Men undertaking AST were consistently impaired across a broad range of physical and functional musculoskeletal performance assessments compared with their age-matched normal controls. These findings are relevant for those patients considering AST for subclinical disease management, but whose physical reserve is marginal. Strategies to counter these adverse effects of AST need to be initiated so that independent living and quality of life can be maintained.

Endocrine and immune responses to resistance training in prostate cancer patients.

This study examined the effect of 20 weeks resistance training on a range of serum hormones and inflammatory markers at rest, and following acute bouts of exercise in prostate cancer patients undergoing androgen deprivation. Ten patients exercised twice weekly at high intensity for several upper and lower-body muscle groups. Neither testosterone nor prostate-specific antigen changed at rest or following an acute bout of exercise. However, serum growth hormone (GH), dehydroepiandrosterone (DHEA), interleukin-6, tumor necrosis factor-alpha and differential blood leukocyte counts increased (P < 0.05) following acute exercise. Resistance exercise does not appear to compromise testosterone suppression, and acute elevations in serum GH and DHEA may partly underlie improvements observed in physical function.

Exercise can prevent and even reverse adverse effects of androgen suppression treatment in men with prostate cancer.

Side effects accompanying androgen deprivation therapy (ADT), including sarcopenia, loss of bone mass and reduction in muscle strength, can compromise physical function, particularly in older patients. Exercise, specifically resistance training, may be an effective and cost-efficient strategy to limit or even reverse some of these adverse effects during and following therapy. In this review, we discuss common morphological and physiological ADT-related side effects or 'Androgen Deprivation and Sarcopenia-Related Disorders' and the existing clinical trials incorporating physical exercise in prostate cancer patients receiving active therapy. Further, training concepts and guidelines are provided for prescribing resistance exercise programs for this population.