Home-based versus supervised group exercise in men with prostate cancer on androgen deprivation therapy: A randomized controlled trial and economic analysis.

INTRODUCTION: Differences between health outcomes, participation/adoption, and cost-effectiveness of home-based (HOME) interventions and supervised group-based training (GROUP) in men with prostate cancer (PC) on androgen deprivation therapy (ADT) are currently unknown. The objective of this study was to assess the clinical efficacy, adherence, and cost-effectiveness of HOME versus GROUP in men on ADT for PC. MATERIALS AND METHODS: This was a multicentre, 2-arm non-inferiority randomized controlled trial and companion cost-effectiveness analysis. Men with PC on ADT were recruited from August 2016 to March 2020 from four Canadian centres and randomized 1:1 to GROUP or HOME. All study participants engaged in aerobic and resistance training four to five days weekly for six months. Fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F)] and functional endurance [6-min walk test (6MWT)] at six months were the co-primary outcomes. Secondary outcomes included quality of life, physical fitness, body composition, blood markers, sedentary behaviour, and adherence. Between-group differences in primary outcomes were compared to margins of 3 points for FACT-F and 40 m for 6MWT using a Bayesian analysis of covariance (ANCOVA). Secondary outcomes were compared with ANCOVA, Costs included Ministry of Health costs, program costs, patient out-of-pocket, and time costs. TRIAL REGISTRATION: #NCT02834416. RESULTS: Thirty-eight participants (mean [standard deviation (SD)] age, 70 [9.0] years) were enrolled (GROUP n = 20; HOME n = 18). There was an 89.8% probability that HOME was non-inferior to GROUP for both fatigue and functional endurance and a 9.5% probability that HOME reduced fatigue compared to GROUP (mean [SD] change, 12.1 [8.1] vs 3.6 [6.1]; p = 0.040) at six months. Adherence was similar among study arms. HOME was cost-saving (mean difference: -$4122) relative to GROUP. DISCUSSION: A HOME exercise intervention appears non-inferior to GROUP for fatigue and functional endurance and requires fewer resources to implement. HOME appears to ameliorate fatigue more than GROUP, but has comparable effects on other clinically relevant outcomes. Although limited by sample size and attrition, these results support further assessment of home-based programs.

The Effect of Yoga Interventions on Cancer-Related Fatigue and Quality of Life for Women with Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Women with breast cancer (BC) are living longer with debilitating side effects such as cancer-related fatigue (CRF) that affect overall well-being. Yoga promotes health, well-being and may be beneficial in reducing CRF. Although there have been previous systematic reviews and meta-analyses, the effects of yoga on CRF and quality of life (QOL) remain unclear, particularly in comparison with other types of physical activity (PA). Our objective is to carry out a systematic review and meta-analysis of the effects of yoga on CRF and QOL in women with BC. METHODS: Electronic databases were searched (MEDLINE, Embase Classic+Embase and EMB Reviews, Cochrane Central CT) from inception to May 2018. Randomized controlled trials were included if they were full text, in English, included a yoga intervention, a comparator (including non-PA usual care or alternate PA intervention), and reported on CRF or QOL. Effects of yoga were pooled using standardized mean difference (SMD) via a random effects model. RESULTS: Of the 2468 records retrieved, 24 trials were included; 18 studies compared yoga to a non-PA comparator and 6 to a PA comparator. Yoga demonstrated statistically significant improvements in CRF over non-PA (SMD -0.30 [-0.51; -0.08]) but not PA (SMD -0.17 [-0.50; 0.17]) comparators. Additionally, yoga demonstrated statistically significant improvements in QOL over non-PA (SMD -0.27 [-0.46; -0.07]) but not PA (SMD 0.04 [-0.22; +0.31]) comparators. DISCUSSION: This meta-analysis found that yoga provides small to medium improvements in CRF and QOL compared to non-PA, but not in comparison to other PA interventions.

Effects of six months of aerobic and resistance training on metabolic markers and bone mineral density in older men on androgen deprivation therapy for prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with metabolic perturbations and declines in bone mineral density (BMD). Exercise interventions provide multiple health benefits to older men on ADT; however, their effect on metabolic biomarkers and BMD remains unclear. METHODS: A secondary analysis of a phase II randomized controlled trial was conducted to assess the effect of a six-month moderate-intensity aerobic and resistance exercise program on metabolic biomarkers and BMD in men on ADT. Participants were randomized to three different exercise delivery models: personal training; supervised group exercise; or home-based exercise. Analysis of metabolic biomarkers (lipid profile and glucose) was conducted at baseline, six and twelve months. BMD of the lumbar spine, femoral neck and hip were assessed at baseline and twelve months. Both within- and between-group analyses of change scores adjusted for baseline values were performed. RESULTS: Forty-eight men (mean age 69.8y) were enrolled. Baseline values of metabolic biomarkers and BMD were comparable between groups and the three groups were combined for the primary analysis. At six months, no changes in metabolic biomarkers were found; however, at twelve months low-density lipoprotein (+0.28 mmol/L; 95%CI, 0.04 to 0.51) and total cholesterol (+0.31 mmol/L; 95%CI, 0.00 to 0.61) were significantly increased from baseline. No changes were found in BMD. In a secondary between-group analysis, no improvements were observed for any metabolic biomarker or BMD measurement. CONCLUSIONS: Different exercise prescription parameters (modality and intensity) or combined diet/exercise interventions may be needed to foster favorable metabolic and skeletal adaptations during ADT.

Aerobic capacity attainment and reasons for cardiopulmonary exercise test termination in people with cancer: a descriptive, retrospective analysis from a single laboratory.

PURPOSE: Aerobic exercise prescriptions in clinical populations commonly involve target intensities based on cardiopulmonary exercise tests (CPET). CPETs are often discontinued prior to a patient achieving true maximum oxygen consumption (VO2 max) which can adversely affect exercise dose and efficacy monitoring; however, reasons for early discontinuation are poorly reported. Accordingly, we explored the CPET termination reasons in persons with cancer participating in exercise intervention studies. METHODS: This study comprised of an exploratory, descriptive analysis of retrospective CPET data (VO2 and anaerobic threshold) and termination reasons in a convenience sample of people with cancer participating in exercise intervention studies in a single laboratory. CPETs were standardized using the modified Bruce treadmill protocol with expired gas collection and analysis using a metabolic cart. VO2 max was considered "met" when participants demonstrated (a) oxygen consumption plateau or (b) two of the following criteria: rating of perceived exertion ≥ 9/10, respiratory exchange ratio ≥ 1.15, and/or heart rate of 95% of age-predicted maximum. The frequency and distribution of reasons for test termination relative to the number of CPET exposures for the participants were reported. RESULTS: Forty-four participants engaged in exercise studies between February 2016 and March 2018 provided data for the analysis. Participants completed up to three CPETs during this period (total of 78 CPETs in the current analysis). Eighty-six percent of all CPETs were terminated prior to achieving VO2 max verification criteria and no tests resulted in an oxygen consumption plateau. For those that did not demonstrate achievement of VO2 max verification criteria, reasons for discontinuation were distributed as follows: equipment discomfort-49%, volitional peak-36%, and physical discomfort-14.9%. For those who met VO2 max criteria, volitional peak was the most common reason for test termination (45.5%), followed by physical discomfort (36.4%), and equipment discomfort (18.2%). CONCLUSIONS: In our sample of cancer survivors, VO2 max criteria were infrequently met with equipment discomfort being a primary reason for participant-driven test termination. Protocol and equipment considerations are necessary for interpretation and application of CPET findings in clinical practice.

A phase II randomized controlled trial of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.

BACKGROUND: Existing evidence demonstrates that 1:1 personal training (PT) improves many adverse effects of androgen deprivation therapy (ADT). Whether less resource-intensive exercise delivery models are as effective remains to be established. We determined the feasibility of conducting a multi-center non-inferiority randomized controlled trial comparing PT with supervised group (GROUP) and home-based (HOME) exercise programs, and obtained preliminary efficacy estimates for GROUP and HOME compared to PT on quality of life (QOL) and physical fitness. METHODS: Men with prostate cancer on ADT were recruited from one of two experienced Canadian centres and randomized 1:1:1 to PT, GROUP, or HOME. Randomization was stratified by length of ADT use and site. Participants completed moderate intensity aerobic and resistance exercises 4-5 days per week for 6 months with a target 150 min per week of exercise. Exercise prescriptions were individualized and progressed throughout the trial. Feasibility endpoints included recruitment, retention, adherence, and participant satisfaction. The efficacy endpoints QOL, fatigue, and fitness (VO2 peak, grip strength, and timed chair stands) in GROUP and HOME were compared for non-inferiority to PT. Descriptive analyses were used for feasibility endpoints. Between-group differences for efficacy endpoints were examined using Bayesian linear mixed effects models. RESULTS: Fifty-nine participants (mean age 69.9 years) were enrolled. The recruitment rate was 25.4% and recruitment was slower than projected. Retention was 71.2%. Exercise adherence as measured through attendance was high for supervised sessions but under 50% by self-report and accelerometry. Satisfaction was high and there was no difference in this measure between all three groups. Between-group differences (comparing both GROUP and HOME to PT) were smaller than the minimum clinically important difference on most measures of QOL, fatigue, and fitness. However, two of six outcomes for GROUP and four of six outcomes for HOME had a > 20% probability of being inferior for GROUP. CONCLUSIONS: Feasibility endpoints were generally met. Both GROUP and HOME interventions in men with PC on ADT appeared to be similar to PT for multiple efficacy outcomes, although conclusions are limited by a small sample size and cost considerations have not been incorporated. Efforts need to be targeted to improving recruitment and adherence. A larger trial is warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02046837 . Date of registration: January 20, 2014.

Protocol for a phase III RCT and economic analysis of two exercise delivery methods in men with PC on ADT.

BACKGROUND: Androgen deprivation therapy (ADT) is commonly used to treat prostate cancer. However, side effects of ADT often lead to reduced quality of life and physical function. Existing evidence demonstrates that exercise can ameliorate multiple treatment-related side effects for men on ADT, yet adherence rates are often low. The method of exercise delivery (e.g., supervised group in-centre vs. individual home-based) may be important from clinical and economic perspectives; however, few studies have compared different delivery models. Additionally, long-term exercise adherence and an understanding of predictors of adherence are critical to achieving sustained benefits, but such data are lacking. The primary aim of this multi-centre phase III non-inferiority randomized controlled trial is to determine whether a home-based delivery model is non-inferior to a group-based delivery model in terms of benefits in fatigue and fitness in this population. Two other key aims include examining cost-effectiveness and long-term adherence. METHODS: Men diagnosed with prostate cancer of any stage, starting or continuing on ADT for at least 6 months, fluent in English, and living close to a study centre are eligible. Participants complete five assessments over 12 months (baseline and every 3 months during the 6-month intervention and 6-month follow-up phases), including a fitness assessment and self-report questionnaires. Biological outcomes are collected at baseline, 6, and 12 months. A total of 200 participants will be randomized in a 1:1 fashion to supervised group training or home-based training supported by smartphones, health coaches, and Fitbit technology. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Outcomes include fatigue, quality of life, fitness measures, body composition, biological outcomes, and program adherence. Cost information will be obtained using patient diary-based self-report and utilities via the EQ-5D. DISCUSSION: To disseminate publicly funded exercise programs widely, clinical efficacy and cost-effectiveness have to be demonstrated. The goals of this trial are to provide these data along with an increased understanding of adherence to exercise among men with prostate cancer receiving ADT. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov (Registration # NCT02834416 ). Registration date was June 2, 2016.

Perceptions of Study Newsletters for Older Cancer Patients in Longitudinal Studies.

To date, no study has examined the value of providing study newsletters in educating and motivating participants taking part in longitudinal intervention studies and reducing attrition in studies. The study team examined perceptions and satisfaction towards study newsletters, and their potential benefits, in a population of older men with prostate cancer participating in two ongoing longitudinal trials. Two study newsletters issues were mailed out 4 months apart to prostate cancer patients participating in a bone health and/or exercise intervention trial. Participants (n = 133) were invited to complete an 18-item custom-designed survey examining perceptions towards and satisfaction with the newsletter, and provide feedback about what makes an ideal study newsletter. Analyses were primarily descriptive. Resources required to produce a study newsletter were also calculated. Of 133 participants, 83 usable surveys were returned (response rate 62.4%). The mean satisfaction rating for the newsletter was 8.5/10 (SD 1.9) (10 = highly satisfied). Seventy eight percent said the newsletter encouraged them to continue to participate in the study, and 93% indicated that providing such study newsletters should be optional (64%) or mandatory (29%). Each newsletter required 31 h of study personnel time (mostly research student) to produce. Study participants were very satisfied with the newsletter and the majority indicated that study newsletters should be a regular practice in all long-term studies and may improve participant retention. Producing a newsletter is a low-cost method of educating participants in longitudinal studies. Its impact on recruitment and retention should be examined in clinical trials.

The neurocognitive basis of borrowed context information.

Falsely remembered items can be accompanied by episodic context retrieval. This finding is difficult to explain because there is no episode that binds the remembered item to the experimenter-controlled context features. The current study examines the neural correlates of false context retrieval when the context features can be traced to encoding episodes of semantically-similar items. Our neuroimaging results support a "dissociated source" mechanism for context borrowing in false memory. We found that parahippocampal cortex (PHc) activation, thought to indicate context retrieval, was greater during trials that involved context borrowing (an incorrect, but plausible source decision) than during baseline correct context retrieval. In contrast, hippocampal activation, thought to indicate retrieval of an episodic binding, was stronger during correct source retrieval than during context borrowing. Vivid context retrieval during false recollection experiences was also indicated by increased activation in visual perceptual regions for context borrowing as compared to other incorrect source judgments. The pattern of findings suggests that context borrowing can arise when unusually strong activation of a semantically-related item's contextual features drives relatively weak retrieval of the associated episodic binding with failure to confirm the item information within that binding. This dissociated source retrieval mechanism suggests that context-driven episodic retrieval does not necessarily lead to retrieval of specific item details. That is, source information can be retrieved in the absence of item memory.

Frontotemporal function]al connectivity and executive functions contribute to episodic memory performance.

The contributions of hemispheric-specific electrophysiology (electroencephalogram or EEG) and independent executive functions (inhibitory control, working memory, cognitive flexibility) to episodic memory performance were examined using abstract paintings. Right hemisphere frontotemporal functional connectivity during encoding and retrieval, measured via EEG alpha coherence, statistically predicted performance on recency but not recognition judgments for the abstract paintings. Theta coherence, however, did not predict performance. Likewise, cognitive flexibility statistically predicted performance on recency judgments, but not recognition. These findings suggest that recognition and recency operate via separate electrophysiological and executive mechanisms.

Working Memory and Recollection Contribute to Academic Achievement.

The contributions of working memory and recollection to academic achievement are typically examined separately and most often with children who have learning difficulties. This study is the first to observe both types of memory in the same study and in typically developing children. Academic achievement focused on standardized assessments of math fluency, calculation, reading fluency, and passage comprehension. As noted in previous studies, working memory was associated with each assessed measure of academic achievement. Recollection, however, specifically contributed to math fluency and passage comprehension. Thus, recollection should be considered alongside working memory in studies of academic achievement.

A phase II RCT and economic analysis of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy is commonly used to treat prostate cancer, the most common visceral cancer in men. However, various side effects often worsen physical functioning and reduce well-being among men on this treatment. Based on existing evidence, both resistance and aerobic training provide benefits for this population yet adherence rates are often low. The method of exercise delivery (supervised in-center or home-based) may be important, yet few studies have compared different models. Additionally, long-term exercise adherence is critical to achieve sustained benefits but long-term adherence data and predictors of adherence are lacking. The primary aim of this phase II, non-inferiority randomized controlled trial is to determine whether three exercise training delivery models are equivalent in terms of benefits in quality of life and physical fitness in this population. Secondary aims include examination of long-term adherence and cost-effectiveness. DESIGN: Men diagnosed with prostate cancer, starting or continuing on androgen deprivation therapy for at least 6 months, fluent in English, and living close to one of two experienced Canadian study centers are eligible. Participants complete five assessments over one year, including a fitness assessment and self-report questionnaires. Socio-demographic and clinical data collection occur at baseline, bone mineral density testing at two time points, and blood work is performed at three time points. Participants are randomized in a 1:1:1 fashion to supervised personal training, supervised group training, or home-based smartphone- and health coach-supported training. Each participant receives a detailed exercise manual, including illustrations of exercises and safety precautions. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Participant intensity levels will be monitored. The intervention duration is 6 months, with 6 months additional follow-up. Outcomes include: body composition, fitness testing, quality of life and fatigue, biological outcomes, and program adherence. Cost information will be obtained using patient diary-based self-report. DISCUSSION: The goals of this study are to gain a better understanding of health benefits and costs associated with commonly used yet currently not compared exercise delivery models as well as an increased understanding of adherence to exercise. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov (Registration # NCT02046837), registered January 20(th), 2014.