Miranda J. Velthuis

Effect of Exercise on Postmenopausal Sex Hormone Levels and Role of Body Fat: A Randomized Controlled Trial

PURPOSE To examine the effects of a 1-year exercise intervention on sex hormone levels in postmenopausal women and whether any effects are mediated by changes in body fat composition. METHODS We randomly assigned 189 sedentary postmenopausal women (age 50 to 69 years, body mass index of 22 to 40 kg/m(2)) to an exercise intervention (n = 96) or a control group (n = 93). The intervention combined aerobic and strength training and comprised supervised group sessions and home-based exercises (a total of 2.5 h/wk). Between-group differences in sex hormone levels (at baseline and 4 and 12 months) were examined with generalized estimating equations. RESULTS In total, 183 women (97%) completed the study. Overall, the exercise intervention did not result in favorable effects on sex hormone levels. Among women who lost more than 2% body fat, declines in all estrogens were not significantly different between exercisers and controls. Androgen levels decreased significantly in the exercise group who lost body fat compared with their peers in the control group. Furthermore, this study confirmed that fat loss was significantly associated with declines in postmenopausal estrogen levels. Although not significant, a similar trend was observed for the androgens. CONCLUSION This study confirms that fat loss is associated with changes in postmenopausal sex hormone levels and suggests that exercise may be effective in inducing favorable changes in these hormones.

Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.

Physical Activity during Cancer Treatment (PACT) Study: design of a randomised clinical trial

BackgroundFatigue is a major problem of cancer patients. Thirty percent of cancer survivors report serious fatigue three years after finishing treatment. There is evidence that physical exercise during cancer treatment reduces fatigue. This may also lead to an improvement of quality of life. Such findings may result in a decrease of healthcare related expenditures and societal costs due to sick leave. However, no studies are known that investigated these hypotheses. Therefore, the primary aim of our study is to assess the effect of exercise during cancer treatment on reducing complaints of fatigue and on reducing health service utilisation and sick leave.Methods/DesignThe Physical Activity during Cancer Treatment study is a multicentre randomised controlled trial in 150 breast and 150 colon cancer patients undergoing cancer treatment. Participants will be randomised to an exercise or a control group. In addition to the usual care, the exercise group will participate in an 18-week supervised group exercise programme. The control group will be asked to maintain their habitual physical activity pattern. Study endpoints will be assessed after 18 weeks (short term) and after 9 months (long term). Validated questionnaires will be used. Primary outcome: fatigue (Multidimensional Fatigue Inventory and Fatigue Quality List) and cost-effectiveness, health service utilisation and sick leave. Secondary outcome: health related quality of life (European Organisation Research and Treatment of Cancer-Quality of Life questionnaire-C30, Short Form 36 healthy survey), impact on functioning and autonomy (Impact on functioning and autonomy questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), physical fitness (aerobic peak capacity, muscle strength), body composition and cognitive-behavioural aspects. To register health service utilisation and sick leave, participants will keep diaries including the EuroQuol-5D. Physical activity level will be measured using the Short Questionnaire to Assess Health-Enhancing Physical Activity and will be monitored with an exercise log and a pedometer.DiscussionThis study investigates the (cost)-effectiveness of exercise during adjuvant treatment of patients with breast or colon cancer. If early physical exercise proves to be (cost) effective, establishing standardised physical exercise programmes during cancer treatment will be planned.Trial registrationCurrent Controlled trials ISRCTN43801571, Dutch Trial Register NTR2138

Cardiopulmonary Exercise Testing in Cancer Rehabilitation A Systematic Review

This systematic review aims to get insight into the feasibility of cardiopulmonary exercise testing (CPET) in patients with cancer prior to a physical exercise programme. We will focus on quality (defined as the adherence to international guidelines for methods of CPET) and safety of CPET. Furthermore, we compare the peak oxygen uptake (V̇O2peak) values of patients with cancer with reference values for healthy persons to put these values into a clinical perspective. A computer aided search with ‘cardiopulmonary exercise testing’ and ‘cancer’ using MEDLINE, EMBASE, Pedro, CINAHL® and SPORTDiscus™ was carried out. We included studies in which CPET with continuous gas exchange analysis has been performed prior to a physical exercise programme in adults with cancer. Twenty studies describing 1158 patients were eligible. Reported adherence to international recommendations for CPET varied per item. In most studies, the methods of CPET were not reported in detail. Adverse events occurred in 1% of patients. The percentage V̇O2peak of reference values for healthy persons varied between 65% and 89% for tests before treatment, between 74% and 96% for tests during treatment and between 52% and 117% for tests after treatment. Our results suggest that CPET is feasible and seems to be safe for patients with cancer prior to a physical exercise programme. We recommend that standard reporting and quality guidelines should be followed for CPET methods. The decreased V̇O2peak values of patients with cancer indicate that physical exercise should be implemented in their standard care.

Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy.

PURPOSE Fatigue is a common problem among colon cancer patients and typically increases during chemotherapy. Exercise during chemotherapy might have beneficial effects on fatigue. To investigate the short- and long-term effects of an exercise program in colon cancer patients during adjuvant treatment, the Physical Activity During Cancer Treatment study was conducted. METHODS In this multicenter randomized controlled trial, 33 colon cancer patients undergoing chemotherapy (21 men and 12 women) were randomly assigned to either a group receiving an 18-wk supervised exercise program (n = 17) or to usual care (n = 16). The primary outcome was fatigue as measured by the Multidimensional Fatigue Inventory and the Fatigue Quality List. Secondary outcomes were quality of life, physical fitness, anxiety, depression, body weight, and chemotherapy completion rate. Outcome assessment took place at baseline, postintervention (18 wk) and at 36 wk. RESULTS Intention-to-treat mixed linear model analyses showed that patients in the intervention group experienced significantly less physical fatigue at 18 wk and general fatigue at 36 wk (mean between group differences, -3.2; 95% confidence interval [CI], -6.2 to -0.2; effect size [ES], -0.9 and -2.7; 95% CI, -5.2 to -0.1; ES, -0.8, respectively), and reported higher physical functioning (12.3; 95% CI, 3.3-21.4; ES, 1.0) compared with patients in the usual care group. CONCLUSION The Physical Activity During Cancer Treatment trial shows that an 18-wk supervised exercise program in colon cancer patients during chemotherapy is safe and feasible. The intervention significantly reduced physical fatigue at 18 wk and general fatigue at 36 wk. Considering the number of patients included in the present study, replication in a larger study population is required.

Control group design, contamination and drop-out in exercise oncology trials: a systematic review.

Purpose Important considerations for exercise trials in cancer patients are contamination and differential drop-out among the control group members that might jeopardize the internal validity. This systematic review provides an overview of different control groups design characteristics of exercise-oncology trials and explores the association with contamination and drop-out rates. Methods Randomized controlled exercise-oncology trials from two Cochrane reviews were included. Additionally, a computer-aided search using Medline (Pubmed), Embase and CINAHL was conducted after completion date of the Cochrane reviews. Eligible studies were classified according to three control group design characteristics: the exercise instruction given to controls before start of the study (exercise allowed or not); and the intervention the control group was offered during (any (e.g., education sessions or telephone contacts) or none) or after (any (e.g., cross-over or exercise instruction) or none) the intervention period. Contamination (yes or no) and excess drop-out rates (i.e., drop-out rate of the control group minus the drop-out rate exercise group) were described according to the three design characteristics of the control group and according to the combinations of these three characteristics; so we additionally made subgroups based on combinations of type and timing of instructions received. Results 40 exercise-oncology trials were included based on pre-specified eligibility criteria. The lowest contamination (7.1% of studies) and low drop-out rates (excess drop-out rate -4.7±9.2) were found in control groups offered an intervention after the intervention period. When control groups were offered an intervention both during and after the intervention period, contamination (0%) and excess drop-out rates (-10.0±12.8%) were even lower. Conclusions Control groups receiving an intervention during and after the study intervention period have lower contamination and drop-out rates. The present findings can be considered when designing future exercise-oncology trials.

Quality criteria and user-friendliness in self-reported questionnaires on cancer-related fatigue: a review

OBJECTIVE Cancer-related fatigue (CRF) is a distressing, persistent, subjective sense of tiredness or exhaustion that occurs in 70-100% of cancer patients. The purpose of this review was to provide an overview of the quality of research performed on existing CRF self-report questionnaires and compare their reported psychometric properties and user-friendliness. METHODS Database searches of CINAHL, Cochrane Library, EMBASE, MEDLINE, Scopus, PEDro, and PsycINFO were undertaken to find published scales. Standardized criteria were used to assess quality and user-friendliness. RESULTS Thirty-five articles were included that described 18 questionnaires-seven one-dimensional questionnaires and 11 multidimensional questionnaires. The mean item count was 20.8 (range: 3-83). The mean overall score of the one-dimensional questionnaires was 10.4 of a maximum of 18 points (range: 7.6-14.3). The mean overall score of the multidimensional questionnaires was 9.4 of a maximum of 18 points (range: 4.3-14.4). CONCLUSION Recommendations were made for the selection of a scale. We argue in favor of repeatedly reassessing psychometric properties of even established questionnaires to ensure they comply with evermore increasing stringent quality criteria.

Role of Fear of Movement in Cancer Survivors Participating in a Rehabilitation Program: A Longitudinal Cohort Study

OBJECTIVE To study the relationship between fear of movement and perceived global health status and the role of rehabilitation with graded activity in cancer survivors. DESIGN Longitudinal cohort study. SETTING Rehabilitation centers. PARTICIPANTS Cancer survivors (N=1236). INTERVENTION Twelve-week graded activity rehabilitation program. MAIN OUTCOME MEASURES Fear of movement (Modified Tampa Scale for Kinesiophobia-Fatigue), fatigue (Functional Assessment of Cancer Therapy-Fatigue), and perceived global health status (European Organisation Research and Treatment of Cancer Quality of Life Questionnaire C30) were measured at baseline and after rehabilitation. We performed multiple linear regression analyses to examine the association between fear of movement and perceived global health status at baseline. Differences between baseline and postintervention scores were assessed with a paired t test and effect sizes (ESs). Hierarchical multiple regression analyses were used to investigate whether changes in fear of movement were associated with perceived global health status. RESULTS Fear of movement was associated with perceived global health status prior to rehabilitation (P=.001). Only participants with high scores on baseline fear of movement showed a considerable decrease in fear of movement after rehabilitation (ES=-.69; 95% confidence interval [CI], -.80 to -.57); the reduction was largest for fears because of a somatic focus (ES=-.57; 95% CI, -.68 to -.45). Changes in fear of movement because of a somatic focus were related to perceived global health status postintervention (P=.001). CONCLUSIONS Fear of movement is associated with the perceived global health status of cancer survivors. Fear of movement decreases after rehabilitation with graded activity in high scorers on baseline fear of movement.

Alternatives for randomization in lifestyle intervention studies in cancer patients were not better than conventional randomization

OBJECTIVE Assessing effects of lifestyle interventions in cancer patients has some specific challenges. Although randomization is urgently needed for evidence-based knowledge, sometimes it is difficult to apply conventional randomization (i.e., consent preceding randomization and intervention) in daily settings. Randomization before seeking consent was proposed by Zelen, and additional modifications were proposed since. We discuss four alternatives for conventional randomization: single and double randomized consent design, two-stage randomized consent design, and the design with consent to postponed information. STUDY DESIGN AND SETTING We considered these designs when designing a study to assess the impact of physical activity on cancer-related fatigue and quality of life. We tested the modified Zelen design with consent to postponed information in a pilot. The design was chosen to prevent drop out of participants in the control group because of disappointment about the allocation. RESULTS The result was a low overall participation rate most likely because of perceived lack of information by eligible patients and a relatively high dropout in the intervention group. CONCLUSION We conclude that the alternatives were not better than conventional randomization.

Targeting Exercise Interventions to Patients With Cancer in Need: An Individual Patient Data Meta-Analysis

Background Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment. Methods Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided. Results Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction < .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were greater in patients with worse baseline values. Conclusion Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment.