Joachim Wiskemann

Impact of resistance training in cancer survivors: A meta-analysis

PURPOSE Current evidence suggests many health benefits from physical activity during and after cancer treatment. However, the optimal exercise program for cancer survivors has not yet been established. The purpose of this meta-analysis was to summarize evidence for the efficacy of resistance training (RT) interventions to improve muscle strength and body composition among adult cancer survivors. We also investigate potential dose-response relationships between intensity, duration, and frequency of RT and assessed outcomes. METHODS A systematic literature review of the Clinical Trial Register, Cochrane Trial Register, MEDLINE, and EMBASE literature databases was undertaken. Studies were included if they were randomized controlled trials (RCT) comparing RT with an exercise or nonexercise control group in cancer survivors during and after treatment. Thirteen articles from 11 RCT met our inclusion criteria. We performed a random-effects meta-analysis to determine weighted mean differences (WMD) with 95% confidence intervals using the Cochrane Review Manager 5.0.25. A random-effects metaregression model was performed to examine dose-response relationships between RT variables and assessed outcomes. RESULTS Quantitative evidence shows a large effect of RT on lower-limb and upper-limb muscle strength (WMD: +14.57 kg, P = 0.0005 and +6.90 kg, P < 0.00001, respectively) and moderate effects on lean body mass and percentage of body fat (WMD: +1.07 kg, P < 0.0001 and -2.08%, P = 0.003, respectively). A small positive effect of RT was noted on Functional Assessment of Cancer Therapy-Fatigue (P = 0.05). Upper-limb muscle strength and percentage of body fat improved to a greater extent when RT interventions were of low to moderate intensity (≤ 75% one-repetition maximum, P = 0.042). CONCLUSIONS RT was shown to be associated with clinically important positive effects on muscular function and body composition in patients during treatment or in long-term follow-up.

Physical exercise as adjuvant therapy for patients undergoing hematopoietic stem cell transplantation

Even when the procedures are successful, patients experience considerable physical, psychological and psychosocial stress before, during and after hematopoietic stem cell transplantation (HSCT). Physical exercise therapy constitutes a potentially promising intervention to reduce such stress within the framework of HSCT because of its multidimensional effectiveness. Up to May 2007, fifteen published studies have examined physical exercise interventions in the context of HSCT, with no study reporting any unexpected or negative effects. The most common intervention involved isolated aerobic exercise programs and occurred during or after the transplantation process; strength training programs and combined intervention strategies are being examined more rarely. Significant benefits from the exercise interventions have been predominantly reported for physical performance, quality of life and fatigue status of the patients. Several other benefits like a faster recurrence of immune cells or reduced severity of therapy-related side effects can be estimated. Future research is needed for the purpose of evidence-based medicine/therapy to provide more rigorous examinations of these interventions, to address existing methodological problems and to identify further effect levels of physical exercise therapy in the context of HSCT.

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.

Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life

BACKGROUND Exercise has been reported to decrease cancer-related fatigue and to increase quality of life (QoL) in various breast cancer (BC) populations. However, studies investigating exercise during radiotherapy or resistance training are scarce. We conducted a randomized, controlled trial (BEST study) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention. PATIENTS AND METHODS One hundred sixty patients with BC stage 0-III were randomly assigned to a 12-week progressive resistance training (2 times/week) or a 12-week relaxation control (RC, 2 times/week). Both interventions were group-based. The primary end point fatigue was assessed with a 20-item multidimensional questionnaire, QoL with EORTC questionnaires. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13. RESULTS Adherence to the intervention program as well as the completion rate (97%) for the primary outcome variable fatigue was high. In intention-to-treat analyses for the N = 155 patients, significant between-group mean differences (MD) favoring the exercise group (EX) were observed for general fatigue (P = 0.044), especially for the subscale physical fatigue [MD = -0.8; 95% confidence interval -1.5 to -0.2, P = 0.013], but not for affective (P = 0.91) or cognitive fatigue (P = 0.65). For QoL, significantly larger improvements regarding the role function (P = 0.035) and pain (P = 0.040) were noted among exercisers compared with RCs. Future perspective improved significantly stronger in the RC group compared with the EX group (P = 0.047). CONCLUSIONS The 12-week resistance training program was a safe, feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy. As exercise was compared with another group-based intervention, results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits, and that the clinically relevant overall benefit of resistance exercise compared with usual care can be assumed to be higher. TRIAL REGISTRATION ClinicalTrials.gov NCT01468766.

Effects of resistance exercise on fatigue and quality of life in breast cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial

Multiple exercise interventions have shown beneficial effects on fatigue and quality of life (QoL) in cancer patients, but various psychosocial interventions as well. It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised, group‐based programs. It needs to be determined which aspects of exercise programs are truly effective. Therefore, we aimed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group‐based interventions. One‐hundred‐one breast cancer patients starting chemotherapy were randomly assigned to resistance exercise (EX) or a relaxation control (RC) group. Both interventions were supervised, group‐based, 2/week over 12 weeks. The primary endpoint fatigue was assessed with a 20‐item multidimensional questionnaire, QoL with the EORTC QLQ‐C30/BR23. Analyses of covariance for individual changes from baseline to Week 13 were calculated. In RC, total and physical fatigue worsened during chemotherapy, whereas EX showed no such impairments (between‐group p = 0.098 and 0.052 overall, and p = 0.038 and 0.034 among patients without severe baseline depression). Differences regarding affective or cognitive fatigue were not significant. Benefits of EX were also seen to affect role and social function. Effect sizes were between 0.43 and 0.48. Explorative analyses indicated significant effect modification by thyroxin use (p‐interaction = 0.044). In conclusion, resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group‐based settings. Thus, resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy.

Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: The BEST study

BackgroundCancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce.Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood.In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy.Methods/designThe BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed.DiscussionThe BEST study is the first randomized controlled trial comparing progressive resistance training with muscle relaxation training in breast cancer patients during adjuvant radiotherapy. Based on the analysis of physiological, immunological and inflammatory parameters it will contribute to a better understanding of the physiological and psychosocial effects and the biological mechanisms of resistance training. The ultimate goal is the implementation of optimized intervention programs to reduce fatigue, improve quality of life and potentially the prognosis after breast cancer.Trial registrationClinicalTrials.gov NCT01468766

Exercise in Patients with Non–small Cell Lung Cancer

PURPOSE This study aimed to evaluate the safety, feasibility, and effects of an 8-wk combined resistance and endurance exercise program in patients with advanced non-small cell lung cancer (NSCLC) during in- and outpatient care. METHODS In this intervention study, 40 patients with predominantly advanced NSCLC receiving simultaneous or sequential radiochemotherapy or chemotherapy alone were enrolled. For a period of 8 wk, patients were instructed to exercise at least five times per week during the inpatient setting and at least three times per week in the outpatient setting. Physical performance status (endurance capacity: 6-min walk test; strength capacity: handheld dynamometry), quality-of-life (Functional Assessment of Cancer Therapy-Lung), fatigue (Multidimensional Fatigue Inventory), and depression (Patient Health Questionnaire) were assessed at baseline (T0), after the exercise intervention (T1), and at a follow-up time point 8 wk later (T2). The primary end point was adequate adherence (feasibility) defined as completing at least two training sessions per week during a minimum of 6 wk. RESULTS Of 40 patients, 31 (77.5%) completed the postexercise assessment (T1) and 22 (55%) completed follow-up (T2). The stages were IIA (5%), IIIA (8%), IIIB (20%), and IV (67%), and the median age was 63 yr (range = 22-75 yr). Overall, adherence was 82% for those patients who completed T1, and 55% of the 40 participating patients fulfilled the adequate adherence criterion. Those who completed the intervention showed a significant improvement in the 6-min walk distance and in knee, elbow, and hip muscle strength after the intervention (T1). Quality of life, fatigue, and depression scores remained stable or declined slightly. Significant improvements in knee-muscle strength were also observed at T2. CONCLUSIONS Exercise training is feasible in advanced and metastatic NSCLC patients during anticancer treatment. In this pilot study, endurance and strength capacity improved over time, indicating the rehabilitative importance of the applied intervention. To investigate the potential impact of exercise training in this patient group, a larger randomized trial is warranted.

Effects of physical exercise on survival after allogeneic stem cell transplantation.

Observational studies have suggested that physical activity may be associated with improved survival after cancer treatment. However, data from controlled clinical trials are required. We analyzed survival data of 103 patients from a previously published randomized controlled trial in allogeneic stem cell transplant patients who were randomized to either an exercise intervention (EX) or to a social contact control group. EX patients trained prior to hospital admission, during inpatient treatment, and for 6–8 weeks after discharge. Survival analyses were used to compare both total mortality (TM) and non‐relapse mortality (NRM) after discharge and transplantation during an observation period of 2 years after transplantation. Analyses were corroborated with Cox and Fine & Gray regression models adjusting for potential confounders. After discharge, EX patients had a significantly lower TM rate than controls (12.0 vs. 28.3%, p = 0.030) and a numerically lower NRM rate (4.0 vs. 13.5%, p = 0.086). When the inpatient period was included, absolute risk reductions were similar but not significantly different (TM: 34.0 vs. 50.9%, p = 0.112; NRM: 26.0 vs. 36.5%, p = 0.293). The number needed to treat (NNT) to prevent one death with EX was about 6. Furthermore, regression analyses revealed that baseline fitness was protective against mortality. The data suggest that exercise might improve survival in patients undergoing allo‐HCT. However, the results should be interpreted with caution as the study was not designed to detect differences in survival rates, and as no stratification on relevant prognostic factors was carried out.

Efficacy of exercise training in SCT patients-who benefits most?

Patients undergoing allo-HCT often experience a substantial loss in physical performance. We have recently published the general effectiveness of an exercise intervention in 105 allo-HCT patients on physical performance and psychosocial well-being. However, predictor variables for differentiated treatment response remained unclear. To determine the impact of basic physical performance on treatment response, we assessed muscle strength and endurance performance at four assessment points before and after allo-HCT. The exercise group started training 2 weeks before admission and ended 6–8 weeks after discharge. Comparing initially fit with unfit classified patients, the fit patients lost 31% of the strength of the knee-extensors, whereas the unfit patients lost only 1% (P<0.05). For endurance capacity, fit patients lost 4% of their walking capability, whereas unfit patients gained 13% (P<0.05). The individual percent change was statistically different at the 0.05 level in all measures of physical performance. Individual training response in allo-HCT patients strongly depends on the initial physical performance level. Unfit patients can be trained safely and may benefit more from this exercise intervention than fit patients. This result is of major clinical relevance and should encourage hematologists to promote exercise even more in impaired/unfit allo-HCT patients.

Cancer-related fatigue shows a stable association with diurnal cortisol dysregulation in breast cancer patients

Fatigue is a major burden for breast cancer patients undergoing adjuvant therapy. Yet, its pathophysiology is still not well understood. Hypothesized mechanisms include dysregulations in the hypothalamic-pituitary-adrenal (HPA) axis, which may be reflected in alterations in the diurnal cortisol patterns. However, studies on the association between cortisol and fatigue during adjuvant cancer therapy are rare. We therefore assessed salivary cortisol at awakening, 0.5h post-awakening, noon, 5 pm and 10 pm/bedtime in 265 breast cancer patients undergoing adjuvant therapy at three timepoints. Cancer-related fatigue was assessed with the Fatigue Assessment Questionnaire (FAQ) covering the physical, affective, and cognitive fatigue dimensions. Multiple linear regression analyses were performed cross-sectionally at the three timepoints as well as longitudinally considering changes in cortisol and fatigue over time. The results showed that the physical dimension of cancer-related fatigue was significantly associated with increased evening cortisol levels and higher overall cortisol secretion. These associations were independent of depressive symptoms. Morning cortisol levels, the cortisol awakening response and the diurnal slope were not consistently associated with physical fatigue. Affective and cognitive fatigue showed no clear association with any of the cortisol parameters. In conclusion, the physical but not the affective or cognitive dimension of fatigue seems associated with cortisol dysregulations in breast cancer patients undergoing adjuvant therapy, characterized by an unaffected cortisol level in the morning but blunted decline to the evening level. Research focusing on disturbances of the cortisol rhythm and HPA dysregulations during and after cancer treatment may open new strategies to reduce cancer-related fatigue.