Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis.

PURPOSE: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. METHODS: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. RESULTS: Minimal significant beneficial exercise effects on self-reported CF (ß=-0.09 [-0.16; -0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, ß=-0.13 [-0.24; -0.02]), and no significant effect during cancer treatment (n=1,162, ß=-0.08 [-0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (ß=-0.14 [-0.25; -0.04]) or 24 weeks or longer (ß=-0.18 [-0.32; -0.02]), whereas no effects were observed in interventions of 12-24 weeks (ß=0.01 [-0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (ß=-0.10 [-0.19; -0.02]) or after completion of treatment in patients with cognitive problems (ß=-0.19 [-0.31; -0.06]). No other significant moderators were identified. CONCLUSIONS: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. IMPLICATIONS FOR CANCER SURVIVORS: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors.

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

Influencing factors of cardiorespiratory fitness in allogeneic stem cell transplant candidates prior to transplantation.

PURPOSE: Cardiorespiratory fitness (CRF) seems to be prognostic prior to allogeneic stem cell transplantation (allo-HSCT). Influencing factors of CRF in allo-HSCT candidates have not been studied so far. Aim was to identify potentially influencing factors on CRF. METHODS: To assess CRF, a maximal cardiopulmonary exercise test (CPET) was performed on average 2.6 ± 7.2 days prior to admission. A regression analysis was conducted, with the following predictors: gender, age, body mass index (BMI), time between last therapy and allo-HSCT (t_Therapies), number of cardiotoxic therapies (n_Cardiotox), number of transplantations (n_Transplantations), comorbidity index (HCT-CI), hemoglobin level of the last 3 months (area under the curve), and physical activity. RESULTS: A total of 194 patients performed a CPET. VO2peak was significantly reduced compared with reference data. In total, VO2peak was 21.4 ml/min/kg (- 27.5%, p < 0.05). Men showed a significant larger percentage difference from reference value (- 29.1%, p < 0.05) than women (- 24.4%). VO2peak was significantly (p < 0.05) influenced by age (ß = - 0.11), female gender (ß = - 3.01), BMI (ß = - 0.44), n_Cardiotox (ß = - 0.73), hemoglobin level (ß = 0.56), and physical activity prior to diagnosis (ß = 0.10). CONCLUSIONS: Our study demonstrates a decreased CRF indicating the potential need of prehabilitative exercise. We revealed some influencing factors on CRF. Those patients could benefit the most from exercise.

Moderators of Exercise Effects on Cancer-related Fatigue: A Meta-analysis of Individual Patient Data.

PURPOSE: Fatigue is a common and potentially disabling symptom in patients with cancer. It can often be effectively reduced by exercise. Yet, effects of exercise interventions might differ across subgroups. We conducted a meta-analysis using individual patient data of randomized controlled trials (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue. METHODS: We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 had complete fatigue data. We performed a one-step individual patient data meta-analysis, using linear mixed-effect models to analyze the effects of exercise interventions on fatigue (z score) and to identify demographic, clinical, intervention- and exercise-related moderators. Models were adjusted for baseline fatigue and included a random intercept on study level to account for clustering of patients within studies. We identified potential moderators by testing their interaction with group allocation, using a likelihood ratio test. RESULTS: Exercise interventions had statistically significant beneficial effects on fatigue (ß = -0.17; 95% confidence interval [CI], -0.22 to -0.12). There was no evidence of moderation by demographic or clinical characteristics. Supervised exercise interventions had significantly larger effects on fatigue than unsupervised exercise interventions (ßdifference = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration ≤12 wk showed larger effects on fatigue (ß = -0.29; 95% CI, -0.39 to -0.20) than supervised interventions with a longer duration. CONCLUSIONS: In this individual patient data meta-analysis, we found statistically significant beneficial effects of exercise interventions on fatigue, irrespective of demographic and clinical characteristics. These findings support a role for exercise, preferably supervised exercise interventions, in clinical practice. Reasons for differential effects in duration require further exploration.

Changes in Trauma-Related Emotions Following Treatment With Dialectical Behavior Therapy for Posttraumatic Stress Disorder After Childhood Abuse.

Dialectical behavior therapy for posttraumatic stress disorder (DBT-PTSD) is a trauma-focused therapy shown to reduce core PTSD symptoms, such as intrusions, hyperarousal, and avoidance. Preliminary data indicate effects on elevated trauma-related emotions (e.g., guilt and shame) and possibly radical acceptance of the traumatic event. However, it is unclear if improvements in these variables are significant after controlling for changes in core PTSD symptoms and to what extent nonclinical levels are obtained. In the current study, 42 individuals who met criteria for PTSD after childhood abuse and were participating in a 3-month residential DBT-PTSD program were evaluated at the start of the exposure phase of DBT-PTSD and the end of treatment; a nonclinical sample with a history of childhood abuse was the reference group. Multivariate analyses of variance and multivariate analyses of covariance controlling for change in core PTSD symptoms were used to evaluate changes in several elevated trauma-related emotions (fear, anger, guilt, shame, disgust, sadness, and helplessness) and in radical acceptance. In a repeated measures multivariate analyses of variance, both elevated trauma-related emotions and radical acceptance significantly improved during DBT-PTSD, λ = 0.34, p < .001; η2 = .56; t(40) = -5.66, p < .001, SMD = 0.88, even after controlling for changes in PTSD symptoms, λ = 0.35, p < .001, η2 = .65; Λ = 0.86, p = .018, η2 = .14, respectively. Posttreatment, 31.0% (for acceptance) to 76.2% (for guilt) of participants showed nonclinical levels of the investigated outcomes, suggesting that both trauma-related emotions and radical acceptance changed after the 3-month residential DBT-PTSD program.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Los Cambios en las Emociones Relacionadas al Trauma posterior al Tratamiento con Terapia Dialéctica Conductual para el Trastorno de Estrés Traumático después de Abuso Infantil EMOCION RELACIONADA AL TRAUMA Y TERAPIA DIALECTICA CONDUCTUAL La terapia dialéctica conductual para el trastorno de estrés traumático (TDC-TEPT) es una terapia centrada en el trauma que ha mostrado una reducción de los síntomas centrales del TEPT, tales como intrusiones, hiperactivación, y evitación. Resultados preliminares indican efectos sobre elevadas emociones relacionadas con el trauma (por ej., culpa y vergüenza) y la aceptación posiblemente radical del evento traumático. Sin embargo, no es claro si las mejoras en estas variables son significativas luego de controlar los cambios en los síntomas centrales del TEPT y en qué medida se obtienen niveles no clínicos. En el presente estudio, 42 individuos que cumplieron con los criterios para el TEPT luego de un abuso infantil y que participaron en un programa residencial de la TDC-TEPT por 3 meses fueron evaluados al principio de su etapa de exposición a la TDC-TEPT y al final del tratamiento; una muestra no clínica con una historia de abuso infantil fue el grupo de referencia. Análisis multivariados de varianza y análisis multivariados de covarianza controlando los cambios en los síntomas centrales del TEPT fueron usados para evaluar los cambios en diferentes emociones relacionadas al trauma elevadas (temor, rabia, culpa, vergüenza, disgusto, tristeza, y desesperanza) y una aceptación radical. En los análisis multivariados de la varianza de medidas repetidas, las elevadas emociones relacionadas al trauma y la aceptación radical mejoraron significativamente durante la TDC-TEPT, λ = 0.34, p < .001; η2 = .56; t(40) = -5.66, p < .001, SMD = 0.88, incluso luego de controlar por los cambios en los síntomas del TEPT, λ = 0.35, p < .001, η2 = .65; Λ = 0.86, p = .018, η2 = .14, respectivamente. Al término del tratamiento, 31.0% (para aceptación) al 76.2% (para culpa) de los participantes mostraron niveles no clínicos de los resultados investigados, sugiriendo que tanto las emociones relacionadas con el trauma como la aceptación radical, cambió luego del programa residencial de la TDC-TEPT por 3 meses.

Effects and moderators of exercise on muscle strength, muscle function and aerobic fitness in patients with cancer: a meta-analysis of individual patient data.

OBJECTIVE: To optimally target exercise interventions for patients with cancer, it is important to identify which patients benefit from which interventions. DESIGN: We conducted an individual patient data meta-analysis to investigate demographic, clinical, intervention-related and exercise-related moderators of exercise intervention effects on physical fitness in patients with cancer. DATA SOURCES: We identified relevant studies via systematic searches in electronic databases (PubMed, Embase, PsycINFO and CINAHL). ELIGIBILITY CRITERIA: We analysed data from 28 randomised controlled trials investigating the effects of exercise on upper body muscle strength (UBMS) and lower body muscle strength (LBMS), lower body muscle function (LBMF) and aerobic fitness in adult patients with cancer. RESULTS: Exercise significantly improved UBMS (ß=0.20, 95% Confidence Interval (CI) 0.14 to 0.26), LBMS (ß=0.29, 95% CI 0.23 to 0.35), LBMF (ß=0.16, 95% CI 0.08 to 0.24) and aerobic fitness (ß=0.28, 95% CI 0.23 to 0.34), with larger effects for supervised interventions. Exercise effects on UBMS were larger during treatment, when supervised interventions included ≥3 sessions per week, when resistance exercises were included and when session duration was >60 min. Exercise effects on LBMS were larger for patients who were living alone, for supervised interventions including resistance exercise and when session duration was >60 min. Exercise effects on aerobic fitness were larger for younger patients and when supervised interventions included aerobic exercise. CONCLUSION: Exercise interventions during and following cancer treatment had small effects on UBMS, LBMS, LBMF and aerobic fitness. Demographic, intervention-related and exercise-related characteristics including age, marital status, intervention timing, delivery mode and frequency and type and time of exercise sessions moderated the exercise effect on UBMS, LBMS and aerobic fitness.

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.

Impact of HSCT Conditioning and Glucocorticoid Dose on Exercise Adherence and Response.

PURPOSE: Evidence from randomized controlled trials (RCT) that exercise interventions have beneficial effects in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is growing. However, intensive chemotherapy conditioning and glucocorticoid (GC) treatment is always part of an allo-HSCT and possibly affect exercise adherence and training response. Therefore, we aimed to examine whether various conditioning protocols or different doses of GC treatment affect exercise adherence and/or training response during the inpatient period. METHODS: We analyzed inpatient data from intervention groups of two large RCT in allo-HSCT patients (n = 113). The intervention incorporated partly supervised endurance and resistance exercise three to five times per week. According to the potentially interfering factors, the patients were divided into groups depending on intensity of conditioning (myeloablative conditioning (MAC), reduced-intensity conditioning (RIC), and nonmyeloablative conditioning (NMC)) and cumulative dose of GC treatment (GC low ≤9 mg·kg prednisone or GC high >9 mg·kg prednisone) and were compared. RESULTS: Median exercise adherence (target value, five sessions weekly) during the inpatient period was 64% in MAC, 54% in RIC, and 63% in NMC. The proportion of prematurely terminated training sessions ranged from 11% to 15%. Tiredness was the most frequent cause of exercise termination in all groups. Exercise adherence, duration (min·wk) and type of training was significantly associated with GC dose. With regard to training response, results suggest that GC-low patients tend to respond better in knee extensor muscle strength. CONCLUSIONS: Exercise adherence during inpatient period is significantly affected by dose of GC treatment but not by condition regimen. However, given the reasonable adherence rates also in the GC-high group, data support the feasibility and importance of exercising for all allo-HSCT patients during the inpatient period.

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 (ß=0.15, 95%CI=0.10;0.20) and PF (ß=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (ßdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (ßdifference_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.

Determinants of exercise adherence and contamination in a randomized controlled trial in cancer patients during and after allogeneic HCT.

BACKGROUND: Evidence from randomized controlled trials is growing that exercise interventions are beneficial in cancer patients receiving allogeneic stem cell transplantation (allo-HCT). However, information about adherence to exercise interventions and exercise contamination in control groups is lacking. This information is crucial for the interpretation of study results. We therefore examined the determinants of exercise adherence and contamination in different treatment periods during (inpatient) and after (outpatient) allo-HCT. METHODS: One hundred fifty-three patients scheduled for allo-HCT were randomized to a 1-year partly supervised exercise intervention (endurance and resistance exercise) or to a control group. Adherence was assessed via exercise logs and contamination via questionnaires. RESULTS: Adherence varied between 66 % (inpatient) and 78 % (outpatient) in different treatment periods. During (inpatient) transplantation period, higher adherence was significantly associated with lower fatigue (P = 0.004) and with having children at home (P = 0.049). Adherence after discharge was positively associated with endurance performance (P = 0.003); higher adherence after day 100 was associated with exercise activity prior allo-HCT (P = 0.010) and higher adherence after discharge (P = 0.001). Contamination among controls was high with 54 % and significantly associated with muscle strength (P = 0.025) and fatigue (P = 0.050). CONCLUSION: Exercise adherence in different treatment periods was determined by different variables, and contamination among controls was evident. These findings may have important implications for correct interpretation of randomized exercise intervention trials.

Physical Exercise Training versus Relaxation in Allogeneic stem cell transplantation (PETRA Study) - Rationale and design of a randomized trial to evaluate a yearlong exercise intervention on overall survival and side-effects after allogeneic stem cell transplantation.

BACKGROUND: Allogeneic stem cell transplantation (allo-HCT) is associated with high treatment-related mortality and innumerable physical and psychosocial complications and side-effects, such as high fatigue levels, loss of physical performance, infections, graft-versus-host disease (GvHD) and distress. This leads to a reduced quality of life, not only during and after transplantation, but also in the long term. Exercise interventions have been shown to be beneficial in allo-HCT patients. However, to date, no study has focused on long-term effects and survival. Previous exercise studies used 'usual care' control groups, leaving it unclear to what extent the observed effects are based on the physical effects of exercise itself, or rather on psychosocial factors such as personal attention. Furthermore, effects of exercise on and severity of GvHD have not been examined so far. We therefore aim to investigate the effects and biological mechanisms of exercise on side-effects, complications and survival in allo-HCT patients during and after transplantation. METHODS/DESIGN: The PETRA study is a randomized, controlled intervention trial investigating the effects of a yearlong partly supervised mixed exercise intervention (endurance and resistance exercises, 3-5 times per week) in 256 patients during and after allogeneic stem cell transplantation. Patients in the control group perform progressive muscle relaxation training (Jacobsen method) with the same frequency. Main inclusion criterion is planned allo-HCT. Main exclusion criteria are increased fracture risk, no walking capability or severe cardiorespiratory problems. Primary endpoint is overall survival after two years; secondary endpoints are non-relapse mortality, median survival, patient reported outcomes including cancer related fatigue and quality of life, physical performance, body composition, haematological/immunological reconstitution, inflammatory parameters, severity of complications and side-effects (e.g. GvHD and infections), and cognitive capacity. DISCUSSION: The PETRA study will contribute to a better understanding of the physiological and psychological effects of exercise training and their biological mechanisms in cancer patients after allo-HCT. The ultimate goal is the implementation of optimized intervention programs to reduce side-effects and improve quality of life and potentially prognosis after allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01374399 .

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.

Exercise intensity classification in cancer patients undergoing allogeneic HCT.

OBJECTIVE: Exercise intervention studies during and after cancer treatment show beneficial effects for various physical and psychosocial outcomes. Current exercise intensity guidelines for cancer patients are rather general and have been adapted from American College of Sports Medicine (ACSM) recommendations for healthy individuals. Intensive cancer treatment regimens such as allogeneic hematopoietic stem cell transplantation (allo-HCT) may change the cardiovascular response to acute exercise. Therefore, we evaluated the relationships between %V˙O2 reserve (%V˙O2R, reference) and %HRR, %HRmax, and %V˙O2max and compared calculated intensities with given intensities by ACSM. METHODS: Measurements before and 180 d after allo-HCT from a randomized controlled trial were used. Only patients who reached maximal effort and at least two exercise stages in our maximal incremental cycling test were included. Before allo-HCT, 106 patients were included, and 180 d after treatment, 49 patients met our inclusion criteria. Individual regression lines were calculated with V˙O2R as the reference. Calculated exercise intensities for endurance training prescription were compared with ACSM values. RESULTS: Before allo-HCT, %HRR values of patients were significantly lower than ACSM values, and %HRmax and %V˙O2max values were significantly higher (except 90% HRmax, which was significantly lower, all P < 0.01). One hundred eighty days after allo-HCT, values for %HRR were not significantly different to ACSM values (except 90%, which was significantly lower, P = 0.01), whereas %HRmax and %V˙O2max were significantly higher (all P < 0.05). Furthermore, regression models revealed no influence of beta-blockers on calculated intensities. CONCLUSIONS: ACSM's exercise intensity recommendations for endurance training may not be applicable for cancer patients during and 180 d after allo-HCT because they may not meet the targeted intensity class, with the exception of %HRR 180 d after allo-HCT.

Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation.

Before, during, and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients experience considerable physical and psychologic distress. Besides graft-versus-host disease and infections, reduced physical performance and high levels of fatigue affect patients' quality of life. This multicenter randomized controlled trial examined the effects of a partly self-administered exercise intervention before, during, and after allo-HSCT on these side effects. After randomization to an exercise and a social contact control group 105 patients trained in a home-based setting before hospital admission, during inpatient treatment and a 6- to 8-week period after discharge. Fatigue, physical performance, quality of life, and physical/psychologic distress were measured by standardized instruments at baseline, admission to, and discharge from hospital and 6 to 8 weeks after discharge. The exercise group showed significantly improvement in fatigue scores (up to 15% improvement in exercise group vs up to 28% deterioration in control; P<.01-.03), physical fitness/functioning (P=.02-.03) and global distress (P=.03). All effects were at least detectable at one assessment time point after hospitalization or repeatedly. Physical fitness correlated significantly with all reported symptoms/variables. In conclusion, this partly supervised exercise intervention is beneficial for patients undergoing allo-HSCT. Because of low personnel requirements, it might be valuable to integrate such a program into standard medical care.