Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer:Individual patient data meta-analyses

Objective Psychosocial interventions can reduce cancer-related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta-analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention-related characteristics on the effect of psychosocial interventions on cancer-related fatigue in patients with non-metastatic breast and prostate cancer. Methods Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta-analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed-effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008). Results Statistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: beta = -0.19 [95% confidence interval (95%CI) = -0.30; -0.08]; prostate cancer: beta = -0.11 [95%CI = -0.21; -0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention-related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (beta = -0.27 [95%CI = -0.40; -0.15]), fatigue-specific interventions (beta = -0.48 [95%CI = -0.79; -0.18]), and interventions that only targeted patients with clinically relevant fatigue (beta = -0.85 [95%CI = -1.40; -0.30]). Conclusions Our findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue

Decisional conflict in breast cancer patients considering immediate breast reconstruction

Background: Breast cancer (BC) patients who are treated with mastectomy are frequently offered immediate breast reconstruction. This study aimed to assess decisional conflict in patients considering immediate breast reconstruction, and to identify factors associated with clinically significant decisional conflict (CSDC). Methods: Baseline data of a multicenter randomized controlled trial evaluating the impact of an online decision

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 &gt;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 &gt;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.</p

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 (β = -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 (βdifference = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration ≤12 wk showed larger effects on fatigue (β = -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

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 &lt; .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction &lt; .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

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=4,519 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

Design of a randomized controlled trial of Internet-based cognitive behavioral therapy for treatment-induced menopausal symptoms in breast cancer survivors

Background Menopausal symptoms are common and may be particularly severe in younger women who undergo treatment-induced menopause. Medications to reduce menopausal symptoms are either contra-indicated or have bothersome side effects. Previous studies have demonstrated that face-to-face cognitive behavioral therapy (CBT) is effective in alleviating menopausal symptoms in women with breast cancer. However, compliance with face-to-face CBT programs can be problematic. A promising approach is to use the Internet to make this form of CBT more accessible and feasible for patients. This study is evaluating the efficacy and cost-effectiveness of an Internet-based CBT program, with or without therapist guidance, in alleviating or reducing the severity of menopausal symptoms. Methods/design In a multicenter, randomized controlled trial we are evaluating the efficacy of two Internet-based CBT programs in alleviating or reducing the impact of menopausal symptoms, and particularly hot flushes and night sweats, in breast cancer survivors who have experienced a treatment-induced menopause. Secondary outcomes include sexual functioning, sleep quality, hot flush frequency, psychological distress, health-related quality of life and cost-effectiveness. We will recruit 248 women who will be randomized to either a therapist guided or a self-management version of the 6-week Internet-based CBT program, or to a usual care, waiting list control group. Self-administered questionnaires are completed at baseline (T0), and at 10 weeks (T1) and 24 weeks (T2) post-randomization. Discussion Internet-based CBT is a potentially useful treatment for reducing menopausal symptoms in breast cancer survivors. This study will provide evidence on the efficacy and cost-effectiveness of such an Internet-based CBT program, with or without therapist support. If demonstrated to be efficacious and cost-effective, the availability of such structured supportive intervention programs will be a welcome addition to standard medical treatment offered to cancer patients with treatment-induced menopause. Trial registration The study is retrospectively registered at ClinicalTrials.gov on January 26th 2016 (NCT02672189)

Measuring decline in white matter integrity after systemic treatment for breast cancer: omitting skeletonization enhances sensitivity

Chemotherapy for non-central nervous system cancers is associated with abnormalities in brain structure and function. Diffusion tensor imaging (DTI) allows for studying in vivo microstructural changes in brain white matter. Tract-based spatial statistics (TBSS) is a widely used processing pipeline in which DTI data are typically normalized to a generic DTI template and then ‘skeletonized’ to compensate for misregistration effects. However, this approach greatly reduces the overall white matter volume that is subjected to statistical analysis, leading to information loss. Here, we present a re-analysis of longitudinal data previously analyzed with standard TBSS (Menning et al., BIB 2018, 324–334). For our current approach, we constructed a pipeline with an optimized registration method in Advanced Normalization Tools (ANTs) where DTI data are registered to a study-specific, high-resolution T1 template and the skeletonization step is omitted. In a head to head comparison, we show that with our novel approach breast cancer survivors who had received chemotherapy plus or minus endocrine therapy (BC + SYST, n = 26) showed a global decline in overall FA that was not present in breast cancer survivors who did not receive systemic therapy (BC-SYST, n = 23) or women without a cancer diagnosis (no cancer controls, NC, n = 30). With the standard TBSS approach we did not find any group differences. Moreover, voxel-based analysis for our novel pipeline showed a widespread decline in FA in the BC + SYST compared to the NC group. Interestingly, the BC-SYST group also showed a decline in FA compared to the NC group, although in much less voxels. These results were not found with the standard TBSS approach. We demonstrate that a modified processing pipeline makes DTI data more sensitive to detecting changes in white matter integrity in non-CNS cancer patients after treatment, particularly chemotherapy

Brain White Matter Microstructure as a Risk Factor for Cognitive Decline after Chemotherapy for Breast Cancer

PURPOSE Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy. METHODS Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n532) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC 1 CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC - CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts. RESULTS Low FA independently predicted cognitive decline early (6 months, P =.013) and late (3 years, P <.001) after chemotherapy. FA did not predict cognitive decline in the BC - CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning. CONCLUSION Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy