Randomized trial of exercise on depressive symptomatology and brain derived neurotrophic factor (BDNF) in ovarian cancer survivors: The Women's Activity and Lifestyle Study in Connecticut (WALC).

OBJECTIVES: Depression is one of the most prevalent mental disorders, and rates are higher among cancer survivors than the general population, and higher in ovarian cancer patients compared to cohorts of other cancer survivors. Physical activity has been associated with lower depressive symptoms in cancer survivors, yet no trial has examined this association in women with ovarian cancer. We examined the effect of exercise on depression symptomatology and serum brain derived neurotrophin factor (BDNF) which has been associated with depression, in women with ovarian cancer. METHODS: We conducted a 6-month home-based randomized trial of exercise vs. attention-control (AC) in 144 ovarian cancer survivors. Depressive symptomatology was measured via the Center for Epidemiologic Studies Depression Scale (CES-D). Serum total and free BDNF was measured at baseline and 6-months. Student's t-statistic and mixed-model repeated measures analysis was used to evaluate six-month change between arms in CES-D scores and BDNF. RESULTS: Women were 57.3 ±â€¯8.6 (mean ±â€¯SD) years old, 1.7 ±â€¯1.0 years post-diagnosis with a baseline CES-D score of 11.79 ±â€¯10.21. The majority (55%) were diagnosed with stage III/IV ovarian cancer. CES-D scores decreased in the exercise arm by 2.7 points (95% CI: -4.4, -0.9) or a 21% decrease compared to a 0.3 point decrease (-2.2, 1.5) (3% decrease) in the AC arm (P = 0.05). There was no difference in change in total or free BDNF between the exercise and AC arms. CONCLUSIONS: Ovarian cancer survivors are able to exercise at recommended levels, and exercise was associated with a significant reduction in depressive symptomatology.

Lymphedema in ovarian cancer survivors: Assessing diagnostic methods and the effects of physical activity.

BACKGROUND: Lymphedema is a poorly understood side effect of gynecologic cancer treatment. This study was designed to determine the prevalence of lower limb lymphedema (LLL) in a sample of ovarian cancer survivors via 3 different diagnostic methods and to assess the effect of a randomized exercise intervention. METHODS: Physically inactive ovarian cancer survivors (n = 95) were enrolled in a 6-month randomized trial of exercise (primarily brisk walking) versus attention control. LLL was measured at baseline and 6-month visits via a self-report questionnaire, optoelectronic perometry, and an evaluation by a certified lymphedema specialist. RESULTS: LLL prevalence ranged from 21% to 38% according to the diagnostic method, and there was substantial agreement between the self-report questionnaire and the lymphedema specialist evaluation (κ = 0.61). There was no agreement between the evaluation with optoelectronic perometry and the specialist evaluation. With LLL defined by any method, the baseline prevalence was 38% in both groups. At 6 months, both groups experienced a decreased LLL prevalence: 28% in the exercise group and 35% in the control group. There was no difference in the change in lymphedema prevalence between the 2 groups (P = .64). Body mass index was a significant predictor of LLL. CONCLUSIONS: With a potential prevalence of LLL as high as 40%, further evaluation of diagnostic methods is required to better characterize this side effect of ovarian cancer treatment. No adverse effect of exercise on LLL was found. Further research is strongly needed to evaluate predictors of LLL and the effects of exercise on LLL in order to develop effective physical activity recommendations for women with ovarian cancer. Cancer 2018;124:1929-37. © 2018 American Cancer Society.

Randomized Trial Evaluating a Self-Guided Lifestyle Intervention Delivered via Evidence-Based Materials versus a Waitlist Group on Changes in Body Weight, Diet Quality, Physical Activity, and Quality of Life among Breast Cancer Survivors.

Background: Lifestyle interventions for breast cancer survivors have proved effective at stimulating positive behavior change and promoting healthy weight loss, although integrating these programs into clinical practice is challenging. We evaluated the effect of a 6-month, unsupervised, self-guided, lifestyle intervention using printed materials and online videos vs. waitlist group on body weight for breast cancer survivors. Methods: The Lifestyle, Exercise and Nutrition (LEAN) Self-Guided trial randomized breast cancer survivors with a body mass index ≥25 kg/m2 to a 6-month lifestyle intervention (N = 102) or waitlist group (N = 103). Effects of the intervention on self-reported body weight, physical activity (PA), diet quality (via Health Eating Index-2010 (HEI-2010)), and quality of life were assessed using mixed model repeated measures analysis. Results: At 6 months, the intervention arm had significantly greater weight loss compared with the waitlist group (mean difference = -1.3 kg, 95% confidence interval [CI] = -2.5, -0.13). We observed suggestive improvements in PA (mean difference = 18.7 min/week, 95% CI = -24.2, 61.6), diet quality (mean difference in HEI = 3.2 points, 95% CI = -0.20, 6.5), and fatigue (mean difference in Functional Assessment of Chronic Illness Therapy-Fatigue scale = 1.4 points, 95% CI = -1.1, 3.9). Conclusions: The LEAN Self-Guided intervention led to favorable weight changes over 6 months. Low-resource-intensive programs have the potential to be delivered in diverse healthcare settings and may support breast cancer survivors in achieving a healthy body weight.

Exercise adherence in a randomized controlled trial of exercise on quality of life in ovarian cancer survivors.

PURPOSE: Factors associated with improving exercise in ovarian cancer survivors remain unknown. We explored characteristics associated with exercise adherence among women treated for ovarian cancer in the Women's Activity and Lifestyle Study in Connecticut (WALC) randomized controlled trial. METHODS: We evaluated adherence among women randomized to the WALC exercise intervention (N = 74). Women had to be exercising ≤ 90 min/week and post-treatment. The intervention included 25 telephone-based exercise counseling sessions over 6 months. Adherence was defined as 150 min/week of moderate/vigorous-intensity exercise. We evaluated factors associated with exercise adherence and duration using multivariate logistic and linear regression. The number of sessions sufficient to achieve 150 min/week was modeled with an unadjusted receiver operating characteristic (ROC) curve. RESULTS: Women were 57.3 ± 8.8 years old and 1.7 ± 1.0 years since diagnosis. The mean exercise time over 6 months was 166.0 ± 66.1 min/week, and 64.9% of women met the 150 min/week goal. Women attended 22.8 ± 3.6 (92%) counseling sessions. No cancer recurrence during the study (OR = 9.15, 95% CI: 1.09-44.02) and greater session attendance (OR = 1.21, 95% CI: 1.02-1.43) were related to meeting the exercise goal. Greater session attendance (P < 0.01) and higher baseline activity level (P = 0.02) were associated with greater average weekly exercise duration. The ROC curve suggested attending 18 counseling sessions was optimal to meet the exercise goal. CONCLUSIONS: Women attending more counseling sessions or with no cancer recurrence during the study were more likely to meet the exercise goal. More research is needed to understand ideal counseling intensity for ovarian cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Eighteen counseling sessions are sufficient for ovarian cancer survivors to achieve 150 min/week exercise.

Effect of Exercise on Chemotherapy-Induced Peripheral Neuropathy Among Patients Treated for Ovarian Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common and severe adverse effects of chemotherapy, is associated with worse quality of life among survivors of ovarian cancer. Currently, there is no effective treatment for CIPN. Objective: To evaluate the effect of a 6-month aerobic exercise intervention vs attention-control on CIPN among women treated for ovarian cancer in the Women's Activity and Lifestyle Study in Connecticut (WALC) to provide evidence to inform the guidelines and recommendations for prevention or treatment of CIPN. Design, Setting, and Participants: This prespecified secondary analysis evaluated the Women's Activity and Lifestyle Study in Connecticut (WALC), a multicentered, open-label, population-based, phase 3 randomized clinical trial of an aerobic exercise intervention vs attention control for CIPN in patients who were diagnosed with ovarian cancer. Only WALC participants who received chemotherapy were included in this analysis. Participants were randomized 1:1 to either a 6-month aerobic exercise intervention or to attention control. All analyses were conducted between September 2022 and January 2023. Interventions: The exercise intervention consisted of home-based moderate-intensity aerobic exercise facilitated by weekly telephone counseling from an American College of Sports Medicine/American Cancer Society-certified cancer exercise trainer. Attention control involved weekly health education telephone calls from a WALC staff member. Main Outcomes and Measure: Change in CIPN was the primary outcome in this secondary analysis. This outcome was represented by CIPN severity, which was self-measured by participants at baseline and 6 months using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale, with a score range of 0 to 44. A mixed-effects model was used to assess the 6-month change in CIPN between the exercise intervention and attention control arms. Results: Of the 134 participants (all females; mean [SD] age, 57.5 [8.3] years) included in the analysis, 69 were in the exercise intervention arm and 65 were in the attention control arm. The mean (SD) time since diagnosis was 1.7 (1.0) years. The mean (SD) baseline CIPN scores were 8.1 (5.6) in the exercise intervention arm and 8.8 (7.9) in the attention control arm (P = .56). At 6 months, the self-reported CIPN score was reduced by 1.3 (95% CI, -2.3 to -0.2) points in the exercise intervention arm compared with an increase of 0.4 (95% CI, -0.8 to 1.5) points in the attention control arm. The between-group difference was -1.6 (95% CI, -3.1 to -0.2) points. The point estimate was larger among the 127 patients with CIPN symptoms at enrollment (-2.0; 95% CI, -3.6 to -0.5 points). Conclusions and Relevance: Findings of this secondary analysis of the WALC trial indicate that a 6-month aerobic exercise intervention vs attention control significantly improved self-reported CIPN among patients who were treated for ovarian cancer. While replication of the findings in other studies is warranted, incorporating referrals to exercise programs into standard oncology care could reduce CIPN symptoms and increase quality of life in patients with ovarian cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02107066.

Randomized trial of exercise on cancer-related blood biomarkers and survival in women with ovarian cancer.

BACKGROUND: In randomized trials in women with breast cancer, exercise has been shown to have beneficial effects on cancer-related circulating biomarkers that may impact survival. Such studies are lacking for ovarian cancer. METHODS: This secondary analysis of a published randomized controlled trial examined the impact of a 6-month exercise intervention versus attention-control on change in prespecified circulating biomarkers (cancer antigen 125 (CA-125), C-reactive protein (CRP), insulin-like growth factor-1(IGF-1), insulin and leptin) in a subset of participants who provided a fasting blood draw (N = 104/144) at enrollment and at 6 months. Change in biomarkers between study arms was compared using a linear mixed effects model analysis. An exploratory analysis of the exercise intervention versus attention-control on all-cause mortality included all (N = 144) participants. All statistical tests were two-sided. RESULTS: Participants included in the biomarker analysis were 57.0 ± 8.8 (mean ± SD) years old and 1.6 ± 0.9 years post-diagnosis. Adherence to the exercise intervention was 176.4 ± 63.5 min/week. Post intervention IGF-1 (group difference in change: -14.2 (-26.1 to -2.3) ng/mL (least squared means (95% CI))) and leptin (-8.9 (-16.5 to -1.4) ng/mL) were significantly reduced in the exercise group (N = 53) compared to those in attention-control (N = 51). No group difference in change was seen for CA-125 (p = 0.54), CRP (p = 0.95), or insulin (p = 0.37). With median follow-up of 70 months [range 6.6-105.4 months], 50/144 (34.7%) (exercise group; 24/74 (32.4%) versus attention-control group; 26/70 (37.1%)) participants died with no between group difference in overall survival (p = 0.99). CONCLUSIONS: Further studies are needed to determine the clinical significance of exercise-induced changes in cancer-related circulating biomarkers in women with ovarian cancer.

Effect of exercise on body composition among women with ovarian cancer.

PURPOSE: Obesity is associated with a higher risk of mortality in women with ovarian cancer. Exercise has improved body composition among cancer survivors, yet no randomized controlled trial has explored the effect of exercise on body composition in women with ovarian cancer. In this analysis, we examined the effect of a six-month aerobic exercise intervention on body composition among ovarian cancer survivors in the Women's Activity and Lifestyle Study in Connecticut (WALC). METHODS: Women with ovarian cancer (N = 144) were randomized in a 1:1 ratio to 6 months of an aerobic exercise intervention or attention-control, and body composition was measured as a secondary outcome at baseline and 6 months via dual-energy X-ray absorptiometry (DEXA). Women with at least one DEXA scan were included in the analysis (N = 103). RESULTS: On average, participants were 57.1 (± 8.7) years old and 1.6 (± 0.9) years since diagnosis. Women randomized to exercise maintained weight during the trial (- 0.11 kg, P = 0.82), while women in attention-control gained weight (+ 1.40 kg, P = 0.03); however, the between-group difference did not reach statistical significance (P = 0.09). We found no statistically significant differences by study arm for changes in body fat percentage, bone mineral density, or lean body mass. CONCLUSIONS: Weight was maintained as a result of a 6-month aerobic exercise intervention among post-treatment ovarian cancer survivors. Future exercise and healthy eating interventions should consider additional measures (e.g., computer tomography scans, D3-creatinine) to more accurately assess changes in body composition. IMPLICATIONS FOR CANCER SURVIVORS: Moderate-intensity aerobic exercise may help ovarian cancer survivors maintain weight.

Randomized Trial of Exercise on Quality of Life in Women With Ovarian Cancer: Women's Activity and Lifestyle Study in Connecticut (WALC).

Background: Ovarian cancer survivors experience a wide range of treatment side effects that can negatively affect health-related quality of life (HRQOL). Physical activity has been shown to improve HRQOL and cancer-related fatigue (CRF) for other cancer survivors; however, no large randomized controlled trial (RCT) has been conducted for ovarian cancer. Methods: This study examined the impact of a six-month RCT of exercise vs attention control on change in HRQOL (Short Form Health Survey-36) and CRF (Functional Assessment of Cancer Therapy-Fatigue Scale) in ovarian cancer survivors. Women (n = 144) were randomly assigned to study arms between May 1, 2010, and March 20, 2014. All statistical tests were two-sided. Results: A total of 74 women were randomly assigned to exercise and 70 to attention control. A total of 113 (78.5%) of the participants completed the six-month assessment. Adherence to the exercise intervention was excellent (166.0±66.1 minutes/week in the exercise arm). At six months, women in the exercise arm had improved physical HRQOL (SF-36 Physical Component Summary Score) compared with the control arm, 1.8 (SD = 1.1) vs -2.0 (SD = 1.2) , respectively (group difference = 3.7, SD = 1.2, 95% confidence interval [CI] = 0.7 to 6.8, P = .02). No group differences were seen for change in mental HRQOL. There was a statistically significant improvement in the fatigue score (Functional Assessment of Cancer Therapy-Fatigue) for exercisers (4.0, SD = 1.1, 95% CI = 1.8 to 6.2, P < .001) but not for controls (1.2, SD = 1.2, 95% CI = -1.1 to 3.5, P = .31), with a between-group difference of 2.8 (SD = 1.5, 95% CI = -0.2 to 5.7, P = .06). Conclusions: We found a six-month home-based, telephone-delivered exercise intervention of primarily brisk walking to be associated with improved physical HRQOL in women with ovarian cancer. Given that higher HRQOL and exercise have both been associated with overall survival in women diagnosed with ovarian cancer, oncologists and primary care providers should recommend and refer women diagnosed with ovarian cancer to clinic- or community-based exercise programs.