The impact of non- and anthracycline-based chemotherapy on fatigue in breast cancer survivors: results from WF-97415.

PURPOSE: To examine the differential effect of non- and anthracycline-based chemotherapy on fatigue over 12 months post-diagnosis among breast cancer survivors. METHODS: This study is based on a prospective Wake Forest NCI Community Oncology Research Program (NCORP) multicenter cohort study (WF-97415) of women with stage I to III breast cancer and non-cancer controls. Analyses compared those: 1) receiving, or 2) not receiving anthracycline chemotherapy, 3) receiving aromatase inhibitors (AIs) without chemotherapy, with 4) a comparator group without a history of cancer. In-person clinic assessments were conducted at: baseline (prior to chemotherapy or start of AI therapy), and 3 and 12 months after baseline. The Functional Assessment of Chronic Illness Therapy-Fatigue scale was the primary outcome. Estimated least squares means by group using mixed models with a random subject effect, fixed effects of time and group, and the interaction between time and group was used to compare groups across time, controlling for age, comorbidities, and treatment variables. RESULTS: Among 284 women (mean age = 53.4 years, sd 11.9 years), there was a significant (p < 0.0001) group by time interaction, with a sharp increase in fatigue at 3 months in the two chemotherapy groups in comparison to the non-chemotherapy and non-cancer controls. The two chemotherapy groups did not significantly differ in fatigue at any time point. CONCLUSION: Women with breast cancer who receive non- or anthracycline-based chemotherapy experience similar trends in and levels of fatigue within the first year of treatment and greater fatigue than women receiving AIs alone or women without breast cancer.

Physical Activity During Breast Cancer Therapy Associates With Preserved Exercise Capacity and Cardiac Function (WF97415).

Background: Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease. Objectives: This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy. Methods: Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance. Results: BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (ß ± SE: 7.1 ± 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 ± 0.07; 95% CI: -0.29 to -0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference ± SE: -29 ± 10 m; P = 0.029), LV end-systolic volume (5.8 ± 1.3 mL; P < 0.001), LV ejection fraction (-3.2% ± 0.8%; P = 0.002), and LV circumferential strain (2.5% ± 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes. Conclusions: PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581).

Preoperative exercise therapy for gastrointestinal cancer patients: a systematic review.

BACKGROUND: Gastrointestinal cancer patients are susceptible to significant postoperative morbidity. The aim of this systematic review was to examine the effects of preoperative exercise therapy (PET) on patients undergoing surgery for GI malignancies. METHODS: In accordance with PRISMA statement, all prospective clinical trials of PET for patients diagnosed with GI cancer were identified by searching MEDLINE, Embase, Cochrane Library, ProQuest, PROSPERO, and DARE (March 8, 2017). The characteristics and outcomes of each study were extracted and reviewed. Risk of bias was evaluated using the Cochrane risk of bias tool by two independent reviewers. RESULTS: Nine studies (534 total patients) were included in the systematic review. All interventions involved aerobic training but varied in terms of frequency, duration, and intensity. PET was effective in reducing heart rate, as well as increasing oxygen consumption and peak power output. The postoperative course was also improved, as PET was associated with more rapid recovery to baseline functional capacity after surgery. CONCLUSIONS: PET for surgical patients with gastrointestinal malignancies may improve physical fitness and aid in postoperative recovery.

Problems Experienced by Ovarian Cancer Survivors During Treatment.

OBJECTIVE: To identify problems at different treatment points (early treatment, mid-treatment, early posttreatment, and late posttreatment) among women with ovarian cancer. DESIGN: Longitudinal and cross-sectional study design. SETTING: An academic and community clinical cancer center in the Southeastern United States. PARTICIPANTS: Sixty-eight women with Stage I to IV ovarian cancer. METHODS: Variables assessed included reported problems (physical, psychosocial, pain, marital, medical interaction), social support, optimism, and responses to open-ended questions. Analysis involved mixed models for longitudinal repeated measures and unpaired t tests and content analysis to describe responses to open-ended questions. RESULTS: Physical and psychosocial problems were greatest during early treatment and decreased throughout the treatment trajectory. Women with greater levels of social support and optimism at baseline had fewer problems over time. Women who did not have trouble paying for basics had fewer problems related to pain and psychological problems. CONCLUSION: Problems across all domains must be addressed throughout the treatment trajectory, even after chemotherapy has ended. Nurses are well positioned to refer women appropriately to social workers and clinical navigators across all domains of care and should consider systematic assessment of patient-reported problems as a routine form of practice.

Effect of Intensive Chemotherapy on Physical, Cognitive, and Emotional Health of Older Adults with Acute Myeloid Leukemia.

OBJECTIVES: To measure short-term changes in physical and cognitive function and emotional well-being of older adults receiving intensive chemotherapy for acute myeloid leukemia (AML). DESIGN: Prospective observational study. SETTING: Single academic institution. PARTICIPANTS: Individuals aged 60 and older with newly diagnosed AML who received induction chemotherapy (N = 49, mean age 70 ± 6.2, 56% male). MEASUREMENTS: Geriatric assessment (GA) was performed during inpatient examination for AML and within 8 weeks after hospital discharge after induction chemotherapy. Measures were the Pepper Assessment Tool for Disability (activity of daily living, instrumental activity of daily living (IADL), mobility questions), Short Physical Performance Battery (SPPB), grip strength, Modified Mini-Mental State examination, Center for Epidemiologic Studies Depression Scale, and the Distress Thermometer. Changes in GA measures were assessed using paired t-tests. Analysis of variance models were used to evaluate relationships between GA variables and change in function over time. RESULTS: After chemotherapy, IADL dependence worsened (mean 1.4 baseline vs 2.1 follow-up, P < .001), as did mean SPPB scores (7.5 vs 5.9, P = .02 for total). Grip strength also declined (38.9 ± 7.7 vs 34.2 ± 10.3 kg, P < .001 for men; 24.5 ± 4.8 vs 21.8 ± 4.7 kg, P = .007 for women). No significant changes in cognitive function (mean 84.7 vs 85.1, P = .72) or depressive symptoms (14.0 vs. 11.3, P = .11) were detected, but symptoms of distress declined (5.0 vs 3.2, P < .001). Participants with depressive symptoms at baseline and follow-up had greater declines in SPPB scores those without at both time points. CONCLUSIONS: Short-term survivors of intensive chemotherapy for AML had clinically meaningful declines in physical function. These data support the importance of interventions to maintain physical function during and after chemotherapy. Depressive symptoms before and during chemotherapy may be linked to potentially modifiable physical function declines.

Relationship of Objectively-Measured Habitual Physical Activity to Chronic Inflammation and Fatigue in Middle-Aged and Older Adults.

BACKGROUND: Habitual (non-exercise) physical activity (PA) declines with age, and aging-related increases in inflammation and fatigue may be important contributors to variability in PA. METHODS: This study examined the association of objectively-measured PA (accelerometry over 7 days) with inflammation (plasma interleukin-6 and C-reactive protein) and with self-reported fatigue (SF-36 Vitality) at baseline and 18 months after a diet-induced weight loss, exercise, or diet-induced weight loss plus exercise intervention in 167 overweight/obese, middle-aged, and older adults. RESULTS: At baseline, individuals with higher plasma interleukin-6, as well as those who reported feeling less energetic (more fatigued), took less steps per day and had lower PA energy expenditure and minutes of light and moderate-vigorous PA (p < .05 for all). At the 18-month follow-up, inflammation was lower in both weight loss groups, fatigue was reduced in all three groups with larger decreases in the combined group, and mean levels of habitual PA were not changed in any group. In longitudinal analyses with all groups combined, we found that participants reporting larger increases in vitality (eg, declines in fatigue) had greater increases in PA (p < .05 for all). Also, changes in steps/d and physical activity energy expenditure were indirectly associated with changes in interleukin-6 (ß [SEM] for steps/d = -565 [253]; ß [SEM] for physical activity energy expenditure = -22.4 [10.17]; p < .05). CONCLUSIONS: Levels of habitual PA are lower in middle-aged and older adults with higher levels of chronic inflammation and greater self-reported fatigue. In addition, participants who experienced greater declines in inflammation during the interventions had greater declines in fatigue and larger increases in PA.

Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial.

IMPORTANCE: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE: To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. MAIN OUTCOMES AND MEASURES: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS: Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ](exercise vs diet )= 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ(exercise vs diet + exercise) = 0.39 pg/mL; 95% CI, -0.03 to 0.81; P = .007; Δ(exercise vs diet )= 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ(exercise vs diet + exercise) = 1.02; 95% CI, 0.33 to 1.71; P(pain) = .004; 18.4; 95% CI, 16.9 to 19.9; Δ(exercise vs diet + exercise), 4.29; 95% CI, 2.07 to 6.50; P(function )< .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δ(exercise vs diet + exercise) = -2.81; 95% CI, -4.76 to -0.86; P = .005). CONCLUSIONS AND RELEVANCE: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00381290.

A randomized trial of exercise on well-being and function following breast cancer surgery: the RESTORE trial.

OBJECTIVES: This study aimed to determine the effect of a moderate, tailored exercise program on health-related quality of life, physical function, and arm volume in women receiving treatment for nonmetastatic breast cancer. METHODS: Women who were within 4-12 weeks of surgery for stage I-III breast cancer were randomized to center-based exercise and lymphedema education intervention or patient education. Functional assessment of cancer therapy-breast cancer (FACT-B), 6-min walk, and arm volume were performed at 3-month intervals through 18 months. Repeated measures analysis of covariance was used to model the total meters walked over time, FACT-B scores, and arm volume. Models were adjusted for baseline measurement, baseline affected arm volume, number of nodes removed, age, self-reported symptoms, baseline SF-12 mental and physical component scores, visit, and treatment group. RESULTS: Of the recruited 104 women, 82 completed all 18 months. Mean age (range) was 53.6 (32-82) years; 88% were Caucasian; 45% were employed full time; 44% were overweight; and 28% obese. Approximately, 46% had breast-conserving surgery; 79% had axillary node dissection; 59% received chemotherapy; and 64% received radiation. The intervention resulted in an average increase of 34.3 ml (SD = 12.8) versus patient education (p = 0.01). Changes in FACT-B scores and arm volumes were not significantly different. CONCLUSIONS: With this early exercise intervention after breast cancer diagnosis, a significant improvement was achieved in physical function, with no decline in health-related quality of life or detrimental effect on arm volume. IMPLICATIONS FOR CANCER SURVIVORS: Starting a supervised exercise regimen that is tailored to an individual's strength and stamina within 3 months following breast cancer surgery appears safe and may hasten improvements in physical functioning.

Weight loss and self-regulatory eating efficacy in older adults: the cooperative lifestyle intervention program.

OBJECTIVES: Using the weight efficacy lifestyle questionnaire (WEL), we examined whether a group-mediated intervention for weight loss among older, obese adults resulted in changes in self-regulatory self-efficacy for eating behavior and whether these changes mediated weight loss. METHODS: This was a randomized controlled design, and 288 older adults received 1 of 3 treatments for 6 months: physical activity only (PA), weight loss + physical activity (WL + PA), or a successful aging (SA) health education program. The WEL was administered prior to randomization and again at the 6-month follow-up visit. RESULTS: A significant treatment effect was observed for the WEL, F (2249) = 15.11, p < .0001, partial eta2 = .11, showing that improvement occurred only in the WL + PA group as compared with PA and SA. Changes in WEL scores partially mediated the effects of the WL + PA intervention on weight loss. DISCUSSION: These results illustrate that WL + PA can be effective in improving older adults' self-efficacy for the self-regulation of eating behavior and that these changes are prospectively related to the amount of weight loss. Further research is warranted on an expanded concept of self-efficacy as well as controlled experimental studies on eating behavior in older adults.

Exercise for older adult inpatients with acute myelogenous leukemia: A pilot study.

OBJECTIVES: Acute myelogenous leukemia (AML) largely affects older adults. Few interventions have sought to improve functional status and health-related quality of life (HRQL) during treatment. The objective of this study is to examine the feasibility of an exercise intervention among older adults with AML undergoing induction chemotherapy. MATERIALS AND METHODS: Pilot study of adults ≥50 years of age hospitalized for AML chemotherapy. The four week exercise intervention included stretching, walking, and strength exercises. Feasibility measures included recruitment, retention, number of exercise sessions completed, and barriers to participation. Physical function, HRQL, depression, and distress were assessed at baseline (week 1), upon completion of intervention (week 5), and during follow-up (weeks 9-13). Exploratory analyses used repeated measures ANCOVA to model changes over time. RESULTS: Among 55 eligible inpatients, 24 enrolled (43.6%). Mean age was 65.1 years (SD 7.8). 87.5% of participants completed baseline measures; 70.8% attended ≥1 exercise sessions, and 50.0% completed post-intervention assessment. Among baseline characteristics, only higher physical performance was associated with greater number of exercise sessions attended (p=0.001). Post intervention, HRQL and depressive symptoms improved (p <0.05). CONCLUSIONS: Recruitment to an exercise intervention was feasible. Exercise shows promise to maintain physical function and enhance HRQL. Strategies to enhance adherence to exercise are needed to maximize benefit.

Restorative yoga for women with breast cancer: findings from a randomized pilot study.

OBJECTIVES: Restorative yoga (RY) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors. Study goals were: to determine the feasibility of implementing a RY intervention for women with breast cancer; and to examine group differences in self-reported emotional, health-related quality of life, and symptom outcomes. METHODS: Women with breast cancer (n=44; mean age 55.8 years) enrolled in this study; 34% were actively undergoing cancer treatment. Study participants were randomized to the intervention (10 weekly 75-minute RY classes) or a waitlist control group. Participants completed questionnaires at Week 0 (baseline) and Week 10 (immediately post-intervention for the yoga group). RESULTS: Group differences favoring the yoga group were seen for mental health, depression, positive affect, and spirituality (peace/meaning). Significant baseline*group interactions were observed for negative affect and emotional well-being. Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group. The yoga group demonstrated a significant within-group improvement in fatigue; no significant difference was noted for the control group. CONCLUSIONS: Although limited by sample size, these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients. This study demonstrates that a RY intervention is feasible for women with breast cancer; implications for study design and implementation are noted with an emphasis on program adoption and participant adherence.