Outcomes for breast cancer survivors with metastatic disease in a physical activity program for medically underserved cancer survivors.

PURPOSE: This study examined the effectiveness and feasibility of the Active Living After Cancer (ALAC) program for metastatic breast cancer (MBC) survivors. METHODS: ALAC is a 12-session community-based program to help cancer survivors improve their physical functioning and quality of life through increased physical activity. ALAC participants with MBC (stage IV) were compared to survivors with early-stage breast cancer (stages I and II). The International Physical Activity Questionnaire, Godin Leisure-Time Physical Activity, 30-second sit-to-stand test, and PROMIS Global Health were administered at baseline and follow-up. Program satisfaction and retention were assessed at week 12. Repeated-measures mixed models were used to compare changes in outcomes between survivors with early-stage breast cancer and MBC. RESULTS: A total of 585 women (59.3 y ± 10.6), most of whom were Hispanic (54%) or non-Hispanic Black (22%), were included (early stage, n = 538; MBC, n = 47). After the ALAC program, a significant increase in physical activity (P < 0.001), improved physical and mental health T-scores (P < 0.001), and more sit-to-stand repetitions (P < 0.001) were observed for both survivors with early-stage breast cancer and MBC. Women with MBC showed significantly lower physical health (P = 0.037) and physical function (P = 0.010) compared to early-stage at baseline. CONCLUSIONS: The ALAC program increased physical activity and improved health-related quality of life and physical function among breast cancer survivors with both early-stage and metastatic disease. IMPLICATIONS FOR CANCER SURVIVORS: This study emphasizes the importance of incorporating physical activity interventions like the ALAC program into the comprehensive care of cancer survivors, including those with metastatic disease.

Expanding active living after cancer to underserved cancer survivors and their caregivers.

BACKGROUND: Physical activity (PA) improves physical and psychological health in cancer survivors. This study evaluated Active Living After Cancer (ALAC), a community-based program to improve PA, physical function, and quality of life (QOL) in minority and medically underserved cancer survivors and their caregivers. METHODS: Participants completed 12 weekly ALAC sessions and assessments of PA, physical functioning, and QOL at baseline and follow-up (week 12). Paired samples t-tests were used to assess changes in outcomes over time. RESULTS: 540 cancer survivors (M age = 61.1 years, SD = 11.3) and 87 caregivers (M age = 62.3 years, SD = 13.1) were enrolled. Most were women (91.4%), Hispanic (61.1%) or non-Hispanic Black (19.3%), and medically underserved (86.4%). The percent of cancer survivors meeting PA recommendations increased from 28.9% to 60.2% (d = 0.75), and the number of sit-to-stand repetitions in a 30-second period increased from 12.3 to 14.3 (d = 0.39) from 0-12 weeks. Cancer survivors reported significant improvements in physical (T-score Δ = 1.7, d = 0.06) and mental (T-score Δ = 2.3, d = 0.31) health-related QOL. Caregivers also improved their PA, physical function, and QOL, and there were no statistically significant differences between breast and other cancer survivors and between cancer survivors and caregivers. CONCLUSIONS: The ALAC program demonstrated increased PA, physical function, and QOL in medically underserved cancer survivors and their caregivers. Furthermore, ALAC was successfully implemented by community partners and serves as a good model for reaching medically underserved cancer survivors and improving survivorship. Additional efforts are warranted to further extend reach, improve cancer survivorship, and reduce cancer health disparities among underserved cancer survivors.

Optimization of mHealth behavioral interventions for patients with chronic lymphocytic leukemia: the HEALTH4CLL study.

PURPOSE: This pilot study of a diet and physical activity intervention (HEALTH4CLL) was conducted to reduce fatigue and improve physical function (PF) in patients with chronic lymphocytic leukemia (CLL). METHODS: The HEALTH4CLL study used a randomized factorial design based on the multiphase optimization strategy (MOST). Patients received diet, exercise, and body weight management instructional materials plus a Fitbit and were randomized to undergo one of 16 combinations of 4 evidence-based mHealth intervention strategies over 16 weeks. Patients' fatigue, PF, health-related quality of life, behavior changes, and program satisfaction and retention were assessed. Paired t-tests were used to examine changes in outcomes from baseline to follow-up among patients. Factorial analysis of variance examined effective intervention components and their combinations regarding improvement in fatigue and PF scores. RESULTS: Among 31 patients, we observed significant improvements in fatigue (+ 11.8; t = 4.08, p = 0.001) and PF (+ 2.6; t = 2.75, p = 0.01) scores. The combination of resistance and aerobic exercise with daily self-monitoring was associated with improved fatigue scores (ß = 3.857, SE = 1.617, p = 0.027). Analysis of the individual components of the MOST design demonstrated greater improvement in the PF score with resistance plus aerobic exercise than with aerobic exercise alone (ß = 2.257, SE = 1.071, p = 0.048). CONCLUSIONS: Combined aerobic and resistance exercise and daily self-monitoring improved PF and reduced fatigue in patients with CLL. IMPLICATIONS FOR CANCER SURVIVORS: This pilot study supported the feasibility of a low-touch mHealth intervention for survivors of CLL and provided preliminary evidence that exercising, particularly resistance exercise, can improve their symptoms and quality of life.

Tissue-infiltrating alloreactive T cells require Id3 to deflect PD-1-mediated immune suppression during GVHD.

ABSTRACT: Persisting alloreactive donor T cells in target tissues are a determinant of graft-versus-host disease (GVHD), but the transcriptional regulators that control the persistence and function of tissue-infiltrating T cells remain elusive. We demonstrate here that Id3, a DNA-binding inhibitor, is critical for sustaining T-cell responses in GVHD target tissues in mice, including the liver and intestine. Id3 loss results in aberrantly expressed PD-1 in polyfunctional T helper 1 (Th1) cells, decreased tissue-infiltrating PD-1+ polyfunctional Th1 cell numbers, impaired maintenance of liver TCF-1+ progenitor-like T cells, and inhibition of GVHD. PD-1 blockade restores the capacity of Id3-ablated donor T cells to mediate GVHD. Single-cell RNA-sequencing analysis revealed that Id3 loss leads to significantly decreased CD28- and PI3K/AKT-signaling activity in tissue-infiltrating polyfunctional Th1 cells, an indicator of active PD-1/PD-L1 effects. Id3 is also required for protecting CD8+ T cells from the PD-1 pathway-mediated suppression during GVHD. Genome-wide RNA-sequencing analysis reveals that Id3 represses transcription factors (e.g., Nfatc2, Fos, Jun, Ets1, and Prdm1) that are critical for PD-1 transcription, exuberant effector differentiation, and interferon responses and dysfunction of activated T cells. Id3 achieves these effects by restraining the chromatin accessibility for these transcription factors. Id3 ablation in donor T cells preserved their graft vs tumor effects in mice undergoing allogeneic hematopoietic stem cell transplantation. Furthermore, CRISPR/Cas9 knockout of ID3 in human CD19-directed chimeric antigen receptor T cells retained their antitumor activity in NOD/SCID/IL2Rg-/- mice early after administration. These findings identify that ID3 is an important target to reduce GVHD, and the gene-editing program of ID3 may have broad implications in T-cell-based immunotherapy.

Relationships between T-lymphocytes and physical function in adults with chronic lymphocytic leukemia: Results from the HEALTH4CLL pilot study.

OBJECTIVE: Examine physical function and T-cell phenotype in patients with chronic lymphocytic leukemia (CLL) before and after a physical activity (PA) intervention. METHODS: Physical function measures and blood samples were collected from CLL patients (Rai stage 0-4, 50% receiving targeted therapy, N = 24) enrolled in a 16-week intervention of at-home aerobic and/or resistance exercise. Flow cytometry characterized T-cells in cryopreserved peripheral blood cells. Wilcoxon signed-rank test compared physical function and T-cell phenotype at baseline and 16-weeks; Kendall's Tau assessed associations between variables. RESULTS: Godin leisure-time PA score increased from baseline to 16-weeks (mean difference: 14.61, p < .01) and fatigue decreased (mean difference: 6.71, p < .001). At baseline, lower fatigue correlated with a lower proportion of CD8+ T-cells (τ = 0.32, p = .03) and cardiorespiratory fitness (CRF) inversely correlated with the percentage of PD-1+CD8+ T-cells (τ -0.31, p = .03). At 16-weeks, CRF inversely correlated with the proportion of PD-1+CD4+ T-cells (τ -0.34, p = .02). Reduced fatigue at 16-weeks correlated with an increased CD4:CD8 ratio (τ = 0.36, p = .02) and lower percentage of HLA-DR+PD-1+CD4+ T-cells (τ = -0.37, p = .01). CONCLUSIONS: This intervention increased leisure-time PA and decreased fatigue in CLL patients. These changes correlated with an increased CD4:CD8 T-cell ratio and reduced proportion of T-cells subsets previously associated with poor outcomes in CLL patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02194387.

Energy balance in advanced breast cancer: extending beyond the curative setting.

Outcomes in early-stage breast cancer, including quality of life, body composition, physical functioning, physiologic biomarkers, cancer recurrence, and mortality, are associated with body weight, diet, and physical activity. These same endpoints may also be relevant in patients with metastatic breast cancer; however, few studies have evaluated the role of energy balance in this setting. Future work is needed to determine how body weight, nutrition, and exercise or other physical activity might affect the disease course of metastatic breast cancer, and whether energy balance may be a component of beneficial supportive or therapeutic interventions for specific patient populations living with metastatic breast cancer.

Feasibility and Effectiveness of a Worksite-Weight-Loss Program for Cancer Prevention among School-District Employees with Overweight and Obesity.

The effects of Vibrant Lives, a 6-month worksite-weight-loss program, were examined in a cohort of school-district employees with overweight or obesity. The VL Basic (VLB) participants received materials and tailored text messages, the VL Plus (VLP) participants additionally received WIFI-enabled activity monitors and scales and participated in health challenges throughout the school year, and the VL Plus with Support (VLP + S) participants additionally received coaching support. The levels of program satisfaction and retention and changes in weight, physical activity (PA), and diet were compared across groups using Pearson chi-square tests, repeated-measure mixed models, and logistic regression. After the program, the VLB (n = 131), VLP (n = 87), and VLP + S (n = 88) groups had average weight losses of 2.5, 2.5, and 3.4 kg, respectively, and average increases in weekly PA of 40.4, 35.8, and 65.7 min, respectively. The VLP + S participants were more likely than the other participants to have clinically significant weight loss (≥3%; p = 0.026). Compared with the VLB participants, the VLP participants were less likely to meet the recommendations for consuming fast food (p = 0.022) and sugar-sweetened beverages (p = 0.010). The VLP and VLP + S participants reported higher program satisfaction than the VLB participants. The VL program facilitates weight loss among school-district employees with overweight and obesity by increasing their PA and healthy diet.