Impact of pre- and post-diagnosis physical activity on the mortality of patients with cancer: Results from the Health Examinees-G study in Korea.

BACKGROUND: Physical activity (PA) is recommended to improve the survival of cancer patients. However, the prognostic impact of specific PAs is not well understood. Therefore, we investigated the associations of the duration, type, intensity, and number of PAs one participates in pre- and post-diagnosis with mortality in Korean patients with cancer. METHODS: Among the participants aged 40-69 years recruited from the Health Examines study, those diagnosed with cancer after baseline (n = 7749) and within 10 years before baseline (n = 3008) were included in the analyses for pre- and post-diagnosis PA, respectively. Duration, intensity, type, and number of leisure-time physical activities participated in were assessed using questionnaires. The Cox proportional hazard model was used to characterize the association between PA and cancer-specific mortality, adjusting for demographics, behaviors, comorbidities, and cancer stage based on the Surveillance, Epidemiology, and End Results program. RESULTS: Pre-diagnosis, patients participating in vigorous-intensity activities (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.61-0.82), walking (HR: 0.85, 95% CI: 0.74-0.97), climbing (HR: 0.65, 95% CI: 0.55-0.77), sports (HR: 0.39, 95% CI: 0.25-0.61), and more than two activities (HR: 0.73, 95% CI: 0.63-0.86) had significantly lower all-cause mortality. Importantly, these associations were only found in patients with colorectal cancer participating in vigorous-intensity activities (HR: 0.40, 95% CI: 0.23-0.70). Post-diagnosis, only patients who performed more than two activities (HR: 0.65, 95% CI: 0.44-0.95) had significantly lower all-cause mortality. Similar associations were found for cancer mortality, both pre- and post-diagnosis. CONCLUSION: Specific characteristics of PA pre- and post-diagnosis may influence the survival of cancer patients.

Feasibility of implementing a supervised telehealth exercise intervention in frail survivors of hematopoietic cell transplantation: a pilot randomized trial.

BACKGROUND: Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer populations, but these have largely been based out of rehabilitation facilities that may act as geographic and logistical barriers. There is a paucity of information on the feasibility of implementing telehealth exercise interventions in long-term HCT survivors. METHODS: We conducted a pilot randomized trial to assess the feasibility of an 8-week telehealth exercise intervention in 20 pre-frail or frail HCT survivors. Participants were randomized to either a telehealth exercise (N = 10) or delayed control (N = 10). We administered a remote physical function assessment at baseline, followed by an 8-week telehealth exercise intervention (30-60 min/session, 3 sessions/week), and post-intervention. The primary endpoint was feasibility as determined by 1) > 70% of participants completing all remote physical functional assessments, and 2) > 70% of participants in the exercise group completing > 70% (17/24) of the prescribed exercise sessions. Exploratory outcomes included changes in gait speed, handgrip strength, and short physical performance battery. RESULTS: The mean [standard deviation] age at study enrollment was 64.7 [9.1] years old. Twelve had undergone allogenic and 8 had undergone autologous HCT at an average of 17 years from study enrollment. Both feasibility criteria were achieved. Nineteen patients (95%) completed all remote study outcome assessments at baseline and post-intervention, and nine participants in the exercise group completed > 70% of prescribed exercise sessions. Overall, no significant group x time interaction was observed on handgrip strength, fatigue, body mass index, and short physical performance battery test (P < 0.05). However, there were significant within-group improvements in four-meter gait speed (+ 13.9%; P = 0.004) and 5-minute gait speed (+ 25.4%; P = 0.04) in the exercise group whereas non-significant changes in four-meter gait speed (-3.8%) and 5-minute gait speed (-5.8%) were observed after 8 weeks. CONCLUSION: Implementing an 8-week telehealth exercise intervention for long-term HCT survivors was feasible. Our findings set the stage for innovative delivery of supervised exercise intervention that reduces the burden of frailty in HCT survivors as well as other at-risk cancer survivors. TRIAL REGISTRATION: The protocol and informed consent were approved by the institutional IRB (IRB#20731) and registered (ClinicalTrials.gov NCT04968119; date of registration: 20/07/2021).

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy.

Cancer survivors exposed to anthracycline chemotherapy are at risk for developing cardiomyopathy, which may have delayed clinical manifestation. In a retrospective cross-sectional study, we evaluated the utility of cardiopulmonary exercise testing (CPET) for detecting early cardiac disease in 35 pediatric cancer survivors by examining the associations between peak exercise capacity (measured via percent predicted peak VO2) and resting left ventricular (LV) function on echocardiography and cardiac magnetic resonance imaging (cMRI). We additionally assessed the relationships between LV size on resting echocardiography or cMRI and percent predicted peak VO2 since LV growth arrest can occur in anthracycline-exposed patients prior to changes in LV systolic function. We found reduced exercise capacity in this cohort, with low percent predicted peak VO2 (62%, IQR: 53-75%). While most patients in our pediatric cohort had normal LV systolic function, we observed associations between percent predicted peak VO2 and echocardiographic and cMRI measures of LV size. These findings indicate that CPET may be more sensitive in manifesting early anthracycline-induced cardiomyopathy than echocardiography in pediatric cancer survivors. Our study also highlights the importance of assessing LV size in addition to function in pediatric cancer survivors exposed to anthracyclines.

Association Between Pretreatment Skeletal Muscle and Outcomes After CAR T-Cell Therapy.

BACKGROUND: The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. PATIENTS AND METHODS: Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. RESULTS: The median age of the cohort was 63.1 years (range, 18.5-82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05-2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; P<.05) compared with those with normal muscle mass. Abnormal skeletal muscle was independently associated with risk of disease progression (HR, 1.70; 95% CI, 1.11-2.57) and worse survival (HR, 2.44; 95% CI, 1.49-4.00) at 1 year compared with normal skeletal muscle. Individuals who had abnormal skeletal muscle and high lactate dehydrogenase (LDH) levels at baseline had poor 1-year PFS (17%) and OS (12%) compared with those with normal skeletal muscle and LDH levels (72% and 82%, respectively; P<.001). Patients who had abnormal skeletal muscle and LDH levels had a 5-fold risk (HR, 5.34; 95% CI, 2.97-9.62) of disease progression and a 10-fold risk (HR, 9.73; 95% CI, 4.81-19.70) of death (reference: normal skeletal muscle, normal LDH), independent of prior lines of therapy, extent of residual disease at time of CAR T-cell therapy, functional status, or product. CONCLUSIONS: This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.

Cardiovascular profile of contemporary treatments of renal cell carcinoma: A single-center prospective study.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Emerging data suggest that these agents can result in clinically significant cardiotoxicity, compromising the care. METHODS: We conducted a prospective longitudinal study to evaluate the incidence of de novo cardiac dysfunction as assessed by echocardiography and blood biomarkers in mRCC patients receiving TKI with or without ICI followed at baseline, 3-month and 6-month. We recruited consecutive newly diagnosed mRCC patients treated at our institution between 2015 and 2018 as well as patients with localized RCC not treated with systemic therapies and healthy control (HC) subjects for comparison. RESULTS: Twenty-eight patients were enrolled in the mRCC group (a mean age of 65.2 ± 7.5 years), 29 patients in the localized RCC group (63.6 ± 8.9 years), and 20 volunteers in the HC group (52.9 ± 9.6 years). At baseline, patients from all three groups had normal cardiac function as measured by left ventricular ejection fraction (LVEF), although patients with mRCC or localized RCC had significantly lower mean LVEF compared to HC (61.9%, 62.4%, and 68.1% respectively). Otherwise, there were no statistically significant changes in echocardiographic parameters or incidence of clinical heart failure from baseline to 6-months in patients with mRCC. Cardiac blood biomarkers including troponin I, brain natriuretic peptide, and galectin-3 remained stable over time. CONCLUSION: Our findings suggest that contemporary treatment strategies of mRCC at this single institution are well tolerated without clinically meaningful overt declines in cardiac function over time. Further studies are warranted to include a larger number of patients to better assess the overall cardiovascular safety associated with contemporary treatments of mRCC.

High-intensity interval training improves metabolic syndrome in women with breast cancer receiving Anthracyclines.

INTRODUCTION: Anthracycline chemotherapy is a frequent treatment for breast cancer, whereas it can increase risk of physiologic side-effects, such as metabolic syndrome (MetS). Exercise has been used as a non-pharmacological strategy to decrease MetS. Specifically, high-intensity interval training (HIIT) has been shown to improve MetS in patients with diabetes or cardiac rehabilitation patients; however, the effects of HIIT on MetS and associated biomarkers in patients with breast cancer receiving anthracycline chemotherapy have not been previously explored. Therefore, we purposed to determine the effects of HIIT on MetS in breast cancer patients undergoing anthracycline chemotherapy. METHODS: In total, 30 patients with breast cancer were recruited prior to initiating treatment and randomized into HIIT (n = 15) or control (n = 15). The HIIT group attended supervised cycling sessions 3 days/week for 8 weeks. MetS was assessed by waist circumference, blood pressure, fasting levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose. Circulating levels of MetS-related biomarkers were also measured (total cholesterol, insulin, HbA1c, leptin, adiponectin, and c-reactive protein). RESULTS: After 8 weeks, MetS z-score was significantly improved in the HIIT group compared with controls (-7.60, 95% CI: -9.08 to -6.13, p < 0.001). MetS variables (HDL-C, glucose, and triglycerides) and circulating levels of MetS-related biomarkers were significantly improved in the HIIT group compared with controls (p < 0.001). Non-significant differences were found in body composition outcomes at the end of the study. CONCLUSIONS: HIIT may be an effective strategy to improve MetS in breast cancer patients undergoing anthracycline chemotherapy. Furthermore, changes in MetS were independent of changes in body composition.

Telehealth exercise to Improve Physical function and frailty in patients with multiple myeloma treated with autologous hematopoietic Stem cell transplantation (TIPS): protocol of a randomized controlled trial.

BACKGROUND: Advances in autologous hematopoietic stem cell transplantation (HSCT) and supportive care have led to marked improvements in survival for patients with multiple myeloma. Despite these improvements, patients with multiple myeloma remain at high risk of physical dysfunction and frailty due to HSCT and its associated exposures. Although traditional supervised exercise programs can improve frailty in cancer patients and survivors, rehabilitation facilities are typically far from a patient's residence, are offered on fixed days/hours, contain uniform activities for everyone, and carry a higher risk of contact cross-infection due to immunosuppression, which can be barriers to exercise participation. Innovative personalized interventions are needed to overcome the limitations of traditional exercise interventions. The purpose of this study is to determine the efficacy and sustainability of a telehealth exercise intervention on physical function and frailty in patients with multiple myeloma treated with HSCT. METHODS: This randomized controlled trial will assess the efficacy of an 8-week telehealth exercise intervention in 60 patients with multiple myeloma who underwent autologous HSCT (30-180 days post-transplant) and are pre-frail or frail. There will be 30 intervention participants and 30 delayed controls. We will administer remote baseline assessments (week 0), followed by an 8-week telehealth intervention (week 1-8), post assessment (week 9), and an additional follow-up assessment (week 17). Our primary endpoint will be improved physical function, as assessed by the Short Physical Performance Battery test. Our secondary endpoint will be a decrease in frailty characteristics such as gait speed, strength, and fatigue. We will also evaluate the sustainability of improved physical function and frailty at week 17. Participants randomized to the intervention group will perform at least 90 min of exercise per week throughout the 8 weeks. DISCUSSION: This study will help optimize the delivery of safe, low-cost, and scalable telehealth exercise interventions to improve health outcomes in patients with multiple myeloma, an understudied population at high risk for physical dysfunction and frailty. Our study may provide the foundation for sustainable telehealth exercise interventions to improve physical function and frailty for other hematologic cancer patients (e.g., acute leukemia, lymphoma) as well as any other cancer population of interest. TRIAL REGISTRATION: ClinicalTrials.gov NCT05142371 . This study was retrospectively registered on December 2nd, 2021, and is currently open to accrual.

Association Between Body Composition and Development of Glucose Intolerance after Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) recipients have increased risk of developing glucose intolerance and diabetes mellitus (DM). The strongest risk factor for glucose intolerance is being overweight/obese, as determined by body mass index (BMI), which does not account for differences in body composition. We examined the association between body composition measures from pre-HCT CT and early-onset (≤30 days) de novo glucose intolerance after HCT, and determined its impact on nonrelapse mortality (NRM). METHODS: This study included 749 patients without pre-HCT DM. Skeletal muscle loss [abnormal skeletal muscle gauge (SMG)] and abnormal visceral adiposity (VA) were defined by sex-specific tertiles. Fine-Gray proportional subdistribution HR estimates and 95% confidence intervals (CI) were obtained to determine the association between muscle loss and VA and development of glucose intolerance. 1 year NRM was calculated for patients alive at day 30. RESULTS: Median age at HCT was 50.2 years. By day 30, 8.1% of patients developed glucose intolerance and 731 remained alive. In multivariable analysis, abnormal SMG was associated with increased risk of glucose intolerance in nonoverweight (BMI < 25 kg/m2) patients (HR = 3.00; 95% CI, 1.15-7.81; P = 0.024); abnormal VA was associated with increased risk of glucose intolerance in overweight/obese patients (HR = 2.26; 95% CI, 1.24-4.12; P = 0.008). Glucose intolerance was independently associated with NRM (HR = 1.88; 95% CI, 1.05-3.39; P = 0.035). CONCLUSIONS: Abnormal SMG and VA were associated with glucose intolerance in nonoverweight and overweight/obese patients, respectively, which contributed to increased risk of 1 year NRM. IMPACT: This information may guide personalized interventions to decrease the risk of adverse outcomes after HCT. See related commentary by Giri and Williams, p. 2002.

Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial {1}.

BACKGROUND: Advances in hematopoietic cell transplantation (HCT) have led to marked improvements in survival. However, adolescents and young adults (AYAs) who undergo HCT are at high risk of developing sarcopenia (loss of skeletal muscle mass) due to the impact of HCT-related exposures on the developing musculoskeletal system. HCT survivors who have sarcopenia also have excess lifetime risk of non-relapse mortality. Therefore, interventions that increase skeletal muscle mass, metabolism, strength, and function are needed to improve health in AYA HCT survivors. Skeletal muscle is highly reliant on mitochondrial energy production, as reflected by oxidative phosphorylation (OXPHOS) capacity. Exercise is one approach to target skeletal muscle mitochondrial OXPHOS, and in turn improve muscle function and strength. Another approach is to use "exercise enhancers", such as nicotinamide riboside (NR), a safe and well-tolerated precursor of nicotinamide adenine dinucleotide (NAD+), a cofactor that in turn impacts muscle energy production. Interventions combining exercise with exercise enhancers like NR hold promise, but have not yet been rigorously tested in AYA HCT survivors. METHODS/DESIGN: We will perform a randomized controlled trial testing 16 weeks of in-home aerobic and resistance exercise and NR in AYA HCT survivors, with a primary outcome of muscle strength via dynamometry and a key secondary outcome of cardiovascular fitness via cardiopulmonary exercise testing. We will also test the effects of these interventions on i) muscle mass via dual energy x-ray absorptiometry; ii) muscle mitochondrial OXPHOS via an innovative non-invasive MRI-based technique, and iii) circulating correlates of NAD+ metabolism via metabolomics. Eighty AYAs (ages 15-30y) will be recruited 6-24 months post-HCT and randomized to 1 of 4 arms: exercise + NR, exercise alone, NR alone, or control. Outcomes will be collected at baseline and after the 16-week intervention. DISCUSSION: We expect that exercise with NR will produce larger changes than exercise alone in key outcomes, and that changes will be mediated by increases in muscle OXPHOS. We will apply the insights gained from this trial to develop individualized, evidence-supported precision initiatives that will reduce chronic disease burden in high-risk cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05194397. Registered January 18, 2022, https://clinicaltrials.gov/ct2/show/NCT05194397 {2a}.

Effect of high-intensity interval training on patient-reported outcomes and physical function in women with breast cancer receiving anthracycline-based chemotherapy.

PURPOSE: The purpose of this study was to determine the effects of an 8-week HIIT intervention on patient-reported outcomes and physical function in breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty breast cancer patients were recruited prior to initiating treatment and randomized into the HIIT group (n = 15) or control (CON) group (n = 15). The HIIT group attended HIIT sessions three days per week for eight weeks. The CON group was asked to maintain their current level of physical activity. Patient-reported outcomes were assessed by the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), Multidimensional Fatigue Inventory with 20 questions (MFI-20), and the 15-item Five-Facet Mindfulness Questionnaire (FFMQ-15). Physical function was assessed using the timed up and go (TUG), 30-s sit-to-stand (30STS), Margaria-Kalamen stair climb test, and 6-min walk test (6MWT). Repeated measures ANCOVA and paired t-tests were performed to assess group differences. RESULTS: All patients completed the 8-week study with 82.3% adherence to the intervention among the HIIT group. Post-intervention, significant improvements were found for the Margaria-Kalamen stair climb test (- 3.39%; P = 0.013) and 6MWT (+ 11.6%; P = 0.008) in the HIIT group compared to baseline and CON group. No changes in patient-reported outcomes, TUG, and 30STS were observed following the 8-week study period in both groups (P > 0.05). CONCLUSIONS: HIIT may be an effective strategy to improve physical function and possibly maintain QOL in breast cancer patients undergoing the anthracycline-based chemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02454777.

Hispanic ethnicity as a moderator of the effects of aerobic and resistance exercise on physical fitness and quality-of-life in breast cancer survivors.

BACKGROUND: Exercise can profoundly affect physical fitness and quality of life in breast cancer survivors; however, few studies have focused on minorities. This secondary analysis examines Hispanic ethnicity as a moderator of the effects of a 16-week aerobic and resistance exercise intervention on physical fitness and quality of life in breast cancer survivors. METHODS: Eligible breast cancer survivors (n = 100) were randomized to exercise (n = 50) or usual care (n = 50). The exercise intervention consisted of supervised moderate-vigorous aerobic and resistance exercise thrice weekly for 16 weeks. Physical fitness and quality of life were measured at baseline, post-intervention, and 28-week follow-up (exercise only). Linear mixed-models adjusted for baseline value of the outcome, age, disease stage, adjuvant treatment, and recent physical activity were used to evaluate effect modification by ethnicity. RESULTS: The study sample included 57% Hispanic and 43% non-Hispanic breast cancer survivors. Hispanic breast cancer survivors were younger, less fit, and diagnosed with more advanced cancers compared with non-Hispanic breast cancer survivors (p < 0.001). Ethnicity was found to moderate the effects of exercise training on all physical fitness and quality-of-life measures including VO2max (8.4 mL/kg/min; 95% confidence interval (95% CI) 3.2 to 13.4), physical well-being (12.3; 95% CI 4.2 to 18.4), and emotional well-being (11.4; 95% CI 5.9 to 15.5). In all cases, Hispanics experienced larger benefits than non-Hispanics. CONCLUSIONS: Hispanic breast cancer survivors have poorer cardiorespiratory fitness, muscle strength, and quality-of-life and therefore may derive larger benefits from exercise than non-Hispanic breast cancer survivors. Clinical exercise interventions may attenuate existing health disparities among minority breast cancer survivors. IMPLICATION OF CANCER SURVIVORS: Here we report psychosocial and fitness-related disparities among Hispanic breast cancer survivors when compared with their non-Hispanic counterparts. Our exercise intervention highlights the importance of exercise for minority cancer survivors and the need for distinct, culturally tailored exercise intervention approaches to reduce psychosocial and fitness-related disparities among this understudied population of cancer survivors.

Aerobic and resistance exercise improves Reynolds risk score in overweight or obese breast cancer survivors.

BACKGROUND: Breast cancer survivors have double the risk of mortality from cardiovascular disease than age-matched women without a cancer history. Reynolds risk score (RRS) is a validated algorithm for the assessment of cardiovascular disease risk. This secondary analysis sought to examine the effects of a 16-week aerobic and resistance exercise intervention on RRS in overweight or obese breast cancer survivors. METHODS AND RESULTS: One hundred overweight or obese (BMI > 25 kg/m2) breast cancer survivors were randomized to exercise or usual care. The exercise group underwent aerobic and resistance exercise sessions for 16 weeks. RRS was calculated using a validated equation. Group differences in mean change for RRS were evaluated using repeated-measures analyses of variance. Post-intervention, RRS was significantly reduced (7.9 ± 0.9% to 1.0 ± 0.5%; p < 0.001) in the exercise group compared to a significant increase (9.0 ± 0.8% to 11.6 ± 1.2%; p = 0.002%) in the usual care group (p < 0.01). RRS was significantly reduced in exercise vs usual care (between group difference, - 10.6; 95% CI, - 16.3 to - 7.4; p < 0.001). CONCLUSION: A 16-week aerobic and resistance exercise intervention is an effective approach to reduce the risk of cardiovascular disease in breast cancer survivors. Exercise during cancer survivorship should be considered to reduce the risk for cardiovascular disease risk in overweight women breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01140282 . Registered 9 June 2010.

Feasibility of quantifying change in immune white cells in abdominal adipose tissue in response to an immune modulator in clinical obesity.

BACKGROUND: Obesity is often associated with inflammation in adipose tissue (AT) with release of mediators of atherogenesis. We postulated that it would be feasible to collect sufficient abdominal AT to quantify changes in a broad array of adaptive and innate mononuclear white cells in obese non-diabetic adults in response to a dipeptidyl protease inhibitor (DPP4i), known to inhibit activation of immune white cells. METHODS: Adults 18-55 years-of-age were screened for abdominal obesity and insulin resistance or impaired glucose tolerance but without known inflammatory conditions. Twenty-one eligible participants consented for study and were randomized 3:1 to receive sitagliptin (DPP4i) at 100mg or matching placebo daily for 28 days. Abdominal AT collected by percutaneous biopsy and peripheral blood mononuclear cell fractions were evaluated before and after treatment; plasma was stored for batch testing. RESULTS: Highly sensitive C-reactive protein, a global marker of inflammation, was not elevated in the study population. Innate lymphoid cells (ILC) type 3 (ILC-3) in abdominal AT decreased with active treatment compared with placebo (p = 0.04). Other immune white cells in AT and peripheral blood mononuclear cell (PBMC) fractions did not change with treatment compared to placebo (p>0.05); although ILC-2 declined in PBMCs (p = 0.007) in the sitagliptin treatment group. Two circulating biomarkers of atherogenesis, interferon-inducible protein-10 (IP-10) and sCD40L declined in plasma (p = 0.02 and p = 0.07, respectively) in the active treatment group, providing indirect validation of a net reduction in inflammation. CONCLUSIONS: In this pilot study, two cell types of the innate lymphoid system, ILC-3 in AT and ILC-2 PBMCs declined during treatment and as did circulating biomarkers of atherogenesis. Changes in other immune cells were not demonstrable. The study showed that sufficient abdominal AT could be obtained to quantify white cells of both innate and adaptive immunity and to demonstrate changes during therapy with an immune inhibitor. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT02576.

Prehabilitative Exercise for the Enhancement of Physical, Psychosocial, and Biological Outcomes Among Patients Diagnosed with Cancer.

PURPOSE OF REVIEW: This review summarizes the effects of prehabilitative exercise interventions on the physical, psychosocial, and biological outcomes among patients with cancer. Current gaps and future directions in prehabilitative exercise research will be addressed. RECENT FINDINGS: Prehabilitative exercise mitigates the detrimental impact of cancer surgery on physical fitness, noted by increases in maximal oxygen consumption and 6-min walk distance. Beneficial effects on psychosocial and biological outcomes remain inconclusive. Aerobic exercise interventions were often prescribed and included low-, moderate-, or high-intensity exercise. Resistance exercise interventions were often performed in conjunction with aerobic exercise. Prehabilitative exercise elicits robust improvements in physical fitness; however, effect on psychosocial and biological outcomes remains inconclusive. Exercise prescription parameters varied greatly by frequency, intensity, time, and type across multiple cancer diagnoses. Future investigations are needed to systematically dose exercise for a wider variety of outcome measures, with an overall goal to set forth pre-operative exercise guidelines.

Interstitial glucose and subsequent affective and physical feeling states: A pilot study combining continuous glucose monitoring and ecological momentary assessment in adolescents.

OBJECTIVE: Circulating glucose may relate to affective and physical feeling states reflective of emotional disorder symptoms. No prior studies have investigated within-day associations between glucose and subsequent affective and physical feeling states (positive affect, negative affect, and fatigue) as they occur naturally among healthy adolescents; this pilot study assessed these associations by combining data collected from ecological momentary assessment (EMA) and continuous glucose monitors (CGM). METHODS: Participants (N = 15, mean age = 13.1[±1.0] years, 66.7% female, 40.0% Hispanic, 66.7% healthy weight) wore a CGM for 7-14 days. Simultaneously, participants reported on their current positive affect, negative affect, and fatigue randomly during specified windows up to 7 times daily via EMA. CGM-measured mean interstitial glucose was calculated during the time windows (mean minutes = 122.5[±47.3]) leading up to each EMA prompt. Multilevel models assessed within-subject (WS) associations between mean interstitial glucose since the previous EMA prompt and EMA-reported affective and physical feeling states at the current prompt. RESULTS: Participants provided 532 interstitial glucose-matched EMA reports of affective and physical feeling states. During intervals when interstitial glucose was higher than one's usual, higher positive affect (WS ß = 0.01, p < .0001, f2 = 0.02) and lower fatigue (WS ß = -0.01, p < .0001, f2 = 0.09) were subsequently reported. Interstitial glucose was unrelated to negative affect (WS ß = -0.002, p = .10, f2 = 0.01). Associations were weakened, but remained significant following further adjustment for time of day. CONCLUSIONS: Though effect sizes were small, within-person variations in interstitial glucose may relate to subsequent affective and physical feeling states among healthy youth. Investigations using similar methodologies in larger, more diverse samples are warranted.

Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy.

Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis. While exercise has been shown to reduce the level of MMP in patients with diabetes, high intensity interval training (HIIT) has not been utilized to improve level of MMP in women with breast cancer receiving anthracycline chemotherapy. Thirty women were randomized to either 8-week HIIT or control (CON) group. The CON group was offered the HIIT intervention after 8 weeks. MMP-1, -2 -7, -9, tissue inhibitor of MMP (TIMP) -1, and-2 were measured at baseline and post-intervention. Repeated measures ANCOVA and paired t-test were performed to assess changes in MMP and TIMP. Post-intervention, no significant between-group differences were observed for MMP and TIMP. However, within-group decrease in MMP-9 was observed in the HIIT group [104.3(51.9) to 65.2(69.1); P = 0.01]. MMP-9 in the CON group was not significantly changed [115.5(47.2) to 90.4(67.9);]. MMP-2 significantly increased in both the HIIT group [76.6(11.2) to 83.2(13.1); P = 0.007) and the CON group [69.0(8.9) to 77.6(11.1) P = 0.003). It is unclear whether an 8-week HIIT intervention influences MMP-9 in breast cancer patients undergoing anthracycline chemotherapy. Additional investigations are required to understand the exercise-induced changes in MMP-2 and -9 in women undergoing anthracycline chemotherapy.

Aerobic and Resistance Exercise Improves Shoulder Function in Women Who Are Overweight or Obese and Have Breast Cancer: A Randomized Controlled Trial.

BACKGROUND: Adverse upper limb musculoskeletal effects occur after surgical procedures and radiotherapy for breast cancer and can interfere with activities of daily living. OBJECTIVE: The objective of this study was to examine the effects of a 16-week exercise intervention on shoulder function in women who are overweight or obese and have breast cancer. DESIGN: This study was a randomized controlled trial. SETTING: The study was performed at the Division of Biokinesiology and Physical Therapy at the University of Southern California. PARTICIPANTS: One hundred women with breast cancer were randomly allocated to exercise or usual-care groups. The mean (SD) age of the women was 53.5 (10.4) years, 55% were Hispanic white, and their mean (SD) body mass index was 33.5 (5.5) kg/m2. INTERVENTION: The 16-week exercise intervention consisted of supervised, progressive, moderate to vigorous aerobic and resistance exercise 3 times per week. MEASUREMENTS: Shoulder active range of motion, isometric muscular strength, and patient-reported outcome measures (including Disabilities of the Arm, Shoulder, and Hand and the Penn Shoulder Scale) were assessed at baseline, after the intervention, and at the 3-month follow-up (exercise group only). Differences in mean changes for outcomes were evaluated using mixed-model repeated-measures analysis. RESULTS: Compared with the usual-care group, the exercise group experienced significant increases in shoulder active range of motion (the mean between-group differences and 95% confidence intervals (CIs) were as follows: shoulder flexion = 36.6° [95% CI = 55.2-20.7°], external rotation at 0° = 23.4° [95% CI = 31.1-12.5°], and external rotation at 90° = 34.3° [95% CI = 45.9-26.2°]), improved upper extremity isometric strength, and improved Disabilities of the Arm, Shoulder, and Hand and Penn Shoulder Scale scores. LIMITATIONS: Limitations include a lack of masking of assessors after the intervention, an attention control group, and statistical robustness (shoulder function was a secondary end point). CONCLUSIONS: A 16-week exercise intervention effectively improved shoulder function following breast cancer treatment in women who were overweight or obese, who were ethnically diverse, and who had breast cancer.

Feasibility of high intensity interval training in patients with breast Cancer undergoing anthracycline chemotherapy: a randomized pilot trial.

BACKGROUND: Anthracycline-based chemotherapy is associated with reduced cardiorespiratory fitness in breast cancer patients. High intensity interval training (HIIT) induces greater benefits on cardiorespiratory fitness than moderate continuous aerobic exercise in patients with heart failure. The study purpose was to determine whether a HIIT intervention is a feasible exercise strategy for breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control group (CON). Participants performed a maximal cycling fitness test to measure peak power output during maximal oxygen uptake (VO2max). The HIIT group participated in an 8-week HIIT intervention occurring 3 times weekly. Feasibility was calculated by computing (1) the average weekly minutes of HIIT over 8 weeks and (2) the number of sessions attended and multiplied by 100 (percentage of sessions). The intervention was considered feasible if more than 50% of participants completed both an average of 70% of weekly minutes (63/90 min) and attended 70% exercise sessions (17/24 sessions). RESULTS: Participants were 46.9 ± 9.8 (mean ± SD) years old, diagnosed with clinical stage II (30%) or III (63%) breast cancer. The average weekly minutes of exercise completed was 78 ± 5.1 out of 90 min. Twelve of 15 participants met both feasibility criteria, attending 19.2 ± 2.1 out of 24 sessions (82.3%). VO2max was maintained (19.7 ± 8.7 to 19.4 ± 6.6 ml/kg/min) in HIIT group (p = 0.94) while there was a significant decrease in VO2max (18.7 ± 7.1 to 16.1 ± 6.0 ml/kg/min) in CON group from baseline to 8 weeks (p = 0.001). CONCLUSIONS: HIIT is a feasible exercise intervention to maintain VO2max in breast cancer patients receiving anthracycline-based chemotherapy. TRIAL REGISTRATION: The protocol and informed consent were approved by the institutional IRB (HS-12-00227) and registered ( ClinicalTrials.gov NCT02454777; date of registration: May 272,015).

Effects of high-intensity interval training on vascular endothelial function and vascular wall thickness in breast cancer patients receiving anthracycline-based chemotherapy: a randomized pilot study.

PURPOSE: The purpose of this study was to determine the effects of an 8-week high-intensity interval training (HIIT) intervention on vascular endothelial function, measured as brachial artery flow-mediated dilation (baFMD), and vascular wall thickness measured by carotid intima media thickness (cIMT) in breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control groups (CON). The HIIT group participated in an 8-week HIIT intervention occurring three times per week on a cycle ergometer. The CON group was offered the HIIT intervention after 8 weeks. baFMD was measured from the brachial artery diameter at baseline (D0) and 1 min after cuff deflation (D1); percent change was calculated by measuring brachial artery diameter after cuff deflation relative to the baseline [baFMD = (D1 - D0)/D0 × 100]. The cIMT was obtained from the posterior wall of common carotid artery 10 mm below the carotid bulb. Paired t test and repeated measures ANCOVA were performed to assess changes in baFMD and cIMT. RESULTS: At baseline, the HIIT (n = 15) and CON (n = 15) groups did not differ by age (46.9 ± 9.8 years), BMI (31.0 ± 7.5 kg/m2), and blood pressure (123.4 ± 16.8/72.3.9 ± 5.6 mmHg). Post-exercise, baFMD significantly increased [4.3; 95% confidence interval (CI): (1.5, 7.0), p = 0.005] in HIIT versus CON group. cIMT did not significantly change [0.003, 95% CI - 0.004, 0.009), p = 0.40] in HIIT group, while IMT significantly increased from baseline to post-intervention (0.009, 95% CI 0.004, 0.010, p = 0.003) in CON group. CONCLUSION: This study may suggest that HIIT improved vascular endothelial function and maintained wall thickness in breast cancer patients undergoing anthracycline-based chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02454777.

The Impact of Obesity on Breast Cancer Diagnosis and Treatment.

PURPOSE OF REVIEW: Obesity is a recognized risk factor for the development of breast cancer and recurrence even when patients are treated appropriately. We reviewed the literature that addresses the impact of obesity on diagnosis and the individual therapeutic interventions, and present a summary of the findings. RECENT FINDINGS: Compared to non-obese women with breast cancer, obese women with breast cancer have a worse disease-free and overall survival despite appropriate local and systemic therapies. In brief, obese breast cancer patients experience more complications related to surgery, radiation, and chemotherapy. Further, obese patients are at increased risk for local recurrence compared to normal-weight women. Similarly, systemic chemotherapy is less effective, even when dosed appropriately on the basis of actual weight. Overall, endocrine therapy is less effective in obese women, and there is a suggestion that aromatase inhibitors may be selectively less effective than tamoxifen. Obese women are less likely to undergo breast reconstruction than normal-weight women, and those who do have surgery experience more surgical complications. The efficacy of cancer treatments is significantly lower in obese breast cancer survivors, posing greater challenges in patient care and disease management in this patient population. Further investigations are warranted to assess the effects on treatment outcomes and optimize therapeutic mechanisms in order to successfully target breast cancer associated with obesity.