Association of self-directed walking with toxicity moderation during chemotherapy for the treatment of early breast cancer.

BACKGROUND: In the field of exercise oncology, there is a need to quantify the potential benefits of moderate, self-directed physical activity during active treatment. In a pooled analysis of three identical single-arm intervention studies, we investigate the association of activity tracker steps with patient-reported toxicities during chemotherapy. METHODS: Women with early breast cancer who were enrolled in the intervention studies reported their symptom severity every 2-3 weeks throughout chemotherapy, and daily steps were documented through a Fitbit activity tracker. Relative risks (RR) and 95% confidence intervals (CI) were calculated using Poisson regression models with robust variance. For outcomes significant in unadjusted models, adjusted RRs were calculated controlling for race, age, and education level. Tracker step cut point (high step, low step) was determined by the means. Cumulative incidence functions of moderate, severe, and very severe (MSVS) symptoms were estimated using the Kaplan-Meier method and compared using a Cox proportional hazard model. RESULTS: In a sample of 283 women, mean age was 56 years and 76% were White. Mean tracker-documented steps/week were 29,625, with 55% walking below the mean (low step) and 45% above (high step). In multivariable analysis, high step patients had lower risk for fatigue [RR 0.83 (0.70, 0.99)] (p = 0.04), anxiety [RR 0.59 (0.42, 0.84)] (p = 0.003), nausea [RR 0.66 (0.46, 0.96)] (p = 0.03), depression [RR 0.59 (0.37, 0.03)] (p = 0.02), and ≥ 6 MSVS symptoms [RR 0.73 (0.54, 1.00)] (p = 0.05) and had 36% lower risk for dose reductions [RR 0.64 (95% CI 0.43, 0.97)] (p = 0.03). CONCLUSION: Self-directed walking at a rate of at least 30,000 steps/week may moderate the severity of treatment side effects during chemotherapy for early breast cancer. TRIAL NUMBERS: NCT02167932, NCT02328313, NCT03761706.

Patient-reported treatment toxicity and adverse events in Black and White women receiving chemotherapy for early breast cancer.

PURPOSE: It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I-III) receiving current chemotherapy regimens and, in turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization. METHODS: Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher's exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes RESULTS: In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White, p = .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (p = .05) and diabetes (p = .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White, p = .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen. CONCLUSION: Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.

Myosteatosis evaluation using erector spinae and psoas muscles to predict adverse events during adjuvant chemotherapy for breast cancer.

BACKGROUND: Myosteatosis (intramuscular adiposity) is predictive of chemotherapy toxicity in women undergoing adjuvant chemotherapy for breast cancer (BC). We evaluated a novel, user-friendly and cost-effective technique utilizing a Picture Archiving and Communication Systems (PACS) tool that is readily available in the electronic medical record (EMR), using skeletal muscle density (SMD) to detect myosteatosis and then compared PACS results with those derived from widely used body composition software (SliceOMatic, QC, Canada). METHODS: Using retrospective data from a sample of women with early BC (Stage I-III) who had CT scan and received chemotherapy. Pearson correlation coefficients were used to compare SliceOMatic with PACS results. Associations of PACS results with chemotherapy-related adverse events were evaluated using multivariable (MV) log-binomial models adjusted for age, race, BMI, anthracycline-based therapy, and number of comorbidities. RESULTS: In 338 patients, mean age was 51, 32% were non-white, and 40% had obesity (BMI ≥ 30 kg/m2). Correlation of SMD using SliceOMatic whole muscle measurements with PACS psoas muscle was 0.76 (p < .0001) and with PACS erector spinae muscle 0.91 (p < .0001). Using PACS psoas muscle, myosteatosis was associated with any adverse event [RR 1.66, CI 1.22-2.26 (p < .0001)], dose reduction [RR 1.63, CI 1.01-2.65 (p = .05)], and early treatment discontinuation [RR 2.14, CI 1.10-4.14 (p = 0.03)]. Using PACS erector spinae muscle, myosteatosis was associated any adverse event [RR 1.59, CI 1.11-2.27 (p = 0.01)] and dose reduction [RR 1.91, CI 1.07-3.42 (p = .03)]. CONCLUSION AND RELEVANCE: Skeletal muscle density measures using PACS correlated strongly with SliceOMatic results and both are similarly predictive of chemotherapy-related adverse events.

The association of body composition parameters and adverse events in women receiving chemotherapy for early breast cancer.

BACKGROUND: Body composition metrics as predictors of adverse events are a growing area of interest in oncology research. One barrier to the use of these metrics in clinical practice is the lack of standardized cut points for identifying patients with at-risk body composition profiles. We examined the association of chemotherapy adverse events with several body composition measures, using alternative cut points from published studies. METHODS: This is a retrospective study of women diagnosed with early breast cancer (EBC). Axial computerized tomography (CT) images from lumbar L3 segments were analyzed for the following body composition measures: myosteatosis (low Skeletal Muscle Density/SMD), sarcopenia (low Skeletal Muscle Index/SMI), and high Visceral Adipose Tissue (VAT). Adverse events during chemotherapy were dose reduction, early treatment discontinuation, and hospitalization. Log-binomial modeling was used to evaluate associations between body composition measures at different cut points with adverse events, adjusting for age, race, Body Mass Index/BMI, and comorbidities. Relative risks were reported as the measure of association. RESULTS: In a sample of 338 women, mean age was 51, 14% were age 65 or older, 32% were non-white, 40% had obesity (/BMI ≥ 30 kg/m2), and mean number of comorbidities was 1.56. In multivariable analysis (MV), all three SMD cut points for myosteatosis had significant associations with total number of adverse events, as well as different cut points having significant associations with either dose reduction, early treatment discontinuation or hospitalization. SMI and VAT were not significant in the MV analysis; however, in some models, age and total comorbidities were significant for adverse events. CONCLUSIONS: Among CT-derived measures of body composition, myosteatosis determined at any of three SMD cut points was associated with total and individual adverse events during chemotherapy for early breast cancer.

Association of body composition with function in women with early breast cancer.

BACKGROUND: Advances in breast cancer research are making treatment options increasingly effective and reducing mortality. Body composition is an example of a prognostic tool that can help personalize breast cancer treatments and further increase their effectiveness. In this study, we examine the association of several body composition measures with comorbidities, physical function, and quality of life. METHODS: This study is a cross-sectional analysis of 99 women with early breast cancer scheduled for chemotherapy. Univariate regression models were used to identify significant associations of body composition metrics with patient demographics, clinical characteristics, measures of physical function, and patient-reported outcomes (PRO)s. Multivariable modeling was used to evaluate associations adjusted for age. RESULTS: Median age was 58 (range 24-83), 27% were non-white, and, 47% were obese (≥ 30 kg/m2). Increasing age was associated with lower Skeletal Muscle Density (SMD) (p = 0.0001), lower Skeletal Muscle Gauge (SMG) (p = 0.0005), and higher Visceral Adipose Tissue (VAT) (p < 0.0001). In patients with a prolonged Timed Up and Go tests (> 14 s), mean VAT was 57.87 higher (p = 0.004), SMD 5.70 lower (p = 0.04), and SMG 325.4 lower (p = 0.02). For each point of higher performance on the Short Physical Performance Battery (SPPB), VAT decreased 12.24 (p = 0.002) and SMD rose 1.22 (p = 0.02). In multivariable analysis adjusting for age, the association of TUG > 14 with higher VAT remained significant (p = 0.02). CONCLUSIONS: Suboptimal body composition prior to treatment is associated poor physical function and may be an indicator of clinical importance.

Myosteatosis and prognosis in cancer: Systematic review and meta-analysis.

BACKGROUND: The evidence that body composition parameters influence multiple cancer outcomes is rapidly expanding. Excess adiposity deposits in muscle tissue, termed myosteatosis, can be detected in CT scans through variations in the density of muscle tissues (Hounsfield Units). Patients with similar muscle mass but different amounts of intramuscular adipose infiltration have increased chemotherapy toxicity, time to tumor progression and other adverse outcomes among different cancer types. Our review examines the impact of myosteatosis on overall survival (OS) in patients with cancer. METHODS: A systematic search of the literature was conducted on PubMed/ MEDLINE, Cochrane CENTRAL, and EMBASE. Meta-analysis was conducted using a random-effects model. Risk of bias was evaluated using the Newcastle-Ottawa Quality assessment for cohort studies, funnel plot (publication bias), and GRADE summary of findings tool from Cochrane. RESULTS: A total of 4880 articles were screened from which 40 articles selected, including 21,222 patients. The overall mean proportion of patients with myosteatosis was 48 % (range 11-85 %). Using skeletal muscle density (SMD), patients classified as having myosteatosis had 75 % greater mortality risk compared to non-myosteatosis patients (HR 1.75 95 % CI 1.60-1.92, 40 studies) (p < .00001) (i2 = 62 %). Specifically, myosteatosis was prognostic for worse OS in patients with gynecological, renal, periampullary/pancreatic, hepatocellular, gastroesophageal, and colorectal carcinoma, and lymphomas. CONCLUSION: Our analysis of the literature shows that cancer patients with myosteatosis have shorter survival. Our findings suggest that in oncological practice, muscle density assessment is valuable as a prognostic parameter.

Muscle composition and outcomes in patients with breast cancer: meta-analysis and systematic review.

PURPOSE: Breast cancer is the most common cancer and leading cause of cancer death in women. Body composition parameters, especially those related to muscle, have become a growing focus of cancer research. In this review, we summarize the literature on breast cancer and muscle parameters as well as combine their outcomes for overall survival (OS), time to tumor progression (TTP), and chemotherapy toxicity in a meta-analysis. METHODS: A systematic search of the literature for randomized controlled trials and observational studies was conducted on MEDLINE, Cochrane CENTRAL, and EMBASE through May 1, 2019. Two reviewers independently searched and selected. Meta-analysis was conducted using a random-effects model. The risk of bias was evaluated using the Newcastle-Ottawa quality assessment for cohorts and GRADE summary of findings tool from Cochrane. RESULTS: A total of 754 articles were screened from which 6 articles and one abstract were selected. Using skeletal muscle index (SMI), patients classified as sarcopenic had a 68% greater mortality risk compared to non-sarcopenic patients (HR 1.68 95% CI 1.09-2.59, 5 studies) (p = .02) (i2 = 70%). Low muscle density was not predictive of OS (HR 1.44 95% CI 0.77-2.68, 2 studies) (p = .25) (i2 = 87%). Patients with sarcopenia (56%) had more grade 3-5 toxicity compared to non-sarcopenic (25%) (RR 2.17 95% CI 1.4-3.34, 3 studies) (p = .0005) (i2 = 0%). TTP was nearly 71 days longer in advanced/metastatic patients classified as non-sarcopenic compared to patients with sarcopenia (MD - 70.75 95% CI - 122.32 to - 19.18) (p = .007) (i2 = 0%). CONCLUSION: Our synthesis of the literature shows that patients with sarcopenia have more severe chemotherapy toxicity as well as shorter OS and TTP, and that low muscle density is prognostic of OS for women with metastatic breast cancer. Our findings suggest that in clinical practice, body composition assessment is valuable as a prognostic parameter in breast cancer.

Correction to: Measuring and understanding adherence in a home-based exercise intervention during chemotherapy for early breast cancer.

In the original publication, the sixth author name was published incorrectly as A. Wood. The correct author name should read as W. A. Wood.

Measuring and understanding adherence in a home-based exercise intervention during chemotherapy for early breast cancer.

PURPOSE: Ensuring and measuring adherence to prescribed exercise regimens are fundamental challenges in intervention studies to promote exercise in adults with cancer. This study reports exercise adherence in women who were asked to walk 150 min/week throughout chemotherapy treatment for early breast cancer. Participants were asked to wear a FitbitTM throughout their waking hours, and Fitbit steps were uploaded directly into study computers. METHODS: Descriptive statistics are reported, and both unadjusted and multivariable linear regression models were used to assess associations between participant characteristics, breast cancer diagnosis, treatment, chemotherapy toxicities, and patient-reported symptoms with average Fitbit steps/week. RESULTS: Of 127 women consented to the study, 100 had analyzable Fitbit data (79%); mean age was 48 and 31% were non-white. Mean walking steps were 3956 per day. Nineteen percent were fully adherent with the target of 6686 steps/day and an additional 24% were moderately adherent. In unadjusted analysis, baseline variables associated with fewer Fitbit steps were: non-white race (p = 0.012), high school education or less (p = 0.0005), higher body mass index (p = 0.0024), and never/almost never drinking alcohol (p = 0.0048). Physical activity variables associated with greater Fitbit steps were: pre-chemotherapy history of vigorous physical activity (p = 0.0091) and higher self-reported walking minutes/week (p < 0.001), and higher outcome expectations from exercise (p = 0.014). Higher baseline anxiety (p = 0.03) and higher number of chemotherapy-related symptoms rates "severe/very severe" (p = 0.012) were associated with fewer steps. In multivariable analysis, white race was associated with 12,146 greater Fitbit steps per week (p = 0.004), as was self-reported walking minutes prior to start of chemotherapy (p < 0.0001). CONCLUSIONS: Inexpensive commercial-grade activity trackers, with data uploaded directly into research computers, enable objective monitoring of home-based exercise interventions in adults diagnosed with cancer. Analysis of the association of walking steps with participant characteristics at baseline and toxicities during chemotherapy can identify reasons for low/non-adherence with prescribed exercise regimens.

Weight gain during adjuvant endocrine treatment for early-stage breast cancer: What is the evidence?

Most breast cancer (BC) tumors are early stage and hormone receptor positive, where treatment generally includes adjuvant endocrine treatment (ET). Oncology providers and women about to start ET want to know about side effects, including potential weight gain. The aim of this study was a literature review to identify the independent effect of ET on post-diagnosis weight gain. Weight gain is of concern with regard to potential associations with BC recurrence, mortality, and quality of life in survivorship. We conducted a targeted review of the literature. Thirty-eight studies met our inclusion criteria. Patient-reported weight gain ranged widely from 18 to 52 % of patients in Year 1 and from 7 to 55 % in Year 5. Some studies reported categories of weight change: lost weight (9-17 %), stable weight (47-64 %), and gained weight (27-36 %). Most studies comparing ET with placebo or tamoxifen with AI reported no significant difference between the two groups. Wide-ranging and inconsistent results point to the need for further research to clarify annual weight change (loss, gain, stability) from BC diagnosis through 5 years of ET and beyond. There is also a need to explore weight change by type of ET and to explore risk factors for weight gain in women on ET, including tumor type, sociodemographic characteristics, and health behaviors. More specific information is needed to identify high-risk BC patients who could be targeted for weight management interventions.

Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain.

AIM: To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. METHODS: We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. RESULTS: Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). CONCLUSION: Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).

Sweating and skin temperature responses of normal and anhidrotic horses to intravenous adrenaline.

Anhidrosis has been recognised for over half a century, but despite some excellent epidemiological studies, there has been little progress in understanding the aetiology of the condition. Using a modified ventilated capsule, we obtained dynamic, quantitative data on sweating responses in anhidrotic horses and normal sweating controls from the same environment. Ten horses with current seasonal anhidrosis and 10 matched normal sweating controls were selected. Each horse was given two 10 min infusions of 1 and 2 micrograms/kg/min adrenaline, separated by at least 6 h. Sweating responses and skin temperatures on the neck and gluteal region were measured. Plasma and sweat for analysis of total protein and electrolytes and plasma for analysis of adrenaline were collected. Anhidrotic horses produced significantly less sweat, had lower initial and peak sweat rates and a greater neck:gluteal ratio for sweat production. Plasma adrenaline at rest or at the time of peak sweating rate was not different between groups. In nearly three-quarters of the anhidrotic horses, the shape of the sweat rate against time curve was different compared to controls. Volume of sweat produced was significantly correlated with skin temperature on the neck of controls and anhidrotic horses and on the gluteal region of controls, but not anhidrotic horses. Plasma total protein and electrolyte concentrations were not different between groups. There were significant differences in sweat electrolyte concentrations between controls and anhidrotic horses. These differences were reduced when sweat electrolytes were expressed per g of total protein, and no differences existed when expressed as g/m2. This study has provided insight into the response of anhidrotic horses to beta 2 adrenergic stimulation and may be a useful technique to investigate this condition.

Brachygnathia in horses: 20 cases (1979-1989).

The medical records of 20 horses admitted to the veterinary medical center with a diagnosis of brachygnathia over a 10-year period (1979 to 1989) were reviewed. The study included 18 foals and 2 adult horses. Males were affected 5.7 times more frequently than females. The amount of disparity between the mandible and premaxilla varied between 0.75 and 3 cm. Sixteen foals were treated surgically with the temporary application of premaxillary tension band devices. Thirteen of the 16 surgical cases were available for follow-up evaluation. All of the surgically treated animals had improved incisive occlusion, and 6 foals had complete resolution of the deformity with corrections ranging from 0.75 to 2.5 cm. Complete correction of the malocclusion was more likely to occur if foals were treated when they were less than or equal to 6 months old. The average amount of correction achieved in foals treated when they were less than or equal to 6 months old was 1.5 cm. (range, 0.75 to 2.5 cm). Foals treated, when they were 7 to 12 months old, had an average of 0.6 cm of reduction in the malocclusion (range, 0.25 to 1 cm). Implant failure was the most common complication and occurred in 9 of the 13 foals treated surgically.

Vascular response of the equine radius to cerclage devices.

The arterial blood supply to the diaphysis of the radius, and the vascular reaction when three cerclage devices (cerclage wire, Parham-Martin band, and a partially contacting band) were applied 2 cm apart, were studied in six adult ponies. The opposite radial diaphysis served as the control. Ponies were euthanatized at weeks 4 and 8. A centrifugal blood flow pattern was demonstrated by microangiography. Larger numbers of medullary arteries exist in equine than in canine and human long bones. Changes in centrifugal blood supply were not identified beneath any of the cerclage devices.

Atresia of the right atrioventricular orifice with complete transposition of the great arteries in a horse.

The heart of a 6-week old Arabian filly with a history of poor health and exercise intolerance revealed at postmortem examination, multiple cardiac malformations which included atresia of the right atrioventricular orifice (tricuspid atresia, with associated atrial and ventricular septal defects), complete transposition of the great arteries, anomalous drainage of the venae cavae and coronary sinus into the left atrium, coarctation of the aorta, and a small but patent ductus arteriosus. The course of blood through the heart was suggested and discussed.

Mononuclear phagocytes of transport-stressed horses with viral respiratory tract infection.

Twelve horses comprised 3 treatment groups; all horses in 2 of the groups had recently been transported and had clinical and laboratory evidence of respiratory tract infection, with equine influenza type 2 virus being the principal pathogen. Mononuclear phagocytes and other leukocytes from blood, lung, and peritoneal cavity were studied in phagocytosis and erythrocyte-antibody (EA) rosette assays. Total numbers of pulmonary alveolar macrophages were increased over control values in bronchoalveolar lavage (BAL) fluid of group 3 horses after recovery from influenza (P less than 0.02), whereas the increase in neutrophils in the fluid of those horses approached significance. Lymphocytes in BAL fluid of group 3 horses (after recovery from influenza) were in larger proportion than those in fluid of group 1 horses during acute influenza (P less than 0.05). Pulmonary alveolar macrophages of group 1 horses formed a lower percentage of EA rosettes than did those of controls (P less than 0.01) or group 3 horses (P less than 0.02). The differential counts of peritoneal macrophages and neutrophils in horses of groups 1 and 3 were virtually identical at the first collection, but differed from controls at the second collection 4 weeks later; peritoneal macrophages were reduced (P less than 0.01), whereas peritoneal neutrophils were increased (P less than 0.01). Peritoneal macrophages and peritoneal neutrophils of horses with acute influenza were phagocytic in larger proportion than were those in controls at both collection times (P less than 0.01 and P less than 0.01 for peritoneal macrophages, and P less than 0.01 and P less than 0.05 for peritoneal neutrophils, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)