Effects of 6 months of abiraterone acetate (AA) on muscle and adipose mass in men with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 222-222 ◽  
Author(s):  
Samuel Craig Brondfield ◽  
Vivian K. Weinberg ◽  
Kathryn M. Koepfgen ◽  
Arturo Molina ◽  
Charles J. Ryan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Wasting ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Adipose Mass

222 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. Androgen deprivation therapy (ADT) has been shown to result in muscle wasting in prostate cancer pts. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential pts who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 pts were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, pts lost an average of 1.9 kg ± 1.9 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (−0.80 ± 1.71, p = 0.18) and total non-adipose mass (−1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (−0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in pts with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.

Effects of 6 months of abiraterone acetate (AA) on muscle and adipose mass in men with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15137-e15137
Author(s):  
Samuel Craig Brondfield ◽  
Vivian K. Weinberg ◽  
Kathryn M. Koepfgen ◽  
Arturo Molina ◽  
Charles J. Ryan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Wasting ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Adipose Mass

e15137 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. ADT has been shown to result in muscle wasting in prostate cancer patients. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential patients who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 patients were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, patients lost an average of 1.9 kg ± 3.6 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (-0.80 ± 1.71, p = 0.18) and total non-adipose mass (-1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (-0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in patients with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.

scholarly journals Passive repetitive stretching increases skeletal muscle mass and myofiber cross-sectional area in senescence-accelerated model mouse

2021 ◽  
Author(s):  
Yumin Wang ◽  
Satoshi Ikeda ◽  
Katsunori Ikoma
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Gastrocnemius Muscle ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Passive Stretching

Abstract Mechanical stimulation has benefits for muscle mass and function. Passive stretching is widely performed in clinical rehabilitation medicine. However, the hypertrophic effects of passive repetitive stretching on senescent skeletal muscles against muscle atrophy remain unknown. We used senescence-accelerated model SAM-P8 mice. The gastrocnemius muscle was passively repetitive stretched by manual ankle dorsiflexion for 15 min, 5 days a week for 2 weeks under deep anesthesia. We examined the effects of passive stretching on muscle mass, myofiber cross-sectional area, muscle fiber type and composition, satellite cell content, mRNA expression of the signaling pathways involved in muscle protein synthesis, muscle-specific ubiquitin ligases, and myogenic regulatory factors. The gastrocnemius muscle weight of the stretched side increased compared with that of the unstretched side. In addition to the increase in muscle mass, muscle fiber cross-sectional area of the stretched side was greater than that of the unstretched side. Passive repetitive stretching significantly increased the mRNA expression level of Akt, p70S6K, 4E-BP1, Myf5, myogenin, MuRF1. Passive repetitive stretching promoted skeletal muscle mass and myofiber cross-sectional area in SAM-P8 mice. These hypertrophic observations are attributable to the stretch-activated signaling pathways involved in protein turnover. These findings are applicable to clinical muscle strengthening and sarcopenia prevention.

scholarly journals Agent-based model illustrates the role of the microenvironment in regeneration in healthy and mdx skeletal muscle

2018 ◽  
Vol 125 (5) ◽  
pp. 1424-1439 ◽  
Author(s):  
Kelley M. Virgilio ◽  
Kyle S. Martin ◽  
Shayn M. Peirce ◽  
Silvia S. Blemker
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Muscle Wasting ◽  
Cross Sectional Area ◽  
Model Parameters ◽  
Sectional Area ◽  
Agent Based Model ◽  
Cross Sectional ◽  
Agent Based ◽  
Initial Injury

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease with no effective treatment. Multiple mechanisms are thought to contribute to muscle wasting, including increased susceptibility to contraction-induced damage, chronic inflammation, fibrosis, altered satellite stem cell (SSC) dynamics, and impaired regenerative capacity. The goals of this project were to 1) develop an agent-based model of skeletal muscle that predicts the dynamic regenerative response of muscle cells, fibroblasts, SSCs, and inflammatory cells as a result of contraction-induced injury, 2) calibrate and validate the model parameters based on comparisons with published experimental measurements, and 3) use the model to investigate how changing isolated and combined factors known to be associated with DMD (e.g., altered fibroblast or SSC behaviors) influence muscle regeneration. Our predictions revealed that the percent of injured muscle that recovered 28 days after injury was dependent on the peak SSC counts following injury. In simulations with near-full cross-sectional area recovery (healthy, 4-wk mdx, 3-mo mdx), the SSC counts correlated with the extent of initial injury; however, in simulations with impaired regeneration (9-mo mdx), the peak SSC counts were suppressed relative to initial injury. The differences in SSC counts between these groups were emergent predictions dependent on altered microenvironment factors known to be associated with DMD. Multiple cell types influenced the peak number of SSCs, but no individual parameter predicted the differences in SSC counts. This finding suggests that interventions to target the microenvironment rather than SSCs directly could be an effective method for improving regeneration in impaired muscle. NEW & NOTEWORTHY A computational model predicted that satellite stem cell (SSC) counts are correlated with muscle cross-sectional area (CSA) recovery following injury. In simulations with impaired CSA recovery, SSC counts are suppressed relative to healthy muscle. The suppressed SSC counts were an emergent model prediction, because all simulations had equal initial SSC counts. Fibroblast and anti-inflammatory macrophage counts influenced SSC counts, but no single factor was able to predict the pathological differences in SSC counts that lead to impaired regeneration.

AGE, OBESITY, SARCOPENIA, AND PROXIMITY TO DEATH EXPLAIN REDUCED MEAN MUSCLE ATTENUATION IN PATIENTS WITH ADVANCED CANCER

2014 ◽  
pp. 1-6
Author(s):  
N. ESFANDIARI ◽  
S. GHOSH ◽  
C.M.M. PRADO ◽  
L. MARTIN ◽  
V. MAZURAK ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Cancer Patients ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Time To Death ◽  
Computed Tomography Images ◽  
Muscle Attenuation

Background:Cancer cachexia is characterized by skeletal muscle loss. A feature of muscle wasting,reduction in the mean muscle attenuation from computed tomography images is believed to reflect pathologicalinfiltration of fat into muscle. It is a reported prognostic indicator in cancer patients. Objectives:To develop anexplanatory multivariate model of muscle attenuation of cancer patients incorporating age, sex, diseasecharacteristics, body composition. Time to death ≤92 days was included in the model as the demarcation of end-stage disease. Design:Multivariate general linear model regression analysis of total mean muscle attenuation andchange in muscle attenuation. Setting:Regional cancer center (Alberta, Canada). Participants: Patients withgastrointestinal and respiratory tract cancers (mean age 64±11 years, 44% female). Measurements: Total adiposetissue and skeletal muscle cross sectional area, and mean muscle attenuation at the 3rd lumbar vertebra wereassessed from baseline computed tomography (n=1719), and a subset with repeated measures (n=246 patientswith a total of 871 images). Results:At baseline, muscle attenuation associated with total skeletal muscle (β 0.09;95% CI 0.07 to 0.11; p<0.001) and adipose tissue (β -0.032; 95% CI -0.035 to -0.029; p<0.001) cross sectionalareas, age (β -0.28; 95% CI -0.32 to -0.24; p<0.001), time to death ≤92 days (β -1.9; 95% CI -3.1 to -0.7;p=0.003) and male sex (β -2.3; 95% CI –3.5 to -1.1; p<0.001). Change in muscle attenuation over time associatedwith total adipose tissue cross sectional area (β -0.008; 95% CI -0.012 to -0.004; p<0.001) and time to death ≤92days (β -1.6; 95% CI -3.0 to -0.2; p=0.03). Conclusions:The radiation attenuation of skeletal muscle is lowest inindividuals who are older, less muscular, have a higher fat mass and are within 92 days of death. Men had lowermuscle attenuation than women when controlled for other variables.

scholarly journals CT-Determined Sarcopenia in GLIM-Defined Malnutrition and Prediction of 6-Month Mortality in Cancer Inpatients

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2647
Author(s):  
Francisco José Sánchez-Torralvo ◽  
Ignacio Ruiz-García ◽  
Victoria Contreras-Bolívar ◽  
Inmaculada González-Almendros ◽  
María Ruiz-Vico ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Nutritional Assessment ◽  
Lumbar Vertebra ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Skeletal Muscle Index ◽  
Increased Risk ◽  
Muscle Cross Sectional Area

Our objective was to evaluate the clinical application of third lumbar vertebra (L3)-computer tomography (CT)-determined sarcopenia as a marker of muscle mass in cancer inpatients diagnosed with malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and to establish its association with 6-month mortality. Methods: This was an observational, prospective study in patients from an inpatient oncology unit. We performed a nutritional assessment according to GLIM criteria, including muscle cross-sectional area at L3 by CT and skeletal muscle index (SMI). Six-month mortality was evaluated. Results: A total of 208 patients were included. The skeletal muscle cross-sectional area at L3 was 136.2 ± 32.5 cm2 in men and 98.1 ± 21.2 cm2 in women. The SMI was 47.4 ± 12.3 cm2/m2 in men and 38.7 ± 8.3 cm2/m2 in women. Sarcopenia (low SMI) was detected in 59.6% of the subjects. Using SMI as a marker of low muscle mass in application of GLIM criteria, we found 183 (87.9%) malnourished patients. There were 104 deaths (50%) at 6 months. The deceased patients had a lower skeletal muscle cross-sectional area (112.9 ± 27.9 vs. 126.1 ± 37.8 cm2; p = 0.003) and a lower SMI (41.3 ± 9.5 vs. 45.7 ± 12.9 cm2/m2; p = 0.006). An increased risk of 6-month mortality was found in malnourished patients according to GLIM criteria using SMI (HR 2.47; 95% confidence interval 1.07–5.68; p = 0.033). Conclusions: Low muscle mass, assessed by L3-CT, was observed to affect more than half of cancer inpatients. The deceased patients at 6 months had a lower skeletal muscle cross-sectional area and SMI. Malnutrition according to GLIM criteria using CT-determined sarcopenia was shown to adequately predict 6-month mortality.

scholarly journals Depletion of Pre-Transplant Skeletal Muscle Is a Significant Poor Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3322-3322
Author(s):  
Yasuhiko Shibasaki ◽  
Kenta Kobayashi ◽  
Tatsuya Suwabe ◽  
Kyoko Fuse ◽  
Miwako Narita ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Muscle Mass ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Hematological Disease ◽  
Cross Sectional ◽  
Poor Prognostic Factor ◽  
Muscle Cross Sectional Area ◽  
Total Muscle

Introduction Depletion of skeletal muscle is a poor prognostic factor for patients with various malignancies; however its significance for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with hematological disease is unclear. Generally, muscle mass is measured by the methods established by the European Working Group on Sarcopenia in Older People, which require the use of dual energy X-ray absorptiometry or bioimpedance analysis, methods that are not performed in routine practice. Therefore, cross-sectional imaging using computed tomography (CT) has been suggested as an alternative method for analyzing muscle mass in clinical practice. Especially, lumbar total muscle cross-sectional area using CT, normalized for body height, which was named lumbar skeletal muscle mass index (SMI), is reported as an indicator of nutritional status, sarcopenia and cancer cachexia in patients with solid organ malignancy. Aims To clarify the usefulness of a pre-transplant lumber SMI as a prognostic indicator for allo-HCT patients. Methods Among 208 patients with hematological disease who underwent allo-HCT between 2006 and 2017 at our facility, 191 patients (95 males and 96 females) underwent CT scans for routine pre-transplant status assessment. Ninety patients had acute myeloid leukemia, 38 patients had acute lymphoblastic leukemia, 24 patients had myelodysplastic syndrome, 20 patients had malignant lymphoma, and 19 patients had other diseases. The median age of the patients was 42 years old (range: 16-66 years). Seventy-eight patients received myeloablative conditioning and the others received reduced intensity conditioning regimens. The number of patients in each HCT-comorbidity index (HCT-CI) risk group was as follows: low: 72, intermediate: 54 and high: 65. Axial images at the iliac crest were selected for analysis of lumber total muscle cross-sectional area (cm2). The rectus abdominus, psoas and paraspinal muscles were identified and quantified. Lumbar total muscle cross-sectional area was normalized for body height in meters squared (m2) and used to calculate lumbar SMI (cm2/m2). This study was performed in accordance with the Japanese Ethical Guidelines for Medical and Health Research Involving Humans and approved by the Ethical Committee of our facility. Results The median pre-transplant lumber SMI of the male patients was significantly higher than that of the female patients (42.7 (24.9-60.2) mm2/m2 vs. 31.9 (20.7-44.6) mm2/m2, p<0.01). We defined the cutoff value of lumber SMI as 42.7cm2/m2 for male and 31.9cm2/m2 for female patients. In the Kaplan-Meier estimate analysis, low lumber SMI was a significant poor prognostic factor for overall survival (p=0.016). In multivariate analysis using Cox regression model, adjusting for age, refined disease risk index, conditioning and HCT-CI, low lumber SMI was extracted as a significant poor prognostic factor for overall survival (hazard ratio 1.56, 95% confidence interval (CI) 1.03-2.36, p=0.036). By logistic regression analysis, adjusted odds ratio of 1-year non-relapse mortality for low lumber SMI was 2.47 (95% CI 1.13-5.41, p=0.024). Conclusion Low pre-transplant lumber SMI is a significant poor prognostic factor in allo-HCT, independent of other risk factors including HCT-CI and refined disease risk index in patients with hematological disease. It is affected by the high rate of non-relapse mortality in the early phase following allo-HCT in patients with low lumber SMI. Disclosures No relevant conflicts of interest to declare.

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