Low Skeletal Muscle Density Research Articles

Low skeletal muscle density assessed by abdominal computerized tomography predicts outcome in children with chronic kidney disease.

Skeletal muscle loss and abnormal fat distribution are predictors of poor clinical outcomes in adults with chronic kidney disease (CKD). However, the relationship between body composition (muscle mass and adipose tissue) and prognosis in children with CKD has not been well elucidated. The retrospective single-center study enrolled children with CKD and healthy group who underwent an abdominal Computerized tomography (CT) examination and compared the body composition of the third lumbar spine (L3) between the two groups. We defined the primary outcome as hemodialysis, peritoneal dialysis, kidney transplantation, or death. Logistic regression analysis was applied to assess the connection between low skeletal muscle density (SMD) and clinical and demographic variables. Multivariate Cox regression analysis was used to evaluate the risk factors for progression to the primary outcome. Kaplan-Meier survival analysis was performed to compare the effect of different body composition on event-free survival rate. 32 patients with CKD [eGFR: 14.89(8.86, 29.88) (mL/min/1.73m2)] and 66 heathy subjects [eGFR: 135.72(121.70, 161.29) (mL/min/1.73m2)] were recruited in our study. From the assessment of body composition assessed by CT, skeletal muscle area, SMD and skeletal muscle index (SMI) in CKD group was lower than those in healthy group (P<0.05). On the other hand, visceral fat area and visceral fat index in CKD group were significantly higher than those in healthy group (P<0.05). In logistic regression analysis, triglyceride (OR: 8.635, 95%CI: 1.153-64.687) was independently associated with low SMD. After adjusting clinical data and body composition, high serum albumin (HR: 0.873, 95%CI: 0.798-0.955) and high SMD (HR: 0.895, 95%CI: 0.822-0.974) were protective factors for delaying renal failure. Based on the Kaplan-Meier analysis, only the group with low SMD had lower event-free survival in comparison to the reference group (P<0.05). These findings suggest that there is significant skeletal muscle loss and decrease in SMD in CKD children. Notably, low SMD is indicative of poor prognosis in CKD children.

Perioperative body composition changes and their clinical implications in patients with gastric cancer undergoing radical gastric cancer surgery: a prospective cohort study

BackgroundThis study aimed to investigate perioperative body composition changes and their clinical implications in patients undergoing radical gastric cancer surgery. MethodsPatient data are prospectively collected. Computed tomography scans were conducted within 30 days preoperatively and on the seventh postoperative day to assess skeletal muscle mass index (SMI), skeletal muscle density (SMD), and subcutaneous adipose tissue (SAT). Changes in these parameters between the 2 scans were quantified. Logistic regression analysis was used to determine factors influencing body composition loss and clinical outcomes. ResultsA total of 335 patients were included, showing varying degrees of decline in SMI, SMD, and SAT during the perioperative period. Multivariate analysis identified age ≥65 and low handgrip strength as independent risk factors for excessive SMI loss, whereas laparoscopic surgery served as a protective factor. For excessive SMD loss, independent risk factors included preoperative low SMD, Nutritional Risk Screening 2002 score ≥3, and hypoalbuminemia. Moreover, age ≥65 was identified as an independent risk factor for excessive SAT loss, whereas laparoscopic surgery remained protective. Excessive SMI and SMD loss are correlated with increased postoperative complications, prolonged hospital stays, and higher costs. Both excessive losses in SMI and SMD are independently associated with the incidence of postoperative complications. Further analysis revealed that excessive SMD loss (odds ratio, 3.164; 95% CI, 1.214–8.243) independently contributed to readmission risk. ConclusionExcessive SMI and SMD loss are associated with adverse clinical outcomes. It is essential to address and improve preoperative modifiable risk factors to reduce perioperative muscle loss and enhance prognosis.

Low muscle mass is associated with efficacy of biologics in Crohn's disease

BackgroundLow muscle mass (LMM) can be a frequent complication in Crohn’s disease (CD). We attempted to explore the effect of LMM on the efficacy of biologics in patients with CD. MethodsThe retrospective cohort study included moderate-to-severe CD patients treated with infliximab or ustekinumab, and appendicitis patients as control. The skeletal muscle area (SMA) of L3 was assessed to evaluate the patients’ muscle mass. After propensity score matching, the impact of LMM on drug efficacy was assessed in CD patients. ResultsA total of 269 patients with CD and 172 appendicitis patients were included. The CD group had lower skeletal muscle density and BMI, and a higher risk of developing LMM than the control group. BMI (OR = 0.48, p < 0.001) and previous use of biologics (OR = 2.94, p = 0.019) were found to be independently associated with LMM. LMM was found to be associated with a decrease in clinical response (at weeks 8-14), clinical remission (at weeks 8-14, 24-30 and 52) and biochemical remission (at week 52). At weeks 24-30 and 52, LMM was independently associated with loss of response (LOR). We found LMM could be a predictor of lower clinical remission at week 30, lower clinical remission at week 52 and higher LOR rate at week 30 in infliximab. While in ustekinumab, LMM was associated with lower endoscopic remission at week 24, biochemical remission at week 52 and a higher LOR rate at weeks 24 and 52. ConclusionsThe prevalence of LMM was higher in the CD group compared to the control group. For CD patients with LMM, the efficacy of infliximab and ustekinumab was relatively poor in both the short-term and long-term.

Relationship between CT-derived cervical muscle mass and quality, systemic inflammation, and survival in symptomatic patients undergoing carotid endarterectomy.

Sarcopenia appears to be associated with inferior outcomes in surgical conditions. Chronic systemic inflammation confers an inferior long-term prognosis in cardiovascular disease and is associated with the development of sarcopenia. The aim of this study was to describe the prognostic role of sarcopenia assessed using computed tomography (CT)-derived body composition analysis and systemic inflammation in patients undergoing carotid endarterectomy for symptomatic carotid stenosis. In this retrospective cohort study, patients undergoing carotid endarterectomy for symptomatic carotid stenosis between 1 January 2011 and 1 October 2021 at four referral centres were included. The C3 skeletal muscle index and C3 skeletal muscle density were recorded from preoperative CT images. Systemic inflammation was assessed using the preoperative systemic inflammatory grade (SIG). The primary outcome was overall mortality during the study interval. A total of 618 patients were included, with a median follow-up of 69 (interquartile range 34-85) months. On univariable analysis, age greater than or equal to 75 years (P < 0.001), American Society of Anesthesiologists (ASA) grade greater than II (P < 0.001), low C3 skeletal muscle index (P = 0.002), low C3 skeletal muscle density (P < 0.001), SIG greater than or equal to 2 (P < 0.001), and low L3 derived skeletal muscle index (P < 0.001) were associated with increased mortality, whereas body mass index greater than or equal to 25 kg/m2 was associated with decreased mortality (P = 0.023). On multivariable analysis, age 75 years or older (HR 2.17 (95% c.i. 1.58 to 2.97), P < 0.001), ASA grade greater than II (HR 2.06 (95% c.i. 1.35 to 3.12), P < 0.001), low C3 skeletal muscle density (HR 1.84 (95% c.i. 1.33 to 2.54), P < 0.001), and SIG greater than or equal to 2 (HR 1.63 (95% c.i. 1.33 to 1.99), P < 0.001) were independently associated with increased mortality. Cervical CT-derived muscle mass and density, and markers of systemic inflammation, such as systemic inflammatory grade, may be associated with an inferior long-term prognosis after carotid endarterectomy.

CT Derived Measurement of Body Composition: Observations from a Comparative Analysis of Patients with Colorectal and Lung Cancer

Background CT-derived measures of body composition have been shown to have prognostic value in patients with cancer. However, few studies have compared these observations across tumor types and stages of disease. The aim of the present study was to compare body composition measures between two types of cancers, i.e. colorectal cancer (CRC), which is less inflammatory and patients maintain body composition over a longitudinal study period, whereas lung cancer (LC) is proinflammatory and patients lose more fat and muscle mass using a standard methodology. Methods Clinicopathological characteristics, including those pertaining to nutritional risk/status and systemic inflammation in patients with colorectal cancer (CRC, n = 1047) and lung cancer (LC, n = 662), were compared. The CT image at L3 was used to assess body composition. Comparison of these cohorts was carried out using the chi-square test. Binary logistic regression analysis was performed to assess the impact of clinico-pathological variables on body composition, and scatter plots were used to examine the relationship between body mass index (BMI) and CT-derived measures of body composition. Results According to CT-derived body composition, high subcutaneous (SFI) and visceral fat index (VFI) were common (>70%) in both CRC and LC. Also, low skeletal muscle index (SMI) and density (SMD) were approximately 40–50% and 60–70% in both CRC and LC. Compared with CRC, patients with LC had a higher American Society of Anaesthesia (ASA) (P < 0.001), Malnutrition Universal Screening Tool (MUST) (P < 0.001), modified frailty index (mFI) (P < 0.001), modified Glasgow Prognostic Score (mGPS) (P < 0.001), and neutrophil lymphocyte ratio (NLR) (P < 0.001) scores. On binary logistic regression analysis, MUST, mFI, and NLR were predictors of subcutaneous adiposity (P < 0.05); type of cancer, MUST, and mFI were predictors of visceral obesity (P < 0.001); age, type of cancer, MUST, and mGPS were predictors of low SMI (P < 0.001); and age, type of cancer, mFI, and mGPS were predictors of low SMD (P < 0.05). There was a similar relationship between BMI and other measures of CT-derived body composition across two types of cancers. Conclusion Obesity and low skeletal muscle mass were common in both CRC and LC cohorts despite large differences in comorbidity, nutritional risk, systemic inflammation, and survival, even when normalized for TNM stage. These observations would support the hypothesis that, although prognostic, CT derived body composition analysis primarily reflects patient constitution rather than the effect of tumor stage in patients with cancer. The systemic inflammatory response, as evidenced by mGPS, can be considered as an important therapeutic target and loss of muscle mass in patients with advanced cancer is related to the systemic inflammatory response.

The chest CT perspective on sarcopenia: Exploring reference values for muscle mass quantity/quality and its application in elderly adults

ObjectiveTo determine reference values for diagnosing sarcopenia through chest CT scans and evaluate their suitability for use among the Chinese elderly population. MethodsChest CT scans were obtained from 500 healthy individuals aged 19–39. Skeletal muscle mass was assessed on chest CT at the level of T4 by the skeletal muscle area (T4SMA), skeletal muscle index (T4SMI), T12 erector spinae muscle area (T12ESMA), and T12 skeletal muscle index (T12SMI), as well as skeletal muscle density (SMD) at T4 and T12 levels. The diagnostic threshold for sarcopenia was defined as a gender-specific value below 2 SD of the mean value in the young group. These cutoff values were then applied to a group of older adults aged 65 and over. ResultsDiagnostic thresholds for low skeletal muscle in men were 110.05 cm², 36.01 cm²/m², 29.56 cm², and 9.65 cm²/m² for T4SMA, T4SMI, T12ESMA, and T12SMI, respectively. For women, the thresholds were: 69.93 cm², 26.51 cm²/m², 17.84 cm²/m², and 6.87 cm²/m², respectively. Diagnostic thresholds for low SMD were 38.63HU in men, 34.74 HU for women at T4 level. At T12 level, the cutoff values were 40.94 HU for men and 36.63 HU for women. Sarcopenia prevalence in men, defined by T4SMA, T4SMI, T12ESMA, and T12SMI cutoffs, was 35.6%, 18.9%, 36.7%, and 23.7%, respectively. In women, sarcopenia prevalence was 5.1%, 3.2%, 3.2%, and 1.9%, respectively. ConclusionThis study established reference values for sarcopenia diagnosis through chest CT scans among the Chinese population, highlighting the importance of utilizing chest CT scans for sarcopenia detection and muscle health monitoring in older adults.

53 Associations between body composition, ClearCode34, and clinical outcomes in localized clear cell renal cell carcinoma

Abstract Background Emerging evidence suggests that pre-surgical body composition is a prognostic factor for cancer outcomes. Lower skeletal muscle quantity and radiodensity have been associated with renal cell carcinoma (RCC) outcomes in other studies, while reports of the relationship between visceral adipose tissue and RCC outcomes have been inconsistent. Mechanisms underlying these associations are unclear but may relate to tumor biology. We leveraged a large molecular epidemiology study of localized clear cell renal cell carcinoma (ccRCC) patients to examine how pre-surgical body composition features were associated with survival post-nephrectomy as well as ClearCode34 status, a previously validated prognostic gene expression signature. Methods The RESOLVE study at Memorial Sloan Kettering Cancer Center is a retrospective study of 1,239 patients with stage I-III ccRCC undergoing nephrectomy without systemic therapy. Pre-surgical CT scans at the third lumbar vertebrae were segmented for the cross-sectional areas and radiodensities of skeletal muscle, subcutaneous adipose and visceral adipose tissues using Automatica software. Formalin-fixed, paraffin-embedded tumor tissue samples were available for 929 patients, which were sent to the University of North Carolina at Chapel Hill and assayed for gene expression. RNA was extracted from these samples and analyzed using the Nanostring nCounter system on a custom panel of 356 genes, including the 34 genes used in the ClearCode34 assay. Of the 929 patients with tumor tissue available, gene expression data from 837 patients (90.1%) passed RNA extraction and data QC. Samples were classified into either ccA or ccB ClearCode34 classes using a reference data set and PAM (prediction analysis of microarrays) centroid-based classification. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) within five years of diagnosis using Cox proportional hazards models for both body composition variables and ClearCode34 subtype. We also estimated odds ratios (ORs) and 95% CIs for associations between ClearCode34 subtype and body composition with logistic regression. All multivariable models were adjusted for age, sex, and all body composition variables. Results Of the 837 patients in our analytic sample, 219 (26%) had ccB tumors. Men, patients with high stage or grade tumors, and patients with chronic kidney disease prior to nephrectomy were more likely to present with ccB tumors. Lower skeletal muscle density (SMD) was significantly associated with lower five-year DFS [HR (95% CI) per 10 HU decrease in SMD: 1.7 (1.2, 2.3)]. While no other body composition features were significantly associated, we also observed non-significantly increased HRs for VATI and VATD [HR (95% CIs): 1.3 (0.8, 2.0) and 1.5 (0.9, 2.7), respectively]. ClearCode34 subtype was significantly associated with five-year DFS, where patients with ccB tumors had poorer DFS [HR (95% CI): 1.7 (1.1, 2.5)] compared to patients with ccA tumors. Notably, we observed no significant associations between any body composition feature and ClearCode34 in univariable analyses. However, in multivariable models that accounted for all body composition variables simultaneously as well as age and sex, lower SMD emerged as significantly associated with ccB subtype [OR (95% CI) per 10 HU decrease in SMD: 1.3 (1.0, 1.7)]. Conclusions Our findings suggest that the associations observed between body composition features and clinical outcomes in ccRCC may be related to tumor biology. Lower pre-surgical SMD, which may represent myosteatosis and metabolic dysregulation in ccRCC patients, was associated with both decreased five-year DFS and an increased likelihood of presenting with a more aggressive ccB tumor. Future studies should investigate body composition features related to ccRCC prognosis and additional markers of tumor biology, such as immune-related gene expression patterns, to extend these findings.

Lower skeletal muscle density and airway structure on computed tomography in asthma

BackgroundLower skeletal muscle density may reflect muscle adiposity and metabolic dysregulation that potentially impair disease control and lung function independent of high body mass index (BMI) in patients with asthma. ObjectiveTo investigate whether the lower density of pectoralis muscles (PMs) and erector spinae muscles (ESMs) on chest computed tomography was associated with airway structural changes in patients with asthma. MethodsConsecutive patients with asthma and healthy controls undergoing chest computed tomography were retrospectively analyzed. The ESM and PM density, areas of subcutaneous adipose tissue near the PM and epicardial adipose tissue, wall area percent of the airways, and airway fractal dimension (AFD) were quantified on computed tomography. ResultsThe study included 179 patients with asthma (52% women) and 88 controls (47% women). All the controls were 60 years old or younger. The PM and ESM density in female patients with asthma who were 60 years old or younger were significantly lower than those in controls after adjustment for BMI. In female patients with asthma at all ages, lower PM and ESM density (but not subcutaneous or epicardial adipose tissue area) was associated with greater wall area percent of the airways and lower AFD after adjusting for age, height, BMI, smoking status, blood eosinophil count, and oral corticosteroid use. The only association between ESM density and AFD was found in male patients with asthma. ConclusionLower skeletal muscle density may be associated with airway wall thickening and less complexity of the airway luminal tree in female patients with asthma.

Body composition measures as a determinant of alpelisib-related toxicity.

e13093 Background: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. Methods: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, and hospitalizations. Results: Sarcopenia was observed in half of the patients (n=19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P=0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P=0.04) and hospitalizations (P=0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. Conclusions: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to predict toxicity, allowing for personalized therapeutic observation and intervention.

The influence of sarcopenia and myosteatosis on severe laboratory toxicity and overall mortality in older adults with cancer receiving chemotherapy.

12131 Background: Older adults with cancer often present with suboptimal muscle quantity and quality prior to treatment due to disease-related catabolic effects combined with the aging process. Muscle catabolism is further exacerbated by cancer treatments leading to worse metabolic health, patient quality of life, and clinical outcomes. Our objective was to examine the impact of sarcopenia and myosteatosis on severe laboratory toxicity and overall mortality in older adults with cancer receiving chemotherapy. Methods: This was a retrospective cohort study of older adults who had undergone chemotherapy at the Princess Margaret Cancer Centre, Toronto, Canada from June 2015 to June 2022. A computed tomography scan after diagnosis but prior to treatment was used to assess skeletal muscle index (SMI) and skeletal muscle density (SMD) for each participant. Sarcopenia was defined as the presence of low muscle strength (grip strength &lt;35.5kg for males and &lt;20kg for females), low SMI, and low physical performance (walking speed &lt;0.8m/s or a total Short Physical Performance Battery score of ≤8) prior to chemotherapy initiation. Myosteatosis was assessed through SMD in Hounsfield Units using previously published cut-offs. Severe laboratory toxicity was defined as occurrence of a grade ≥3 adverse event per the Common Terminology Criteria for Adverse Events (version 4.0). Severe laboratory toxicity and overall mortality were assessed from treatment initiation until treatment termination or loss to follow up. Multivariable logistic regression was used to determine the role of sarcopenia and myosteatosis in predicting occurrence of severe laboratory toxicity. Multivariable Cox regression was used to assess the risk of overall mortality. Results: A total of 115 older adults (mean age: 77.1 y) were included, of whom 63.5% had metastatic disease. Sarcopenia was identified in 27% of the cohort, whereas 80% had myosteatosis. A total of 132 severe laboratory toxicities occurred during the study period in 41 participants (35.7%). Sarcopenia was a significant predictor of severe laboratory toxicity (adjusted odds ratio (aOR)=3.19, 95%CI= 1.19 to 8.52, p= 0.012) after adjusting for sex, body mass index, and hemoglobin. Myosteatosis was significantly associated with overall mortality (adjusted hazard ratio (aHR)= 2.51, 95%CI= 1.12-5.61, p=0.025) after adjusting for albumin, alkaline phosphatase, and treatment intent. Conclusions: Sarcopenia may be used to inform the risk of severe laboratory toxicity in older adults prior to chemotherapy. Pre-treatment myosteatosis defined by low SMD predicts overall mortality in the same cohort. Optimization of skeletal muscle health through targeted exercise and nutritional interventions may improve patient quality of life and clinical outcomes in older adults with cancer receiving chemotherapy.

Body composition measures as a determinant of Alpelisib related toxicity

BackgroundBody composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity.MethodsA retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, hospitalizations, time to treatment failure and overall survival.ResultsSarcopenia was observed in half of the patients (n = 19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P = 0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P = 0.04) and hospitalizations (P = 0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity.ConclusionBody composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to caution toxicity risk, allowing for personalized therapeutic observation and intervention.

Myosteatosis predicts postoperative complications and long-term survival in robotic gastrectomy for gastric cancer: A propensity score analysis.

Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy. This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3). Propensity score matching addressed potential confounding between myosteatosis and non-myosteatosis groups. Outcomes were postoperative complications, 30 days mortality, 30 days readmissions and survival. Myosteatosis was present in 33.6% of patients. Myosteatosis associated with increased overall (47.7% vs. 26.5%, p < 0.001) and severe complications (12.4% vs. 4.9%, p < 0.001). After matching, myosteatosis remained associated with increased overall complications, major complications, intensive care unit (ICU) transfer and readmission (all p < 0.05). Myosteatosis independently predicted overall [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.57-5.20, p = 0.001] and severe complications (OR = 4.81, 95% CI: 1.51-15.27, p = 0.008). Myosteatosis also associated with reduced overall (85.0% vs. 93.2%, p = 0.015) and disease-free survival (80.3% vs. 88.4%, p=0.029). On multivariate analysis, myosteatosis independently predicted poorer survival [hazard ratio (HR) = 2.83, 95% CI: 1.32-6.08, p=0.012] and disease-free survival (HR = 1.83, 95% CI: 1.01-3.30, p=0.032). Preoperative CT-defined myosteatosis independently predicts increased postoperative complications and reduced long-term survival after robotic gastrectomy for gastric cancer. Assessing myosteatosis on staging CT could optimize preoperative risk stratification.

CT-derived body composition: Differential association with disease, age and inflammation in a retrospective cohort study.

Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients. Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG). 1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38-1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09-1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66-2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55-7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08-1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03-1.37, p = 0.02) were independently associated with increased odds of low SMD. Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease.

The consistency of skeletal muscle mass measured by CT at L1 and L3 levels and the correlation of skeletal muscle density at L1 level with prognosis in dialysis patients

Objective: To investigate the consistency of skeletal muscle mass by CT at 1st lumbar vertebrae (L1) and 3rd lumbar vertebrae (L3) levels and the correlation of skeletal muscle density (SMD) at L1 level with prognosis in dialysis patients. Methods: A total of 1 020 patients who underwent initial dialysis and had CT examination data in four centers (Zhongda Hospital Affiliated to Southeast University, the Third Affiliated Hospital of Soochow University, Taizhou People's Hospital Affiliated to Nanjing Medical University and the Affiliated Hospital of Yangzhou University) from January 2014 to December 2019 were retrospectively collected. The skeletal muscle index (SMI) and SMD at L1 and L3 CT images were measured and calculated in patients with both L1 and L3 level CT images. The consistency of SMI and SMD at L1 and L3 levels was analyzed, and the cut-off value of SMI and SMD at L1 level for predicting all-cause mortality and their correlation with the prognosis of dialysis patients were studied. Cox regression model was used to analyze the risk factors for all-cause death and cardiac death. Results: A total of 383 patients had both L1 and L3 level images, including 233 males and 150 females. The average SMD value of 16 samples (4.2%) exceeded the 95% consistency limit range (-8.71 to 7.75 HU), and the average SMI value of 15 samples (3.9%) exceeded the 95% consistency limit range (-20.45 to 9.53 HU). The optimal cut-off value of SMD at L1 level for predicting all-cause mortality was 36.46 HU and the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.658 (95%CI: 0.596-0.721, P<0.001), with the sensitivity and specificity of 83.8% and 57.5%, respectively. SMI at L1 level was not significantly associated with all-cause mortality (P=0.299). Multivariate Cox regression analysis showed that low SMD at L1 level was associated with all-cause mortality (HR=2.861, 95%CI: 1.576-5.193, P=0.001) and cardiac death (HR=3.771, 95%CI:1.462-9.724, P=0.006). Conclusions: SMD at L1 levelis consistent with SMD at L3 level and can be used to evaluate muscle mass. Low SMD is a risk factor for mortality in dialysis patients.

Computed tomography-determined skeletal muscle density predicts 3-year mortality in initial-dialysis patients in China.

Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT-determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)-determined skeletal muscle mass and quality at L1 are associated with mortality in initial-dialysis patients. This 3-year multicentric retrospective study included initial-dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass [by skeletal muscle index, (SMI), cm2 /m2 ] and quality [by skeletal muscle density (SMD), HU]. Skeletal muscle measures at L1 were compared with those at L3. The sex-specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all-cause mortality. The outcomes were all-cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death. A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P<0.001), and that between L1 and L3 SMD was 0.90 (P<0.001). No significant association between L1 SMI and mortality was observed (P>0.05). Low L1 SMD (n=280, 57.73%) was diagnosed based on the optimal cutoff value (<39.56 HU for males and <33.06 HU for females). Multivariate regression analysis revealed that the low L1 SMD group had higher risks of all-cause death (hazard ratio 1.80; 95% confidence interval 1.05-3.11, P=0.034) and cardiac death (hazard ratio 3.74; 95% confidence interval 1.43-9.79, P=0.007). In initial-dialysis patients, there is high agreement between the L1 and L3 measures for SMI and SMD. Low SMD measured at L1, but not low SMI, is an independent predictor of both all-cause death and cardiac death.

Skeletal muscle morphology in patients receiving primary versus interval cytoreductive surgery for advanced high-grade serous ovarian cancer

ObjectiveOur primary aim was to compare muscle morphology (skeletal muscle mass and density) between patients who underwent primary cytoreductive surgery versus interval cytoreductive surgery for advanced high-grade serous ovarian cancer....

Poor Sit-to-Stand Performance in Adolescent and Young Adult Patients with Sarcoma.

Background: Adolescents and young adult (AYA) patients with sarcoma are at heightened risk of reduced physical capacity and disease-related weakness. Sit-to-stand (STS) performance correlates with lower extremity functionality and activities of daily living; however, little is known regarding the relationship between muscular status and STS performance in patients with sarcoma. This study assessed STS performance in patients with sarcoma and the association between STS performance and the skeletal muscle index (SMI) and skeletal muscle density (SMD). Methods: This study included 30 patients with sarcoma (15-39 years old) treated with high-dose doxorubicin. Patients performed the five-times-STS test before starting treatment and 1 year after the baseline test. STS performance was correlated with SMI and SMD. SMI and SMD were quantified using computed tomography scans taken at the level of the 4th thoracic vertebra (T4). Results: Mean performance on the STS test at baseline and 1 year was 2.2-fold and 1.8-fold slower than the age-matched general population, respectively. A lower SMI was associated with worse performance on the STS test (p = 0.01). Similarly, lower SMD at baseline was also associated with poorer STS performance (p < 0.01). Conclusion: Patients with sarcoma have very poor STS performance at baseline and 1 year, which was accompanied by low SMI and SMD at T4.The inability for AYAs to return to healthy age normative STS standards by 1 year may indicate a need for early interventions to enhance skeletal muscle recovery and promote physical activity during and after treatment.

The association of body composition with postoperative complications and length of hospital stay after radical or partial nephrectomy in patients with renal cell cancer: a multicenter population-based cohort study.

Body mass index (BMI) and body composition have been associated with postoperative outcomes in oncological surgery. Evidence in renal cell cancer (RCC) is limited and inconsistent. Therefore, we examined BMI and body composition in relation to postoperative outcomes in patients with RCC. We conducted a multicenter population-based historical cohort study including 801 patients with RCC treated with radical (79%) or partial (21%) nephrectomy between 2008-2012. Computed Tomography images at third lumbar vertebrae were assessed for skeletal muscle (SM) index, SM density, visceral adipose tissue (VAT) index and subcutaneous adipose tissue index (SATI). Multivariable multilevel logistic regression analyses were used to examine associations between BMI, body composition and (major) postoperative complications and extended length of hospital stay (LOHS) (≥7 days). Discrimination of models for major complications was compared using receiver operating characteristics (ROC) curves. In total, 19.6% of the patients had postoperative complications (6.2% Clavien grade ≥III) and 24.1% had extended LOHS. A 10-unit increase in SM density was inversely associated with extended LOHS [odds ratio (OR) 0.58; 95% confidence interval (95% CI): 0.44-0.78]. Associations of high BMI and lower SM density with risk of major complications and of higher VAT index with extended LOHS were also observed but statistical significance differed according to surgical procedure. Models predicting major complications with or without body composition parameters were not different. Lower SM density was associated with extended LOHS and non-significantly associated with higher risk of major postoperative complications. High BMI was associated with higher risk of major postoperative complications. Higher VAT was non-significantly associated with higher risk of extended LOHS. Results by surgical procedure were in the same direction but were only statistically significant for some subgroups. Validation of these results and investigation of the added value of body composition parameters to anatomic classification systems is needed.

Impact of low skeletal muscle mass and quality on clinical outcomes in patients with head and neck cancer undergoing (chemo)radiation.

The study aimed to explore the impact of low skeletal muscle mass and quality on survival outcomes and treatment tolerance in patients undergoing radical chemo-radiation therapy for head and neck cancer (HNC). This is significant given the growing interest in sarcopenia as a possible negative predictive/prognostic factor of disease progression and survival. From 2010 to 2017, 225 patients were included in the study. Pre-treatment computed tomography (CT) scans of HNC patients undergoing (chemo)radiation therapy were retrospectively reviewed. The skeletal muscle area, normalized for height to obtain the skeletal muscle index (SMI), the skeletal muscle density (SMD) and the intramuscular adipose tissue area (IMAT) were measured at the level of the L3 vertebra. Low SMD and low SMI were defined according to previously reported thresholds, while high IMAT was defined using population-specific cut-point analysis. SMI, SMD, and IMAT were also measured at the proximal thigh (PT) level and tested as continuous variables. Clinical morpho-functional parameters, baseline nutritional markers with a known or suspected impact on HNC treatment, clinical outcomes and sarcopenia were also collected. In multivariate analyses, adjusted by age, sex, stage, diabetes, body mass index (BMI), and weight loss, L3-SMI was not significantly associated with survival, while poor muscle quality was negatively associated with overall survival (OS) (HR = 1.88, 95% CI = 1.09-3.23, p = 0.022 and HR = 2.04, 95% CI = 1.27-3.27, p = 0.003, for low L3-SMD and high L3-IMAT, respectively), progression-free survival (PFS) (HR = 2.26, 95% CI = 1.39-3.66, p = 0.001 and HR = 1.97, 95% CI = 1.30-2.97, p = 0.001, for low L3-SMD and high L3-IMAT, respectively) and cancer-specific survival (CSS) (HR = 2.40, 95% CI = 1.28-4.51, p = 0.006 and HR = 1.81, 95% CI = 1.04-3.13, p = 0.034, for low L3-SMD and high L3-IMAT, respectively). Indices at the PT level, tested as continuous variables, showed that increasing PT-SMI and PT-SMD were significant protective factors for all survival outcomes (for OS: HR for one cm2/m2 increase in PT-SMI 0.96; 95% CI = 0.94-0.98; p = 0.001 and HR for one HU increase in PT-SMD 0.90; 95% CI = 0.85-0.94; p < 0.001, respectively). PT-IMAT was a significant risk factor only in the case of CSS (HR for one cm2 increase 1.02; 95% CI = 1.00-1.03; p = 0.046). In conclusion, pre-treatment low muscle quality is a strong prognostic indicator of death risk in patients affected by HNC and undergoing (chemo)radiotherapy with curative intent.

Longitudinal Assessment of Body Composition in Children with Lymphoma

Introduction: Five-year overall survival after childhood lymphoma has steadily increased; however, patients continue to experience chemotherapy-related toxicities (chemotoxicities). We have previously demonstrated that lower skeletal muscle density (SMD) at diagnosis is associated with greater odds of ≥grade 4 hematologic toxicity (Wadhwa, Cancer 2021) in children with lymphoma and rhabdomyosarcoma. Body composition is likely to change after cancer diagnosis; however, the longitudinal trajectory of body composition after cancer diagnosis and the association of the change in body composition with chemotoxicity remains unknown. We examined these gaps in knowledge in a cohort of 87 children with lymphoma (Hodgkin lymphoma [HL]: n=45 and non-Hodgkin lymphoma [NHL]: n=42) treated at a single center between 2000 and 2015. Methods: We used two consecutive computed tomography [CT] scans (first scan at diagnosis) to measure body composition (automated module [ABACS] of sliceOmatic [Tomovision, Quebec, Canada]). Using a single cross-sectional slice at the third lumbar vertebra, we calculated skeletal muscle index (SMI in cm2/m2), SMD (in Hounsfield Units) and height-adjusted total adipose tissue (hTAT, in cm2/m2) at both time points. Body-mass index (BMI, converted into percentile using CDC growth charts, BMI%ile) and body surface area (BSA) were also calculated at each time point. Demographics and clinical details including chemotoxicities (hematologic and non-hematologic, graded using CTCAE v5) during the first six months post-diagnosis were abstracted from electronic medical records. Changes in body composition from baseline to follow up CT scan were analyzed using generalized linear regression models adjusting for time between scans, age at cancer diagnosis, sex, race/ethnicity, primary cancer diagnosis and disease-specific risk stratification. Association between changes in body composition and chemotoxicity was evaluated using linear regression models. Results: Median age at diagnosis for the cohort was 12.9y (range 2-18.6). The majority of patients were non-Hispanic white (59.8%) and male (60.9%). Of the 87 patients with available baseline CT scan (scan 1), 62 (71%) had a follow-up scan (scan 2); the median interval between the two scans was 45 days (range, 8-207). Longitudinal change in body composition: Figure highlights changes in body composition (BMI%ile, BSA, SMI, SMD and hTAT) after adjusting for covariates. SMD showed a significant decline from scan 1 to scan 2 (βscan1_scan2= -4.8, SE=1.4, P=0.002). hTAT showed a non-significant increase (βscan1_scan2=6.4, SE=3.7, P=0.08), as did BMI%ile (βscan1_scan2=7.6, SE=4.5, P=0.1). BSA and SMI did not show a change between scans 1 and 2. Prevalence and risk of chemotoxicity: With a median of 158 days from diagnosis (range, 66-223), we observed ≥grade 4 hematologic toxicities in 60% of the cycles and ≥grade 3 non-hematologic toxicities in 23.6% of the cycles. Per unit decline in SMD between scan 1 and scan 2 was associated with an increase in risk of ≥grade 3 non-hematologic toxicity (β=1.37; 95%CI=0.2-2.4, P=0.02) after adjusting for sex and race/ethnicity. We did not identify an association between change in SMD and hematologic toxicities (β=0.2; 95%CI=-0.9-1.3, P=0.7). We did not identify any association between other body composition metrics and chemotoxicity. Conclusions: Children with lymphoma undergo a significant decline in SMD during early treatment, which may be associated with increased risk of chemotoxicities. Importantly, BSA (and hence chemotherapy dosing) remains stable, suggesting that other body composition metrics may need to be incorporated into chemotherapy dosing to optimize survival while reducing the risk of toxicity. Further validation of these findings in larger cohorts of uniformly treated patients with lymphoma across clinical trials is currently underway. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal