Indicators of mineral bone density in male patients with osteoarthritis of knee joint of elderly and old age depending on condition of muscular system

Objective. To evaluate bone mineral density (BMD) indices in elderly and old age male patients with knee osteoarthritis (OA) depending on the state of the muscular system.Subjects and methods. The trial enrolled 32 patients with knee OA. The mean age of the patients was 68.7 (66.1; 70.3) years. The diagnosis of knee OA was established according to the diagnostic criteria of the American College of Rheumatologists (ACR, 1991). For comparative analysis, all patients with knee OA were divided into 3 groups according to muscle condition (EWGSOP, 2010: muscle mass was assessed by multispiral computed tomography, muscle strength was measured using a wrist dynamometer, muscle function was examined using a battery of short tests): the 1st – 9 patients without sarcopenia, the 2nd – 11 patients with presarcopenia, and the 3rd – 12 patients with sarcopenia. BMD was assessed by dual-energy X-ray absorptiometry in the neck and proximal femur as a whole and in the lumbar spine.Results. Osteopenic syndrome in the study cohort was diagnosed in 23 (71,9%) patients: osteopenia – in 19 (59,4%) patients, osteoporosis – in 4 (12,5%). Normal BMD values were observed in 9 (28.1%) patients. Osteopenic syndrome was detected in patients with sarcopenia signifcantly more often compared to patients without sarcopenia (p > 0.05) and with presarcopenia (p = 0.05). BMD indices in patients with sarcopenia in the neck and proximal femur in general were statistically signifcantly lower than in patients without sarcopenia and with presarcopenia (p < 0.05). There was a direct correlation between total skeletal muscle area at the LIII level and densitometric indices of the femoral neck.Conclusions. Sarcopenia is associated with low BMD indices in the neck and proximal femur in general in elderly and senile male patients with knee OA

Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study

Body composition performed by computed tomography (CT) impacts on cancer patients’ prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p &lt; 0.001 and p &lt; 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07–6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31–25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52–2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33–1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

Abnormal body composition in patients with adrenal adenomas

Objective: Increased visceral fat and sarcopenia are cardiovascular risk factors that may explain increased cardiovascular morbidity and frailty in patients with adrenal adenomas. Our objective was to compare body composition measurement of patients with adrenal adenomas to referent subjects without adrenal disease Design: Cross-sectional study, 2014-2018 Methods: Participants were adults with nonfunctioning adrenal tumor (NFAT), mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS), and age, sex and body mass index 1:1 matched referent subjects without adrenal disorders. Main outcome measures were body composition measurements calculated from abdominal computed tomography imaging. Intraabdominal adipose tissue and muscle mass measurements were performed at the 3rd lumbar spine level. Results: Of 227 patients with adrenal adenomas, 20 were diagnosed with CS, 76 with MACS and 131 with NFAT. Median age was 56 years (range, 18-89), and 67% were women. When compared to referent subjects, patients with CS, MACS, and NFAT demonstrated a higher visceral fat (odds ratio (OR) of 2.2 [95% CI 0.9-6.5], 2.0 [1.3-3.2], and 1.8 [1.2-2.7] and a lower skeletal muscle area (OR of 0.01 [95% CI 0-0.09], 0.31 [0.18-0.49], and 0.3 [1.2-2.7]), respectively. For every 1 mcg/dL cortisol increase after overnight dexamethasone, visceral fat/muscle area ratio increased by 2.3 (P=0.02) and mean total skeletal muscle area decreased by 2.2cm2 (P=0.03). Conclusion: Patients with adrenal adenomas demonstrate a lower muscle mass and a higher proportion of visceral fat when compared to referent subjects, including patients with NFAT. Even a subtle abnormality in cortisol secretion may impact health of patients with adenomas.

Comparison between skeletal muscle and adipose tissue measurements with high-dose CT and low-dose attenuation correction CT of 18F-FDG PET/CT in elderly Hodgkin lymphoma patients: a two-centre validation

Objectives: High-dose CT (HDCT) is considered the gold-standard imaging for the measurements of skeletal muscle area (SMA), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) areas in the abdomen. These parameters may reflect sarcopenia, which can have a prognostic impact in several oncological diseases. The aim of this study was to compare the agreement of measurements of SMA, VAT, SAT and IMAT areas between HDCT and low-dose CT (LDCT) of 18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in elderly patients affected by Hodgkin lymphoma (HL). Methods: We retrospectively included 90 patients affected by HL who underwent baseline 18F-FDG-PET/CT and HDCT within a mean interval of 7 days. HDCT and LDCT images were analysed by two blinded observers using segmentation software (Slice-O-Matic, Tomovision) to quantify the areas. HDCT and LDCT measurements were compared using Bland–Altman plots and Passing-Bablock regression analyses. Pearson correlation coefficient (r) was used to correlate measurements from the two imaging modalities. Results: Comparison of HDCT and LDCT data demonstrated a strong correlation for measurement of VAT(r = 0.942, p < 0.0001), SAT (r = 0.894, p < 0.0001) and SMA (r = 0.934, p < 0.0001). Instead considering IMAT, correlation was good but less significant (r = 0.742). The mean difference between the two methods was found to be very small, with a difference of 1% for SAT,+6.1% for VAT,+2.5% for SMA and −1.9% for IMAT. Conclusion: LDCT of PET/CT is a safe, accurate and precise method for the measurements of skeletal muscle area, visceral and subcutaneous adipose tissue. Their measurements are reproducible and correlate closely with HDCT. Advances in knowledge: LLDCT of PET/CT is a safe and accurate method for the measurements of SMA, VAT and SAT; their measurements are closely correlated with HDCT. LDCT can be considered an accurate alternative tool for measuring abdominal fat and muscles in the clinical practice.

The effect of everolimus on body composition (BC) in patients with metastatic breast cancer (MBC).

e13026 Background: BC measurement can distinguish adipose tissue distribution, as well as the quantity and quality of muscle. Dysregulation in the mammalian target of rapamycin (mTOR) signaling pathway is associated with obesity and its related diseases. Everolimus (Eve), an mTOR inhibitor, is used in combination with endocrine therapy (ET) in hormone positive, HER2 negative (HR+/HER2-) MBC. However, there is limited data on the effect of Eve on BC. We aim to assess the effect of Eve on BC in patients (pts) with HR+/HER2- MBC. Methods: Pts with HR+/HER2- MBC who received Eve and ET between 2012 and 2019 at our institution were identified. We collected information about breast cancer diagnosis and treatment, weight (wt), body mass index (BMI), and computed tomography (CT). BC measurements; including skeletal muscle area (SMA), skeletal muscle density (SMD), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscle adiposity (MA); were analyzed at the L3 region on CT scans using Tomovision’s SliceOmatic Version 5.0. Total adipose tissue (TAT) was defined as SAT+VAT+MA. To isolate the effect of Eve on BC we also identified a cohort of pts who received ET only. We compared change in wt, BMI, and BC before and after 3 and 6 months of therapy. Wilcoxon signed rank test was used to compare BC parameters. Results: Our study included 42 pts who received Eve plus ET; 43% were Hispanic and 33% were Black. The median number of prior ET and chemotherapy lines were 1 and 0, respectively. The cohort who received ET alone included 63 patients. Median age was 68 years (interquartile range [IQR] 56-74) for the Eve and ET group and 67 years (IQR 55-74) for the ET only group (p = 0.74). Median baseline BMI was 25.8 kg/m2 (IQR 23.1-28.2) for the Eve and ET group and 28.5kg/m2 (IQR 24.2-30.8) for ET only (p = 0.08). Visceral disease was present in 24 (57%) pts on Eve and ET and 41 (65%) pts on ET only (p = 0.54). At month 3 of treatment with Eve and ET, there was a significant decrease in wt (-2.75kg, IQR -4.53-0.40, p < 0.005), BMI (-1.15kg/m2, IQR -1.71-0.14, p < 0.01), SAT (-21.93cm2, IQR -50.13-5.08, p < 0.01), and TAT (-22.34cm2, IQR -69.89-11.98, p = 0.02), which remained statistically significant at month 6 (wt: -5.70kg, IQR –7.75-1.83, p < 0.01; BMI: -2.3kg/m2, IQR -2.83-0.72, p < 0.01; SAT: -43.00cm2, IQR -73.81-10.69, p < 0.01; TAT: -32.56cm2, IQR –92.18-9.61, p = 0.03). These findings were not seen in pts who received ET only at 3 months (wt: 0.00kg, IQR –2.65-2.38, p = 0.99; BMI: 0.00kg/m2, IQR –1.07-0.91, p = 0.94; SAT: -1.82cm2, IQR -26.10-25.15, p = 0.59; TAT: 0.71cm2, IQR -44.39-27.43, p = 0.35), with similar results at 6 months. There were no statistically significant changes in VAT, SMA, SMD, or MA in both groups at 3 or 6 months. Conclusions: Everolimus is associated with decrease in SAT, with no significant change in VAT, SMA, or SMD. Further investigation is required to determine if these changes are associated with disease outcomes or everolimus toxicities.

Does oxaliplatin pharmacokinetics (PKs) explain associations between body composition and chemotherapy toxicity risk in older adults with gastrointestinal (GI) cancers?

3095 Background: Considerable inter-individual variability in oxaliplatin toxicity exists in older adults with GI cancers. Low lean body mass (LBM), commonly known as sarcopenia, influences toxicity and is not incorporated in standard body surface area-based dosing, which may affect oxaliplatin PK and tolerability, but has not been examined systematically. Methods: We examined oxaliplatin PK in 26 older adults (103 concentrations) with GI cancers (NCT03998202). Using the transverse section at L3, skeletal muscle area (SMA) and total adipose tissue (TAT) were quantified (Slice-O-Matic software) and LBM was calculated (LBM = 0.30 × SMA + 6.06). Noncompartmental methods (WinNonlin 7.0) were used for PK estimates and a one compartment population PK model (PopPK) was developed. Covariates included age, sex, LBM, TAT, weight, BMI, creatinine clearance, BSA, serum albumin, and body composition phenotypes (i.e. low LBM-high TAT, etc.). Results: Median age was 68yrs, 69% male, 88% white, and mostly colorectal (62%) and pancreatic (27%) cancers. There was wide variability in oxaliplatin volume of distribution (Vd: 12.5-259L), peak concentrations (Cmax: 404-3642ng/mL), and clearance (CL: 26.7-270L/hr). Participants with lower LBM had lower Vd (r = 0.51, p< 0.01); those with higher TAT had higher Cmax (r = 0.53, p< 0.01). Higher albumin was associated with lower Cmax (r = -0.49, p= 0.01) and higher CL (r = 0.47, p= 0.01). The phenotype of low LBM + high TAT had the lowest Vd (Relative Risk [RR] 0.32, p= 0.01), lowest CL (RR 0.39, p< 0.01), and highest Cmax (RR 3.3, 95% CI 1.7-6.5, p< 0.01). Eleven patients (44%) had grade 3-5 chemotoxicity. Vd (r = -0.46, p= 0.02) and Cmax (r = 0.44, p= 0.03) were associated with grade 3-5 chemotoxicity. The phenotype of low LBM + high TAT was associated with a 45% higher risk of grade 3-5 chemotoxicity (RR = 1.45, 95% CI 1.1-2.1, p= 0.04), while BSA was not (r = -0.04, p= 0.9). In the popPK model, body composition was associated with PK (TAT with Vd [p = 0.006] and CL [p < 0.001]), as was albumin (Vd p = 0.004; CL p = 0.002), while BSA was not (Vd p = 0.08; CL p = 0.2). Compared to BSA, an additional 11-17% in oxaliplatin PK variability was explained by LBM (11%), TAT (14%), and albumin (17%). Conclusions: Relationships between body composition, oxaliplatin PK, and severe chemotoxicity suggest the need for novel dosing strategies that incorporate body composition to reduce chemotoxicity and improve outcomes. Clinical trial information: NCT03998202.

A Deep Learning Model to Automate Skeletal Muscle Area Measurement on Computed Tomography Images

BackgroundMuscle wasting (Sarcopenia) is associated with poor outcomes in cancer patients. Early identification of sarcopenia can facilitate nutritional and exercise intervention. Cross-sectional skeletal muscle (SM) area at the third lumbar vertebra (L3) slice of a computed tomography (CT) image is increasingly used to assess body composition and calculate SM index (SMI), a validated surrogate marker for sarcopenia in cancer. Manual segmentation of SM requires multiple steps, which limits use in routine clinical practice. This project aims to develop an automatic method to segment L3 muscle in CT scans.MethodsAttenuation correction CTs from full body PET-CT scans from patients enrolled in two prospective trials were used. The training set consisted of 66 non-small cell lung cancer (NSCLC) patients who underwent curative intent radiotherapy. An additional 42 NSCLC patients prescribed curative intent chemo-radiotherapy from a second trial were used for testing. Each patient had multiple CT scans taken at different time points prior to and post- treatment (147 CTs in the training and validation set and 116 CTs in the independent testing set). Skeletal muscle at L3 vertebra was manually segmented by two observers, according to the Alberta protocol to serve as ground truth labels. This included 40 images segmented by both observers to measure inter-observer variation. An ensemble of 2.5D fully convolutional neural networks (U-Nets) was used to perform the segmentation. The final layer of U-Net produced the binary classification of the pixels into muscle and non-muscle area. The model performance was calculated using Dice score and absolute percentage error (APE) in skeletal muscle area between manual and automated contours.ResultsWe trained five 2.5D U-Nets using 5-fold cross validation and used them to predict the contours in the testing set. The model achieved a mean Dice score of 0.92 and an APE of 3.1% on the independent testing set. This was similar to inter-observer variation of 0.96 and 2.9% for mean Dice and APE respectively. We further quantified the performance of sarcopenia classification using computer generated skeletal muscle area. To meet a clinical diagnosis of sarcopenia based on Alberta protocol the model achieved a sensitivity of 84% and a specificity of 95%.ConclusionsThis work demonstrates an automated method for accurate and reproducible segmentation of skeletal muscle area at L3. This is an efficient tool for large scale or routine computation of skeletal muscle area in cancer patients which may have applications on low quality CTs acquired as part of PET/CT studies for staging and surveillance of patients with cancer.