Evaluation of the impact of cachexia on clinical outcomes in aggressive lymphoma.

Cancer cachexia is a state of involuntary weight loss and altered body composition triggered by an underlying malignancy. We sought to correlate measures of cachexia with clinical outcomes in aggressive lymphomas and to identify biological pathways involved in the cachexia phenotype for possible druggable targets. Radiographic measures of cachexia were collected in a retrospective cohort of 109 patients with aggressive B-cell lymphoma and followed for clinical outcome. We found males with sarcopenia had reduced progression-free survival (5·4 vs. 72·3 months, P < 0·0005) and overall survival (OS; 30·2 months vs. not reached, NR, P = 0·02); males with adipopenia also had decreased OS (21·6 months vs. NR, P = 0·04). A trend for increased OS was observed in female sarcopenics only (32·8 months vs. NR, P = 0·08). Additionally, we analysed a prospective cohort of 14 patients for differences in circulating molecular targets involved in various biological pathways. There was a significant correlation with cachexia for reduced serum levels of mediators within the glucose utilization [insulin -like growth factor (IGF)-binding protein 6, P = 0·04; IGF-1, P = 0·02], inflammation (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells; LIGHT, P = 0·005), and energy intake/expenditure (leptin, P = 0·004). We conclude that cachexia in patients with aggressive lymphomas has sex-specific prognostic utility and correlates with measurable changes in metabolism and immune function.

Prognostic impact of skeletal muscle assessed by computed tomography in patients with acute myeloid leukemia.

Skeletal muscle atrophy and loss of adipose tissue, referred to as sarcopenia and adipopenia, respectively, are often observed in cancer patients. We investigated the impact of sarcopenia and adipopenia on clinical outcomes in 90 adult patients with newly diagnosed acute myeloid leukemia (AML) who received induction chemotherapy. Computed tomography (CT) before treatment revealed sarcopenia in 39 patients (43%) and adipopenia in 35 patients (39%). We analyzed the treatment efficacy of induction chemotherapy and survival outcomes. Three-year overall survival (OS) was 35% in the sarcopenic group and 67% in the non-sarcopenic group (P < 0.001). Three-year OS was 33% in the adipopenic group and 67% in the non-adipopenic group (P < 0.005). Multivariate analysis showed an association between sarcopenia and lower OS (hazard ratio, 2.27; 95% confidence interval, 1.11-4.79; P < 0.05), with other prognostic factors of performance status > 2 (P < 0.05) and adverse cytogenetic risk (P < 0.05). In elderly patients over 60 years old, 3-year OS was 0% for the sarcopenic group and 49% for the non-sarcopenic group (P < 0.0005). These results indicate the prognostic values of sarcopenia in adult patients with AML.

Prognostic impact of fat tissue loss and cachexia assessed by computed tomography scan in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

OBJECTIVES: Approximately 30% of DLBCL patients are older than 70 yr. This study evaluated the prognostic impact of a cachexia score (CS) including fat tissue loss (adipopenia) and sarcopenia as assessed by computed tomography (CT scan) in elderly DLBCL patients treated with chemotherapy and rituximab (R). METHODS: This retrospective analysis included 80 DLBCL patients older than 70 yr treated with R-CHOP or R-miniCHOP. Skeletal muscle (SM) and visceral (V) and subcutaneous (S) adipose (A) tissues were measured by analysing CT images at the third lumbar (L3) level. RESULTS: The median age of the patients was 78 yr. Forty-four and 46 patients were considered sarcopenic and adipopenic, respectively. The median progression-free survival (PFS) was 13.6 months in the adipopenic group and 49.4 months in the non-adipopenic group [hazard ratio (HR) = 2.27; 95% confidence interval (CI): 1.3-4; P = 0.0042]. The median overall survival (OS) was 25.7 months in the adipopenic group and 57.1 months in the non-adipopenic group (HR = 1.93; 95% CI: 1.05-3.55; P = 0.0342). A two-point CS including adipopenia and sarcopenia was created and defined two distinct risk groups with differences in outcomes that were highly significant. The CS was predictive of the prognosis in a multivariate analysis including body mass index (BMI) (< or ≥ 25 kg/m(2) ), age (< or ≥ 80 yr), international prognostic index (IPI) and albuminaemia (HR = 3.67; 95% CI = 1.93-6.97; P < 0.0001). CONCLUSION: A CS including sarcopenia and adipopenia, assessed by a single CT scan slice, predicts outcome independent of BMI and the IPI.

Adipopenia is associated with osteoporosis in community-dwelling non-underweight adults independent of sarcopenia.

The effect of fat deficit on bone metabolism is understudied. This study showed that low body fat percent (adipopenia) in non-underweight community adults was associated with elevated odds of osteoporosis independent of low lean mass, highlighting potential clinical importance of adipopenia as an osteoporosis risk factor particularly in older adults. PURPOSE: Although underweight is risk factor for osteoporosis, the association of low body fat percent (adipopenia) with osteoporosis in non-underweight adults remains unclear. METHODS: Among individuals aged ≥ 50 years with body mass index ≥ 18.5 kg/m2 in the Korean National Health and Nutrition Examination Survey 2008-2011, appendicular lean mass (ALM) and body fat percent (BFP) were measured using dual-energy x-ray absorptiometry. Low lean mass was defined as ALM/height2 < 7.0 kg/m2 and < 5.4 kg/m2 in men and women, respectively. Osteoporosis was defined as a bone mineral density (BMD) T-score ≤ -2.5 at the lumbar spine, femoral neck, or total hip. Participants were grouped into adipopenia (BFP < 17% in men; < 30%, in women; 1 standard deviation below the mean), normal, and obesity (BFP > 30% in men; > 40% in women) groups. RESULTS: Of the 5,830 participants (women 50.2%, mean age 63.9 years), 793 had adipopenia. The adipopenia group had a higher prevalence of osteoporosis (31%) than the normal (21%) or obesity groups (27%; p < 0.001). The presence of adipopenia was associated with 61% elevated odds of prevalent osteoporosis (p < 0.001) independent of low lean mass and covariates, which remained robust using different thresholds for adipopenia. Individuals with adipopenia and low lean mass had 3.5-fold elevated odds of osteoporosis compared to those with normal lean mass and fat percent. The association between adipopenia and osteoporosis was stronger in older women compared to middle-aged women (OR 1.93 vs. 0.99, P for interaction = 0.023). CONCLUSION: Adipopenia was associated with osteoporosis in non-underweight adults, independent of low lean mass and covariates.

Association Between Pelvic Bone Computed Tomography-Derived Body Composition and Patient Outcomes in Older Adults With Proximal Femur Fracture.

OBJECTIVE: To investigate the association between pelvic bone computed tomography (CT)-derived body composition and patient outcomes in older adult patients who underwent surgery for proximal femur fractures. MATERIALS AND METHODS: We retrospectively identified consecutive patients aged ≥ 65 years who underwent pelvic bone CT and subsequent surgery for proximal femur fractures between July 2018 and September 2021. Eight CT metrics were calculated from the cross-sectional area and attenuation of the subcutaneous fat and muscle, including the thigh subcutaneous fat (TSF) index, TSF attenuation, thigh muscle (TM) index, TM attenuation, gluteus maximus (GM) index, GM attenuation, gluteus medius and minimus (Gmm) index, and Gmm attenuation. The patients were dichotomized using the median value of each metric. Multivariable Cox regression and logistic regression models were used to determine the association between CT metrics with overall survival (OS) and postsurgical intensive care unit (ICU) admission, respectively. RESULTS: A total of 372 patients (median age, 80.5 years; interquartile range, 76.0-85.0 years; 285 females) were included. TSF attenuation above the median (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.41-4.05), GM index below the median (adjusted HR, 2.63; 95% CI, 1.33-5.26), and Gmm index below the median (adjusted HR, 2.33; 95% CI, 1.12-4.55) were independently associated with shorter OS. TSF index (adjusted odds ratio [OR], 6.67; 95% CI, 3.13-14.29), GM index (adjusted OR, 3.45; 95% CI, 1.49-7.69), GM attenuation (adjusted OR, 2.33; 95% CI, 1.02-5.56), Gmm index (adjusted OR, 2.70; 95% CI, 1.22-5.88), and Gmm attenuation (adjusted OR, 2.22; 95% CI, 1.01-5.00) below the median were independently associated with ICU admission. CONCLUSION: In older adult patients who underwent surgery for proximal femur fracture, low muscle indices of the GM and gluteus medius/minimus obtained from their cross-sectional areas on preoperative pelvic bone CT were significant prognostic markers for predicting high mortality and postsurgical ICU admission.

Prognostic Impact of Quantifying Sarcopenia and Adipopenia by Chest CT in Severe Aplastic Anemia Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation.

RATIONALE AND OBJECTIVES: To investigate the prognostic role of chest CT-defined sarcopenia and adipopenia in severe aplastic anemia (SAA) patients treated with hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: This was a retrospective study of 123 consecutive SAA patients treated with HSCT. CT imaging was performed to quantify the pectoralis muscle (including major and minor) index (PMI) and the corresponding subcutaneous adipose tissue index (SAI). Sarcopenia and adipopenia were defined as PMI and SAI lower than the respective sex-specific medians. Correlations of the PMI and SAI with anthropometric indexes were calculated. Transplant-related outcomes were compared between the sarcopenia and adipopenia groups. Prognostic factors for overall survival (OS) and fail-free survival (FFS) were identified by Cox regression and were used to create a nomogram. The accuracy of the nomogram was evaluated by ROC curves. RESULTS: PMI showed good correlation with BMI and fat-free mass index (p < 0.001). SAI correlated with BMI and fat mass index (p < 0.001). The sarcopenia group (47.2%) had a significantly worse 3-year OS (90.8% vs. 77.6%, p = 0.045) and 3-year FFS (89.2% vs. 74.1%, p = 0.035) than the nonsarcopenia group. Sarcopenia status and diagnostic category were used to construct the nomogram of OS, as these were independent prognostic factors in the multivariate analysis for OS and FFS (p < 0.05). The area under the curve of the nomogram at one year and three years was 0.801 and 0.721, respectively. CONCLUSION: Sarcopenia indicates a poor prognosis in SAA patients undergoing HSCT. Intensive supportive care is suggested for SAA patients with sarcopenia before transplantation.

High prevalence of pre-existing sarcopenia in critically ill patients with hematologic malignancies admitted to the intensive care unit for sepsis or septic shock.

BACKGROUND & AIMS: We aimed to evaluate body composition (BC) by computed tomography (CT) in hematologic malignancy (HM) patients admitted to the intensive care unit (ICU) for sepsis or septic shock. METHODS: We retrospectively assessed BC and its impact on outcome of 186 patients at the 3rd lumbar (L3) and 12th thoracic vertebral levels (T12) using CT-scan performed before ICU admission. RESULTS: The median patient age was 58.0 [47; 69] years. Patients displayed adverse clinical characteristics at admission with median [q1; q3] SAPS II and SOFA scores of 52 [40; 66] and 8 [5; 12], respectively. The mortality rate in the ICU was 45.7%. Overall survival rates at 1 month after admission in the pre-existing sarcopenic vs. non pre-existing sarcopenic patients were 47.9% (95% CI [37.6; 61.0]) and 55.0% (95% CI [41.6; 72.8]), p = 0.99), respectively, at the L3 level and 48.4% (95% CI [40.4; 58.0]) vs. 66.7% (95% CI [51.1; 87.0]), p = 0.062), respectively, at the T12 level. CONCLUSIONS: Sarcopenia is assessable by CT scan at both the T12 and L3 levels and is highly prevalent in HM patients admitted to the ICU for severe infections. Sarcopenia may contribute to the high mortality rate in the ICU in this population.

Diagnosis and Pathogenesis of Sarcopenia in Chronic Liver Disease Using Liver Magnetic Resonance Imaging.

Background Liver magnetic resonance imaging (MRI) is rarely used to evaluate sarcopenia. This study sought to develop new diagnostic criteria for MRI in Asians and investigate the relationship between adipopenia and sarcopenia using MRI proton density fat fraction (PDFF), which is correlated with body fat mass. Methodology This study included 512 patients with chronic liver disease (CLD) who underwent magnetic resonance elastography (MRE). The following parameters were assessed: paraspinal muscle area/height index (PSMI) measured at the level of the superior mesenteric artery and PDFF. The cutoff PSMI and PDFF values for the diagnosis of sarcopenia and adipopenia, respectively, were determined using receiver operating characteristic analysis of Asians with low body mass index. Results Among patients with CLD, the prevalence rates of sarcopenia and adipopenia were 25% and 17%, respectively. We found that sarcopenia increased from stage 3 fibrosis and was inversely correlated with steatosis grade. Multivariate analysis found that MRI-PDFF was associated with sarcopenia. The Kaplan-Meier method in cirrhosis (n = 122) showed that the non-sarcopenia, sarcopenia, and sarcopenia/adipopenia groups had three-year survival rates of 97%, 55% (p < 0.01), and 23%, respectively. The Cox proportional hazards model identified the Child-Pugh score and sarcopenia/adipopenia as independent prognostic factors. Conclusions The new diagnostic criteria for sarcopenia confirmed that the prognosis of cirrhosis can be stratified. Furthermore, sarcopenia with adipopenia was shown to be a phenotype of severe sarcopenia in cirrhosis, and screening for sarcopenia should include cases in the precirrhotic stage.

Machine learning-featured Secretogranin V is a circulating diagnostic biomarker for pancreatic adenocarcinomas associated with adipopenia.

Background: Pancreatic cancer is one of the most fatal malignancies of the gastrointestinal cancer, with a challenging early diagnosis due to lack of distinctive symptoms and specific biomarkers. The exact etiology of pancreatic cancer is unknown, making the development of reliable biomarkers difficult. The accumulation of patient-derived omics data along with technological advances in artificial intelligence is giving way to a new era in the discovery of suitable biomarkers. Methods: We performed machine learning (ML)-based modeling using four independent transcriptomic datasets, including GSE16515, GSE62165, GSE71729, and the pancreatic adenocarcinoma (PAC) dataset of the Cancer Genome Atlas. To find candidates for circulating biomarkers, we exported expression profiles of 1,703 genes encoding secretory proteins. Integrating three transcriptomic datasets into either a training or test set, ML-based modeling distinguishing PAC from normal was carried out. Another ML-model classifying long-lived and short-lived patients with PAC was also built to select prognosis-associated features. Finally, circulating level of SCG5 in the plasma was determined from the independent cohort (non-tumor = 25 and pancreatic cancer = 25). We also investigated the impact of SCG5 on adipocyte biology using recombinant protein. Results: Three distinctive ML-classifiers selected 29-, 64- and 18-featured genes, recognizing the only common gene, SCG5. As per the prediction of ML-models, the SCG5 transcripts was significantly reduced in PAC and decreased further with the progression of the tumor, indicating its potential as a diagnostic as well as prognostic marker for PAC. External validation of SCG5 using plasma samples from patients with PAC confirmed that SCG5 was reduced significantly in patients with PAC when compared to controls. Interestingly, plasma SCG5 levels were correlated with the body mass index and age of donors, implying pancreas-originated SCG5 could regulate energy metabolism systemically. Additionally, analyses using publicly available Genotype-Tissue Expression datasets, including adipose tissue histology and pancreatic SCG5 expression, further validated the association between pancreatic SCG5 expression and the size of subcutaneous adipocytes in humans. However, we could not observe any definite effect of rSCG5 on the cultured adipocyte, in 2D in vitro culture. Conclusion: Circulating SCG5, which may be associated with adipopenia, is a promising diagnostic biomarker for PAC.

Prediction of clinical outcomes through assessment of sarcopenia and adipopenia using computed tomography in adult patients with acute myeloid leukemia.

Sarcopenia and adipopenia have prognostic significance in cancer. Analysis of a single abdominal computed tomography (CT) section at the third lumbar vertebra has been widely adopted for this purpose. The approach using a single section at the first lumbar vertebra level (L1) may extend clinical viability. We evaluated the prognostic value of sarcopenia and adipopenia assessed using a CT section at L1 in acute myeloid leukemia (AML). Data from 96 patients with available imaging were retrospectively reviewed. Patients with sarcopenia (37.5%) had significantly worse overall survival (OS) (median 17.8 months vs. not reached, p = 0.038) and treatment-related mortality (TRM) (22.2% vs. 3.0%, p = 0.0019) than those without. Subcutaneous adipopenia (51.0%) was significantly associated with inferior OS (median 17.9 months vs. not reached, p = 0.0011), progression-free survival (PFS) (median 6.2 months vs. not reached, p = 0.004), and TRM (16.3% vs. 4%, p = 0.024). Visceral adipopenia (30.2%) was associated with poor OS (12.7 vs. 31.7 months, p = 0.0055) and PFS (3.7 vs. 31.7 months, p = 0.003). Multivariable analyses found sarcopenia, subcutaneous adipopenia and visceral adipopenia were significant negative prognostic factors for OS. Sarcopenia and adipopenia assessed using a single CT section at the L1 level are useful in predicting the prognosis of AML.