Body composition measures as a determinant of Alpelisib related toxicity.

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, hospitalizations, time to treatment failure and overall survival. 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. CONCLUSION: 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 caution toxicity risk, allowing for personalized therapeutic observation and intervention.

Negative prognostic impact of sarcopenia before and after neoadjuvant chemotherapy for pancreatic cancer.

OBJECTIVES: To elucidate the prognostic impact of sarcopenia before and after neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). METHODS: We retrospectively studied 75 consecutive PC patients who underwent neoadjuvant gemcitabine plus S-1 combination therapy followed by pancreatectomy between 2008 and 2016. According to the skeletal muscle volume index (SMI), the patients were divided into the muscle attenuation group (MAG) and normal group (NG) before or after NAC. Prognostic factors for overall survival (OS) were analyzed by Cox proportional hazards models. RESULTS: The MAG showed significantly poorer OS than the NG before and after NAC. Pre-NAC, median OS was 20.0 months in the MAG versus 49.0 months in the NG (p = 0.006). Post-NAC, median OS was 21.3 months in the MAG versus 48.8 months in the NG (p = 0.014). Multivariate analysis, excluding muscle attenuation after NAC because of confounding factors and lower hazard ratio (2.08, 95% confidence interval: 1.14-3.78, p = 0.016) than that before NAC (2.14, 1.23-3.70, p = 0.007) by univariate analysis, revealed the following independent prognostic factors: muscle attenuation pre-NAC (2.25, 1.26-4.05, p = 0.007); borderline resectability (1.96, 1.04-3.69, p = 0.038); operative blood loss (2.60, 1.38-4.88, p = 0.003); and distant metastasis (3.31, 1.40-7.82, p = 0.006). CONCLUSIONS: Sarcopenia before and after NAC for PC is suggested to be a poor prognostic factor, with a stronger impact before than after NAC.

Impact of Muscle Measures on Outcome in Patients Receiving Endocrine Therapy for Metastatic Breast Cancer: Analysis of ECOG-ACRIN E2112.

BACKGROUND: Observational data investigating the relationship between body habitus and outcomes in breast cancer have been variable and inconsistent, largely centered in the curative setting and focused on weight-based metrics. This study evaluated the impact of muscle measures on outcomes in patients with metastatic breast cancer receiving endocrine-based therapy. METHODS: Baseline CT scans were collected from ECOG-ACRIN E2112, a randomized phase III placebo-controlled study of exemestane with or without entinostat. A CT cross-sectional image at the L3 level was extracted to obtain skeletal muscle mass and attenuation. Low muscle mass (LMM) was defined as skeletal muscle index <41 cm2/m2 and low muscle attenuation (LMA) as muscle density <25 HU or <33 HU if overweight/obese by body mass index (BMI). Multivariable Cox proportional hazard models determined the association between LMM or LMA and progression-free survival (PFS) and overall survival (OS). Correlations between LMM, LMA, and patient-reported outcomes were determined using 2-sample t tests. RESULTS: Analyzable CT scans and follow-up data were available for 540 of 608 patients. LMM was present in 39% (n=212) of patients and LMA in 56% (n=301). Those with LMA were more likely to have obesity and worse performance status. LMM was not associated with survival (PFS hazard ratio [HR]: 1.13, P=.23; OS HR: 1.05, P=.68), nor was LMA (PFS HR: 1.01, P=.93; OS HR: 1.00, P=.99). BMI was not associated with survival. LMA, but not LMM, was associated with increased frequency of patient-reported muscle aches. CONCLUSIONS: Both low muscle mass and density are prevalent in patients with hormone receptor-positive metastatic breast cancer. Muscle measures correlated with obesity and performance status; however, neither muscle mass nor attenuation were associated with prognosis. Further work is needed to refine body composition measurements and select optimal cutoffs with meaningful endpoints in specific breast cancer populations, particularly those living with metastatic disease.

The impact of sarcopenia on prognosis of patients with pancreatic cancer: A systematic review and meta-analysis.

OBJECTIVE: To summarize recent findings on the association of low skeletal muscle mass and muscle quality with overall survival and recurrence-free survival in patients with pancreatic cancer. METHODS: A systematic search was conducted using Medline (via PubMed), Embase and Scopus databases for observational studies reporting on the overall survival and recurrence-free survival. Pooled effect sizes were reported as hazards ratio along with 95% confidence intervals. RESULTS: A total of 34 studies were included. Low skeletal muscle index (indicating muscle mass) was associated with poor overall survival (hazards ratio: 1.50; 95% confidence interval: 1.34, 1.67) and lower recurrence-free survival (hazards ratio: 1.28, 95% confidence interval: 1.15, 1.43). Low skeletal muscle attenuation (indicating muscle quality) was associated with poor overall survival (hazards ratio: 1.32; 95% confidence interval: 1.05, 1.66). Recurrence-free survival was similar in patients with low and normal/high skeletal muscle attenuation (hazards ratio: 1.12, 95% confidence interval: 0.89, 1.40). CONCLUSION: Both low skeletal muscle mass and poor muscle quality are associated with poor long-term survival. Low skeletal muscle index, but not low skeletal muscle attenuation, are associated with poor recurrence-free survival.

Modified Glasgow prognostic score (mGPS) is correlated with sarcopenia and dominates the prognostic role of baseline body composition parameters in advanced gastric and esophagogastric junction cancer patients undergoing first-line treatment from the phase III EXPAND trial.

BACKGROUND: Sarcopenia represents an established adverse prognostic factor in cancer patients. Consequently, different means to counteract sarcopenia have been proposed to improve cancer treatment. Computed tomography (CT)-based measurements, also labor intensive, are well validated for the analysis of sarcopenia. As inflammation plays a key role in the development of sarcopenia, we here studied the role of the modified Glasgow prognostic score (mGPS), consisting of inflammation parameters plasma C-reactive protein (CRP) and albumin, to predicting sarcopenia and adipose tissue-related body composition (BC) parameters at baseline and their changes during treatment and to analyze its prognostic role in conjunction with BC parameters. PATIENTS AND METHODS: CT measurements of BC parameters were carried out at baseline and week 12 in patients with advanced gastric or esophagogastric junction cancer from the phase III EXPAND trial, undergoing first-line platinum-fluoropyrimidine chemotherapy. mGPS was calculated from baseline CRP and albumin plasma levels. Pearson correlation and Cox regression analyses were carried out. RESULTS: mGPS is strongly prognostic for overall survival (OS). Baseline mGPS is significantly correlated with baseline mean muscle attenuation (MA; P < 0.0001). Baseline mGPS did not predict a decline in muscle or adipose tissue parameters during 12 weeks of treatment and a decline in muscle or adipose tissue parameters was not prognostic for OS. MA lost its prognostic role for OS when mGPS or CRP was entered into the Cox models. Eastern Cooperative Oncology Group performance status together with CRP or mGPS remained the sole baseline prognostic factors for OS. CONCLUSIONS: Our findings support a model where tumor-mediated inflammatory response represents a strong prognostic factor, which is causally related to sarcopenia, but with no direct causal path from sarcopenia to survival. Therefore, therapeutic targeting of systemic inflammation should be further explored as a promising strategy to improve both sarcopenia and the efficacy and tolerability of cancer treatment.

The impact of nutritional risk factors and sarcopenia on survival in patients treated with pelvic exenteration for recurrent gynaecological malignancy: a retrospective cohort study.

PURPOSE: The aim of the present study is to investigate the prognostic significance of nutritional risk factors and sarcopenia on the outcome of patients with recurrent gynaecological malignancies treated by pelvic exenteration. METHODS: We retrospectively evaluated muscle body composite measurements based on pre-operative CT scans, nutritional risk factors as assessed by a validated pre-operative questionnaire, and clinical-pathological parameters in 65 consecutive patients with recurrent gynaecological malignancies, excluding ovarian cancer, treated by pelvic exenteration at the Royal Marsden Hospital London. Predictive value for postoperative morbidity was investigated by logistic regression analyses. Relevant parameters were included in uni- and multivariate survival analyses. RESULTS: We found only (1) low muscle attenuation (MA)-an established factor for muscle depletion-and (2) moderate risk for malnutrition to be independently associated with shorter overall survival (p = 0.006 and p = 0.008, respectively). MA was significantly lower in overweight and obese patients (p = 0.04). Muscle body composite measurements were not predictive for post-operative morbidity. CONCLUSION: The study suggests that pre-operative low MA and moderate risk for malnutrition are associated with shorter survival in patients with recurrent gynaecological malignancies treated with pelvic exenteration. Further studies are needed to validate these findings in larger cohorts.

Relationship between nonalcoholic fatty liver disease and muscle quality as well as quantity evaluated by computed tomography.

BACKGROUND & AIMS: Sarcopenia is reported to be associated with nonalcoholic fatty liver disease (NAFLD). Evaluation of skeletal muscle attenuation and area by computed tomography (CT) may represent a promising approach for evaluation of the risk of NAFLD. We examined the association between skeletal muscle characteristics and NAFLD and investigated the combined effect of these parameters on the prevalence of NAFLD. METHODS: In this cross-sectional study, we analysed data from 632 middle-aged Japanese subjects without daily alcohol intake (353 men and 279 women) from a cohort of employees undergoing annual health examinations. The cross-sectional skeletal muscle area was evaluated on the basis of CT data at the level of the third lumbar vertebrae, and the skeletal muscle index (SMI) and density (SMD) were calculated. The subjects were divided into four study groups according to their SMI and SMD relative to median values. RESULTS: One hundred forty men and forty-three women had NAFLD. Total SMI (odds ratio [OR] per 1.0 cm2 /kg/m2 increase 0.43, 95% confidence interval [CI] 0.29-0.64 in men and OR 0.21, 95% CI 0.10-0.42 in women) and total SMD (OR, per 1.0 Hounsfield Unit increase 0.88, 95% CI 0.83-0.93 in men and 0.88, 0.82-0.95 in women) were significantly associated with the prevalence of NAFLD after adjusting for covariates. The subgroup with simultaneous presence of low SMI and low SMD was associated with a significantly higher prevalence of NAFLD compared with other groups. CONCLUSIONS: Both SMI and SMD are independently associated with the prevalence of NAFLD.

Chemotherapy-Induced Sarcopenia.

OPINION STATEMENT: Sarcopenia is being consistently recognized as a condition not only associated with the presence of a malignancy but also induced by the oncologic therapies. Due to its negative impact on tolerance to chemotherapy and final outcome in both medical and surgical cancer patients, sarcopenia should be always considered and prevented, and, if recognized, should be appropriately treated. A CT scan at the level of the third lumbar vertebra, using an appropriate software, is the more common and easily available way to diagnose sarcopenia. It is now acknowledged that mechanisms involved in iatrogenic sarcopenia are several and depending on the type of molecule included in the regimen of chemotherapy, different pharmacologic antidotes will be required in the future. However, progression of the disease and the associated malnutrition per se are able to progressively erode the muscle mass and since sarcopenia is the hallmark of cachexia, the therapeutic approach to chemotherapy-induced sarcopenia parallels that of cachexia. This approach mainly relies on those strategies which are able to increase the lean body mass and include the use of anabolic/anti-inflammatory agents, nutritional interventions, physical exercise and, even better, a combination of different therapies. There are some phase II studies and some small controlled randomized trials which have validated these treatments using single agents or combined multimodal approaches. While these approaches may require the cooperation of some specialists (nutritionists with a specific knowledge on pathophysiology of catabolic states, accredited exercise physiologists and physiotherapists), the oncologist too should directly enter these issues to coordinate the choice and priority of the treatments. Who better than the oncologist knows the natural history of the disease, its evolution, and the probability of tolerance and response to the oncologic therapy? Only the oncologist knows when it is essential to potentiate any effort to better achieve a control of the disease, using all the available armamentarium, and when the condition is too advanced and hence requires a more palliative than supporting care. The oncologist also knows when to expect a gastrointestinal toxicity (mucositis, nausea, vomiting, and diarrhea) and hence it is more convenient using a parenteral than an enteral nutritional intervention or, on the contrary, when patient is suitable for discharge from hospital and oral supplements should be promptly tested for compliance and then prescribed. When patients are at high risk for malnutrition or if, regardless of their nutritional status, they are candidate to aggressive and potentially toxic treatments, they should undergo a jointed evaluation by the oncologist and the nutritionist and physical therapist to assess together a combined approach. In conclusion, the treatment of both cancer- or chemotherapy-related sarcopenia represents a challenge for the modern oncologist who must be able to coordinate a new panel of specialists with the same skill necessary to decide the priority of different oncologic treatments within a complex multidisciplinary context.

Trunk muscle quality and quantity predict the development of metabolic syndrome and the increase in the number of its components in individuals without metabolic syndrome.

BACKGROUND AND AIMS: The metabolic syndrome has been reported by cross-sectional studies to have an association with skeletal muscle quality and quantity. Using a longitudinal study design, this study aimed to explicate the association between muscle characteristics assessed with computed tomography (CT) and the incidence and progression of metabolic syndrome. METHODS AND RESULTS: In this retrospective study on a cohort of employees undergoing annual physical examinations, we evaluated data from 554 participants without metabolic syndrome. The cross-sectional skeletal muscle area was determined based on CT data at the level of the third lumbar vertebra, and the skeletal muscle density (SMD) and skeletal muscle index (SMI) were measured. The participants were divided into four study groups according to the sex-specific median values for SMI and SMD. We followed the participants for a mean period of 3.1 years. In the sex- and age-adjusted model, SMI and SMD had an interaction effect on the longitudinal change in number of metabolic syndrome components (ß = -0.074, p = 0.0727). Multiple regression analyses revealed that both low SMI and SMD was significantly associated with the change (ß = 0.131, p = 0.0281), whereas the low SMI and high SMD, and high SMI and low SMD were not. Both low SMI and SMD (hazard ratio (HR), 2.42; 95% confidence interval, 1.28-4.78) showed an increased adjusted HR for incident metabolic syndrome. CONCLUSION: The participants with both low quality and quantity of skeletal muscles were associated with the incidence and progression of metabolic syndrome, whereas those with only low quantity or quality of skeletal muscles were not.

Power of computed-tomography-defined sarcopenia for prediction of morbidity after pancreaticoduodenectomy.

BACKGROUND: The goal of our study was to evaluate the current approach in prediction of postoperative major complications after pancreaticoduodenectomy (PD), especially symptomatic pancreatic fistula (POPF), using parameters derived from computed tomography (CT). METHODS: Patients after PD were prospectively collected in a database of the local department of surgery and all patients with CT scans available were assessed in this study. CT parameters were measured at the level of the intervertebral disc L3/L4 and consisted of the areas of the visceral adipose tissue (AVAT), the diameters of the pancreatic parenchyma (DPP) and the pancreatic duct (DPD), the areas of ventral abdominal wall muscle (AMVEN), psoas muscle (AMPSO), paraspinal muscle (AMSPI), total muscle (AMTOT), as well as the mean muscle attenuation (MA) and skeletal muscle index (SMI). Mann-Whitney-U Test for two independent samples and binary logistic regression were used for statistical analysis. RESULTS: One hundred thirty-nine patients (55 females, 84 males) were included. DPD was 2.9 mm (Range 0.7-10.7) on median and more narrow in patients with complications equal to or greater stadium IIIb (p < 0.04) and severe POPF (p < 0.01). DPP median value was 17 (6.9-37.9) mm and there was no significant difference regarding major complications or POPF. AVAT showed a median value of 127.5 (14.5-473.0) cm2 and was significantly larger in patients with POPF (p < 0.01), but not in cases of major complications (p < 0.06). AMPSO, AMSPI, AMVEN and AMTOT showed no significant differences between major complications and POPF. MA was both lower in groups with major complications (p < 0.01) and POPF (p < 0.01). SMI failed to differentiate between patients with or without major complications or POPF. CONCLUSION: Besides the known factors visceral obesity and narrowness of the pancreatic duct, the mean muscle attenuation can easily be examined on routine preoperative CT scans and seems to be promising parameter to predict postoperative complications and POPF.

Changes in body composition and muscle attenuation during taxane-based chemotherapy in patients with metastatic breast cancer.

PURPOSE: Body composition parameters including low muscle mass, muscle attenuation (which reflects muscle quality) and adipose tissue measurements have emerged as prognostic factors in cancer patients. However, knowledge regarding the possibility of excessive muscle loss during specific systemic therapies is unknown. We describe the changes in body composition and muscle attenuation (MA) during taxane- and anthracycline-based regimens and its association with overall survival (OS) in metastatic breast cancer patients. METHODS: The lumbar skeletal muscle index (LSMI) was used as marker of muscle mass. LSMI, MA, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and intramuscular adipose tissue (IMAT) were measured before and after first-line treatment with paclitaxel (n = 73) or 5-fluorouracil-doxorubicin-cyclophosphamide (FAC) (n = 25) using CT-images. Determinants of the change of LSMI and MA were analyzed using multiple linear regression. OS was assessed using Cox proportional hazard models. RESULTS: MA significantly decreased during paclitaxel treatment (- 0.9 HU, p = 0.03). LSMI (p = 0.40), SAT (p = 0.75), VAT (p = 0.84) and IMAT (p = 0.10) remained stable. No significant alterations in body composition parameters during FAC-treatment were observed. Previous (neo-)adjuvant chemotherapy contributed to larger loss of MA during the current treatment. Body composition changes during chemotherapy were not associated with OS. CONCLUSIONS: MA decreased during treatment with paclitaxel, while muscle mass was stable. Body composition changes are not associated with survival in the absence of progressive disease.

Impact of myosteatosis on skeletal muscle volume loss in patients with chronic liver disease.

BACKGROUND AND AIM: Severe muscle volume loss is a recognized negative prognostic factor in patients with chronic liver disease. However, the effect of skeletal muscle fat deposition, referred to as myosteatosis on muscle volume loss remains unclear. The aim of this study was to investigate the relationships between myosteatosis and skeletal muscle volume loss. METHODS: We enrolled 362 patients with chronic liver disease (186 men, 176 women; mean age 68.4 ± 10.0 years, 94 with cirrhosis) who underwent liver biopsy and computed tomography scanning between January 2013 and February 2017. A transverse computed tomography image of each scan at the third lumbar vertebra was used to evaluate skeletal muscle tissues. RESULTS: Prevalence of skeletal muscle volume loss and myosteatosis were 36% and 82%, respectively. Of those with skeletal muscle volume loss, 93% have concomitant myosteatosis. Univariate analysis revealed that higher age, female, lower body mass index (BMI), higher serum albumin, lower alanine aminotransferase (ALT), lower gamma-glutamyl transpeptidase, lower total bilirubin, lower α-fetoprotein, lower skeletal muscle attenuation, and liver steatosis were significantly associated with skeletal muscle volume loss. Multivariate logistic regression analysis confirmed that lower BMI (odds ratio [OR] 5.26, 95% confidence interval [CI], 3.21-8.54; P < 0.001), presence of myosteatosis (OR, 2.82; 95% CI, 1.26-6.30; P < 0.001), lower ALT (OR, 2.04; 95% CI, 1.18-3.52; P = 0.010), and female (OR, 1.71; 95% CI, 1.04-2.28; P = 0.034) were significant independent factors associated with skeletal volume loss. CONCLUSIONS: Myosteatosis, low BMI, low ALT, and female are associated with skeletal muscle volume loss in patients with chronic liver disease.

Body composition predictors of therapy response in patients with primary extremity soft tissue sarcomas.

Background Recent studies have suggested that the quantity and quality of adipose tissue and muscle, assessed on non-contrast computed tomography (CT), may serve as imaging biomarkers of survival in patients with and without neoplasms. Purpose To assess body composition measures that could serve as predictors of therapy response in patients with extremity soft tissue sarcomas treated with radiation therapy and surgery. Material and Methods The study was IRB-approved. Sixty patients had a history of extremity soft tissue sarcoma and underwent FDG-PET/CT prior to radiation therapy and surgical resection. Cross-sectional areas and CT attenuation (HU) of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle were assessed on non-contrast CT. Clinical information on predictors of tumor recurrence and post-surgical wound infections were recorded. Cox proportional hazard models were used to determine longitudinal associations between body composition and tumor recurrence/wound infections. Results Twenty-three tumor recurrences occurred over a follow-up period of 43 ± 35 months. Higher SAT and lower psoas attenuation were associated with tumor recurrence which remained significant after adjustment for covariates ( P ≤ 0.01). There were 13 post-surgical wound infections. Higher VAT and SAT attenuation were associated with post-surgical wound infections ( P < 0.04); however, VAT attenuation lost significance after adjustment for covariates. Conclusion Abdominal adipose tissue and psoas muscle attenuation assessed on non-contrast CT may predict tumor recurrence and post-surgical infections in patients with extremity soft tissue sarcomas.

Skeletal muscle loss and prognosis of breast cancer patients.

PURPOSE: The aim of this study was to clarify the changes in the cross-sectional area of skeletal muscle and muscle attenuation (MA) during 12-month period before death in breast cancer patients. METHODS: Breast cancer patients who received treatment between September 2002 and July 2014 at Shizuoka Cancer Center or between December 2005 and July 2014 at Teikyo University Hospital were identified. Computed tomography (CT) scans during the 12-month period before death of consecutive female patients who died of breast cancer were reviewed. Skeletal muscle quantity and quality were evaluated by a cross-sectional area of skeletal muscle and MA, respectively, on CT scans taken 10-12 months (T1), 7-9 months (T2), 4-6 months (T3), and within 3 months (T4) prior to death. Wilcoxon signed rank test was used to compare the differences between the two-time points with Bonferroni correction (p = 0.0083). RESULTS: The medical records of 99 patients (median age at death, 57 years; range, 40-83 years) were retrospectively analyzed. Both the cross-sectional area and MA continued to decrease during 12-month period before death. Statistically significant differences were observed in the cross-sectional areas between T1 and T4 (p = 0.0011), T2 and T4 (p = 0.0019), and T3 and T4 (p = 0.0026), as well as in MA between T2 and T4 (p = 0.0012) and T3 and T4 (p = 0.0061). CONCLUSIONS: These results suggest that both quantity and quality of the skeletal muscle continued to decrease during 12-month period before death in breast cancer patients.

Muscle composition measured by CT scan is a measurable predictor of overall survival in advanced ovarian cancer.

OBJECTIVES: To assess the impact of muscle composition and sarcopenia on overall survival in advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). METHODS: Women with stage IIIC/IV EOC who underwent PDS with curative intent between 1/1/2006 and 12/31/2012 were included. Patient variables and vital status were abstracted. Body composition was evaluated in a semi-automated process using Slice-O-Matic software v4.3 (TomoVision). Skeletal muscle area and mean skeletal muscle attenuation were recorded. Associations with overall survival were evaluated using Cox proportional hazards models and recursive partitioning. RESULTS: We identified 296 patients and 132 (44.6%) were classified as sarcopenic. The average mean skeletal muscle attenuation of the entire cohort was 33.4 Hounsfield units (HU). A multivariate model of overall risk of death included histology, residual disease, and mean skeletal attenuation. Among patients without residual disease, overall survival, but not progression free survival was significantly different between patients with low versus high mean skeletal attenuation (median survival, 2.8 vs. 3.3years). Among patients with residual disease, overall survival was significantly different between patients with low versus high mean skeletal attenuation ≥36.40 vs. <36.40 HU (median survival, 2.0 vs. 3.3years). CONCLUSIONS: Sarcopenia and low mean skeletal muscle attenuation are common in women undergoing PDS for advanced EOC. These factors are associated with poorer outcomes, and can be used in preoperative risk stratification and patient counseling. Further research into body composition and whether this risk factor can be altered via nutrition or fitness in this population is warranted.

Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas.

OBJECTIVES: To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. METHODS: Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. RESULTS: There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. CONCLUSION: Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. KEY POINTS: • CT-attenuation of adipose tissue and muscle predict mortality in sarcoma patients • CT-attenuation predicts mortality independent of established prognostic factors • Patients with sarcomas often undergo CT for staging or surveillance • Adipose tissue and muscle attenuation could serve as biomarkers for mortality.

Epigenetic Aging Is Associated With Measures of Midlife Muscle Volume and Attenuation in CARDIA Study.

BACKGROUND: GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with age-related diseases including cancer and cardiovascular diseases. However, the associations between GAA and muscle mass and function are unknown. METHODS: We estimated measures of GAA in 1 118 Black and White participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at exam years (Y) 15 (2000-2001) and 20 (2005-2006). Abdominal muscle composition was measured using CT scans at the Y25 (2010-2011) visit. We used multivariate regression models to examine associations of GAA estimates with muscle imaging measurements. RESULTS: In the CARDIA study, each 1-year higher GAA was associated with an average 1.1% (95% confidence interval [CI]: 0.6%, 1.5%) higher intermuscular adipose tissue (IMAT) volume for abdominal muscles. Each 1-year higher GAA was associated with an average -0.089 Hounsfield unit (HU; 95% CI: -0.146, -0.032) lower lean muscle attenuation and an average -0.049 HU (95% CI: -0.092, -0.007) lower IMAT attenuation for abdominal muscles. Stratified analyses showed that GAA was more strongly associated with higher abdominal muscle IMAT volume in females and significantly associated with lower lean muscle attenuation for White participants only. CONCLUSIONS: Higher GAA is associated with higher abdominal muscle IMAT volume and lower lean muscle attenuation in a midlife population.

Muscle attenuation, not skeletal muscle index, is an independent prognostic factor for survival in gastric cancer patients with overweight and obesity.

OBJECTIVES: Skeletal muscle index (SMI) is insufficient for evaluating muscle in obesity, and muscle attenuation (MA) may be a preferred indicator. This study aimed to investigate whether MA has greater prognostic value than SMI in gastric cancer patients with overweight and obesity. METHODS: Clinical parameters of 1312 patients with gastric cancer who underwent radical gastrectomy were prospectively collected between 2013 and 2019. MA and SMI were analyzed by computed tomography scan. Overweight/obesity was defined as body mass index (BMI) ≥24 kg/m2. The hazard ratio (HR) for death was calculated using Cox regression analysis. RESULTS: Among all patients, 405 were identified as overweight and obese, and 907 were identified as normal and underweight. MA was inversely associated with BMI and visceral fat area. Among the 405 patients with overweight and obesity, 212 patients (52%) were diagnosed with low MA. In the overweight/obese group, MA was an independent predictor for overall survival (HR, 1.610; P = 0.021) in multivariate Cox regression analyses, whereas SMI did not remain in the model. In the normal/underweight group, both low MA (HR, 1.283; P = 0.039) and low SMI (HR, 1.369; P = 0.008) were independent factors of overall survival. Additionally, 318 patients were identified as having visceral obesity in the overweight/obese group, and low MA was also an independent prognostic factor for survival in these patients (HR, 1.765; P = 0.013). CONCLUSION: MA had a higher prognostic value than SMI in overweight and obese patients with gastric cancer after radical gastrectomy.

Assessment of body composition in breast cancer patients: concordance between transverse computed tomography analysis at the fourth thoracic and third lumbar vertebrae.

Introduction: Specific body composition markers derived from L3 axial computed tomography (CT) images predict clinical cancer outcomes, including chemotherapy toxicity and survival. However, this method is only applicable to those undergoing lumbar (L3) CT scanning, which is not universally conducted in early breast cancer cases. This study aimed to evaluate CT analysis at T4 as a feasible alternative marker of body composition in breast cancer. Method: All patients participated in the Investigating Outcomes from Breast Cancer: Correlating Genetic, Immunological, and Nutritional (BeGIN) Predictors observational cohort study (REC reference number: 14/EE/1297). Staging chest-abdomen-pelvic CT scan images from 24 women diagnosed with early breast cancer at University Hospital Southampton were analysed. Adipose tissue, skeletal muscle, and muscle attenuation were measured from the transverse CT slices' cross-sectional area (CSA) at T4 and L3. Adipose tissue and skeletal muscle area measurements were adjusted for height. Spearman's rank correlation coefficient analysis was used to determine concordance between body composition measurements using CT analysis at L3 and T4 regions. Results: Derived estimates for total adipose tissue, subcutaneous adipose tissue, and intramuscular adipose tissue mass following adjustment for height were highly concordant when determined from CSAs of CT slices at T4 and L3 (Rs = 0.821, p < 0.001; Rs = 0.816, p < 0.001; and Rs = 0.830, p < 0.001). In this cohort, visceral adipose tissue (VAT) and skeletal muscle estimates following height adjustment were less concordant when measured by CT at T4 and L3 (Rs = 0.477, p = 0.039 and Rs = 0.578, p = 0.003). The assessment of muscle attenuation was also highly concordant when measured by CT at T4 and L3 (Rs = 0.840, p < 0.001). Discussion: These results suggest that the CT analysis at T4 and L3 provides highly concordant markers for total adipose, subcutaneous adipose, and intramuscular adipose estimation, but not VAT, in this breast cancer population. High concordance between T4 and L3 was also found when assessing skeletal muscle attenuation. Lower concordance was observed for the estimates of skeletal muscle area, potentially explained by differences in the quantity and proportions of axial and appendicular muscle between the thorax and abdomen. Future studies will determine the value of T4 metrics as predictive tools for clinical outcomes in breast cancer.

Associations of Abdominal Muscle Density and Area and Incident Cardiovascular Disease, Coronary Heart Disease, and Stroke: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Muscle density is inversely associated with all-cause mortality, but associations with cardiovascular disease (CVD) risk are not well understood. This study evaluated the association between muscle density and muscle area and incident total CVD, coronary heart disease (CHD), and stroke in diverse men and women. METHODS AND RESULTS: Adult participants (N=1869) in the Multi-Ethnic Study of Atherosclerosis Ancillary Body Composition Study underwent computer tomography scans of the L2-L4 region of the abdomen. Muscle was quantified by density (Hounsfield units) and area in cm2. Sex-stratified Cox proportional hazard models assessed associations between incident total CVD, incident CHD, and incident stroke across sex-specific percentiles of muscle area and density, which were entered simultaneously into the model. Mean age for men and women at baseline were 64.1 and 65.1 years, respectively, and median follow-up time was 10.3 years. For men, associations between muscle density and incident CVD were inverse but not significant in fully adjusted models (P trend=0.15). However, there was an inverse association between density and CHD (P trend=0.02; HR, 0.26 for 95th versus 10th percentile), and no association with stroke (P trend=0.78). Conversely, for men, there was a strong positive association between muscle area and incident CVD (HR, 4.19 for 95th versus 10th percentile; P trend<0.001). Associations were stronger for CHD (HR, 6.18 for 95th versus 10th percentile; P trend<0.001), and null for stroke (P trend=0.67). Associations for women were mostly null. CONCLUSIONS: For men, abdominal muscle density is associated with lower CHD risk, whereas greater muscle area is associated with markedly increased risk of CHD.