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Background: Low muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle radiodensity (quality). We sought to describe the associations of muscle mass and radiodensity with symptom burden, healthcare use, and survival in hospitalized patients with advanced cancer. Methods: We prospectively enrolled hospitalized patients with advanced cancer from September 2014 through May 2016. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used CT scans performed per routine care within 45 days before enrollment to evaluate muscle mass and radiodensity. We used regression models to examine associations of muscle mass and radiodensity with patients’ symptom burden, healthcare use (hospital length of stay and readmissions), and survival. Results: Of 1,121 patients enrolled, 677 had evaluable muscle data on CT (mean age, 62.86 ± 12.95 years; 51.1% female). Older age and female sex were associated with lower muscle mass (age: B, –0.16; PPPP=.014), and higher BMI was associated with higher muscle mass (B, 0.58; PPPP=.016), ESAS-Total (B, –0.29; P=.002), PHQ-4-Depression (B, –0.03; P=.006), and PHQ-4-Anxiety (B, –0.03; P=.008) symptoms, as well as decreased hospital length of stay (B, –0.07; P=.005), risk of readmission or death in 90 days (odds ratio, 0.97; PPConclusions: Although muscle mass (quantity) only correlated with survival, we found that muscle radiodensity (quality) was associated with patients’ symptoms, healthcare use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address adverse muscle changes in oncology.

Background Survival in patients with metastatic colorectal cancer (mCRC) has been associated with tumor mutational status, muscle loss, and weight loss. We sought to explore the combined effects of these variables on overall survival. Materials and Methods We performed an observational cohort study, prospectively enrolling patients receiving chemotherapy for mCRC. We retrospectively assessed changes in muscle (using computed tomography) and weight, each dichotomized as >5% or ≤5% loss, at 3, 6, and 12 months after diagnosis of mCRC. We used regression models to assess relationships between tumor mutational status, muscle loss, weight loss, and overall survival. Additionally, we evaluated associations between muscle loss, weight loss, and tumor mutational status. Results We included 226 patients (mean age 59 ± 13 years, 53% male). Tumor mutational status included 44% wild type, 42% RAS‐mutant, and 14% BRAF‐mutant. Patients with >5% muscle loss at 3 and 12 months experienced worse survival controlling for mutational status and weight (3 months hazard ratio, 2.66; p < .001; 12 months hazard ratio, 2.10; p = .031). We found an association of >5% muscle loss with BRAF‐mutational status at 6 and 12 months. Weight loss was not associated with survival nor mutational status. Conclusion Increased muscle loss at 3 and 12 months may identify patients with mCRC at risk for decreased overall survival, independent of tumor mutational status. Specifically, >5% muscle loss identifies patients within each category of tumor mutational status with decreased overall survival in our sample. Our findings suggest that quantifying muscle loss on serial computed tomography scans may refine survival estimates in patients with mCRC. Implications for Practice In this study of 226 patients with metastatic colorectal cancer, it was found that losing >5% skeletal muscle at 3 and 12 months after the diagnosis of metastatic disease was associated with worse overall survival, independent of tumor mutational status and weight loss. Interestingly, results did not show a significant association between weight loss and overall survival. These findings suggest that muscle quantification on serial computed tomography may refine survival estimates in patients with metastatic colorectal cancer beyond mutational status., Cancer cachexia has traditionally been defined using weight loss; however, loss of skeletal muscle may be a more objective measure. This article reports the results of a retrospective study that assessed whether skeletal muscle loss is associated with overall survival in patients with metastatic colorectal cancer, independent of tumor mutational status and weight loss.

OBJECTIVE. CT-based body composition analysis quantifies skeletal muscle and adipose tissue. However, acquisition parameters and quality can vary between CT images obtained for clinical care, which...

Introduction: Intermuscular adipose tissue (IMAT) reflects skeletal muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with BMI, inflammation and risk of heart failure, myocardial infarction and death. Using a novel neural networks algorithm for body composition analysis, we sought to investigate the relationship between skeletal muscle quality, CMD and cardiovascular outcomes. Methods: Consecutive patients (N=669) undergoing evaluation for CAD with cardiac stress PET demonstrating normal perfusion and preserved LVEF were followed over median 6 years for events (MACE), including death and hospitalization for myocardial infarction or heart failure. CFR was calculated as the stress/rest myocardial blood flow ratio. Subcutaneous fat (SAT) and IMAT areas (cm 2 ) were obtained from PET attenuation correction CTs using a fully automated algorithm validated by manual segmentation at T10 and T12 levels, respectively. Results: Median age was 63 years, 70% were female and 46% nonwhite. Nearly half of patients were obese (46% with BMI 30-61) and BMI correlated closely with SAT and IMAT (r=0.8 and 0.7, respectively, p2 IMAT, p≤0.01]. Patients with both CMD and poor muscle quality demonstrated highest risk of MACE (adjusted p Conclusion: Increased intermuscular fat is associated with CMD and adverse cardiovascular outcomes independently of BMI and traditional risk factors. Combined assessment of skeletal muscle quality and coronary microvascular function may help to redefine at-risk cardiometabolic phenotypes.

Aim Research has identified patients with chronic liver disease as a risk group for colorectal neoplasia. In this study, we aimed to identify liver disease subgroups at enhanced risk of developing colorectal neoplasia, as well as causal factors. Methods The present retrospective study included patients with chronic liver disease undergoing colonoscopy during liver transplantation evaluations, and liver-healthy patients as part of the German screening protocol. We assessed inflammatory laboratory values, Model for End-stage Liver Disease score, portal hypertension, and liver disease etiologies as explanatory variables. Outcomes included polyps, adenomas, high-risk situations, and colorectal cancer, tested in uni- and multivariable analyses. Results A total of 1046 patients were included, 407 with liver disease, 639 without. Alcohol-toxic, metabolic, cryptogenic, non-alcoholic fatty liver disease, and hepatocellular carcinoma were significantly associated with colorectal neoplasia, as were low compared with high Model for End-stage Liver Disease scores. Portal hypertension showed no associations with neoplasia. Inflammatory markers were associated with colorectal neoplasia, independent of liver disease severity. Conclusions Low Model for End-stage Liver Disease score, inflammatory markers, and certain etiologies were associated with colorectal neoplasia. Our findings suggest that inflammation may play an important role in the development of colonic adenomas in patients with chronic liver disease. Findings need to be confirmed in prospective studies, but may allow risk stratification and, possibly, development of prophylactic treatments.

Body composition analysis, also referred to as analytic morphomics, morphomics, or morphometry, describes the measurement of imaging biomarkers of body composition such as muscle and adipose tissue, most commonly on computed tomography (CT) images. A growing body of literature supports the use of such metrics derived from routinely acquired CT images for risk prediction in various patient populations, including those with lung cancer. Metrics include cross-sectional area and attenuation of skeletal muscle and subcutaneous, visceral, and intermuscular adipose tissue. The purpose of this review is to provide an overview of the concepts, definitions, assessment tools, segmentation techniques and associated pitfalls, interpretation of those measurements on chest and abdomen CT, and a discussion of reported outcomes associated with body composition metrics in patients with early-stage and advanced lung cancer.

7006 Background: Loss of skeletal muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle density (quality). Hospitalized patients with advanced cancer are a highly symptomatic population at risk for the adverse effects of muscle loss. Thus, we sought to describe associations between muscle mass and density, symptom burden, health care use, and survival in these patients. Methods: We prospectively enrolled hospitalized patients with advanced cancer from 9/2014-4/2017. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire 4 [PHQ4]) symptoms. We used computed tomography (CT) scans performed per routine care ≤45 days prior to enrollment to evaluate muscle mass and density at the level of the third lumbar vertebral body. We categorized patients as sarcopenic using validated sex specific cutoffs. We used regression models to examine associations between muscle mass and density and patients’ symptom burden, health care use, and survival. Results: Of 1,121 patients enrolled, 677 had evaluable CT scan data (mean age = 62.86±12.95 years; 51.1% female). The most common cancer types were gastrointestinal (36.8%) and lung (16.7%) cancer. Most met criteria for sarcopenia (64.0%). Older age and female sex were associated with lower muscle mass (age: B = -0.16, p < .01; female: B = -6.89, p < .01) and density (age: B = -0.33, p < 0.01; female: B = -1.66, p = .01), while higher BMI was associated with higher muscle mass (B = 0.58, p < .01) and lower muscle density (B = -0.61, p < .01). Higher muscle mass was significantly associated with improved survival (HR = 0.97, p < .01), but not with symptom burden or health care use. Higher muscle density was significantly associated with lower ESAS physical (B = -0.17, p = .02), ESAS total (B = -0.29, p < .01), PHQ4 depression (B = -0.03, p < .01) and PHQ4 anxiety (B = -0.03, p < .01) symptoms. Higher muscle density was also associated with decreased hospital length of stay (B = -0.07, p < .01), risk of readmission or death in 90 days (OR = 0.97, p < .01), and improved survival (HR = 0.97, p < .01). Conclusions: Most hospitalized patients with advanced cancer have muscle loss consistent with sarcopenia. We found that muscle mass (quantity) correlated with survival, whereas muscle density (quality) was associated with patients’ symptoms, health care use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address the adverse effects of muscle loss in oncology.

A brain tumor diagnosis poses a significant psychological burden and it severely impacts quality of life (QOL), both in patients and relatives. However, comprehensive strategies addressing QOL in this setting remain rare. Here, we aim to share our findings of a one-week ski exercise intervention, with emphasis on feasibility, safety, QOL, and physical exercise. The intervention consisted of week-long daily ski sessions with professional ski guides as well as dedicated physicians present. The participants were handed questionnaires, including distress and QOL items before, during, and after the intervention. Using fitness watches, exercise intensity was also tracked at these timepoints. During the intervention, patients were checked for adverse events daily. Fifteen participants, nine patients after multidisciplinary treatment, and six relatives were included in the study. Additionally, 13 children participated in the exercise, but not in the study. All of the participants completed the entire program. No severe adverse events were documented during daily checks. There was a strong increase in quantified activity and QOL with a corresponding decrease in distress during the intervention, and, partly, afterwards. This prospective brain tumor rehabilitation study demonstrates the feasibility and safety of challenging ski exercise in brain tumor patients. The findings also underline the exercise-mediated QOL benefits, emphasizing the need for more comprehensive brain tumor rehabilitation programs.

Background Research increasingly focuses on identifying individuals at greater risk of colorectal cancer (CRC) to enhance colonoscopy screening efficacy. Objective The objective of this article is to determine associations between chronic liver disease and lesions along the colorectal adenoma-carcinoma sequence. Methods This retrospective study encompasses consecutive liver disease patients (LDPs) of all etiologies evaluated for liver transplantation at a single institution and a control group of liver-healthy patients (LHPs) undergoing colonoscopy as part of the German CRC screening program. Rates of polyps, adenomas, high-risk situations (HRS) and CRC were analyzed in univariable and multivariable settings adjusting for age, gender, body mass index and number of colonoscopies. Differences between LHPs and LDPs and between cirrhotic and noncirrhotic hepatopathy were assessed. Results In total, 1046 patients (52.6% male, median age 59.6 years) were included, of whom 38.9% had liver disease. A total of 41.0% of all patients showed polyps, 23.2% adenomas, 10.0% HRS, and 0.5% CRC. LDPs were more likely to develop polyps, adenomas and HRS than LHPs, both in univariable and multivariable analysis. There were no significant differences between cirrhotic and noncirrhotic patients. Conclusion Chronic liver disease of any etiology is associated with colonic lesions of the colorectal adenoma-carcinoma sequence, independent of cirrhosis. LDPs should receive intensified, and earlier, colonoscopy screening.

In his editorial “ Sarcopenia is a potential factor for optimized treatment selection for elderly patients with early stage non-small-cell lung cancer recent retrospective analysis” Dr. Matsuo comments on our study “Thoracic Skeletal Muscle Is Associated With Adverse Outcomes After Lobectomy for Lung Cancer ” (1). We appreciate the opportunity to reply to his comments and discuss how body composition metrics derived from routine computed tomography (CT) images of the thorax could improve lung cancer care.

Background: Skeletal muscle (SM) fat infiltration, or intermuscular adipose tissue (IMAT), reflects muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with BMI, inflammation and risk of heart failure, myocardial infarction and death. We sought to investigate the relationship between skeletal muscle quality, CMD and cardiovascular outcomes. Methods: Consecutive patients (N=669) undergoing evaluation for CAD with cardiac stress PET demonstrating normal perfusion and preserved left ventricular ejection fraction were followed over median 6 years for major adverse cardiovascular events (MACE), including death and hospitalization for myocardial infarction or heart failure. CFR was calculated as stress/rest myocardial blood flow and CMD defined as CFR<2. Subcutaneous adipose tissue (SAT), SM and IMAT areas (cm 2 ) were obtained from simultaneous PET attenuation correction CTs using semi-automated segmentation at the twelfth thoracic vertebra (T12) level. Results: Median age was 63 years, 70% were female and 46% nonwhite. Nearly half of patients were obese (46%, BMI 30-61) and BMI correlated highly with SAT and IMAT (r=0.84 and 0.71, respectively, p<0.001) and moderately with SM (r=0.52, p<0.001). Decreased SM and increased IMAT, but not BMI or SAT, remained independently associated with decreased CFR (adjusted p=0.03 and p=0.04, respectively). In adjusted analyses, both lower CFR and higher IMAT were associated with increased MACE [HR 1.78 (1.23-2.58) per -1U CFR and 1.53 (1.30-1.80) per +10 cm 2 IMAT, adjusted p=0.002 and p<0.0001, respectively], while higher SM and SAT were protective [HR 0.89 (0.81-0.97) per +10 cm 2 SM and 0.94 (0.91-0.98) per +10 cm 2 SAT, adjusted p=0.01 and 0.003, respectively]. Every 1% increase in fatty muscle fraction [IMAT/(SM+IMAT)] conferred an independent 2% increased odds of CMD [CFR<2, OR 1.02 (1.01-1.04), adjusted p=0.04] and a 7% increased risk of MACE [HR 1.07 (1.04-1.09), adjusted p<0.001]. There was a significant interaction between CFR and IMAT, not BMI, such that patients with both CMD and fatty muscle demonstrated highest MACE risk (adjusted p=0.02). Conclusion: Increased intermuscular fat is associated with CMD and adverse cardiovascular outcomes independently of BMI and conventional risk factors. The presence of CMD and skeletal muscle fat infiltration identified a novel at-risk cardiometabolic phenotype.