Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Longitudinal Assessment of Body Composition in Children with Lymphoma

Simple SummaryMalnutrition and changes in body composition, such as weight loss and sarcopenia, are frequent in pancreatic cancer patients and are associated with worse survival outcomes according to several studies; however, research has not univocally determined whether or not they are specifically associated with a higher likelihood of toxicity from chemotherapy. This study retrospectively evaluated chemotherapy-related toxicity in a cohort of patients with metastatic pancreatic cancer and explored its relationship with body composition parameters including radiological measurements performed with a specialized software on CT scan images. Statistical analysis failed to show a clear and clinically significant association between the evaluated parameters and chemotoxicity, suggesting that relevant confounding factors likely play a more significant role in determining prognosis.Background: Malnutrition, loss of weight and of skeletal muscle mass are frequent in pancreatic cancer patients, a majority of which will undergo chemotherapy over the course of their disease. Available data suggest a negative prognostic role of these changes in body composition on disease outcomes; however, it is unclear whether tolerance to chemotherapeutic treatment is similarly and/or negatively affected. We aimed to explore this association by retrospectively assessing changes in body composition and chemotherapy-related toxicity in a cohort of advanced pancreatic cancer patients. Methods: Body composition was evaluated through clinical parameters and through radiological assessment of muscle mass, skeletal muscle area, skeletal muscle index and skeletal muscle density; and an assessment of fat distribution by subcutaneous adipose tissue and visceral adipose tissue. We performed descriptive statistics, pre/post chemotherapy comparisons and uni- and multivariate analyses to assess the relation between changes in body composition and toxicity. Results: Toxicity risk increased with an increase of skeletal muscle index (OR: 1.03) and body mass index (OR: 1.07), whereas it decreased with an increase in skeletal muscle density (OR: 0.96). Multivariate analyses confirmed a reduction in the risk of toxicity only with an increase in skeletal muscle density (OR: 0.96). Conclusions: This study suggests that the retrospective analysis of changes in body composition is unlikely to be useful to predict toxicity to gemcitabine—nab-paclitaxel.

Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent and prognostic of adverse outcomes in oncology. However, there is limited information on adults with early breast cancer and examination of other skeletal muscle indices, despite the potential prognostic importance. This study characterizes and examines age-related changes in body composition of adults with early breast cancer and describes the creation of a novel integrated muscle measure. Female patients diagnosed with stage I-III breast cancer with abdominal computerized tomography (CT) scans within 12weeks from diagnosis were identified from local tumor registry (N=241). Skeletal muscle index (muscle area per height [cm2 /m2 ]), skeletal muscle density, and subcutaneous and visceral adipose tissue areas, were determined from CT L3 lumbar segments. We calculated a novel integrated skeletal measure, skeletal muscle gauge, which combines skeletal muscle index and density (SMI×SMD). 241 patients were identified with available CT imaging. Median age 52years and range of 23-87. Skeletal muscle index and density significantly decreased with age. Using literature based cut-points, older adults (≥65years) had significantly higher proportions of sarcopenia (63 vs 28%) and myosteatosis (90 vs 11%) compared to younger adults (<50years). Body mass index was positively correlated with skeletal muscle index and negatively correlated with muscle density. Skeletal muscle gauge correlated better with increasing age (ρ=0.52) than with either skeletal muscle index (ρ=0.20) or density (ρ=0.46). Wide variations and age-related changes in body composition metrics were found using routinely obtained abdominal CT imaging. Skeletal muscle index and density provide independent, complementary information, and the product of the two metrics, skeletal muscle gauge, requires further research to explore its impact on outcomes in women with curable breast cancer.

Imaging skeletal muscle volume, density, and FDG uptake before and after induction therapy for non-small cell lung cancer

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 &lt; 0.005), BMI (-1.15kg/m2, IQR -1.71-0.14, p &lt; 0.01), SAT (-21.93cm2, IQR -50.13-5.08, p &lt; 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 &lt; 0.01; BMI: -2.3kg/m2, IQR -2.83-0.72, p &lt; 0.01; SAT: -43.00cm2, IQR -73.81-10.69, p &lt; 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.

TPS11633 Background: The World Cancer Research Fund and the American Cancer Society provide diet and exercise guidelines for cancer survivors. Many women with breast cancer do not follow these guidelines. Adoption of recommended lifestyle behaviors soon after diagnosis may prevent adverse changes in body composition, breast cancer biomarkers, and may improve adherence to treatment thereby improving breast cancer prognosis. The Lifestyle, Exercise, and Nutrition Early after Diagnosis (LEANER) study is testing the impact of a healthy lifestyle intervention on chemotherapy completion and endocrine therapy adherence. Secondary endpoints include changes in inflammatory and metabolic biomarkers, body composition, and patient reported outcomes. Methods: Eligible participants are women with stage I-III breast cancer undergoing chemotherapy. 250 participants are being recruited and randomized 1:1 to a yearlong, 16 session, healthy diet and exercise counseling intervention or usual care group. The intervention is delivered in person and/or via telephone by registered dietitians with training in exercise science. Materials include workbooks, videos, cookbooks, fit bits, and home-based exercise equipment. Intervention is focused on graduated goal setting to meet the recommended diet and exercise guidelines for cancer survivors. The primary endpoint, chemotherapy completion rate, is gathered from the Electronic Medical Record and the average Relative Dose Intensity for the originally planned regimen is calculated based on standard formulas. Assessments are completed at baseline, post chemotherapy, 1- and 2- year time points (to assess adherence to endocrine therapy). Body composition is measured using dual energy X-ray absorptiometry, blood samples and patient reported outcomes are collected. At time of submission, 39 women have been randomized. Discussion: If successful, this study has the potential to make healthy lifestyle interventions initiated shortly after diagnosis a standard component of breast cancer treatment. Clinical trial information: NCT03314688.

BackgroundPatients with pancreatic cancer often lose weight during chemotherapy with associated changes in body composition. The goal of the present analysis was to describe changes in body composition in pancreatic cancer patients on an exercise regimen. The long‐term goal is to determine whether an exercise intervention may attenuate changes in body composition and function.MethodsTwenty‐two pancreatic cancer patients of all stages who were to receive chemotherapy were recruited into a pre‐post exercise intervention study. A standard exercise prescription was individualized to include aerobic, resistance, stretch, and balance exercises. Pre‐ and post‐intervention computed tomography‐derived measures of body composition [skeletal muscle index (SMI), skeletal muscle density, visceral fat area, and subcutaneous fat area] and physical function measures (grip strength, timed up and go, 30‐s chair stand, and tandem balance stand) were evaluated using pairedt‐tests, χ2tests, and Pearson correlation coefficients.ResultsThe subjects were, on average, 62 years of age, 55% were female, 95% non‐Hispanic White, and 45% were Stage IV. Body composition changes included a median 4.6% decrease in SMI (P = 0.04), 7.91% increase in skeletal muscle density (P = 0.05), 25.07% decrease in visceral fat area (P = 0.0001), and 22.08% decrease in subcutaneous fat area (P = 0.001). Adherence to aerobic and strength exercise was 65% and 57%, respectively. Some physical function measures improved, though not significantly: chair stands increased from a mean of 11.5 to 13.0 (P = 0.59) and timed up and go improved from a mean of 11.7 to 10.3 (P = 0.26). Change in right hand grip strength was marginally positively associated with changes in SMI (r = 0.53,P = 0.06). Improvements in skeletal muscle density were seen in 63% of patients, including Stage IV patients but did not correlate with change in function.ConclusionsExercise is feasible during neoadjuvant chemotherapy for pancreatic cancer patients of all stages and may assist with maintaining physical function and improving body composition. Further research is needed.

BackgroundOlder adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults.ObjectiveThis study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults.MethodsThis is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m2) and prediabetes or well-controlled T2DM (hemoglobin A1c 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors α, and β galactosidase staining.ResultsThe study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024.ConclusionsDespite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide.Trial RegistrationClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521International Registered Report Identifier (IRRID)DERR1-10.2196/62667

BACKGROUND Older adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults. OBJECTIVE This study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults. METHODS This is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m&lt;sup&gt;2&lt;/sup&gt;) and prediabetes or well-controlled T2DM (hemoglobin A&lt;sub&gt;1c&lt;/sub&gt; 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors α, and β galactosidase staining. RESULTS The study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024. CONCLUSIONS Despite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide. CLINICALTRIAL ClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/62667

296 Background: Muscle mass, muscle quality, and adipose tissue volumes have been shown to affect colon cancer survival. Further research is required to understand how change in body composition during treatment impacts colon cancer outcomes, and how covariables such mental health and socioeconomic status affect this relationship. The aim of this project was to examine how changes in body composition during chemotherapy for colon cancer impact the duration of disease-free survival (DFS) and how sociodemographic covariables (age, sex, social isolation, depression, anxiety, income, community size) influence this relationship. Methods: Computed tomography (CT) scans from the time of diagnosis and the end of chemotherapy were obtained from individuals treated for stage III colon cancer with oxaliplatin at BC Cancer between 2012 and 2016. Whole body tissue volumes were estimated based on CT images at the level of the third lumbar vertebra, analysed using DAFS Express (Voronoi Health Analytics Inc., Vancouver BC). Muscle quantity was measured as skeletal muscle index (SMI), and muscle quality was measured as skeletal muscle density (SMD) and skeletal muscle gauge (SMG). Quantity of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and total adipose tissue (TAT) were also measured. Social isolation, anxiety, and depression symptoms were measured using the validated Psychosocial Screen for Cancer–Revised. Neighbourhood income and community population were estimated using postal codes. Cox proportional hazard models were calculated for the effect of body composition variables on DFS, and interactions with sociodemographic variables. Results: Significant reductions in SMI, SMD, SMG, VAT, IMAT and TAT were observed between diagnosis and post-chemotherapy (n=282). Improved survival was associated with higher SMD and lower IMAT at diagnosis and post-chemotherapy, lower VAT at diagnosis, and an increase in VAT or TAT during chemotherapy. Body composition had a more significant effect on survival in individuals who were older, female, or lived in smaller communities. Conclusions: Significant reductions in SMI, SMD, SMG, VAT, IMAT and TAT were observed between diagnosis and post-chemotherapy (n=282). Improved survival was associated with higher SMD and lower IMAT at diagnosis and post-chemotherapy, lower VAT at diagnosis, and an increase in VAT or TAT during chemotherapy. Body composition had a more significant effect on survival in individuals who were older, female, or lived in smaller communities.

Rheumatoid arthritis (RA) is characterised by functional disability and inflammation. This review explores the beneficial effects of exercise on function and cardiovascular disease risk in RA and explores the possibility that some of these beneficial effects may be moderated via exercise-induced improvements in body composition.

e13033 Background: CDKIs with endocrine therapy (ET) is first-line treatment in HR+/HER2- MBC. Mouse models have shown that CDKIs prevent pRB phosphorylation in the mediobasal hypothalamus, a pathway hyper-activated in diet-induced obesity; and CDKIs lead to fat mass decrease without significant effect on lean mass. We aimed to assess the impact of CDKIs on weight (wt) and BC in pts with HR+/HER2- MBC. Methods: We identified pts with HR+/HER2- MBC who received CDKIs and ET from 2015-2018. To isolate the effect of CDKIs on BC, we identified another cohort of pts who only received ET. Body mass index (BMI), wt, and computed tomography (CT) records were reviewed. BC was analyzed at L3 on CT scans using Tomovision’s SliceOmatic v5.0 and included skeletal muscle area (SMA), skeletal muscle density (SMD), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscle adiposity (MA). Total adipose tissue (TAT) was defined as SAT+VAT+MA. BC changes at 3 and 6 months of therapy were evaluated using paired t-tests. Results: There were 107 pts who received CDKI plus ET - 43% were Black, and 41% were Hispanic. CDKIs used were palbociclib (85%), abemaciclib (9%), and ribociclib (6%). ETs used were letrozole (47%), fulvestrant (39%), anastrozole (12%), and exemestane (2%). Median number of prior chemo and ET lines was 0 (range 0-5). 63 pts received ET alone. There was no difference in age (63 vs. 65 years, p = 0.26), BMI (28.80 vs. 28.12kg/m2, p = 0.48), and visceral disease (69% vs. 65%, p = 0.64) between CDKI plus ET and ET alone group. At month 3 of CDKI plus ET, there was a significant decrease in wt (-0.30kg, Interquartile range [IQR] -2.55-0.95, p = 0.02), BMI (-0.12kg/m2, IQR -1.06-0.46, p = 0.02), SAT (-8.05cm2, IQR -32.58-14.74, p = 0.01), and TAT (-8.51cm2, IQR -50.42-17.84, p &lt; 0.01), with similar results at month 6. These findings were not seen in pts on ET only at 3 months (wt: 0.00kg, IQR -2.65-2.38, p = 0.98; BMI: 0.00kg/m2, IQR -1.07-0.91, p = 0.93; SAT: -2.97cm2, IQR -26.10-25.15, p = 0.60; TAT: -0.58cm2, IQR -44.39-27.43, p = 0.18), or at 6 months. There were no significant changes in VAT, SMA, SMD, or MA in both groups at 3 or 6 months. In the CDKI plus ET group, baseline wt (74.64 vs. 72.72kg, p = 0.60), BMI (29.21 vs. 27.88kg/m2, p = 0.31), and SAT (280.29 vs. 252.75cm2, p = 0.31) were not significantly different for those who did or did not develop grade 3/4 toxicities. We obtained similar results when stratifying toxicities into hematological- and GI-related events. Conclusions: CDKIs are associated with decrease in BMI and SAT with no significant effect on VAT, SMA, or SMD. Given the known effect of obesity on breast cancer prognosis, CDKIs may have an additional effect on breast cancer prognosis by modulating body fat. Further studies are required to determine if decrease in SAT is associated with breast cancer outcomes or toxicities in pts on CDKIs.

Changes in skeletal muscle and adipose tissue during cytotoxic chemotherapy for testicular germ cell carcinoma and associations with adverse events.

e15134 Background: Sarcopenia, or skeletal muscle wasting, is an independent prognostic factor in advanced malignancy (Prado Lancet Onc 2008). Decreased muscle and increased fat are recognized side effects of androgen deprivation therapy. AA is a CYP17 inhibitor administered with corticosteroids (C), approved for treatment of advanced CRPC. AA reduces circulating androgens to ‘super-castrate’ levels; we hypothesized that AA + C would impact body composition. Methods: We retrospectively evaluated 54 CRPC pts treated on a Phase I/II trial. Pts received AA alone followed by combination AA + C on biochemical progression. CT scans at baseline, on AA alone and on AA + C were analyzed. Cross-sectional areas of fat and muscle were measured on 3 consecutive images at L4 using OsiriX 4.0. Muscle area was used to calculate skeletal muscle index (SMI); sarcopenia was defined as SMI &lt;52.4 cm2/m2. Data were analyzed using t-tests and Kaplan-Meier analysis with overall survival (OS) measured from day 1 of AA. Results: Median duration on AA alone was 7.4 months (m; range 1.4-37.5); median duration on concurrent AA + C was 7.4m (range 0.9-46.2). Body composition did not change between two pre-treatment scans (n=29; median 3m apart). On AA alone there was a decrease in total fat (-8.5%, p=0.0001), visceral fat (-9.8%, p=0.0015) and muscle mass (-3.9%, p=0.0023) with a significant decrease in mean body mass index (BMI; -3.4 %, p=0.0118). Conversely AA + C was associated with increased total fat (+15.1%, p&lt;0.0001) and visceral fat (+21.4%, p&lt;0.0001) but no further change in muscle mass. Mean BMI significantly increased on the addition of C, returning to baseline levels (p&lt; 0.0001). Overall, 13 pts (24%) were sarcopenic prior to commencing AA compared to 22 (41%) at the end of treatment. Pts who were sarcopenic at baseline had significantly reduced OS: 26.1m (95%CI 16.6 – 41) vs 46.5m (95%CI 28.6 – 57.5, p=0.0253). Conclusions: Treatment with AA alone resulted in decreased fat and muscle. AA + C increased body fat without further alteration in muscle mass. Changes in BMI did not reflect changes in body composition. Sarcopenia at baseline was a negative prognostic factor in this population.

Selecting study endpoints in prospective cancer cachexia trials remains poorly defined. The aim of this study was to further evaluate associations in changes in weight, body composition, functional outcomes, and patient-reported outcomes (PROs) in patients with metastatic cancer. We completed a 2-year (2016-2018) observational study in patients with metastatic solid cancer and ECOG performance status 0 to 2 while receiving chemotherapy and/or immunotherapy. We completed assessments at study enrollment and 3months from enrollment. We analyzed longitudinal changes in weight and body composition using validated methods. Functional assessments included the 6-Min Walk Test, Timed Up and Go Test, and Short Physical Performance Battery. PROs included the Functional Assessment of Anorexia/Cachexia Therapy and Functional Assessment of Cancer Therapy Fatigue. We analyzed changes in body composition and functional assessment using paired t tests. Additionally, we utilized linear regression models to assess relationships between changes in body composition and function outcomes and PROs, adjusting for age and sex. A total of 57 patients completed baseline assessments, but 19 patients did not complete 3-month assessments (5 died, 1 hospice, 13 withdrew). Of the 38 patients with complete data, the mean age was 61.8years and 47% were female. Metastatic cancer types included 71% gastrointestinal, 13% lung, and 8% gynecologic. Half received chemotherapy, 16% immunotherapy, and 34% a combination. From enrollment to 3months, we did not observe a change in weight or skeletal muscle but did find an increase in total adipose tissue (16.9 ± 52.4cm2, 95% CI -33.79-0.63; p= 0.059; ~ 1.5 pounds). We did not observe any association with changes in weight with any functional outcomes or PROs. However, greater losses in skeletal muscle were associated with greater declines in physical function (6-Min Walk Test [B= 0.04, p= 0.01], Short Physical Performance Battery [B= 2.44, p< 0.01]). Patients with metastatic cancer receiving cancer-directed therapy may not experience a change in body weight. However, we found an association between losses in skeletal muscle and greater declines in physical function. Therefore, when selecting study endpoints, prospective cancer cachexia studies may consider selecting changes in body composition over weight.