Baseline Skeletal Muscle Index Research Articles

Skeletal muscle index as a prognostic marker for sudden cardiac death in heart failure patients with reduced ejection fraction

Abstract Background The association between sarcopenia and sudden cardiac death remains unclear. Therefore, this study aimed to explore the association between sarcopenia, sudden cardiac death, and all-cause mortality in heart failure (HF) patients with reduced ejection fraction based on the skeletal muscle index (SMI) predicted by a formula. Methods A total of 300 patients with heart failure who were admitted to our Hospital, National Center for Cardiovascular Diseases, between March 2013 and November 2015 and met the inclusion criteria were retrospectively analyzed. Baseline SMI was divided into two groups: lower than or equal to the median (n=151) and higher than the median (n=149). The primary endpoints were a composite outcome of sudden cardiac death (SCD) or an equivalent event (sustained ventricular events, or appropriate implantable cardioverter-defibrillator (ICD) therapy).The secondary end point was all-cause mortality. Results The average follow-up period was 24.40 ± 14.07 months. Atotal of 42 patients (42/300,14.0%) experienced sudden cardiac death or an equivalent event, and 97 patients (97/300, 32.2%) experienced all-cause mortality. Analysis of the Kaplan–Meier survival curves showed that patients with an SMI lower than or equal to the median had a higher risk of sudden cardiac death (P=0.0015) and all-cause mortality (P<0.0001). Multivariate Cox analysis showed that an SMI lower than the median was an independent risk factor for sudden cardiac death (hazard ratio (HR): 2.837, 95% confidence interval (CI): 1.009–7.980, P=0.048) and all-cause mortality (HR: 2.597, 95% CI: 1.384–4.871, P=0.003). Conclusions Decreased SMI significantly increased the risk of sudden cardiac death and all-cause mortality in patients with HF and reduced ejection fraction. In a HF population with reduced ejection fraction, attention should be paid to the effect of sarcopenia on prognosis, and active intervention is expected to improve the prognosis of patients.

Effects of muscle mass and muscle quality estimated by phase angle on functional outcomes in older patients undergoing rehabilitation: A prospective cohort study.

Both skeletal muscle mass and muscle quality are important predictors of poor prognosis in older patients. However, the effects of muscle mass and muscle quality estimated by the phase angle (PhA) on functional outcomes in older patients undergoing rehabilitation have yet to be reported. This study aimed to investigate whether appendicular skeletal muscle index (SMI) and muscle quality estimated by PhA were independently associated with activities of daily living (ADL) and physical function in older patients undergoing rehabilitation. This prospective cohort study included older patients in a subacute rehabilitation hospital (n = 443). Baseline SMI and PhA were measured using bioelectrical impedance analysis, and low SMI or low PhA were determined using each cutoff value. The primary outcomes were ADL abilities measured using the functional independence measure for motor function (FIM-M) score and physical function measured using the short physical performance battery (SPPB) score at hospital discharge. Association between low SMI and low PhA and FIM-M or SPPB scores at discharge were determined using multiple regression analysis adjusted for confounding factors. There were significant differences between the normal- and low-PhA groups in the FIM-M and SPPB scores at discharge (P < 0.001). In multiple regression analysis, low PhA was independently associated with FIM-M (β = -0.109, P = 0.013) and SPPB scores (β = 0.535, P < 0.001) at discharge; however, low SMI was not independently associated with these functional outcomes. Decreased muscle quality estimated by the PhA was independently associated with poor ADL abilities and poor physical function in older patients undergoing rehabilitation.

Associations between body composition measurements (BCM) and phase 1 (P1) oncology clinical trial outcomes.

e18648 Background: Cancer-related malnutrition and cachexia can lead to body composition changes. BCM can be assessed at the third lumbar (L3) vertebra by CT, which is available as part of pre-trial evaluation. We previously found that malnutrition and low psoas muscle area (PMA) are associated with adverse P1 outcomes including higher rates of ≥ Grade 3 toxicity (G3T). Here we evaluate the relationships between comprehensive cross-sectional muscle and adipose tissue BCM at L3 on P1 outcomes. Methods: Baseline CT scans for 82 patients (pts) were reviewed and images at the level of L3 were identified by 3 independent reviewers. A CT L3 image selected by at least 2 reviewers underwent analysis by Slice-O-Matic software (Tomovision, Canada) to generate BCM including: skeletal muscle area (SMA), skeletal muscle radiodensity (SMD), and adipose tissue area [intermuscular (IMAT), visceral (VAT), subcutaneous (SAT), and total adipose (TAT)] in cm2. SMA was normalized by height (m2), yielding cross-sectional skeletal muscle index (SMI). We stratified pts by having a SMI, SMD, IMAT, VAT, SAT, and TAT above or below the median value. We evaluated for associations between BCM and the following outcomes: rates of ≥ G3T, frequency of dose reductions/interruptions, hospitalizations, tumor response, disease control, duration on study (DOS), and overall survival (OS). Chi-square analysis was used to determine statistical significance between groups. Kaplan-Meier curves were used to compare DOS and OS. A multivariable analysis (MVA) was conducted via logistic regression to evaluate the association between SMI, VAT, PMA and ≥ G3T controlling for age and gender. Results: 82 P1 pts were included (38 M, 45 F), with a median age of 60 (range 28-85). The most common disease site was gastrointestinal (33%). Mean SMI was 44.78 cm2/m2 (range 25.70-79.89). Higher SMI was associated with a reduced risk of ≥ G3T (36.6% vs 58.5%; p = 0.047) and a trend towards improved OS (p = 0.07). There was no association between SMD, IMAT, SAT, or TAT and toxicity, however, higher VAT was associated with reduced risk of ≥ G3T (31.7% vs 63.4%, p = 0.004), and improved response to therapy (p = 0.001). A MVA controlling for age and gender showed that reduced SMI (AUC 0.7072), increased VAT (AUC 0.7597), and reduced PMA (AUC 0.757) were similar in their ability to predict ≥ G3T. Conclusions: P1 trials are designed to determine the safety and tolerability of investigational agents. In this population of P1 pts, BCM including higher baseline CT L3 SMI and VAT were associated with a reduced risk of ≥ G3T. BCM were also tied to efficacy as high VAT was associated with improved tumor response while a trend towards improved OS was noted for pts with higher baseline SMI. Future research should examine the value of integrating CT-based BCM into dose-selection algorithms when evaluating safety in P1 trials to minimize treatment-related toxicity and optimize therapeutic benefit.

Randomised clinical trial: effect of adding branched chain amino acids to exercise and standard-of-care on muscle mass in cirrhotic patients with sarcopenia.

BackgroundThe role of branched-chain amino acids (BCAA) in improving muscle mass in cirrhosis is presently debatable.AimsTo evaluate the role of BCAA in improving muscle mass in a double-blind randomized placebo-controlled trial in patients with cirrhosis having sarcopenia.MethodsConsecutive patients with cirrhosis with Child–Pugh score < 10 and sarcopenia were randomized to receive either 12 g/day of BCAA orally or a placebo (1:1) for 6 months in addition to a home-based exercise program (30 min/day), dietary counselling and standard medical therapy. Sarcopenia was defined according to gender-specific axial skeletal muscle index (SMI) cut-offs. The primary endpoint was a change in muscle mass based on CT scan (SMI) after 6 months of supplementation.ResultsSixty patients [mean age 41.6 ± 9.9 years; males (66.6%) of predominantly viral (40%) and alcohol-related (31.7%) cirrhosis] were randomized. Baseline clinical and demographic characters were similar except MELD score (10.2 ± 2.8 vs. 12.2 ± 3.5, p = 0.02) and calorie intake (1838.1 kcal ± 631.5 vs. 2217.5 kcal ± 707.3, p = 0.03), both being higher in the placebo arm. After adjusting for both baseline confounders, baseline SMI and protein intake, the change in SMI at 6 months was similar in both groups [mean adjusted difference (MAD) + 0.84, CI − 2.9; + 1.2, p = 0.42] by intention-to-treat analysis. The secondary outcomes including change in handgrip strength (p = 0.65), 6-m gait speed (p = 0.20), 6-min walk distance (p = 0.39) were similar in both arms. Four patients had minor adverse events in each arm.ConclusionAddition of BCAA to exercise, dietary counselling and standard medical therapy did not improve muscle mass in patients with cirrhosis having sarcopenia. (CTRI/2019/05/019269).Trial registration numberCTRI/2019/05/019269 (Clinical Trials Registry of India).Supplementary InformationThe online version contains supplementary material available at 10.1007/s12072-022-10334-7.

Changes in body composition during neoadjuvant platinum-based chemotherapy associations prior to radical cystectomy: Implications for chemotherapy-associated adverse events and oncologic outcomes.

476 Background: Low skeletal muscle index (SMI) is associated with an increased risk of mortality in muscle-invasive bladder cancer (MIBC) and chemotherapy-related adverse events (AE) across numerous other malignancies. Small case series suggest neoadjuvant chemotherapy (NAC) is associated with a significant decline in SMI in patients with MIBC. However, limited data exists regarding changes in fat mass during NAC. Herein, we examine changes in SMI, visceral fat index (VFI), and subcutaneous fat index (SFI) in patients receiving NAC for MIBC before radical cystectomy (RC). We describe associations between body composition changes and NAC-associated AE and all-cause mortality (ACM) in patients with MIBC. Methods: Retrospective review of patients with MIBC (≥pT2 N0/x/1 M0) who received NAC (2006-2019). Patients with digitized abdominal computed tomography scans (CT) within 75 days prior (T1) and 75 days following completion (T2) of NAC were included. We segmented and calculated the indices (cm2/m2) for SMI, VFI, and SFI at the third lumbar vertebra level at T1 and T2 using validated methodology. Associations with AE during NAC and ACM were evaluated with multivariate logistic regression and Cox proportional hazards models. Results: Included 170 patients, median age 63 years receiving a median of 4 (IQR 3-5) cycles of Gemcitabine/Cisplatin (52%), MVAC (28%), or other NAC (20%). Absolute and relative changes in SMI, VFI, and SFI over a median of 112 days (IQR 94-146) between measurements are presented in the Table. 117 (69%) patients experienced grade ≥3 chemotherapy-related AE. No associations between baseline body composition or change in body composition during NAC with chemotherapy-related AE. T1 SMI (HR: 0.98; 0.97-0.99, p = 0.008), as well as T2 SMI (HR: 0.98; 0.96-0.99, p = 0.003), T2 VFI (HR: 0.99; 0.99-1.0, p = 0.05) and T2 SFI (HR: 0.99; 0.98-1.0, P = 0.03) were associated with ACM after adjusting for age, clinical T and N stage, and performance status. Conclusions: Patients undergoing NAC prior to RC experienced a 6.4% decrease in SMI and a 5.2% decrease in VFI during an average of 112 days. Chemotherapy-related AE were not associated with a change in body composition. Baseline SMI and T2 SMI, SFI, and VFI were associated with ACM on multivariable analysis. Future work is needed to understand the mechanisms underpinning such changes and the extent to which potentially detrimental changes in body composition may be mitigated before surgery.[Table: see text]

Impact of Skeletal Muscle Loss and Visceral Obesity Measured Using Serial CT on the Prognosis of Operable Breast Cancers in Asian Patients.

ObjectiveThis study aimed to investigate the impact of baseline values and temporal changes in body composition parameters, including skeletal muscle index (SMI) and visceral adipose tissue area (VAT), measured using serial computed tomography (CT) imaging on the prognosis of operable breast cancers in Asian patients.Materials and MethodsThis study retrospectively included 627 Asian female (mean age ± standard deviation [SD], 53.6 ± 8.3 years) who underwent surgery for stage I–III breast cancer between January 2011 and September 2012. Body composition parameters, including SMI and VAT, were semi-automatically calculated on baseline abdominal CT at the time of diagnosis and follow-up CT for post-treatment surveillance. Serial changes in SMI and VAT were calculated as the delta values. Multivariable Cox regression analysis was used to evaluate the association of baseline and delta SMI and VAT values with disease-free survival.ResultsAmong 627 patients, 56 patients (9.2%) had breast cancer recurrence after a median of 40.5 months. The mean value ± SD of the baseline SMI and baseline VAT were 43.7 ± 5.8 cm2/m2 and 72.0 ± 46.0 cm2, respectively. The mean value of the delta SMI was -0.9 cm2/m2 and the delta VAT was 0.5 cm2. The baseline SMI and VAT were not significantly associated with disease-free survival (adjusted hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.937–1.031; p = 0.475 and adjusted HR, 1.001; 95% CI, 0.995–1.006; p = 0.751, respectively). The delta SMI and VAT were also not significantly associated with disease-free survival (adjusted HR, 0.894; 95% CI, 0.766–1.043; p = 0.155 and adjusted HR, 1.001; 95% CI, 0.989–1.014; p = 0.848, respectively).ConclusionOur study revealed that baseline and early temporal changes in SMI and VAT were not independent prognostic factors regarding disease-free survival in Asian patients undergoing surgery for breast cancer.

Levocarnitine Supplementation Suppresses Lenvatinib-Related Sarcopenia in Hepatocellular Carcinoma Patients: Results of a Propensity Score Analysis.

This study investigated the inhibitory effect of levocarnitine supplementation on sarcopenia progression in hepatocellular carcinoma (HCC) patients treated with lenvatinib. We evaluated the skeletal muscle index (SMI). After propensity score matching for age, sex, modified albumin-bilirubin grade, baseline presence of sarcopenia, and branched-chain amino acid administration, we selected 17 patients who received levocarnitine supplementation after starting lenvatinib therapy and 17 propensity-score-matched patients who did not receive levocarnitine. Sarcopenia was present in 76% of the patients at baseline. Changes in baseline SMI at 6 and 12 weeks of treatment were significantly suppressed in the group with levocarnitine supplementation compared with those without (p = 0.009 and p = 0.018, respectively). While there were no significant differences in serum free carnitine levels in cases without levocarnitine supplementation between baseline and after 6 weeks of treatment (p = 0.193), free carnitine levels were significantly higher after 6 weeks of treatment compared with baseline in cases with levocarnitine supplementation (p < 0.001). Baseline SMI and changes in baseline SMI after 6 weeks of treatment were significantly correlated with free carnitine levels (r = 0.359, p = 0.037; and r = 0.345, p = 0.045, respectively). Levocarnitine supplementation can suppress sarcopenia progression during lenvatinib therapy.

The impact of sarcopenia and acute muscle mass loss on long-term outcomes in critically ill patients with intra-abdominal sepsis.

BackgroundSarcopenia is a known risk factor for poor outcomes across many chronic diseases. The impact on outcomes of both pre‐existing sarcopenia and acute muscle wasting (AMW) in acute critical illness caused by sepsis remain unclear.MethodsWe conducted a prospective longitudinal cohort study of critically ill patients with intra‐abdominal sepsis utilizing abdominal computed tomography at sepsis onset to determine baseline skeletal muscle index (SMI). Biomarkers of inflammation and catabolism were measured through 28 days while hospitalized. We performed follow‐up evaluations of strength and physical function at 3, 6, and 12 months, with interval CT analyses at 3 and 12 months to evaluate changes in muscle mass. Measured clinical outcomes included development of chronic critical illness (≥14 days in intensive care with persistent organ dysfunction), long‐term functional status, and 1 year mortality.ResultsAmong 47 sepsis patients enrolled (mean age 53 ± 14 years), half (n = 23; 49%) were sarcopenic at baseline. Overall, sepsis patients exhibited acute and persistent muscle wasting with an average 8% decrease in SMI from baseline at 3 months (P = 0.0008). Sarcopenic (SAR) and non‐sarcopenic (NSAR) groups were similar in regards to age and comorbidity burden. SAR patients had greater acute physiologic derangement (APACHE II, 18 vs. 12.5), higher incidence of multiple organ failure (57% vs. 17%), longer hospital (21 vs. 12 days) and intensive care unit length of stays (13 vs. 4 days), and higher inpatient mortality (17% vs. 0%; all P < 0.05). Pre‐existing SAR was a strong independent predictor of early death or developing chronic critical illness (odds ratio 11.87, 95% confidence interval CI 1.88–74.9; P = 0.009, area under the curve 0.880) and was associated with significantly higher risk of 1‐year mortality (34.9% vs. 4.2%, p = 0.007). Lower baseline SMI was also predictive of poor functional status at 12 months (OR 0.89, 95% confidence interval 0.80–0.99; p = 0.039, area under the curve 0.867). Additionally, SAR patients had AMW with persistent muscle mass loss at 3 months that was associated with decreased health‐related quality of life and SF‐36 physical function domains (P < 0.05). Persistent AMW at 3 months was not predictive of mortality or poor functional status, with return to near‐baseline muscle mass among sepsis survivors by 6 months.ConclusionsCritically ill patients have an acute and persistent loss of muscle mass after intra‐abdominal sepsis, which is associated with decreased health‐related quality of life and physical function at 3 months. However, pre‐existing sarcopenia, rather than persistent acute muscle mass loss at 3 months after sepsis, is independently associated with poor long‐term functional status and increased 1 year mortality.

Predictive Value of Skeletal Muscle Mass in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients Treated With Immune Checkpoint Inhibitors.

BackgroundReduced muscle mass has been associated with increased treatment complications in several tumor types. We evaluated the impact of skeletal muscle index (SMI) on prognosis and immune-related adverse events (IrAEs) in a cohort of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoints inhibitors (ICI).MethodsA single-institutional, retrospective study was performed including 61 consecutive patients of R/M HNSCC diagnosed between July 2015 and December 2018. SMI was quantified using a CT scan at L3 to evaluate body composition. Median baseline SMI was used to dichotomize patients in low and high SMI. Kaplan-Meier estimations were used to detect overall survival (OS) and progression-free survival (PFS). Toxicity was recorded using Common Terminology Criteria for Adverse Event v4.3.ResultsPatients were 52 men (85.2%) with mean of age 57.7 years (SD 9.62), mainly oral cavity (n = 21; 34.4%). Low SMI was an independent factor for OS in the univariate (HR, 2.06; 95% CI, 1.14–3.73, p = 0.017) and multivariate Cox analyses (HR, 2.99; 95% CI, 1.29–6.94; p = 0.011). PFS was also reduced in patients with low SMI (PFS HR, 1.84; 95% CI, 1.08–3.12; p = 0.025). IrAEs occurred in 29 (47.5%) patients. There was no association between low SMI and IrAEs at any grade (OR, 0.56; 95% CI, 0.20–1.54; p = 0.261). However, grades 3 to 4 IrAEs were developed in seven patients of whom three had low SMI.ConclusionsLow SMI before ICI treatment in R/M HNSCC patients had a negative impact on OS and PFS. Further prospective research is needed to confirm the role of body composition as a predictive biomarker in ICI treatment.

Automated computed tomography (CT)-derived skeletal muscle mass determination as a significant prognostic factor in colorectal cancer patients using deep neural network model.

3534 Background: Although recent evidence suggests skeletal muscle depletion predicts the survival of patients with cancer, the retrieval and manual measurement of the computed tomography (CT) images hinder clinical application in routine clinical practice. The advent of recent deep learning applications enables highly accurate noninvasive longitudinal evaluation of skeletal muscle mass (SMM) changes. Here, we evaluated the prognostic impact of DNN-measured skeletal muscle changes in colorectal cancer (CRC) patients. Methods: A total of 6,196 newly diagnosed CRC patients were analyzed in the Yonsei Cancer Registry Database between Jan 1, 2010, and Sep 30, 2020. SMM is measured by the Skeletal muscle index (SMI). The formula used was: L3 skeletal muscle cross-sectional area (cm2)/height2 (m2). Patients’ SMI patterns were grouped by difference ratio of initial and last SMI. Patients were also classified by BMI pattern with the result of K-means clustering. Association of baseline SMI, baseline body mass index (BMI), SMI changes, BMI changes, and demographic factors with overall survival (OS) were evaluated. Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test the predictive accuracy of survival models. Results: Fully automated UNet architecture-based deep learning algorithms were applied for the third lumbar transverse CT detection, skeletal muscle segmentation, and skeletal muscle area quantification in CRC patients undergoing abdominal CT between at the time of diagnosis and one year after the diagnosis. Baseline BMI distribution was 28% obese, 26% overweight, 42% normal weight, and 4% underweight. Patients in all SMI categories varied widely in BMI. Changes in SMI were categorized into three groups: SMI increase (33%), steady (45%), and decrease (22%) group. Similarly, BMI changes were categorized into three groups: BMI increase (24%), BMI stable (57%), and BMI decrease (19%) group. Low baseline SMI, low baseline BMI, SMI decrease, and BMI decrease were independently prognostic of survival. Intriguingly, BMI and SMI changes had a different prognostic impact in men and women. For women, the SMI increase group (hazard ratio [HR], 0.4; 95% CI, 0.3-0.7; P= 0.001) was associated with longer OS, while the SMI decrease group (HR, 1.2; 95% CI, 0.6-2.2; P= 0.619) was not associated with shorter OS, both compared with SMI steady group. Conclusions: Automated CT-derived SMM depletion had a negative prognostic impact independent of BMI and age in CRC patients. A noninvasive automatic deep learning algorithm provides a unique opportunity to apply to routine clinical practice and understand how and when cachexia impacts cancer prognosis.

The Prognostic Relevance of Computed Tomography-assessed Skeletal Muscle Index and Skeletal Muscle Radiation Attenuation in Patients With Gynecological Cancer.

The evaluation of the whole skeletal muscle area at the level of the third lumbar vertebra on computed tomography (CT) scans has often detected loss of skeletal muscle mass, defined as sarcopenia, and reduced skeletal muscle radiation attenuation (SMRA) in patients with different malignancies. Baseline sarcopenia has been detected in 33.3%-51.8% of patients with advanced cervical cancer, 33.6%-50% of those with endometrial cancer, and 11%-64% of those with advanced ovarian cancer. We reviewed the literature data on the clinical relevance of CT-assessed skeletal muscle status in gynecological malignancies. Overall, baseline skeletal muscle index and SMRA have an uncertain prognostic relevance, whereas their changes during treatment usually correlate with progression-free survival and overall survival. Multicenter clinical trials are strongly warranted to assess the effects of pharmacological agents and physical exercise in the management of skeletal muscle damage in patients with gynecological cancer.

Cancer cachexia syndrome in the prediction of outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): Results from a single-institution, prospective, observational study.

e21644 Background: Cancer cachexia syndrome (CCS) is a multifactorial inflammatory syndrome affecting a large subset of patients (pts) with NSCLC which in preclinical models negatively impairs antitumor immunity. We conducted a prospective, observational study to investigate the effect of CCS and sarcopenia on the efficacy of ICIs in NSCLC. Methods: CCS was defined as weight loss of &gt; 5% in the last 6 months or any degree of weight loss &gt; 2% in combination with BMI &lt; 20% or baseline skeletal muscle index at the level of the 3rd lumbar vertebra consistent with sarcopenia. Skeletal muscle index was calculated using slice-o-matic tomovision software in the abdominal CT scan before starting ICIs. Results: 83 pts were included in the analysis. Median follow up was 9.5 months. Median age was 66 years, 61.4% had non-squamous histology, 20.5% received ICIs as first and the remaining as second-line therapy. 20.5% of pts experienced partial response (PR), 31% had stable disease (SD) and 48.2% had disease progression (PD). Median progression-free survival (PFS) was 4.4 months and median overall survival (OS) was 10.33 months. 43.4% of the whole group were categorized as having CCS, whereas 63.3% of 30 pts evaluated using tomovision had sarcopenia. CCS negatively affected response rates (p = 0.003) but not response duration (p = 0.266). CCS was associated with reduced PFS (2.46 vs 5.77 months, p = 0.006) and OS (4.8 vs 14.53 months, p = 0.001). In the multivariate analysis, CCS independently predicted for shorter OS (HR = 2.01; CI: 1,14-3,54; p = 0.014). Sarcopenia was also associated with reduced OS (5.4 vs 17.9 months, p = 0.012). Analysis on the whole pt population will be presented at the conference. Conclusions: CCS is associated with lower response rates and independently predicts for shorter OS in pts with NSCLC treated with ICIs. Further research on CCS could better define its role as a potential biomarker and a research platform for maximizing immunotherapy efficacy.

Associations between baseline body composition and cancer-specific mortality following neoadjuvant chemotherapy and radical cystectomy for bladder cancer.

e17015 Background: Sarcopenia is a modifiable risk factor independently associated with cancer-specific mortality (CSM) in bladder cancer (BC). Sarcopenic obesity, where obesity is measured by fat mass index [FMI, total body fat (kg)/height(m)2], has been proposed as an additive insult. To date, studies have overwhelmingly been performed in patients treated without neoadjuvant chemotherapy (NAC). Herein, we evaluate associations between baseline skeletal muscle index (SMI), FMI, and CSM in patients treated with NAC and radical cystectomy (RC). Methods: Lumbar SMI (cross sectional area of skeletal muscle/height2, cm2/m2) was measured on a computed tomography (CT) image at the level of the third lumbar vertebral body, within 60 days prior to NAC. Total body FMI was calculated from visceral and subcutaneous fat cross-sectional areas. Patients were classified as being sarcopenic, according to sex-specific consensus definitions: Male: SMI &lt; 55, Female: SMI &lt; 39, and as obese if Male: FMI &gt; 9, Female: &gt; 13. Cancer-specific survival (CSS) was estimated using the Kaplan Meier method. Associations with CSM were summarized with multivariable Cox proportional hazards models. Results: 143 patients had CT scans of sufficient quality (2005-18). There were no significant differences in clinicopathologic characteristics between the study cohort and patients without available imaging (N = 261). Cisplatin-based NAC was given to 125 patients (87%), and 18 (13%) received other regimens. In total, 86 (60%) patients were sarcopenic, 52 (36%) obese, and 25 (17%) both sarcopenic and obese, while 48 (34%) were sarcopenic with normal FMI. Median follow-up was 2.7 years (IQR 1.2-6.2), and 43 patients died from BC. Three-year CSS was 61% (sarcopenic) vs. 77% (p &lt; 0.05). Sarcopenic patients with normal FMI had the worst 3-year CSS (55%) compared to those with sarcopenia and FMI-obesity (79%), normal SMI with FMI-obesity (69%), and normal body composition (88%, p = 0.03). On multivariable analysis, neither FMI (HR: 0.77, 95% CI: 0.47-1.3, p = 0.3) nor SMI was independently associated with CSM (HR: 0.98, 95% CI: 0.96-1, p = 0.07) after adjustment for ASA score, pathologic tumor, and nodal stage. Conclusions: In patients treated with NAC+RC, pretreatment SMI trended towards independently predicting risk of CSM. Patients with sarcopenia and normal fat demonstrated the worst CSS. Further study is warranted on the impact of NAC on body composition and the role of the latter in risk stratification of this high-risk patient population.

Skeletal muscle index and adverse events during a bladder cancer treatment episode.

e17016 Background: While sarcopenia is associated with increased mortality in bladder cancer, there is limited data in patients treated with neoadjuvant chemotherapy (NAC) that associates skeletal muscle index (SMI) and adverse treatment-associated outcomes. Herein, we evaluate associations between baseline SMI and severe adverse events (SAEs) during NAC and post-radical cystectomy (RC) 90-day Clavien ≥3 complications. Methods: SMI (cross sectional area of skeletal muscle, cm2 / height2, m2) was measured on an axial computed tomography (CT) image at the level of the third lumbar vertebral body, within 60 days prior to NAC and RC. Patients were classified as being sarcopenic, according to sex-specific consensus definitions: Male: SMI &lt; 55, Female: SMI &lt; 39. Associations with SAEs during NAC and 90-day Clavien grade 3-5 complications were assessed with multivariable logistic regression. Results: CT scans of sufficient quality (2005-18) were available for 143 patients. There were no significant differences in clinicopathologic characteristics between the study cohort and patients without available imaging (N = 261). Median SMI for men and women was 52.1 and 40.9 cm2/m2; 86 (60%) were sarcopenic. SAEs were observed in 92 patients (64%), resulting in hospitalization during NAC in 27 (19%), while 20 (14%) patients did not complete planned NAC due to SAEs. After adjusting for age, performance status, and clinical stage, SMI was not independently associated with NAC-associated SAEs. Postoperative complications occurred in 82 (57%) patients, including infectious complications (39; 27%), wound dehiscence (8; 6%), 90-day readmission (27; 19%). Wound healing complications including dehiscence, clinically significant hernia, urine leaks, or fistulae occurred in 33 (23%). While SMI was not independently associated with risk of complications overall (OR: 1.00, 95% CI: 0.96 - 1.03), it was associated with infectious complications (OR: 0.96, 95% CI: 0.92 - 0.99, p = 0.02), and wound dehiscence (OR: 0.93, 95% CI: 0.86 - 0.99, p = 0.02) with a trend towards significance for associations with any wound-healing complications (OR: 0.96, 95% CI: 0.91 - 1.00, p = 0.08). Conclusions: In the largest reported series of post-NAC patients with RC and detailed follow-up, pretreatment SMI was not associated with SAEs during NAC but was associated with serious infectious complications and wound dehiscence after RC. This data highlights the potential value in measuring SMI to identify patients at risk for select SAEs. Future studies should assess the benefit of prehabilitation before and during NAC.

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/−25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05–2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31–3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31–3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.

Cancer cachexia, sarcopenia and hand-GRIP strength (HGS) in the prediction of outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): A prospective, observational study.

9099 Background: Cancer cachexia syndrome, affecting up to 80% of patients (pts) with NSCLC, is characterized by systemic inflammation, negative protein and energy balance and poor patient outcome. HGS has been independently correlated with outcome in pts with advanced cancer. We investigated the potential association between cachexia, sarcopenia and HGS with outcome in pts with advanced NSCLC treated with ICIs. Methods: Fifty-five pts with NSCLC treated with ICIs were included in the analysis. Patient and disease characteristics and data on outcome measures were prospectively collected. Cancer cachexia was defined as weight loss &gt; 5% in the last 6 months, BMI &lt; 20% (or baseline skeletal muscle index at the level of the 3rd lumbar vertebra consistent with sarcopenia) and any degree of weight loss &gt; 2%. Baseline HGS was measured using the JAMAR analogue dynamometer. Results: Median age was 69 years, 50% of pts had non-squamous histology, 69% had PS 0-1, 61% had cancer cachexia and mean HGS was 27 kgs. Partial response, stable disease and progressive disease was recorded in 16%, 33% and 51% of pts, respectively. Median PFS was 4 months and median OS was 7.8 months. There was no association of cachexia or HGS with tumor burden, number of metastatic sites, LDH or neutrophil/lymphocyte ratio. Cachexia had a negative impact on HGS (p = 0,001). Pts with cachexia had lower response rates (4% vs 37%, p = 0.002), disease stabilization rates (32% vs 81%, p = 0.003) and shorter PFS (3.7 vs 8.2 months, p = 0.008) compared to non-cachectic pts. In multivariate analysis, cachexia independently predicted for shorter PFS (HR = 2.7, CI: 1.15 – 6.46, p = 0.023). Data on sarcopenia are being analyzed and will be presented at the meeting. Conclusions: Cancer cachexia is associated with lower response rates and disease stabilization rates and independently predicts for shorter PFS in pts with NSCLC treated with ICIs. To our knowledge this is the first report demonstrating a between the host’s immune and metabolic responses. The study of cancer cachexia may offer a new platform for the development of novel biomarkers of resistance to ICIs.

Skeletal Muscle Mass Predicts Poor Prognosis in Patients with Advanced Pancreatic Cancer Undergoing Second-Line FOLFIRINOX Chemotherapy

Objectives: Although the significance of skeletal muscle mass has been investigated in pancreatic cancer, there are no reports regarding the impact of skeletal muscle mass on prognosis in patients who have undergone second-line chemotherapy. We aimed to identify prognostic factors in patients with advanced pancreatic cancer treated with second-line FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin).Methods: We retrospectively reviewed the data of 57 pancreatic cancer patients treated with second-line FOLFIRINOX. Age, sex, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, carbohydrate antigen 19-9 levels, skeletal muscle area, skeletal muscle index (SMI), progression free survival (PFS), and overall survival (OS) were analyzed.Results: The median age of the 57 patients (male, 56.1%) was 60.4 years (38–78). Median PFS and OS were 2.6 and 6.6 months. On Kaplan-Meier curves, high SMI was associated with prolonged OS and PFS (P value = 0.003 and 0.015). In multivariate analysis, baseline SMI was significant independent prognostic factor in patients treated with second-line FOLFIRINOX.Conclusion: Baseline SMI has an impact on prognosis in patients who undergoing second-line chemotherapy for pancreatic cancer. Skeletal muscle mass may warrant consideration as a predictive factor with which to identify candidates for second-line chemotherapy for advanced pancreatic cancer.

Sarcopenia as a Predictive Factor for Response to Upfront Cisplatin-Based Chemotherapy in Patients with Muscle-Invasive Urothelial Bladder Cancer

Purpose: We hypothesized sarcopenia as predictive factor as a response to upfront chemotherapy of muscle-invasive urothelial bladder cancer (MIBC). Methods: We retrospectively studied 30 patients who received upfront cisplatin-based chemotherapy for MIBC (pT2–4 N0/+ M0) before planned radical cystectomy. Skeletal muscle index (SMI) was calculated by CT at study baseline and following completion of chemotherapy. Patients were stratified according to the presence of sarcopenia. Endpoints included clinical and pathological response. Results: Sixteen of the 30 patients (53.3%) had sarcopenia at baseline. The median SMI was 51.2 cm²/m² (IQR 45.6–57.9). Throughout the course of chemotherapy, 22 patients (73.3%) experienced a decline in SMI, which ranged from 1 to 20% (median decline 3%, p < 0.01). All 16 patients with baseline sarcopenia persisted, while 5 of 14 patients (35.7%) without baseline sarcopenia became sarcopenic (p = 0.06). None of the clinical variables were predictive of clinical or pathological response, including SMI (p = 0.78 and p = 0.59), sarcopenia (p = 0.65 and p = 0.16) and SMI kinetics (p = 0.54 and p = 0.77). Conclusion: Sarcopenia is present in a considerable proportion of patients with MIBC undergoing upfront cisplatin-based chemotherapy before planned RC. SMI decreases during treatment, but neither baseline SMI nor its kinetics is associated with response to chemotherapy.

P2.03b-060 Baseline Skeletal Muscle Index (SMI) Values Are Associated with Biomarkers of Insulin Resistance in Stage IV Non-Small Cell Lung Cancer: Topic: Biomarkers

The aim of this project was to correlate pretreatment levels of circulating biomarkers of insulin resistance with computed tomography measured evidence of sarcopenia in stage IV NSCLC patients receiving platinum doublet chemotherapy. Pretreatment serum from 93 patients with frontline stage IV NSCLC was evaluated for 13 metabolism biomarkers with the Bio-Plex Pro Human Diabetes Assay Panel and 20 inflammation-related biomarkers using the Milliplex Human High Sensitivity T Cell Panel. All patients were treated with standard platinum doublet based chemotherapy. All patients had skeletal muscle index (SMI) calculated from baseline CT images using the Slice-O-Matic software package (Tomovision); where SMI = (muscle cross sectional area in cm2) / height in m2. Associations of biomarkers with SMI were assessed using a Spearman’s Rank Correlation Coefficient. The Log-Rank test was performed to evaluate the association of individual biomarkers with overall survival (OS). High levels of adiponectin (with low levels of adiponectin being correlating with obesity in the literature) were associated with good OS (p=0.036) and low baseline SMI value specifically for males (p=0.00029). High levels adipsin was associated with favorable OS (p=0.015) and a higher baseline SMI specifically for females (p=0.66 x10-5). Low levels of ghrelin were associated with favorable OS (p=0.005) and were inversely associated with SMI values for both genders (p=0.021). Altered values of several biomarkers of insulin resistance were associated with inferior survival and a greater degree of sarcopenia in frontline NSCLC patients receiving platinum double therapy. These findings suggest a certain subset of patients that may have improvements in cancer cachexia by targeting insulin resistance.