Lumbar Skeletal Muscle Index Research Articles

Predictive Role Of Body Composition Parameters In Operable Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

BackgroundFat tissue is strongly involved in BC tumorigenesis inducing insulin resistance, chronic inflammation and hormonal changes. Computed tomography (CT) imaging instead of body mass index (BMI) gives a reliable measure of skeletal muscle mass and body fat distribution. The impact of body composition parameters (BCPs) on chemosensitivity is still debated. We examined the associations between BCPs and tumor response to neoadjuvant chemotherapy (NC) in patients treated for operable breast cancer (BC).MethodsA retrospective review of BC patients treated with NC in Modena Cancer Center between 2005 and 2017 was performed. BCPs, such as subcutaneous fat area (SFA), visceral fat area (VFA), lumbar skeletal muscle index (LSMI) and liver-to-spleen (L/S) ratio were calculated by Advance workstation (General Electric), software ADW server 3.2 or 4.7. BMI and BCPs were correlated with pathological complete response (pCR) and survival outcomes.Results407 patients were included in the study: 55% with BMI < 25 and 45% with BMI ≥ 25. 137 of them had pre-treatment CT scan imagines. Overweight was significantly associated with postmenopausal status and older age. Hormonal receptor positive BC was more frequent in overweight patients (p<0.05). Postmenopausal women had higher VFA, fatty liver disease and obesity compared to premenopausal patients. No association between BMI classes and tumor response was detected. High VFA and liver steatosis were negative predictive factors for pCR (pCR rate: 36% normal VFA vs 20% high VFA, p= 0.048; no steatosis 32% vs steatosis 13%, p=0.056). Neither BMI classes nor BCPs significantly influenced overall survival and relapse-free survival.ConclusionVisceral adiposity as well as steatosis were closely involved in chemosensitivity in BC patients treated with NC. Their measures from clinically acquired CT scans provide significant predictive information that outperform BMI value. More research is required to evaluate the relationship among adiposity site and survival outcomes.

1783P - Sarcopenia and pretreatment anemia as prognostic factors for patients with localized muscle invasive bladder cancer treated by neoadjuvant chemotherapy and radical cystectomy

BackgroundSeveral studies suggested the prognostic importance of sarcopenia and anemia in survival or treatment complications in cancer. The aim of our study was to identify prognosis factors on chemotherapy toxicities and survival in patients (pts) with localized muscle invasive bladder cancer (MIBC). MethodsBetween January 2012 and December 2017, pts who underwent neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) for cT2-T4 N0 M0 MIBC were retrospectively selected, from a single institution cohort. Sarcopenia was evaluated according to the Lumbar Skeletal Muscle Index (SMI) in L3 using CT scan before NAC, after NAC and after RC. Pretreatment anemia was defined as hemoglobin rate < 13g/dL for men and < 12g/dL for women, prior to treatment. ResultsOf 82 pts selected, 62 are men (75.6%) and 20 women (24.4%), with a median age of 64.5 years (31 to 80). Median SMI was 47.5cm2/m2 for men and 36.6cm2/m2 for women. Pretreatment sarcopenia was significantly associated with nausea (p=0.003), hypokalemia (p=0.023) and with platinum dose-intensity during NAC (p=0.007). 46 out of 74 pts had a SMI decrease greater than 5% during chemotherapy, that was associated with poor OS (HR=4.8, CI95% [1.42-16.4], p=0.003). Pretreatment anemia was significantly associated with OS (HR=2.86, CI95% [1.21-6.76], p=0.026). Transfusion during chemotherapy was not associated with survival. In multivariate analysis, factors associated with OS were SMI loss > 5% (HR=4.62, CI95% [1,25-11,9]), positive pN status (HR=7.66, CI95% [2,53-23,1]), histological complete response (HR=0.22, CI95% [0,053-0,88]), pretreatment anemia (HR=7.34, CI95% [2,26-23,8]) and ECOG status ≥ 1 (HR=4.1, CI95% [1,41-11,9]). ConclusionsFor localized MIBC, sarcopenic status before NAC could predict some chemotherapy toxicities whereas pretreatment anemia could be associated with poor OS. Loss in SMI during chemotherapy is an independent prognostic factor for OS. Improve pts care by prehabilitation during NAC and before surgery, using physical, nutritional and psycho-social supports, could decrease chemotherapy toxicities and improve survival. Legal entity responsible for the studyInstitut Paoli-Calmettes. FundingHas not received any funding. DisclosureJ. Walz: Research grant / Funding (self): Exact Imaging; Honoraria (self), Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Blue Earth Diagnostics; Travel / Accommodation / Expenses: Ipsen. S. Dermeche: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: AstraZeneca. C. Vicier: Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Pfizer. G. Pignot: Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: Bouchara; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Takeda. All other authors have declared no conflicts of interest.

Immunohistochemical phenotyping of T cells, granulocytes, and phagocytes in the muscle of cancer patients: association with radiologically defined muscle mass and gene expression

BackgroundInflammation is a recognized contributor to muscle wasting. Research in injury and myopathy suggests that interactions between the skeletal muscle and immune cells confer a pro-inflammatory environment that influences muscle loss through several mechanisms; however, this has not been explored in the cancer setting. This study investigated the local immune environment of the muscle by identifying the phenotype of immune cell populations in the muscle and their relationship to muscle mass in cancer patients.MethodsIntraoperative muscle biopsies were collected from cancer patients (n = 30, 91% gastrointestinal malignancies). Muscle mass was assessed histologically (muscle fiber cross-sectional area, CSA; μm2) and radiologically (lumbar skeletal muscle index, SMI; cm2/m2 by computed tomography, CT). T cells (CD4 and CD8) and granulocytes/phagocytes (CD11b, CD14, and CD15) were assessed by immunohistochemistry. Microarray analysis was conducted in the muscle of a second cancer patient cohort.ResultsT cells (CD3+), granulocytes/phagocytes (CD11b+), and CD3−CD4+ cells were identified. Muscle fiber CSA (μm2) was positively correlated (Spearman’s r = > 0.45; p = < 0.05) with the total number of T cells, CD4, and CD8 T cells and granulocytes/phagocytes. In addition, patients with the smallest SMI exhibited fewer CD8 T cells within their muscle. Consistent with this, further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively associated (Pearson’s r = ≥ 0.5; p = <0.0001) with key genes within muscle catabolic pathways for signaling (ACVR2B), ubiquitin proteasome (FOXO4, TRIM63, FBXO32, MUL1, UBC, UBB, UBE2L3), and apoptosis/autophagy (CASP8, BECN1, ATG13, SIVA1).ConclusionThe skeletal muscle immune environment of cancer patients is comprised of immune cell populations from the adaptive and innate immunity. Correlations of T cells, granulocyte/phagocytes, and CD3−CD4+ cells with muscle mass measurements indicate a positive relationship between immune cell numbers and muscle mass status in cancer patients. Further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively correlated with components of muscle catabolism.

Decrease in skeletal muscle index 1 year after radical cystectomy as a prognostic indicator in patients with urothelial bladder cancer.

ABSTRACTPurpose The present study aimed to determine whether sarcopenia after radical cystectomy (RC) could predict overall survival (OS) in patients with urothelial bladder cancer (UBC).Materials and Methods The lumbar skeletal muscle index (SMI) of 80 patients was measured before and 1 year after RC. The prognostic significance of sarcopenia and SMI decrease after RC were evaluated using Kaplan–Meier analysis and a multivariable Cox regression model.Results Of 80 patients, 26 (32.5%) experienced sarcopenia before RC, whereas 40 (50.0%) experienced sarcopenia after RC. The median SMI change was -2.2 cm2/m2. Patients with sarcopenia after RC had a higher pathological T stage and tumor grade than patients without sarcopenia. Furthermore, the overall mortality rate was significantly higher in patients with sarcopenia than in those without sarcopenia 1 year after RC. The median follow-up time was 46.2 months, during which 22 patients died. Kaplan-Meier estimates showed a significant difference in OS rates based on sarcopenia (P=0.012) and SMI decrease (P=0.025). Multivariable Cox regression analysis showed that SMI decrease (≥2.2 cm2/m2) was an independent predictor of OS (hazard ratio: 2.68, confidence interval: 1.007-7.719, P = 0.048).Conclusions The decrease in SMI after surgery might be a negative prognostic factor for OS in patients who underwent RC to treat UBC.

Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer

BackgroundPancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy. MethodsThe diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic™. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values. ResultsSeventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03–1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08–1.35, p = 0.001). ConclusionsSarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk.

Change in Skeletal Muscle Following Resection of Stage I-III Colorectal Cancer is Predictive of Poor Survival: A Cohort Study.

Sarcopenia at time of diagnosis predicts worse survival outcomes. It is currently unknown how changes in muscle mass over time interact with sarcopenia in colorectal patients treated with curative intent. Objectives of this study were to quantify sarcopenia and skeletal muscle loss from time of diagnosis to end of surveillance and determine its effect on survival outcomes after completion of 2 years of surveillance. Retrospective cohort study of stage I-III colorectal cancer patients from 2007-2009, who underwent resection and had preoperative and 2-year surveillance computed tomography scans, without recurrence during that time. Body composition analysis was done at both time points to determine lumbar skeletal muscle index, radiodensity and adiposity. Change over time was standardized as a percentage per year. Cox proportional hazard regression modeling was used for survival analysis. Of 667 patients included, median survival from surgery was 7.96years, with 75 recurrences occurring after 2years. On average patients lost muscle mass (-0.415%/year; CI -0.789, -0.042) and radiodensity (-5.76 HU/year; CI -6.74, -4.80), but gained total adipose tissue (7.06%/year; CI 4.34, 9.79). Patients with sarcopenia at diagnosis (HR 1.80; CI 1.13, 2.85) or muscle loss over time (HR 1.55; CI 1.01, 2.37) had worse overall survival, with significantly worse joint effect (HR 2.73; CI 1.32, 5.65). Sarcopenia at diagnosis combined with ongoing skeletal muscle loss over time resulted in significantly worse survival. Patients with these features who are recurrence-free at 2years are more likely to have a non-colorectal cancer cause of death.

Prognostic and predictive implications of sarcopenia in Western patients undergoing gastric resections for carcinoma of the stomach.

Sarcopenia is highly prevalent in patients with gastrointestinal malignancies, including gastric cancer, but there is a lack of adequate data from Western populations. Computed tomography scans of 138 Caucasian patients subject to stomach resections due to gastric adenocarcinoma between 2012 and 2015 were reviewed to evaluate the impact of sarcopenia. The definition of sarcopenia was based on the lumbar skeletal muscle index (SMI) using cut-off values formulated by the international consensus definitions of sarcopenia (SMI <52.4 cm2 /m2 for men and <38.5 cm2 /m2 for women). Sixty (43%) of 138 patients were sarcopenic. Sarcopenia was associated with postoperative morbidity (43% vs 23%; P = .011), major postoperative complications (Clavien-Dindo ≥3a; 36% vs 21%; P = .035), and reoperations (23% vs 9%; P = .020). Patients with sarcopenia also had prolonged postoperative hospital stay (8.0 vs 6.5 days; P = .010). The overall median survival of patients with sarcopenia was significantly lower than those with normal skeletal muscles (11.0 vs 36.7 months; P = .005) and sarcopenia remained an independent prognostic factor with an odds ratio of 1.94 (95% confidence interval, 1.08 to 3.48; P = .026). Sarcopenia, defined by SMI, is associated with an increased risk of postoperative morbidity and impaired long-term survival.

Impact of sarcopenia for patients with localized muscle invasive bladder cancer treated by neoadjuvant cisplatin based chemotherapy and radical cystectomy.

e18286 Background: Several studies suggested the prognostic importance of sarcopenia in survival or treatment complications in cancer. The concept of cancer prehabilitation before surgery is gaining wide recognition. The aim of our study was to assess the impact of sarcopenia on chemotherapy toxicities and survival in patients with localized muscle invasive bladder cancer (MIBC). Methods: Between January 2012 and December 2017, patients who underwent neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) for cT2-T4 N0 M0 MIBC were retrospectively selected, from a single institution cohort. Using CT scan: before NAC, after NAC and after cystectomy, sarcopenia was defined according to the Lumbar Skeletal Muscle Index (SMI) in L3 assessed by two observers blinded to patients’ status. Results: 82 patients were selected, 62 men (75.6%) and 20 women (24.4%), with a median age of 64.5 years (31 to 80). 35 were considered severe sarcopenic (SMI &lt; 35cm2/m2 for women and SMI &lt; 50 cm2/m2 for men) before NAC. The characteristics between severe and non-severe sarcopenic patients were not significantly different except for weight (71.7 vs 81.1kg, p = 0.006) and BMI (24.0 vs 28.4kg/m2, p = 8.0x10-6). Sarcopenia pre-chemotherapy was significantly associated with nausea (p = 0.003), hypokalemia (p = 0.023) and with platinum dose-intensity during NAC (p = 0.007) but was not significantly associated with overall survival (OS) or disease-free survival (DFS). Sarcopenia post-cystectomy was correlated with the OS (HR = 0.94, CI95% [0.89-0.99], p = 0.01), but not DFS. In multivariate analysis, factors associated with OS were post cystectomy sarcopenia (p = 0.038), pN status (p = 0.001) and glomerular filtration rate (p = 0.045). Conclusions: For localized MIBC, sarcopenic status before platinum based NAC could predict some chemotherapy toxicities. After radical cystectomy, sarcopenia is an independent prognostic factor for OS. Improve patients care by prehabilitation during NAC and before surgery, using physical, nutritional and psycho-social supports, could decrease chemotherapy toxicities and improve survival particularly for sarcopenic patients.

Sarcopenia (SMI(+)) in patients (pts) with advanced or metastatic soft tissue sarcoma (a/mSTS): Potential parameter for risk prediction during multimodal therapy (MT)?

11069 Background: Objective parameters identifying ideal pts for MT from pts with a/mSTS remain scarce. Here, we analysed the impact of sacropenia in a/mSTS pts on treatment outcome of MT, retrospectively. Methods: Pts. with a/m STS treated at our centre (12/98-5/16ere identified. 89/181 pts were evaluable for analysis (CT-scans: -14 days before MT onset). Lumbar skeletal muscle index (SMI) was measured with MeVisLab 2.7 by manually segmentation of preinterventional CTs. SMI cut-off were defined through optimal fitting method (sarcopenia = SMI(+) in male: &lt; 44 , in female: 38). Progression was defined by clinical or radiological judgment. Descriptive statistics, Kaplan-Meier-analysis and Cox-regression were administered. Results: At MT onset 28/89 pts (31%) suffered from sarcopenia, and SMI(+) pts were older than SMI(-) pts (p = 0.025). SMI(+) pts tends to receive lower numbers of medical treatments, received less often surgery, and more frequently radiotherapy, although differences were not significant. Further on, SMI(+) pts tends to profit less from first line medical treatment, compared to SMI(-) pts (objective responses: 14,3% vs. 27.9%, p = .161, clinical benefit rate: 25% vs. 65.6%, p = .032, PFS: 1 (95%-CI:.35-1.65) vs. 16 (95%CI:8.8-23.2) months, p = .002). OS was inferior in SMI(+) compared to SMI(-) pts. (4 (95%CI:2-6) vs. 16 (95%CI:8.8-23.2), p = .002). Multivariable analysis showed a trend for SMI(+) to be associated with PFS (HR: 1.7 (95%CI: 0.9-2.8), p = .067) and were independently associated with OS (HR: 2.53 (95%CI: 1.5-4.2), p &lt; .001). Conclusions: In our cohort sarcopenia tends to be associated with less aggressive therapy in a/mSTS pts. However, sarcopenia tends to be associated with inferior PFS and was identified as independent risk factor for inferior OS. Although this analysis is limited due to its sample size sarcopenia might offer an attractive tool as guidance for treatment intensity modulation in a/mSTS patients, avoiding overtreatment in this cohort with dismal prognosis.

Predictors of Discordance in the Assessment of Skeletal Muscle Mass between Computed Tomography and Bioimpedance Analysis.

Computed tomography (CT) and bioimpedance analysis (BIA) can assess skeletal muscle mass (SMM). Our objective was to identify the predictors of discordance between CT and BIA in assessing SMM. Participants who received a comprehensive medical health check-up between 2010 and 2018 were recruited. The CT and BIA-based diagnostic criteria for low SMM are as follows: Defined CT cutoff values (lumbar skeletal muscle index (LSMI) <1 standard deviation (SD) and means of 46.12 cm2/m2 for men and 34.18 cm2/m2 for women) and defined BIA cutoff values (appendicular skeletal muscle/height2 <7.0 kg/m2 for men and <5.7 kg/m2 for women). A total of 1163 subjects were selected. The crude and body mass index (BMI)-adjusted SMM assessed by CT were significantly associated with those assessed by BIA (correlation coefficient = 0.78 and 0.68, respectively; p < 0.001). The prevalence of low SMM was 15.1% by CT and 16.4% by BIA. Low SMM diagnosed by CT was significantly associated with advanced age, female gender, and lower serum albumin level, whereas low SMM diagnosed by BIA was significantly associated with advanced age, female gender, and lower BMI (all p < 0.05). Upon multivariate analysis, age >65 years, female and BMI <25 kg/m2 had significantly higher risks of discordance than their counterparts (all p < 0.05). We found a significant association between SMM assessed by CT and BIA. SMM assessment using CT and BIA should be interpreted cautiously in older adults (>65 years of age), female and BMI <25 kg/m2.

Impact of sarcopenia on kidney function during neoadjuvant chemotherapy and post cystectomy complications in patients treated for localized muscle-invasive bladder cancer.

387 Background: Sarcopenia is suspected to influence the complication rates in patients undergoing radical cystectomy. The aim of our study was to assess variations in sarcopenia in patients scheduled for neoadjuvant cisplatin-based chemotherapy (NAC) and radical cystectomy for muscle invasive bladder cancer (MIBC) and to explore the impact of sarcopenia on complications linked to NAC and surgery. Methods: Between January 2012 and December2017, 82 consecutive patients who underwent NAC and RC for cT2-T4 N0 M0 MIBC were retrospectively selected. Using CT scan before and after NAC, Lumbar Skeletal Muscle Index (SMI) was assessed by two observers blinded to patient’s status. We defined severe sarcopenia as SMI &lt; 50 cm2/m2 for men and SMI &lt; 35 cm2/m2 for women. We evaluated pre- and post-NAC cisplatin-based chemotherapy renal function and post-operative complication rates after cystectomy using the Clavien-Dindo classification. We explored risk factors of complications by logistic regression models. Results: According to the SMI cut offs, 47 patients (57.3%) were classified as sarcopenic and 35 patients (42.7%) non-sarcopenic. Patients’ characteristics between sarcopenic and non-sarcopenic patients were not significantly different except for BMI (p &lt; 0.001). Among patients non-sarcopenic before NAC, 9 (19.1%) became sarcopenic after NAC. In multivariate analysis, sarcopenia was an independent significant predictor of renal impairment after NAC (OR 3.01; 95% CI 1.13–8.05; p = 0.02). There was a trend towards a higher rate of stage 3B kidney failure (GFR &lt; 45 mL/min/1.73m2) after NAC in sarcopenic patients (OR 2.79; 95% CI 0.70–11.1) but the difference was not statistically significant (p = 0.14). Moreover, sarcopenia and ASA score were independent significant predictors of postoperative early complications ≤90 days (p = 0.01 and p = 0.02 respectively). Conclusions: We observed significant changes in sarcopenic status during NAC. Sarcopenia, estimated by the lumbar SMI measurement, was an independent predictor associated with the risk of renal impairment during NAC and early postoperative complications after RC.

Increasing adipose burden in young men with metastatic testicular cancer following front-line cytotoxic chemotherapy.

525 Background: Exposure to cytotoxic chemotherapy (CC) has been observed to be associated with significant changes in body composition, namely marked lean muscle mass losses, with implications for treatment-related toxicity and oncologic outcomes. However, prior studies predominately include elderly patients who, a priori, are at risk for sarcopenia or severe skeletal muscle deficiency. To date, the impact of CC on body composition in young men with testicular cancer remains undefined. Methods: A retrospective analysis of 19 patients with metastatic testicular cancer treated with CC was performed (2015-17). Lumbar skeletal muscle index (SMI), visceral (VAI), subcutaneous (SCAI), and intramuscular adipose (IMAI) indices (cm2/m2), as well as fat-free mass (FFM, kg) and fat mass (FM, kg) were calculated using cross-sectional soft tissue area measurements on pre- and post-CC computed tomography (CT) axial scans and compared using paired Wilcoxon Signed Rank Tests. Results: Median age was 29 years. According to the NHANES FMI-based classification, 5 (26.3%), 9 (47.4%), 4 (21.1%), and 1 (5.3%) patients had normal, excess, class I, and class II obesity, respectively. Median pre- and post-CC BMI was 27.7 vs. 29.6 kg/m2(p = 0.03). Median pre- and post-CC SMI, VAI, SAI, and IAI were 63.5 vs 57.8 (p = 0.14), 19.9 vs 30.8 (p = 0.01), 47.9 vs 58.2 (p = 0.03), and 3.0 vs 5.2 (p = 0.002), respectively. Median muscle density pre- and post-CC were 47.0 vs 43.6 HU (p = 0.002). Pre- and post-chemotherapy FFM were 21.5 vs 19.5 kg, representing an overall median loss of 2.8%, (IQR -10.1, +4.7; Range -49.5 - +16.3; p = 0.14). Conversely, pre- and post-CC FM were 6.6 vs 7.5 kg, representing an overall median gain of 13.3% (IQR -3.3, +17.0; -24.9 - +50; p = 0.01). Median time between imaging assessments was 121 days. Specific median measures of adiposity each increased significantly, such that VIA increased by 29% (p = 0.01), SCAI increased by 39.7% (p = 0.03), and IMIA increased by 39.7% (p = 0.002). Conclusions: While lean muscularity remained stable, we observed significant increases in total body adipose mass with decreased muscle density in this consecutive case series of testicular cancer patients following CC.

Sarcopenia is independently associated with decreased overall survival after surgery for inferior vena cava tumor thrombus patients.

674 Background: The presence of sarcopenia, a lean muscle mass deficiency is independently associated with inferior survival following the surgical treatment of localized renal cell carcinoma (RCC). This association has not yet been studied in more advanced disease such as patients with RCC and concomitant IVC thrombus tumors. In this study we retrospectively examined the association between preoperative sarcopenia and overall survival following definitive surgery for IVC tumor thrombus patients. Methods: Baseline lumbar skeletal muscle index (SMI) for patients who underwent surgical treatment for known IVC thrombus tumors between 2006 and 2018 by a single surgeon were quantified at the 3rd lumbar vertebra from preoperative computerized tomography (CT) or magnetic resonance imaging (MRI). The SMI thresholds used to define sarcopenia were developed using ROC analysis of our data and had the most significant relation to overall survival. Overall survival was compared between patients with and without sarcopenia using the Kaplan-Meier method as well as univariate and multivariate cox proportional hazards regression models. Results: The cohort consisted of 194 patients of whom 128 (65%) were male and 146 (75%) were non-Hispanic white. There were 143 (74%) clear cell renal cell carcinoma cases. 110 patients (57%) were sarcopenic. Patients with sarcopenia had significantly decreased overall survival, log-rank p=0.009 (Figure). The presence of sarcopenia was also associated with decreased overall survival in univariate analysis, (hazard ratio (HR)=1.80, 95% CI 1.15-2.83; p=0.010). In multivariable analysis controlled for age, number of comorbidities, and AJCC Stage, sarcopenia maintained significance as a predictor of decreased overall survival (HR= 1.66, 95% CI 1.05-2.61; p=0.030). Conclusions: Preoperative sarcopenia is independently associated with mortality in patients with IVC thrombus tumors.

Association Between Sarcopenia and AFP Level in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

BackgroundSarcopenia is one of the most common complications of cirrhosis. Liver transplantation (LT) is the treatment of choice for patients with early-stage hepatocellular carcinoma (HCC) that are unsuitable for resection. MethodsWe performed a retrospective analysis of 163 patients transplanted at our institution with HCC from 1998 to 2016. Sarcopenia was diagnosed based on the skeletal muscle mass on computed tomography imaging using SliceOmatic 5.0 software at L3 level (≤52.4 cm2/m2 in males and ≤38.5 cm2/m2 in females). ResultsFrom the 163 patients who underwent LT for HCC, 119 had available computed tomography scan. From those, 61 were identified as sarcopenic by lumbar skeletal muscle index (LSMI), of which 53 patients were male (86.9%) with a median age of 59 y (56-64). The most common etiologies of cirrhosis were hepatitis C virus infection (55.7%) and alcohol liver disease (46.7%). A multivariable analysis was performed to find predictors of sarcopenia. Alpha-fetoprotein level >100 mg/dL (OR, 6.577; 95% CI: 1.370-51.464; P = 0.034) and gender (male) (OR, 5.878; 95% CI: 1.987-20.054; P = 0.002) were independently associated with the presence of sarcopenia in this cohort. Patients in the lowest quartile for LSMI had prolonged length of stay compared to the rest of the patients (P = 0.029). ConclusionsAlpha-fetoprotein level >100 mg/dL is associated with almost 6-fold increased risk of sarcopenia in patients with HCC undergoing LT. Patients in the lowest quartile of the LSMI are associated with 70% increased risk of prolonged length of stay in this cohort.

Sarcopenia is associated with postoperative complication after pancreaticoduodenectomy

Introduction: The sarcopenia which is skeletal muscle depletion has been reported to be associated with postoperative recurrence as well as postoperative complications. The aim of this study was to examine whether sarcopenia affects postoperative complications and cancer recurrence. Method: From January 2010 to December 2016, the data of 128 patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, distal bile duct cancer, or ampulla of Vater cancer were consecutively collected. Sarcopenia was validated by lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). The index was measured before surgery, within 1 month after surgery, and between 2 months and 8 months after surgery. The risk factors of postoperative complication and tumor recurrence were investigated. Result: The median age was 69 years (range, 23 to 95). The value obtained by dividing the measured muscle mass by BMI was associated with both postoperative general complications and severe complications in multivariate analysis (p = 0.008 and p = 0.033, respectively). However, the muscle mass index was not associated with clinically relevant pancreatic fistula (p = 0.253). The index measured between 2 months and 8 months after surgery was lower than that measured before surgery. However, the index was not associated with cancer recurrence or death in the survival analysis. Conclusion: The skeletal muscle index measured by CT image was associated with general complication but not pancreatic fistula or survival after pancreaticoduodenectomy.

Muscle Depletion Is an Important and Clinically Relevant Predictor of Outcomes after Autologous Hematopoietic Cell Transplantation

▪Introduction: High intensity treatments such as autologous hematopoietic cell transplantation (HCT) can be curative for patients with relapsed/refractory lymphoma (Hodgkin [HL], non-Hodgkin [NHL]), but this needs to be balanced by the risk of non-relapse mortality (NRM) associated with HCT and potentially sub-optimal disease response with less intensive treatments. Measures of pre-treatment body composition such as quantity and quality of muscle are prognostic in patients with solid tumors, but their association with post-HCT outcomes is unknown. We examined the prognostic significance of muscle depletion prior to HCT, defined by having both low muscle quantity (lumbar skeletal muscle index [SMI]) and quality (muscle attenuation [MA]) on computed tomography (CT) imaging, in a population-based cohort of patients undergoing autologous HCT for lymphoma. Next, we examined the prognostic significance of muscle depletion after HCT in a subset of patients with normal muscle composition prior to HCT, allowing us to examine the impact of change in body composition over time.Methods: 440 consecutive patients with lymphoma, age ≥18y, who underwent a first HCT between 2009 and 2014 at a single institution were included in the study. Measures of muscle quantity (SMI) and quality (MA) were ascertained from pre- and post-HCT abdominal CT scans using image analysis software (SliceOmatic; Tomovision, Quebec, Canada). SMI was calculated as the ratio of skeletal muscle area (cm2) divided by height (m)2. Sex and body mass index (BMI)-specific cutoff values of low SMI and MA were used to identify patients with muscle depletion (J Clin Oncol 2013 31:1539). Measurements were made by trained researchers blinded to patient demographics and HCT outcome (Figure 1); 3rd lumbar vertebra was used as a landmark because of its high correlation with whole-body muscle mass (J Clin Oncol 2016 34:1339). This report is limited to 321 (73%) patients with CT scans performed ≤90 days from HCT. Cumulative incidence of NRM was calculated taking into consideration competing risk of disease-related mortality. Kaplan-Meier method was used to examine overall survival (OS). Multivariable Cox regression analysis was used to calculate the hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates (demographics, diagnosis, pre-HCT Karnofsky performance score [KPS] and comorbidity index [HCT-CI]).Results: Sixty-two (19.3%) patients had muscle depletion pre-HCT. Median age at HCT was 53y (range: 18-78); 62.0% were male; 54.0% were non-Hispanic white; Diagnoses: HL (N=84 [26.2%]), NHL (N=237 [73.8%]); KPS ≤80 (N=87 [27.1%]); HCT-CI ≥3 (N=52 [16.2%]). Impact of pre-HCT muscle depletion: Patients with pre-HCT muscle depletion had significantly worse 5-y OS (56.4% vs. 77.8%, p<0.001; Figure 2) and higher NRM (11.4% vs. 5.1%, p=0.05) when compared to those with normal body composition. OS was especially poor for patients who were obese (BMI ≥30 kg/m2) and had muscle depletion (20.0% vs. 77.1%, p<0.001) pre-HCT. Median length of hospitalization was also significantly longer (27d vs. 23d; p=0.03) among patients with muscle depletion. Muscle depletion was associated with a 2.2-fold (HR=2.2 [CI: 1.0-4.5]) risk of NRM and 1.8-fold (HR=1.8 [CI: 1.1-3.1]) risk of all-cause mortality when compared to those with normal body composition. Impact of post-HCT muscle depletion: Among 223 patients with normal body composition prior to HCT, 24 (9.3%) developed muscle depletion after HCT, detected at a median 63d (range 27-165) from HCT. In these patients, there was a 3-fold (HR=3.1 [CI: 1.5-6.4]) risk of all-cause mortality compared to those who maintained normal muscle composition throughout HCT.Conclusion: Muscle depletion is an important and independent predictor of outcomes after HCT, with potential additional downstream impacts on health-economic outcomes such as length of hospitalization and the burden of chronic morbidity in long-term survivors. Taken together, these data form the basis for real-time decision making prior to HCT (e.g. pre-habilitation, less intensive treatment approaches), or during HCT (e.g. dietary optimization, increased supportive care services, resistance training), setting the stage for innovative strategies to improve outcomes after HCT. DisclosuresChen:Affimed: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech Inc.: Consultancy; Millennium Pharmaceuticals: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Changes in Lean Muscle Mass Associated with Neoadjuvant Platinum-Based Chemotherapy in Patients with Muscle Invasive Bladder Cancer.

Background: Baseline sarcopenia or severe lean muscle deficiency is independently associated with increased mortality after cystectomy for muscle-invasive urothelial carcinoma of the bladder (MIUC). The impact of chemotherapy on muscle mass in MIUC patients remains undefinedObjectives: To describe preoperative changes in body composition in MIUC patients receiving platinum-based neoadjuvant chemotherapy (NC).Methods: Patients with cT2-4 N0-1 M0 UC of the bladder who received NC were identified. Lumbar skeletal muscle index (SMI, cm2/m2), visceral adipose index (VAI, cm2/m2), and the subcutaneous and intramuscular adipose index (SAI, cm2/m2) were calculated using validated methodology (cross sectional area of skeletal muscle/height2 at L3) from measurement of soft tissue areas on pre- (pre-NC) and post-NC (post-NC) computed tomography. Patients were classified as sarcopenic according to consensus definitions: Male: SMI <55 cm2/m2, Female: SMI <38.5 cm2/m2. Pre-NC and post-NC median body mass index (BMI kg/m2), SMI, and adipose indices were compared.Results: The study cohort consisted of 26 patients, with a median age 70 years, including 7 females (27%). Chemotherapy regimens included dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (31%), gemcitabine/cisplatin (62%) and gemcitabine/carboplatin (3.8%) with a median of 3.5 (range 2–6) cycles. Median pre- and post-NC BMI were 27.1 kg/m2 and 27.2 kg/m2 (p = 0.36). Median pre- and post-NC SMI were 49.1 cm2/m2 and 44.5 (p < 0.001) respectively. Median percent change in SMI was –6.4% (range –30% to 10%). Pre-NC, 18 (69%) patients were sarcopenic vs. 21 (81%, p = 0.002) post-NC. Median time between initiation of chemotherapy and cystectomy was 110 days.Conclusions: We observed a significant decrease in lean muscle mass among MIUC patients treated with platinum-based NC prior to cystectomy, with an associated increase in the prevalence of sarcopenia. Patients undergoing NC may benefit from pre-habilitative interventions to mitigate lean muscle loss prior to cystectomy.

Lean and fat-mass changes following upfront docetaxel compared to androgen deprivation monotherapy in metastatic castration-naïve prostate cancer.

e17020Background: Sarcopenia refers to the functional decline associated with severe deficiency of skeletal muscle mass (lumbar skeletal muscle index (SMI) < 55cm2/m2 for males). The objective of t...

Sarcopenia predicts 90-day mortality and postoperative complications after radical cystectomy for bladder cancer

A single-center study was conducted to investigate the impact of sarcopenia as a predictor for 90-day mortality (90dM) and complications within 90days after radical cystectomy for bladder cancer. In total, 327 patients with preoperative available digital computed tomography (CT) scans of the abdomen and pelvis were identified. The lumbar skeletal muscle index was measured using preoperative abdominal CT to assess sarcopenia. Complications were recorded and graded according to Clavien-Dindo (CD). Predictors of 90dM and complications within 90days were analyzed by uni- and multivariable logistic regression. Of the 327 patients, 262 (80%) were male and 108 (33%) patients were classified as sarcopenic. Within 90days, 28 (7.8%) patients died, of whom 15 patients were sarcopenic and 13 were not. In multivariable logistic regression analysis, sarcopenia (OR 2.59; 95% CI 1.13-5.95; p = 0.025), ASA 3-4 (OR 2.53; 95% CI 1.10-5.82; p = 0.029) and cM + (OR 7.43; 95% CI 2.34-23.64; p = 0.001) were independent predictors of 90-day mortality. Sarcopenic patients experienced significantly more complications, i.e., CD 4a-5 (p = 0.003), compared to non-sarcopenic patients. In multivariable logistic regression analysis, sarcopenia was independently associated with CD ≥ 3b complications corrected for age, BMI, ASA-Score and type of urinary diversion. We reported that sarcopenia proved an independent predictor for 90 dM and complications in patients undergoing RC for bladder cancer.

Impact of Low Muscularity and Myosteatosis on Long-term Outcome After Curative Colorectal Cancer Surgery: A Propensity Score-Matched Analysis.

Muscle loss, characterized by reduced muscle mass (myopenia), and infiltration by intermuscular and intramuscular fat (myosteatosis), predicts a poor short-term prognosis in patients with colorectal cancer. However, little is known about the influence of myopenia and myosteatosis on long-term outcomes. The present study aimed to evaluate the prognostic influence of both myopenia and myosteatosis on long-term outcomes after curative colorectal cancer surgery. This is a retrospective analysis using a propensity score-matched analysis to reduce the possibility of selection bias. The study was conducted at a single institution. We performed a retrospective analysis of 211 consecutive patients with stage I to III colorectal cancer who underwent curative surgery between 2010 and 2011. CT scans were analyzed to calculate the lumbar skeletal muscle index and mean muscle attenuation using a SYNAPS VINCENT. The primary outcome measure was cancer-specific survival. Secondary end points included overall survival and disease-free survival. Of 211 patients, a total of 102 and 106 were matched for myopenia and myosteatosis analyses. The median follow-up was 57.6 months. Versus the nonmyopenia group, the myopenia group manifested a significantly shorter cancer-specific survival, overall survival, and disease-free survival. Significantly shorter cancer-specific survival and overall survival times were also identified for the myosteatosis versus the nonmyosteatosis group. Before matching, multivariate analyses identified both myopenia and myosteatosis as independent prognostic factors for cancer-specific survival (p = 0.04 and p < 0.01), overall survival (p = 0.03 and p < 0.01), and disease-free survival (p < 0.01 and p < 0.01). This study is limited by its retrospective, nonrandomized design. Myopenia and myosteatosis adversely affect long-term outcomes after curative colorectal cancer resection. See Video Abstract at http://links.lww.com/DCR/A463.