Low Skeletal Muscle Density Research Articles

The relationship between computed tomography-derived body composition, systemic inflammatory response, and survival in patients undergoing surgery for colorectal cancer.

IntroductionColorectal cancer is the fourth leading cause of cancer mortality in developed countries. There is evidence supporting a disproportionate loss of skeletal muscle as an independent prognostic factor. The importance of the systemic inflammatory response as a unifying mechanism for specific loss of skeletal muscle mass in patients with cancer is increasingly recognized. The aim of the present study was to delineate the relationship between the systemic inflammatory response, skeletal muscle index (SMI), skeletal muscle density (SMD), and overall survival in patients with colorectal cancer.Materials and methodsThe study included 650 patients with primary operable colorectal cancer. Computed tomography scans were used to define the presence of visceral obesity, sarcopenia (low SMI), and myosteatosis (low SMD). Tumour and patient characteristics were recorded. Survival analysis was carried out using univariate and multivariate Cox regression.ResultsA total of 650 patients (354 men and 296 women) were included. The majority of patients were over 65 years of age (64%) and overweight or obese (68%). On univariate survival analysis, age, ASA, TNM stage, modified Glasgow Prognostic Score (mGPS), body mass index, subcutaneous fat index, visceral obesity, SMI, and SMD were significantly associated with overall survival (all P < 0.05). A low SMI and SMD were significantly associated with an elevated mGPS (<0.05). On multivariate analysis, SMI (Martin) [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.04–2.18, P = 0.031], SMD (Xiao) (HR 1.42, 95% CI 0.98–2.05, P = 0.061), and mGPS (HR 1.44, 95% CI 1.15–1.79, P = 0.001) were independently associated with overall survival. SMD but not SMI was significantly associated with ASA (P < 0.001).ConclusionsThis study delineates the relationship between the loss of quantity and quality of skeletal muscle mass, the systemic inflammatory response, and survival in patients with operable colorectal cancer.

Body Composition Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma Treated with Sorafenib

Background: Previous studies have suggested body composition as a predictor of sorafenib toxicity and outcome in patients with advanced hepatocellular carcinoma (HCC). Large studies on the impact of body composition parameters in European HCC patients are lacking. Our aim was to validate the prognostic value of body composition parameters in Dutch patients with HCC treated with sorafenib. Patients and Methods: A retrospective analysis was performed in a cohort of HCC patients treated with sorafenib at two Dutch tertiary referral centers between 2007 and 2016. Body composition (adipose and skeletal muscle tissue) was measured at baseline by computed tomography (CT). Low skeletal muscle mass (SMM) and density were defined using published cut-offs. Body composition parameters were correlated with overall survival (OS), time to progression, response rate, and toxicity. Results: A total of 278 patients were included, mostly Child-Pugh class A (85%) and Barcelona Clinic Liver Cancer (BCLC) stage C (73%), with a median OS of 9.5 months (95% CI 8.1–11.0). Patients with combined low SMM and low total adipose tissue index (TATI) (n = 68, 25%) had a poor median OS (5.8, 95% CI 4.8–6.8) compared with other patients (11.7, 95% CI 9.4–14.0). Combined low SMM and low TATI remained an independent predictor of OS (HR 1.56, 95% CI 1.15–2.11, p = 0.004) after adjusting for known prognostic factors. There was no association between body composition and sorafenib toxicity. Conclusions: In Dutch HCC patients treated with sorafenib, the combined presence of low SMM and low TATI was associated with impaired survival, independent of known prognostic factors. CT assessment of body composition may provide additional prognostic information prior to sorafenib treatment.

The Impact of Low Skeletal Muscle Mass and Density on Patients with Head and Neck Cancer Receiving Concurrent Chemoradiation

Sarcopenia (decrease in skeletal muscle) is a predictor of poor prognosis in cancer patients. Head and neck cancer patients are at risk for sarcopenia from nutritional compromise from their disease. Skeletal muscle index (SMI) and skeletal muscle density (SMD) are measures of sarcopenia that can be obtained from diagnostic imaging studies. While SMI has been studied in head and neck cancer, SMD is thought to be a more specific marker for poor outcomes and has not been previously reported in this population. To better understand the impact of SMD in head and neck cancer, we conducted a review of patients receiving concurrent chemoradiation and assessed outcomes with respect to SMI and SMD. Medical records of consecutive patients treated for histologically-proven head and neck cancer at a single center between 2011 and 2015 were reviewed. All patients received concurrent chemoradiation. Chemotherapy varied per medical oncology discretion. Measurements of SMI and SMD were obtained from treatment planning computed tomography (CT) scans using previously published methods. Image analysis was performed by a single, blinded observer using NIH ImageJ software. SMI was calculated as the cross-sectional area of the paravertebral and sternocleidomastoid muscles at a single axial CT slice at the level of the C3 vertebral body, while SMD was calculated using the mean radiation attenuation at the same level. Thresholds for low SMI and SMD were defined based on previously validated criteria. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method with comparison between groups performed using the log-rank test. Association between patient factors and survival was calculated in univariate and multivariate analysis. Two hundred and twenty-two patients met criteria for inclusion. Median follow-up was 31 months (range 1-73 months). The most common subsite was oropharyngeal cancer (63%). Post-op patients comprised 24% of the sample. Fifty-six percent of patients met criteria for low SMI and 38% met criteria for low SMD. Thirty-nine percent of patients experienced chemotherapy delays of >1 week and 36% missed radiation days due to toxicity. There was no difference in OS (p=0.93) or PFS (p=0.33) between patients with low versus normal SMI. Patients with low SMD had significantly worse OS (p=0.01) and PFS (p=0.02) compared to those with normal SMD. On multivariate analysis, age>60 (p=0.03), radiation delays (p=0.01), low albumin (p=0.01), and low SMD (p=0.04) were all associated with decreased OS, while radiation delays (p<.01) and low SMD were associated with decreased PFS (p=0.04). Low SMD is associated with worse cancer-related outcomes in patients with head and neck cancer receiving concurrent chemoradiation and may serve as a stronger predictor for poor survival than low SMI.

Pre-operative muscle density and not muscle mass is associated with overall mortality in early-stage colorectal cancer patients

Rationale: In cancer patients with a relatively poor prognosis, both low skeletal muscle mass and low skeletal muscle density are thought to be associated with higher mortality. Whether these associations also hold for earlier stage cancer is less clear. We aimed to study the association between muscle mass, density and overall mortality among early-stage (stage I-III) colorectal cancer (CRC) patients with a relatively good prognosis.

Low radiographic muscle density is associated with lower overall and disease-free survival in early-stage colorectal cancer patients

BackgroundIn cancer patients with a poor prognosis, low skeletal muscle radiographic density is associated with higher mortality. Whether this association also holds for early-stage cancer is not very clear. We aimed to study the association between skeletal muscle density and overall mortality among early-stage (stage I–III) colorectal cancer (CRC) patients. Furthermore, we investigated the association between skeletal muscle density and both CRC-specific mortality and disease-free survival in a subset of the study population.MethodsSkeletal muscle density was assessed in 1681 early-stage CRC patients, diagnosed between 2006 and 2015, using pre-operative computed tomography images. Adjusted Cox proportional hazard models were used to evaluate the association between muscle density and overall mortality, CRC-specific mortality and disease-free survival.ResultsThe median follow-up time was 48 months (range 0–119 months). Low muscle density was detected in 39% of CRC patients. Low muscle density was significantly associated with higher mortality (low vs. normal: adjusted HR 1.91, 95% CI 1.53–2.38). After stratification for comorbidities, the association was highest in patients with ≥ 2 comorbidities (HR 2.11, 95% CI 1.55–2.87). Furthermore, low skeletal muscle density was significantly associated with poorer disease-free survival (HR 1.68, 95% CI 1.14–2.47), but not with CRC-specific mortality (HR 1.68, 95% CI 0.89–3.17) in a subset of the study population.ConclusionIn early-stage CRC patients, low muscle density was significantly associated with higher overall mortality, and worse disease-free survival.

Impact of low skeletal muscle mass and density on short and long-term outcome after resection of stage I-III colorectal cancer

BackgroundPreoperative low skeletal muscle mass and density are associated with increased postoperative morbidity in patients undergoing curative colorectal cancer (CRC) surgery. However, the long-term effects of low skeletal muscle mass and density remain uncertain. MethodsPatients with stage I-III CRC undergoing surgery, enrolled in a prospective observational cohort study, were included. Skeletal muscle mass and density were measured on CT. Patients with high and low skeletal muscle mass and density were compared regarding postoperative complications, disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). ResultsIn total, 816 patients (53.9% males, median age 70) were included; 50.4% had low skeletal muscle mass and 64.1% low density. The severe postoperative complication rate was significantly higher in patients with low versus high skeletal muscle and density (20.9% versus 13.6%, p = 0.006; 20.0% versus 11.8%, p = 0.003). Low skeletal muscle mass (OR 1.91, p = 0.018) and density (OR 1.87, p = 0.045) were independently associated with severe postoperative complications. Ninety-day mortality was higher in patients with low skeletal muscle mass and density compared with patients with high skeletal muscle mass and density (3.6% versus 1.7%, p = 0.091; 3.4% versus 1.0%, p = 0.038). No differences in DFS were observed. After adjustment for covariates such as age and comorbidity, univariate differences in OS and CSS diminished. ConclusionsLow skeletal muscle mass and density are associated with short-term, but not long-term, outcome in patients undergoing CRC surgery. These findings recommend putting more emphasis on preoperative management of patients at risk for surgical complications, but do not support benefit for long-term outcome.

Proteomic identification of potential markers of myosteatosis in human urine

Myosteatosis, the infiltration of fat in skeletal muscle, is associated with lower skeletal muscle density (SMD) as detected by computed tomography (CT). It increases with aging and obesity and is thought to play a role in the aetiology of insulin resistance and type II diabetes. The clinical significance of myosteatosis in cancer cachexia, however, remains to be determined. Along with demonstrable subcutaneous and visceral lipolysis, myosteatosis may also be a key component of the syndrome. We aimed to investigate the use of human urine as a non-invasive way to screen for molecular biomarkers of myosteatosis/reduced SMD using SELDI-TOF mass spectrometry. Pre-operative CT scans of patients undergoing surgery for upper gastrointestinal or hepatopancreaticobiliary cancer were analysed at the level of the third lumbar vertebrae. Myosteatosis was inferred as the presence of reduced SMD, which was defined as Hounsfield units for skeletal muscle <39.5 (two standard deviations below a normal healthy cohort). Urine was analysed by mass spectrometry using CM10 and IMAC30 SELDI-chips. Peaks observed in the CM10 and IMAC30 chip types, showed marked expressional differences between control and myosteatosis, were further investigated by mascot SELDI matrix matching. A total of 55 patients was recruited; 31 patients were found to be myosteatotic on CT scan. Application of the IMAC30-derived model to the entire cohort showed a sensitivity of 97%, specificity of 71% and an overall correctness of 85%. Application of the CM10 chipset-based model to the entire cohort, showed a 77% sensitivity, 67% specificity and 73% overall correctness. Analysis of the peaks of interest resulted in the identification of significant fragments of cathepsin C, argin, arylsulfatase A and glial fibrillary acidic protein. We identified several potential urinary molecular biomarkers associated with reduced SMD in cancer. Such markers are potentially useful in deriving a clinical screening test for myosteatosis.

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment

Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7–9.3) and high (HR 12.1, 95% CI 8.1–16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03–3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44–1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.

Abstracts of the 10th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Rome, Italy, 8-10 December 2017 (Part 1)

Abstracts of the 10th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Rome, Italy, 8-10 December 2017 (Part 1)

Contrast-enhancement influences skeletal muscle density, but not skeletal muscle mass, measurements on computed tomography

Low skeletal muscle mass and density have recently been discovered as prognostic and predictive parameters to guide interventions in various populations, including cancer patients. The gold standard for body composition analysis in cancer patients is computed tomography (CT). To date, the effect of contrast-enhancement on muscle composition measurements has not been established. The aim of this study was to determine the effect of contrast-enhancement on skeletal muscle mass and density measurements on four-phase CT studies. In this observational study, two observers measured cross-sectional skeletal muscle area corrected for patients' height (skeletal muscle index [SMI]) and density (SMD) at the level of the third lumbar vertebra on 50 randomly selected CT examinations with unenhanced, arterial, and portal-venous phases. The levels of agreement between enhancement phases for SMI and SMD were calculated using intra-class correlation coefficients (ICCs). Mean SMI was 42.5 (±9.9)cm2/m2 on the unenhanced phase, compared with 42.8 (±9.9) and 43.6 (±9.9)cm2/m2 for the arterial and portal-venous phase, respectively (both p<0.01). Mean SMD was lower for the unenhanced phase (30.9±8.0Hounsfield units [HU]) compared with the arterial (38.0±9.9HU) and portal-venous (38.7±9.2HU) phase (both p<0.001). No significant difference was found between SMD in the portal-venous and arterial phase (p=0.161). The ICCs were excellent (≥0.992) for all SMIs and for SMD between the contrast-enhanced phases (0.949). The ICCs for the unenhanced phase compared with the arterial (0.676) and portal-venous (0.665) phase were considered fair to good. Statistically significant differences in SMI were observed between different enhancement phases. However, further work is needed to assess the clinical relevance of these small differences. Contrast-enhancement strongly influenced SMD values. Studies using this measure should therefore use the portal-venous phase of contrast-enhanced CT examinations.

Low skeletal muscle density is associated with early death in patients with suspected perihilar cholangiocarcinoma

Low skeletal muscle density is associated with early death in patients with suspected perihilar cholangiocarcinoma

The Association of Computed Tomography-Assessed Body Composition with Mortality in Patients with Necrotizing Pancreatitis

BackgroundIdentification of patients with necrotizing pancreatitis at high risk for a complicated course could facilitate clinical decision-making. In multiple diseases, several parameters of body composition are associated with impaired outcome, but studies in necrotizing pancreatitis are lacking. MethodsA post hoc analysis was performed in a national prospective cohort of 639 patients with necrotizing pancreatitis. Skeletal muscle mass, skeletal muscle density, and visceral adipose tissue were measured at the third lumbar vertebra level (L3) on contrast-enhanced computed tomography (CT) within 10 days after initial admission and 1 month thereafter. ResultsIn total, 496 of 639 patients (78%) were included. Overall mortality rate was 14.5%. Skeletal muscle mass and density and visceral adipose tissue on first CT were not independently associated with in-hospital mortality. However, low skeletal muscle density was independently associated with increased mortality in patients ≥65 years (OR 2.54 (95%CI 1.12–5.84, P = 0.028). Skeletal muscle mass and density significantly decreased within 1 month, for both males and females, with a median relative loss of muscle mass of 12.9 and 10.2% (both P < 0.001), respectively. Skeletal muscle density decreased with 7.2 and 7.5% (both P < 0.001) for males and females, respectively. A skeletal muscle density decrease of ≥10% in 1 month was independently associated with in-hospital mortality: OR 5.87 (95%CI 2.09–16.50, P = 0.001). ConclusionFirst CT-assessed body composition parameters do not correlate with in-hospital mortality in patients with necrotizing pancreatitis. Loss of skeletal muscle density ≥10% within the first month after initial admission, however, is significantly associated with increased mortality in these patients.

Skeletal muscle quality as assessed by CT-derived skeletal muscle density is associated with 6-month mortality in mechanically ventilated critically ill patients.

BackgroundMuscle quantity at intensive care unit (ICU) admission has been independently associated with mortality. In addition to quantity, muscle quality may be important for survival. Muscle quality is influenced by fatty infiltration or myosteatosis, which can be assessed on computed tomography (CT) scans by analysing skeletal muscle density (SMD) and the amount of intermuscular adipose tissue (IMAT). We investigated whether CT-derived low skeletal muscle quality at ICU admission is independently associated with 6-month mortality and other clinical outcomes.MethodsThis retrospective study included 491 mechanically ventilated critically ill adult patients with a CT scan of the abdomen made 1 day before to 4 days after ICU admission. Cox regression analysis was used to determine the association between SMD or IMAT and 6-month mortality, with adjustments for Acute Physiological, Age, and Chronic Health Evaluation (APACHE) II score, body mass index (BMI), and skeletal muscle area. Logistic and linear regression analyses were used for other clinical outcomes.ResultsMean APACHE II score was 24 ± 8 and 6-month mortality was 35.6%. Non-survivors had a lower SMD (25.1 vs. 31.4 Hounsfield Units (HU); p < 0.001), and more IMAT (17.1 vs. 13.3 cm2; p = 0.004). Higher SMD was associated with a lower 6-month mortality (hazard ratio (HR) per 10 HU, 0.640; 95% confidence interval (CI), 0.552–0.742; p < 0.001), and also after correction for APACHE II score, BMI, and skeletal muscle area (HR, 0.774; 95% CI, 0.643–0.931; p = 0.006). Higher IMAT was not significantly associated with higher 6-month mortality after adjustment for confounders. A 10 HU increase in SMD was associated with a 14% shorter hospital length of stay.ConclusionsLow skeletal muscle quality at ICU admission, as assessed by CT-derived skeletal muscle density, is independently associated with higher 6-month mortality in mechanically ventilated patients. Thus, muscle quality as well as muscle quantity are prognostic factors in the ICU.Trial registrationRetrospectively registered (initial release on 06/23/2016) at ClinicalTrials.gov: NCT02817646.

Circulating Activin A is predictive of survival of cancer patients

Introduction and aim We demonstrated that human cancer cachexia is associated with increased circulating concentrations of Activin A. Given the cachectic and anorectic effect of Activin A demonstrated in animal models, our observation suggests that Activin A might play a role in the development of human cancer cachexia. Indeed, circulating Activin A was correlated positively with weight loss and negatively with skeletal muscle density, two well-established prognosis factors in cancer patients. Our goal was to investigate the value of circulating Activin A as a marker of survival in cancer patients. Material and methods Patients with colorectal or lung cancer were recruited at the time of diagnosis or at relapse and had clinical, nutritional (SNAQ score) and functional (ECOG, QLQC30) assessment. Body composition and skeletal muscle density were measured by CT-scan and plasma concentrations of Activin A were determined. Overall survival was estimated during 12 months (–1/ + 2 months) after inclusion. Results Among 152 patients included in the study, survival data was available for 149 patients. Patients with high levels of Activin A (> 665 pg/mL) had lower overall survival (68%) than those with levels in the normal range (84%; P Conclusion In cancer patients, a high circulating concentration of Activin A was associated with a shorter overall survival. Significant weight loss, low muscularity and low skeletal muscle density, were also associated with a poor prognosis.

Low skeletal muscle density is associated with poor survival in patients who receive chemotherapy for metastatic gastric cancer.

Low skeletal muscle density (SMD) and low skeletal muscle index (SMI) are associated with poor overall survival (OS) in patients with various types of cancer. We retrospectively studied SMD and SMI using computed tomographic (CT) scans in patients with gastric cancer receiving chemotherapy to evaluate its prognostic significance. SMD and SMI were obtained from CT-based analysis using Slice-O-Matic® medical imaging software in patients who received S-1 plus cisplatin chemotherapy for metastatic gastric cancer. The CT images taken within 1 month before starting chemotherapy were used. The cut-off values for determining low SMD [<33 Hounsfield units (HU) in obese and <41 HU in non-obese patients] and low SMI (<41 cm2/m2 in females, <43 cm2/m2 in non-obese males and <53 cm2/m2 in obese males) were referenced from a large population based study. The CT images of 53 patients were reviewed. The median SMD was 36.8 HU (range, 19.5-59.3 HU), and the median SMI was 39.8 cm2/m2 (range, 23.7-60.0 cm2/m2). Patients with low SMD had significantly shorter OS compared with patients having normal SMD (8.9 vs. 12.8 months, P=0.03). However, OS did not differ significantly between patients with low and normal SMI (11.1 and 14.3 months, P=0.18). Multivariate analyses confirmed that low SMD was an independent predictor of poor outcomes (P<0.01). SMD is an important prognosticator of survival in patients with metastatic gastric cancer receiving chemotherapy.

Low Skeletal Muscle Density is Predictive for Febrile Neutropenia in Patients Treated By Doxorubicin/Trabectedin/Pegfilgrastim Combination As a First-Line Treatment of Advanced or Metastatic Leiomyosarcoma (Lms) (Lms02 Study)

ABSTRACT Background: Studies have shown that skeletal muscle mass (SMM) and skeletal muscle densities (SMD) are associated to chemotherapy toxicity. In 110 patients treated with a combination of doxorubicin (doxo) and trabectedin (trab), neutropenia and febrile neutropenia are still observed despite the use of granulocyte colony stimulating factor (G-CSF) (ASCO 2013; abstract 10505). Our aim was to analyze whether SMM or SMD are predictive of febrile neutropenia Methods: SMM and SMD were assessed with computed tomography (CT) imaging before treatment by measuring cross-sectional areas of the tissues for SMM and the mean muscle Hounsfield Units (HU) for SMD. SMD assessed by this method reflects fatty muscle infiltration with lower mean HU reflecting lower density, and more fatty infiltration. Toxicity profile was collected for all cycles. Therefore severe toxicity is defined as any grade 3 or 4 toxicity. The cut-off level which predicts the occurrence of toxicity most accurately was deduced from the receiver operating characteristic curve (for SMD the value is: 37.1 HU). Pts received doxo 60 mg/m2 followed by trab 1.1 mg/m2 IV in 3-h at day 1, and pegfilgrastim 6 mg on day 2 every 21 days for a maximum of 6 cycles Results: 55 pts were included (46 females and 9 males), with median age of 58 years, 27 pts with uterine LMS and 28 with soft tissue LMS were analyzed. Only 2 pts had an ECOG PS score >1. Pts received a total of 285 cycles with a median of 6 cycles per pt. Pts with a low density (SMD 37.1 (6/36; 17%) (p=0.05). No association between toxicity and SMM was found. Conclusions: Despite the use of GCSF, febrile neutropenia is observed in pts treated with doxo+trab. In this pilot study including a few pts, muscle density has been found to be associated with a high probability of febrile neutropenia. These interesting results need to be confirmed. They might highlight the concept of frailty i.e. a group of non-oncologic parameters associated with a higher susceptibility to events Disclosure: S. Antoun: Advisory board for Baxter nutrition; P. Pautier: Expert board for PHARMAR. All other authors have declared no conflicts of interest.

Low skeletal muscle density as predictive for febrile neutropenia in patients treated by doxorubicin/trabectedin/pegfilgrastim combination as a first-line treatment of advanced or metastatic leiomyosarcoma (LMS) (LMS02 study).

e20640 Background: Studies have shown that skeletal muscle mass (SMM) and skeletal muscle densities (SMD) are associated to chemotherapy toxicity. In 110 patients treated with a combination of doxo...

Indolent Non-Hodgkin Lymphoma: Skeletal Muscle Density Predicts Overall Survival With Rituximab Based Chemotherapy

IntroductionSarcopenia is an adverse risk factor for solid organ malignancies. Recent evidence suggests sarcopenia confers a poor prognosis in diffuse large B-cell lymphoma, but further study is needed to evaluate its role in other Non-Hodgkin Lymphoma (NHL) subtypes. Low skeletal muscle density (SMD) has also been identified as a risk factor for poor prognosis; it is more prognostic than sarcopenia in renal cell carcinoma and melanoma. Low SMD is hypothesized to be a marker of inflammation that suggests more active disease. SMD can be approximated using computed tomography (CT) images and measuring muscle radiation attenuation in Hounsfield Units (HU). An average muscle SMD of <30 HU is considered to be poorly functioning muscle and has the appearance of ectopic fat production. This study examines sarcopenia and SMD in follicular lymphoma (FL). MethodsFL patients from 2004-2009 who received rituximab-based chemotherapy at our institution were retrospectively reviewed. Aside from baseline information (stage, age, gender, height, weight, performance status, FL International Prognostic Index 1 score [FLIPI-1], chemotherapy regimen received), progression free survival (PFS) and overall survival (OS) was collected as primary endpoints. Sarcopenia and SMD were calculated using Slice-o-Matic (Tomovision, Montreal Canada) with patients' pre-treatment CT images. Skeletal muscle was defined as between -29 to 150 HU, intramuscular adipose tissue -190 to -30 HU; and visceral adipose tissue -150 to -50 HU. Skeletal muscle surface area and average radiation attenuation at the L3 vertebral body level were measured. Sarcopenia was pre-defined using skeletal muscle surface area cut-offs outlined in prior solid organ malignancy studies and from the elderly DLBCL study. Results145 FL patients were identified. Median age was 59 years (range 29-83 years), with a median FLIPI-1 score of 2, median stage III, 79 male, and 66 female. The majority of patients received R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) chemotherapy with a median 8 cycles received (range 1-8) and 87 patients given maintenance rituximab. Median PFS and OS were 44.7 and 56.8 months, respectively. Patients with sarcopenia failed to have significant differences in either PFS or OS. The PFS hazard ratio (HR) of 1.26 suggested a trend for poor outcomes in sarcopenic patients (p=0.17). A specific cut-off for sarcopenia was not identifiable. However, comparing patients with SMD below the median to those above yielded a PFS of 40.9 vs 49.7 months (HR 1.91; p=0.01), respectively. Significant differences in OS similarly occurred for below and above the median SMD with 52.8 vs 63.3 months (HR 2.61;p=0.01). A discernible cut-off parameter for SMD was identified at 36.61 HU. PFS for those with lower than this SMD was a more pronounced detriment at 39.3 vs 55.3 months (HR 2.76; p=0.0005), respectively. OS of 51.9 vs 64.7 months (HR 4.67; p=0.0001) was also more pronounced at levels below and above the SMD cut-off parameter, respectively. Multivariate analysis found OS (HR = 4.08; p=0.004) in favor of the higher SMD group and independent of FLIPI-1 or gender. ConclusionsIn FL, SMD is a strong prognostic marker independent of the FLIPI-1 scores while sarcopenia has less of a prognostic role. SMD can be used as an additional tool to stratify FL patients. Evaluation of SMD and its mechanistic link with inflammation requires further study. Disclosures:No relevant conflicts of interest to declare.

Aggressive Non-Hodgkin Lymphoma: Predictive Value Of Sarcopenia and Skeletal Muscle Density On Prognosis With Rituximab Containing Therapy

IntroductionSarcopenia is an established adverse risk factor for solid organ malignancies. Recent evidence suggests sarcopenia predicts a poor prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL) independent of Revised International Prognostic Index (R-IPI) scores. Because of the focus on an elderly population, it is difficult to generalize to the DLBCL population as a whole. Newer evidence suggests low skeletal muscle density (SMD) is a more significant indicator of poor prognosis in renal cell carcinoma and melanoma than sarcopenia. SMD can be approximated using computed tomography (CT) images and measuring muscle radiation attenuation in Hounsfield Units (HU). An average muscle SMD of <30 HU is considered to be poorly functioning muscle and has the appearance of ectopic fat production. This study examines sarcopenia and SMD in DLBCL. MethodsDLBCL patients from 2004-2009 who received rituximab-based chemotherapy through our institution were retrospectively reviewed. Aside from baseline information (stage, age, gender, height, weight, performance status, R-IPI score, chemotherapy regimen and cycles received), progression free survival (PFS) and overall survival (OS) were collected as primary endpoints. Sarcopenia and SMD were calculated using Slice-o-Matic (Tomovision, Montreal Canada) with patients' pre-treatment CT images. Skeletal muscle was defined as between -29 to 150 HU, intramuscular adipose tissue -190 to -30 HU; and visceral adipose tissue -150 to -50 HU. Skeletal muscle surface area and average radiation attenuation at the L3 vertebral body level were measured. Sarcopenia was pre-defined using skeletal muscle surface area cut-offs outlined in prior solid organ malignancy studies and from the elderly DLBCL study. ResultsWe identified 224 DLBCL patients. Median age at diagnosis was 62 years (range 21-88 years), with 124 male, and 100 female. Median stage at diagnosis was III with a median IPI score of 3. The majority received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with a median of 6 cycles (range 1-8). Median PFS and OS were 55.2 and 56.3 months, respectively. Patients with sarcopenia did not have a significant difference in either PFS or OS. In fact, the PFS hazard ratio (HR) of 0.70 would suggest sarcopenia as being protective but it was not statistically significant (p=0.19). Subgroup analysis of elderly DLBCL patients (defined as >70 years), found sarcopenia was protective for both PFS and OS yielding HRs of 0.24 and 0.45, respectively (p=0.002 and 0.05). A statistically insignificant PFS improvement by SMD was seen above and below the median SMD with 61.0 and 52.8 months, HR 1.28 (p=0.32), respectively. However, OS was significantly better in those above the median SMD at 65.5 vs 51.4 months, HR 2.02 (p=0.006). A cut-off point in SMD was noticeable at 26.63 HU where PFS was significantly worse in those that had lower SMD with 53.3 vs 56.3 months, HR 1.74 (p=0.03). OS was also significantly poorer with SMD lower than this cut-off, 51.9 vs 59.2 months, HR 1.92 (p=0.01), respectively. This difference though failed to maintain significance in multivariate analysis taking into consideration R-IPI and gender. ConclusionsContrary to recent evidence suggesting sarcopenia as a poor prognostic factor in elderly patients with DLBCL, our study demonstrates that sarcopenia may in fact be protective. Perhaps patients with lower lean body mass may be exposing their disease to relatively higher concentrations of chemoimmunotherapy. SMD is more prognostic than sarcopenia in DLBCL patients. While these findings suggest muscle mass and muscle quality play a strong role in the disease process, factors captured in the R-IPI score predict clinical course more strongly. Disclosures:No relevant conflicts of interest to declare.

Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies

Studies have shown that skeletal muscle and adipose tissue are linked to overall survival (OS) and progression-free survival (PFS). Because targeted therapies have improved the outcome in patients with metastatic renal cell carcinoma (mRCC), new prognostic parameters are required. The objective of the current study was to analyze whether body composition parameters play a prognostic role in patients with mRCC. Adipose tissue, skeletal muscle, and skeletal muscle density (SMD) were assessed with computed tomography imaging by measuring cross-sectional areas of the tissues and mean muscle Hounsfield units (HU). A high level of mean HU indicates a high SMD and high quality of muscle. OS and PFS were estimated using the Kaplan-Meier method and compared with the log-rank test. The multivariable Cox proportional hazards model was adjusted for Heng risk score and treatment. In the 149 patients studied, the median OS was 21.4 months and was strongly associated with SMD; the median OS in patients with low SMD was approximately one-half that of patients with high SMD (14 months vs 29 months; P = .001). After adjustment for Heng risk score and treatment, high SMD was associated with longer OS (hazards ratio, 1.85; P = .004) and longer PFS (hazards ratio, 1.81; P = .002). Adding SMD will separate the intermediate-risk and favorable-risk groups into 3 groups, with different median OS periods ranging from 8 months (95% confidence interval [95% CI], 6 months-12 months) for an intermediate-risk Heng score/low SMD to 22 months (95% CI, 14 months-27 months) for an intermediate-risk Heng score/high SMD and a favorable-risk Heng score/low SMD to 35 months (95% CI, 24 months-43 months) for a favorable-risk Heng score/high SMD. High muscle density appears to be independently associated with improved outcome and could be integrated into the prognostic scores thereby enhancing the management of patients with mRCC.