Rapid Depletion of Subcutaneous Adipose Tissue during Sorafenib Treatment Predicts Poor Survival in Patients with Hepatocellular Carcinoma

The aim of this study was to assess the annualized changes in body composition, including skeletal muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) before, during, and after sorafenib treatment in patients with hepatocellular carcinoma (HCC). This retrospective study evaluated 61 HCC patients treated with sorafenib. Annualized changes (Δ; cm2/m2/year) in skeletal muscle index (SMI), SAT index (SATI), and VAT index (VATI), which were defined as the cross-sectional areas (cm2) of those areas on computed tomography normalized by the square of one’s height (m2), before (pre), during (during), and after (post) sorafenib treatment, were calculated. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion group and the effects of these values on survival were analyzed using the Kaplan-Meier analysis and Cox proportional-hazards model. Annualized depletion rates of SMI (ΔSMIpre: −3.5, ΔSMIduring: −3.5, ΔSMIpost: −8.0) and VATI (ΔVATIpre: −3.2, ΔVATIduring: −2.8, ΔVATIpost: −15.1) accelerated after the cancellation of sorafenib, whereas that of SATI (ΔSATIpre: −4.8, ΔSATIduring; −7.6, ΔSATIpost; −8.0) had already accelerated during sorafenib treatment. Patients with rapid depletion of ΔSATIduring experienced significantly worse survival rates (p < 0.001), and it was an independent predictor of survival (p = 0.009), together with therapeutic effect (p < 0.001). Rapid depletion of SAT during sorafenib treatment can be used to predict survival in patients with HCC.

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27 Can Sarcopenia be Used to Estimate Outcomes in Elderly Patients Treated with Chemoradiotherapy for Bladder Cancer?

Age and Ageing ◽

10.1093/ageing/afab029.06 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

pp. i7-i11

Author(s):

M Corden

Keyword(s):

Skeletal Muscle ◽

Bladder Cancer ◽

Proportional Hazards Model ◽

Performance Status ◽

Survival Function ◽

Age Distribution ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

International Consensus ◽

Skeletal Muscle Index

Abstract Introduction Ageing is a risk factor for bladder cancer, with a median age at diagnosis of 71 years. In addition, sarcopenia shows promise as a prognostic biomarker for bladder cancer. This study evaluates sarcopenia as a predictor of overall survival (OS) for older patients treated with chemoradiotherapy for bladder cancer. Methods 185 bladder cancer patients treated (from 2010–2017) with chemoradiotherapy were available for analysis. Pre-therapeutic computed tomography scans were identified and single slices at the L3 level were identified. Machine learning software was used to segment skeletal muscle and obtain its cross-sectional area. This was normalised against height squared to calculate a skeletal muscle index for each patient. Sarcopenia was defined using international consensus definitions (<39 cm2/m2 in females and < 55 cm2/m2 in males). Differences in survival function between patients ≤75 and > 75 years were visualised using Kaplan–Meier curves. Age distribution between sarcopenic and non-sarcopenic patients was also explored. Finally, a multivariable Cox proportional hazards model was conducted to investigate interactions between sarcopenia and increased age with respect to OS. Results Of 185 patients, 114 (61.6%) were sarcopenic and 71 (38.4%) were non-sarcopenic; 101 (54.6%) and 84 (45.4%) patients were ≤ 75 and > 75 years old respectively. No differences in OS were observed between the two age groups (p = 0.50). There was no interaction between sarcopenia and age as a continuous variable was observed with respect to OS (p = 0.682); however, when age was categorised an interaction was seen (p = 0.058). Nevertheless, after adjusting for performance status, T-stage, hydronephrosis, albumin, haemoglobin, neutrophil and lymphocyte counts, the interactions between age and sarcopenia were no longer observed (age continuous, p = 0.474; age categorized, p = 0.765). Conclusions Patients with bladder cancer over 75 years of age have a modest increase in probability of developing sarcopenia but this does not impact on OS.

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Impact of HCV treatment in patients with advanced hepatocellular carcinoma on sorafenib.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15645 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15645-e15645

Author(s):

Michael Herman ◽

Yuhua Zhang ◽

Lisa Wang ◽

Hao-Wen Sim ◽

Jennifer J. Knox

Keyword(s):

Hepatocellular Carcinoma ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Early Stage ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Advanced Hepatocellular Carcinoma ◽

Sorafenib Treatment ◽

Advanced Hcc ◽

Significant Difference

e15645 Background: Hepatocellular carcinoma (HCC) is the 4th leading cause of global cancer deaths. In North America, HCC is most commonly caused by Hepatitis C virus (HCV). Direct acting antivirals (DAAs) have dramatically increased sustained virologic response (SVR) rates for HCV. Studies of DAAs in early stage HCC have had conflicting results on HCC outcomes. A small Asian study of 58 advanced HCC patients treated with sorafenib demonstrated SVR improved survival, but whether the same effect occurs in North American patients is unknown. Methods: Inclusion criteria for this retrospective study were: biopsy or clinically proven advanced incurable HCC, sorafenib treatment at Princess Margaret Cancer Centre between January 1 2008-June 30 2018 and a history of HCV. Survival was analyzed using the Kaplan Meier method and a cox proportional hazards model was fit to determine the effect of SVR on OS. Results: 93 patients were included with a median duration of sorafenib therapy of 3 months. 89% were ECOG 0-1 and 96% were BCLC-C (See table 1). Of those receiving antivirals, 95% were given before sorafenib. Overall, SVR was achieved in 23 (50%) patients. Median OS of patients achieving SVR vs not in SVR was 10.3 vs 8.9 months respectively (HR 0.67, 95% CI 0.36-1.24, p = 0.20). Median PFS was 6.4 vs 5.0 months in patients with or without SVR (HR 0.66, 95% CI 0.39-1.13, p = 0.13). There was no significant difference between mean dose of sorafenib or discontinuation due to toxicity in patients by SVR status. Conclusions: Antiviral therapy with SVR lead to a non-statistically significant improvement in OS in patients with Child-Pugh A-B liver disease, advanced HCC treated with sorafenib and HCV. These results should be validated in larger data-sets. [Table: see text]

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Rapid Depletions of Subcutaneous Fat Mass and Skeletal Muscle Mass Predict Worse Survival in Patients with Hepatocellular Carcinoma Treated with Sorafenib

Cancers ◽

10.3390/cancers11081206 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1206 ◽

Cited By ~ 6

Author(s):

Kenji Imai ◽

Koji Takai ◽

Takao Miwa ◽

Daisuke Taguchi ◽

Tatsunori Hanai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Muscle Mass ◽

Fat Mass ◽

Skeletal Muscle Mass ◽

Subcutaneous Fat ◽

Cox Proportional Hazards Model ◽

Sorafenib Treatment ◽

Skeletal Muscle Index ◽

Fat Mass Index

The aim of this study was to investigate whether rapid depletions of fat mass and skeletal muscle mass predict mortality in hepatocellular carcinoma (HCC) patients treated with sorafenib. This retrospective study evaluated 61 HCC patients. The cross-sectional areas of visceral and subcutaneous fat mass and skeletal muscle mass were measured by computed tomography, from which the visceral fat mass index (VFMI), subcutaneous fat mass index (SFMI), and skeletal muscle index (L3SMI) were obtained. The relative changes in these indices per 120 days (ΔVFMI, ΔSFMI, and ΔL3SMI) before and after sorafenib treatment were calculated in each patient. Patients within the 20th percentile cutoffs for these indices were classified into the rapid depletion (RD) group. Kaplan–Meier analysis revealed that with respect to ΔL3SMI (p = 0.0101) and ΔSFMI (p = 0.0027), the RD group had a significantly poorer survival. Multivariate analysis using the Cox proportional-hazards model also demonstrated that ΔL3SMI (≤−5.73 vs. >−5.73; hazard ratio [HR]: 4.010, 95% confidence interval [CI]: 1.799–8.938, p = < 0.001) and ΔSFMI (≤−5.33 vs. >−5.33; HR: 4.109, 95% CI: 1.967–8.584, p = < 0.001) were independent predictors. Rapid depletions of subcutaneous fat mass and skeletal muscle mass after the introduction of sorafenib indicate a poor prognosis.

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Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study

Scientific Reports ◽

10.1038/s41598-021-81176-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shou-Sheng Chu ◽

Yu-Hsuan Kuo ◽

Wen-Shan Liu ◽

Shih-Chang Wang ◽

Chung-Han Ho ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Registry ◽

Proportional Hazards Model ◽

Combined Treatment ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Rank Test ◽

Study Cohort ◽

Advanced Hepatocellular Carcinoma ◽

Sorafenib Treatment

AbstractSorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) patients. This study aims to determine whether combining radiotherapy with sorafenib administration increases its efficacy. The study cohort included 4763 patients with diagnosed advanced HCC who received sorafenib between January 2012 and December 2015, as reported in medical records in the Taiwan Cancer Registry database. The effect of sorafenib with or without radiotherapy on survival was calculated using the Kaplan–Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Patients receiving sorafenib plus radiotherapy had greater 1-year survival than did those receiving sorafenib alone (P < 0.001). Uni- and multivariate analyses also showed that radiotherapy increased survival after adjusting for confounders (adjusted HR 0.57; 95% CI 0.51–0.63). Further stratified analysis according to the timing of radiotherapy relative to sorafenib treatment revealed that patients who underwent radiotherapy after sorafenib had greater 1-year survival than did those undergoing radiotherapy within sorafenib use or sorafenib alone (adjusted HR 0.39; 95% CI 0.27–0.54). Combined treatment with sorafenib and radiotherapy results in greater HCC patient survival and should be considered an option for treating this challenging disease.

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METABOLISM IN ADIPOSE TISSUE AND MUSCLE OF THE YOUNG PIG

Canadian Journal of Animal Science ◽

10.4141/cjas90-022 ◽

1990 ◽

Vol 70 (1) ◽

pp. 199-206 ◽

Cited By ~ 1

Author(s):

O. ADEOLA ◽

B. W. McBRIDE ◽

R. O. BALL ◽

L. G. YOUNG

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Adipose Tissue ◽

Key Words ◽

Adenosine Deaminase ◽

Subcutaneous Adipose Tissue ◽

Muscle Metabolism ◽

Acetate Incorporation ◽

Glycerol Release ◽

Subcutaneous Adipose

Subcutaneous adipose tissue and intercostal and sartorius muscles from five barrows and five gilts at 20 kg liveweight were used to study lipogenesis, lipolysis, Na+, K+-ATPase-dependent respiration and protein synthesis. Lipogenesis rate measured by 14C-acetate incorporation into lipid was similar between barrows and gilts; and 100 μg insulin per mL enhanced (P < 0.1) subcutaneous adipose tissue lipogenesis by 74%. Lipolysis rate quantitated by glycerol release was similar between barrows and gilts (3546 and 4160 nmol g−1 2 h−1). Adenosine deaminase and norepinephrine together enhanced adipose tissue lipolytic response by 102%. Fractional and absolute rates of protein synthesis were similar between barrows and gilts (3.24 and 3.69% d−1; 6.01 and 6.06 mg g−1 d−1); and between intercostal and sartorius muscles. Barrows had lower Na+, K+-ATPase-dependent respiration than gilts and the maintenance of Na+ and K+ transmembrane ionic gradient in the muscle preparations accounted for 23–26% of total respiration. Key words: Pigs, adipose tissue, skeletal muscle, metabolism

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Comparison of β-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle

Acta Physiologica Scandinavica ◽

10.1111/j.1748-1716.1978.tb06095.x ◽

1978 ◽

Vol 102 (4) ◽

pp. 469-476 ◽

Cited By ~ 11

Author(s):

Erik Belfrage

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Subcutaneous Adipose

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Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.5.e850 ◽

1992 ◽

Vol 263 (5) ◽

pp. E850-E855 ◽

Cited By ~ 13

Author(s):

L. Simonsen ◽

J. Bulow ◽

J. Madsen ◽

N. J. Christensen

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Energy Expenditure ◽

Oxygen Uptake ◽

Glucose Uptake ◽

Subcutaneous Adipose Tissue ◽

Whole Body ◽

Epinephrine Infusion ◽

Basal Period ◽

Subcutaneous Adipose

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

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