Total skeletal, psoas, and rectus abdominis muscle mass as prognostic factors for patients with advanced hepatocellular carcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 568-568
Author(s):  
Yu Yun Shao ◽  
Chih-Horng Wu ◽  
Po-Chin Liang ◽  
Chih-Hung Hsu ◽  
Tiffany Ting-Fang Shih
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Body Height ◽  
Rectus Abdominis ◽  
The Body ◽  
Advanced Hepatocellular Carcinoma ◽  
Disease Etiology ◽  
Sorafenib Treatment ◽  
Advanced Hcc

568 Background: We investigated whether low skeletal muscle mass (LSMM) defined according to different muscle groups on computed tomography (CT) scans could predict prognosis of advanced hepatocellular carcinoma (HCC). Methods: We analyzed patients who received first-line sorafenib treatment for advanced HCC in a prospective patient cohort between 2007 and 2012. The muscels areas of total skeletal muscle (TSM), paraspinal muscle (PS), psoas muscle (PM), rectus abdominis (RA), and abdominal wall (AW) were evaluated using a single CT slice at the third lumbar vertebra before treatment. LSMM was determined according to the TSM, PS, PM, RA and AW indices, which was calculated as the parameters divided by the square of the body height. Results: We enrolled 137 patients, with a mean age of 57.5 years; 120 were male and 17 were female. Liver disease etiology was hepatitis B virus in 94 (68.6%) patients and hepatitis C virus in 28 (20.4%) patients. All patients had Child–Pugh class A liver reserve. Women had significantly lower TSM index than men did ( p < .001). Among men, the optimal cut points of the TSM, PM and RA indices for LSMM diagnosis were 39.1, 8.3 and 2.9 cm2/m2, respectively. Patients with LSMM exhibited poorer overall survival than patients without LSMM, whether LSMM was defined by TSM index (median 5.1 vs. 8.0 months, p = 0.007), PM index (median 5.8 vs. 11.8 months, p < 0.001), or RA index (median 7.2 vs. 8.1 months, p = 0.003). After adjusting for clinical variables including underweight, age, tumor extent, and performance status, LSMM defined by TSM index (hazard ratio [HR]: 2.123, 95% confidence interval [CI]: 1.124-4.010, p = 0.020), PM index (HR: 1.855, 95% CI: 1.163-2.959, p = 0.009), or RA index (HR: 1.650, 95% CI: 1.004-2.710, p = 0.048) remained independent predictors for poor OS. Conclusions: LSMM defined by TSM, PM and RA indices are independent predictors for poor prognosis of advanced HCC, even after adjusted for body weight.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

scholarly journals Skeletal muscle mass is associated with toxicity, treatment tolerability, and additional or subsequent therapies in patients with hepatocellular carcinoma receiving sorafenib treatment

JGH Open ◽  
2019 ◽  
Vol 3 (4) ◽  
pp. 329-337 ◽  
Author(s):  
Koji Sawada ◽  
Yoshinori Saitho ◽  
Hidemi Hayashi ◽  
Takumu Hasebe ◽  
Shunsuke Nakajima ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Sorafenib Treatment

scholarly journals Pre-sarcopenia determines post-progression outcomes in advanced hepatocellular carcinoma after sorafenib failure

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tsung-Yi Cheng ◽  
Pei-Chang Lee ◽  
Yi-Tzen Chen ◽  
Yee Chao ◽  
Ming-Chih Hou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Body Height ◽  
Psoas Muscle ◽  
Muscle Thickness ◽  
Female Gender ◽  
Nutrition Support ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Class B ◽  
Risk Patients

Abstract Many second-line therapies are recently approved for patients with advanced hepatocellular carcinoma (HCC), in whom protein malnutrition is prevalent that would affect treatment outcomes. In this study, we aimed to investigate the role of pre-sarcopenia and muscle restoration in patients with sorafenib-failed advanced HCC. From August 2012 to March 2017, 385 patients who developed radiology-proven HCC progression after sorafenib treatment were enrolled in the study. Pre-sarcopenia is defined as transverse psoas muscle thickness per body height < 16.8 mm/m, which was prevalent (64.7%) in our patients. Age > 60 years, female gender, and body mass index < 22 kg/m2 were independent predictors to the development of pre-sarcopenia. Patients with muscle depletion had significantly worse post-progression survival (PPS) compared with their counterparts (median PPS: 3.8 vs. 5.8 months, p = 0.003), particularly in those with intermediate liver reserves (Child–Pugh class B or Albumin-bilirubin grade 2). Besides, pre-sarcopenia independently predicted post-progression mortality in sorafenib-failed HCC (hazard ratio: 1.340, p = 0.012). In patients who developed pre-sarcopenia before sorafenib treatment, muscle restoration was associated with a longer PPS compared with their counterparts (6.3 vs. 3.6 months, p = 0.043). In conclusion, pre-sarcopenia independently determined the outcomes of sorafenib-failed HCC. Nutrition support to restore muscle mass would prolong survival for higher-risk patients.

Association of hypophosphatemia-occurring sorafenib with prognosis and hepatic impairment in patients with advanced hepatocellular carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 188-188
Author(s):  
M. Aizawa ◽  
S. Mitsunaga ◽  
H. Okuyama ◽  
K. Nakachi ◽  
I. Ohno ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Serum Levels ◽  
Observation Time ◽  
Advanced Hepatocellular Carcinoma ◽  
Metabolic Demand ◽  
Sorafenib Treatment ◽  
Significance Level ◽  
Advanced Hcc ◽  
Pre Treatment ◽  
Hbs Ag

188 Background: Hypophosphatemia is observed during sorafenib treatment. At the increased metabolic demand of the liver, hypophosphatemia is considered to be associated with a good clinical course. Hypophosphatemia associated with sorafenib treatment may also be a favorable event, but this has not yet been elucidated. The aim of this study was to evaluate the clinical significance of hypophosphatemia developing during sorafenib treatment for advanced hepatocellular carcinoma (HCC). Methods: The data of 41 advanced HCC patients (median age: 68 years, female/male: 4/37, HBs-Ag(+)/HCV-Ab(+):10/22) who received sorafenib treatment (800 mg, daily) for more than 30 days were reviewed. There were 27 and 14 patients with Child-Pugh class A and B. UICC stage II/III/IV was observed in 13/10 /18 patients. Clinical data, including those on the serum level of inorganic phosphate (IP), were collected before and after 30 days of sorafenib treatment. Overall survival time (OS) was calculated from the start of sorafenib treatment. The significance level was set at p<0.05. Results: Mean serum IP level before sorafenib treatment was 3.2mg/dL (range 2.4-4.5). After 30 days treatment, IP level was decreased (mean 2.6mg/dL, range 1.3-3.9), compared to that at pre-treatment (p<0.001). The patients in whom the serum IP was less than 2.4mg/dL at 30 days was assigned to the decreased IP group (N=14, mean IP 2.1mg/dL, range1.3-2.3). The decreased IP group showed a better prognosis (no event of death during the observation time) than the nondecreased IP group (MST 286 days, p=0.024). In the non-decreased IP group, the serum Alb (mean 3.6g/dL) and T.Bil (mean 0.8mg/dL) were worse after 30 days treatment (Alb 3.4g/dL p=0.007, T.Bil 1.1mg/dL p=0.037). However, deterioration of Alb (mean 3.7 vs. 3.6g/dL p=0.505) and T.Bil (mean 0.7 vs. 0.8mg/dL p=0.404) could be avoided in the decrease IP group. Conclusions: Hypophosphatemia occurring during sorafenib treatment for advanced HCC was associated with a favorable prognosis. The serum Alb and T.Bil levels were indicators of liver function and were preserved in patients with decreased serum levels of phosphate. No significant financial relationships to disclose.

scholarly journals RAF1 expression is correlated with HAF, a parameter of liver computed tomographic perfusion, and may predict the early therapeutic response to sorafenib in advanced hepatocellular carcinoma patients

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 167-174
Author(s):  
Ninzi Tian ◽  
Dong Wu ◽  
Ming Tang ◽  
Huichuan Sun ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Response ◽  
Therapeutic Effects ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Expression Levels ◽  
Portal Vein Flow ◽  
Tumor Tissues ◽  
Resistant Group

AbstractObjectivesMonitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.MethodsA total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels.ResultsAccording to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value.ConclusionRAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

A population-based analysis of prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 163-163
Author(s):  
Alan D. Smith ◽  
Winson Y. Cheung
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Elevated Serum ◽  
Advanced Hepatocellular Carcinoma ◽  
Clinical Factors ◽  
Conventional Chemotherapy ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Staging Systems

163 Background: Available clinical prognostic scoring systems for advanced hepatocellular carcinoma (HCC) were developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care for advanced HCC due to its survival benefit. The utility of these prognostic models in the setting of sorafenib is unclear. Our aims were to assess for new prognostic factors in patients treated with sorafenib and compare these with known prognostic systems. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 in British Columbia, Canada and treated with sorafenib at any 1 of 5 regional cancer centers were eligible. Based on the established Okuda, CLIP, Barcelona, and French staging systems, we collected baseline demographic and disease characteristics of patients prior to receipt of sorafenib. Multivariate logistic regression models were constructed to examine for associations between these clinical factors and overall survival. Results: Of 183 patients identified, 152 were evaluable: median age was 63 years, 78% were men, average number of sorafenib treatment was 5.3 cycles, and median overall survival was 9.6 months. The prevalence of hepatitis B, hepatitis C, and alcohol-related liver disease were 32%, 15%, and 11%, respectively. Univariate analyses showed that poor performance status, presence of clinical ascites, as well as elevated serum AST, GGT, ALP, bilirubin and platelet levels were each associated with worse overall survival (all p<0.05). In multivariate analyses, however, none of these clinical factors continued to be independently predictive of outcome (all p>0.05). Conclusions: Traditional clinical prognostic factors developed in the era of conventional chemotherapy do not appear to have the same prognostic utility in this contemporary Western cohort of advanced HCC patients treated with sorafenib. This observation underscores the need to identify molecular biomarkers that provide better prognostic information.

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

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]

Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: A randomized, placebo-controlled, double-blind, phase III study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4507-4507 ◽  
Author(s):  
Qiu Li ◽  
Shukui Qin ◽  
Shanzhi Gu ◽  
Xiaoming Chen ◽  
Lizhu Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Chinese Patients ◽  
Biological Behavior ◽  
Advanced Hepatocellular Carcinoma ◽  
Double Blind ◽  
Sorafenib Treatment ◽  
Advanced Hcc

4507 Background: Chinese patients (pts) account for more than 50% of hepatocellular carcinoma (HCC) cases in the world and have special features in etiology, biological behavior, treatment strategy and prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib, an inhibitor targeting vascular endothelial growth factor receptor-2, in Chinese pts with pretreated advanced HCC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 trial done in 31 sites in China, pts with HCC who had received at least one line of systemic therapy (including sorafenib and oxaliplatin-based chemotherapy, which is another first-line standard-of-care in China) and had Child-Pugh liver function class A or B ≤7 points were enrolled. The pts were randomly assigned (2:1) to receive 750 mg apatinib orally once daily or placebo and stratified by ECOG performance status (0 or 1), previous sorafenib treatment (yes or no), and extrahepatic spread and/or macrovascular invasion (yes or no) in 28-day treatment cycles. The primary endpoint was overall survival (OS). Results: Between Apr 01, 2014 and May 03, 2017, 393 pts were randomized and received at least one dose of study treatment (261 in apatinib arm and 132 in placebo arm). The median OS was significantly longer with apatinib than that with placebo (8.7 months [95% CI 7.5-9.8] vs 6.8 months [95% CI 5.7-9.1]; hazard ratio 0.785 [95% CI 0.617-0.998]; p=0.0476). Pts in the apatinib arm also had prolonged median progression free survival (PFS) compared with those in the placebo arm (4.5 months [95% CI 3.9-4.7] vs 1.9 months [95% CI 1.9-2.0]; hazard ratio 0.471 [95% CI 0.369-0.601]; p˂0.0001). The objective response rate was 10.7% (95% CI 7.2-15.1) with apatinib versus 1.5% (95% CI 0.2-5.4) with placebo. Treatment-related adverse events (TRAEs) were reported in 250 (97.3%) pts in the apatinib arm and 92 (70.8%) pts in the placebo arm. The most common TRAEs of grade 3 and 4 were hypertension (71 [27.6%] pts in the apatinib arm vs 3 [2.3%] pts in the placebo arm), hand-foot syndrome (46 [17.9%] vs 0), decreased platelet count (34 [13.2%] vs 1 [0.8%]), and decreased neutrophil count (27 [10.5%] vs 0). 24 (9.3%) pts with apatinib and 13 (10.0%) pts with placebo died due to adverse events, and none were deemed treatment-related by investigators. Conclusions: Apatinib significantly prolonged OS and PFS in Chinese pts with pretreated advanced HCC, and was well tolerated with a manageable safety profile. Clinical trial information: NCT02329860 .

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