The impact of inflammatory biomarkers, BMI, and sarcopenia on survival in advanced hepatocellular carcinoma treated with immunotherapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 553-553
Author(s):  
Mehmet Akce ◽  
Yuan Liu ◽  
Katerina Mary Zakka ◽  
Dylan J. Martini ◽  
Amber Draper ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Cox Regression ◽  
Statistical Significance ◽  
Inflammatory Biomarkers ◽  
Advanced Hepatocellular Carcinoma ◽  
Skeletal Muscle Index ◽  
The Impact ◽  
Baseline Bmi ◽  
Gender Specific

553 Background: Sarcopenia and inflammation are independently associated with worse survival in cancer patients. This study aims to determine the impact of inflammatory biomarkers, BMI and sarcopenia on survival in advanced hepatocellular carcinoma (HCC) patients treated with immunotherapy. Methods: We performed a retrospective review of advanced HCC patients treated with immunotherapy-based therapies at Winship Cancer Institute between 2015 and 2019. Baseline computed tomography and magnetic resonance imaging scans were collected at mid-L3 level, assessed for skeletal muscle density using SliceOmatic (TomoVision, version 5.0) and converted to skeletal muscle index (SMI) by dividing it by height (m)2. Gender-specific sarcopenia was defined by median value of SMI. The optimal cut for continuous inflammation biomarker was determined by bias-adjusted log-rank test. Overall Survival (OS) was set as primary outcome and Cox proportional hazard model was performed. Results: 57 patients were included; 77.2% male, 52.6% Caucasian, 58.5% ECOG PS 0-1, 80.7% Child Pugh A. Treatment was second line and beyond in 71.9%. The median follow-up time was 6 months. Sarcopenia cut-off for males and females was SMI of 43 and 39, respectively. 49.1% of patients had sarcopenia. Median OS was 5 vs. 14.3 months in sarcopenic vs. non-sarcopenic patients (p=0.054). Median OS was 5 and 17.5 months in patients with BMI <25 and BMI ≥25 respectively (p=0.034). Median OS was 3.6 and 14.3 months for patients with neutrophil to lymphocyte ratio (NLR) ≥ 5.15 vs. NLR < 5.15 (p<0.001). In multivariable Cox regression model, higher baseline NLR was associated with worse OS (HR: 4.17, 1.52-11.39, p=0.005). Gender specific sarcopenia showed a trend of worse OS (HR: 1.71, 0.73-4.00, p=0.215) but was not statistically significant. BMI<25 was associated with worse OS (HR: 2.73, 1.15-6.53, p=0.023). In the association with PFS, neither baseline BMI nor gender specific sarcopenia showed statistical significance. Conclusions: Baseline BMI and NLR may predict OS after immunotherapy treatment. After controlling for baseline Child Pugh Score and NLR, gender specific sarcopenia was not associated with OS significantly.

Myopenia as a significant prognostic factor in BCLC-B intermediate-stage hepatocellular carcinoma treated with sorafenib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15639-e15639
Author(s):  
Mao Okada ◽  
Hiroyuki Nakanishi ◽  
Masayuki Kurosaki ◽  
Sakura Kirino ◽  
Leona Osawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Intermediate Stage ◽  
Significant Prognostic Factor ◽  
Poor Prognostic Factor ◽  
Skeletal Muscle Index ◽  
The Impact

e15639 Background: Tyrosine kinase inhibitors (TKI) are important treatment options for unresectable hepatocellular carcinoma (HCC). The survival benefit of sorafernib was demonstrated not only in advanced stage but also for BCLC-B intermediate stage who are refractory to transcatheter arterial chemoembolization by OPTIMIS study. Skeletal muscle mass depletion (Myopenia) is a poor prognostic factor in HCC treated by resection or loco-reginal ablation, but its effect on survival in TKI treated patients, especially in those within BCLC-B stage remains unclear. The aim of the present study is to elucidate the impact of myopenia on survival among HCC treated with sorafenib, especially in BCLC-B stage. Methods: In 213 patients who started treatment with sorafenib between 2009 and 2016, myopenia at baseline was determined by using skeletal muscle index calculated from CT images of the third lumber vertebra level. The impact of myopenia on survival was analyzed in whole patients, after stratification by BCLC stage, and after matching for backgrounds within BCLC-B patients. Results: The median survival in whole, BCLC-C, and –B was 13.7, 8.7 and 15.2 months, respectively. Myopenia was not a significant prognostic factor in whole patients and in BCLC-C stage. However, among BCLC-B patients (n = 104), survival was significantly better in patients with no myopenia (p = 0.05). Among them, 85 patients who continued sorafenib for more than 8 weeks were extracted and those with or without myopenia were matched for backgrounds by propensity score. Backgrounds including etiology, Child-Pugh score, BMI, AFP and PIVKA-Ⅱwas not different between myopenia (n = 30) and no myopenia group (n = 30) after matching. The overall survival at 6-, 12-, and 24-months was 96%, 74%, and 62% in no myopenia group which was significantly better compared to 89%, 64%, and 28% in myopenia group (p = 0.019). The hazard ratio was 2.12 (95% CI 1.11-4.03). Conclusions: Absence of myopenia predicts favorable outcome in sorafenib treated HCC patients within BCLC-B intermediate stage.

Impact of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) on time to progression and overall survival (OS) in metastatic colorectal cancer (mCRC) patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10087-10087 ◽  
Author(s):  
Sophie Kurk ◽  
Petra H.M. Peeters ◽  
Rebecca K. Stellato ◽  
Bram Dorresteijn ◽  
Marion Jourdan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Overall Survival ◽  
Disease Progression ◽  
Cox Regression ◽  
Systemic Treatment ◽  
P Value ◽  
Multiple Time ◽  
Time To Progression ◽  
Skeletal Muscle Index ◽  
The Impact

10087 Background: Evidence for a strong link between skeletal muscle depletion and poor outcomes in mCRC is growing. However, the impact of SMI changes over time on progression and OS during palliative systemic Tx is not known. The CAIRO3 study (Simkens et al. Lancet 2015) randomized 556 mCRC patients after 6 cycles capecitabine+oxaliplatin+bevacizumab (CAPOX-B) to maintenance CAP-B Tx (Main) vs. observation (Obs). Upon 1st disease progression (PD1), CAPOX-B or other treatment was reintroduced until 2nddisease progression (PD2). This is the first analysis using scan data of multiple time-points to investigate SMI changes during palliative systemic treatment Tx and its association with survival. Methods: 1227 CT-scans of a random selection of 416 CAIRO3 patients (mean age 64±9 years, Main n = 206; Obs n = 210) were analyzed for SMI (skeletal muscle area at the L3 level in cm2/m2). Using mixed model analysis, SMI changes were analyzed for two intervals; interval 1: from randomization to PD1, and interval 2: from PD1 to PD2. Three Cox regression models were used to study the association between SMI loss and time to PD2 and death for interval 1, and time to death for interval 2. Main and Obs groups were combined in the analyses since the p-value for interaction was not significant. Hazard ratios (HR) were reported per 2 units change in SMI. Results: Median times from randomization to PD1, PD2 and death were 7.7, 13.5 and 24 months resp. During interval 1 (less intensive or no Tx) patients gained SMI on average (1.2 units; 95%CI 0.6-1.8), but 23% of patients still lost SMI. SMI loss was associated with shorter time to PD2 (HR 0.88; 0.81-0.98, p= .01), but not with shorter OS (HR 0.94; 0.86-1.02, p= .17). During interval 2 (more intensive Tx) average SMI loss was -2.2 units ( 1.5-2.8) and 63% of patients lost SMI. SMI loss was associated with shorter OS (HR 0.73; 0.62-0.86, p< .00). Conclusions: Loss of SMI was related to shorter time to progression during first line less intensive main Tx or obs and shorter overall survival during more intensive reinduction Tx. This large longitudinal study suggests that SMI preservation may be a therapeutic goal. Clinical trial information: NCT00442637.

scholarly journals Impact of Grip Strength in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2146 ◽  
Author(s):  
Kei Endo ◽  
Hidekatsu Kuroda ◽  
Jo Kanazawa ◽  
Takuro Sato ◽  
Yudai Fujiwara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Muscle Strength ◽  
Grip Strength ◽  
Cox Proportional Hazards Model ◽  
University Hospital ◽  
Poor Prognostic Factor ◽  
Skeletal Muscle Index ◽  
Increased Risk ◽  
The Impact

Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We evaluated the impact of sarcopenia-related factors (grip strength (GS) and the skeletal muscle index (SMI)) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that modified albumin-bilirubin-grade (mALBI) 2b (hazard ratio (HR) 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.

scholarly journals Impact of Grip Strength in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

2020 ◽  
Author(s):  
Kei Endo ◽  
Hidekatsu Kuroda ◽  
Jo Kanazawa ◽  
Takuro Sato ◽  
Yudai Fujiwara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Muscle Strength ◽  
Grip Strength ◽  
Cox Proportional Hazards Model ◽  
University Hospital ◽  
Poor Prognostic Factor ◽  
Skeletal Muscle Index ◽  
Increased Risk ◽  
The Impact

Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We separately evaluated the impact of sarcopenia-related factors (grip strength [GS] and the skeletal muscle index [SMI]) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that ALBI2b (hazard ratio [HR] 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.

Impact of Hybrid Operating Rooms on Long-Term Clinical Outcomes Following Fenestrated and Branched Endovascular Aortic Repair

2021 ◽  
pp. 152660282199672
Author(s):  
Giovanni Tinelli ◽  
Marie Bonnet ◽  
Adrien Hertault ◽  
Simona Sica ◽  
Gian Luca Di Tanna ◽  
...  
Keyword(s):  
Operating Room ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Statistical Significance ◽  
Aortic Aneurysms ◽  
Study Patient ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
The Impact

Purpose: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. Materials and Methods: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. Results: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. Conclusion: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.

scholarly journals Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

scholarly journals Impact of Extrahepatic Metastases on Overall Survival in Patients with Advanced Liver Dominant Hepatocellular Carcinoma: A Subanalysis of the SORAMIC Trial

Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 771-786
Author(s):  
Kerstin Schütte ◽  
Regina Schinner ◽  
Mathias P. Fabritius ◽  
Melina Möller ◽  
Christiane Kuhl ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Median Survival ◽  
Pulmonary Metastases ◽  
Study Entry ◽  
Extrahepatic Disease ◽  
Advanced Hepatocellular Carcinoma ◽  
Significant Difference ◽  
Distant Organ ◽  
Extrahepatic Metastases ◽  
The Impact

<b><i>Introduction:</i></b> Extrahepatic spread is reported as a prognostic factor in patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. However, clinical studies have reported conflicting results for the clinical impact of the pattern of tumor progression during treatment and the role of new extrahepatic metastases in length of survival. <b><i>Objective:</i></b> To evaluate the impact of extrahepatic metastases on survival in patients with HCC treated with sorafenib or with a combination of sorafenib and selective internal radiation treatment (SIRT). <b><i>Methods:</i></b> SORAMIC is a randomized, controlled trial comprising diagnostic, local ablation, and palliative cohorts. In the palliative cohort, patients not eligible for transarterial chemoembolization (TACE) were randomized 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. This exploratory subanalysis evaluated the impact of extrahepatic metastases on survival. <b><i>Results:</i></b> In the intent-to-treat cohort, 216 patients were randomized to SIRT + sorafenib and 208 to sorafenib alone. Seventeen patients with distant organ metastases (bone, <i>n</i> = 11; adrenal glands, <i>n</i> = 5; peritoneum, <i>n</i> = 1) and 262 without distant metastases at study entry were analyzed in this substudy. Patients with (Group A) and without (Group B) distant organ metastases at study entry presented with a median survival of 11.3 and 14.8 months, respectively (<i>p</i> = 0.2807). During follow-up of patients with no organ metastases at baseline, extrahepatic disease progression occurred in 50 patients (19.1%). No statistically significant difference in survival was observed between patients without extrahepatic progression and those with new extrahepatic disease during treatment (14.8 vs. 14.9 months; <i>p</i> = 0.6483). Development of new pulmonary metastases during treatment significantly shortened median survival (7.6 vs. 15.0 months, <i>p</i> = 0.0060). <b><i>Conclusions:</i></b> This subanalysis of the SORAMIC trial suggests that in patients with liver-dominant advanced HCC, metastases to distant organs with the exception of pulmonary metastases do not in general exert a negative impact on patient prognosis. The choice of palliative treatment should incorporate a personalized analysis of the pattern of tumor distribution.

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

2017 ◽  
Vol 36 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Christian Labenz ◽  
Vera Prenosil ◽  
Sandra Koch ◽  
Yvonne Huber ◽  
Jens U. Marquardt ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The Metabolic Syndrome ◽  
The Impact

Background/Aim: Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. Methods: Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. Results: The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. Conclusions: Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.

scholarly journals Sarcopenia and intramuscular fat deposition are associated with poor survival in Indonesian patients with hepatocellular carcinoma: a retrospective study

2019 ◽  
Author(s):  
Yan Mardian ◽  
Yoshihiko Yano ◽  
Neneng Ratnasari ◽  
Lina Choridah ◽  
Widya Wasityastuti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Large Scale ◽  
Cox Regression ◽  
Clinical Laboratory ◽  
Multivariable Analysis ◽  
Lumbar Vertebra ◽  
Intramuscular Fat ◽  
Skeletal Muscle Index ◽  
Computed Tomography Images ◽  
Jis Score

Abstract Background A large-scale Japanese study showed that low skeletal muscle index (SMI) and intramuscular fat (IMF) deposition are associated with hepatocellular carcinoma (HCC) survival. Here, we evaluated the effects of SMI and IMF on the survival of Indonesian HCC patients, whose characteristics differ from those of Japanese patients.Methods SMI and mean muscle attenuation (MA) were evaluated using computed tomography images of the third lumbar vertebra (L3) in a prospective cohort of 100 Indonesian HCC patients. Clinical, laboratory and body composition data were analysed using the Kaplan–Meier method and Cox regression model to investigate which factors are associated with prognosis.Results Of 100 patients, 31 were diagnosed with sarcopenia (L3 SMI value ≤36.2 cm 2 /m 2 for men and ≤29.6 cm 2 /m 2 for women), and 65 had IMF deposition (MA value ≤44.4 HU for men and ≤39.3 HU for women). These groups had shorter median survival than the reference groups (both P <0.0001). In multivariable analysis, sarcopenia (hazard ratio [HR], 1.921; P = 0.016), IMF deposition (HR, 3.580; P <0.001), Barcelona Clinic Liver Cancer (BCLC) stages C and D (HR: 2.396, P <0.01 and HR: 6.131, P <0.01, respectively), Japan Integrated Staging (JIS) score 4 (HR: 2.067, P = 0.020), and male gender (HR: 3.211, P <0.001) were independently associated with mortality.Conclusion Sarcopenia and IMF deposition showed superior value in combination with BCLC stage and JIS score for predicting the survival of Indonesian HCC patients. Increased awareness and strategies to prevent or reverse these factors might improve patient outcomes. (Electric word counts: 249)

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