Serologically assessed fragments of type VI collagen are predictors of progression free survival and death in patients with hepatocellular carcinoma

2020 ◽  
Vol 73 ◽  
pp. S703-S704
Author(s):  
Diana Julie Leeming ◽  
Mette Juul Nielsen ◽  
Signe Holm Nielsen ◽  
Raj Uchila ◽  
Mohammed Eslam ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Progression Free Survival ◽  
Type Vi Collagen ◽  
Free Survival

scholarly journals Endotrophin, a pro-peptide of Type VI collagen, is a biomarker of survival in cirrhotic patients with hepatocellular carcinoma

2021 ◽  
pp. HEP32
Author(s):  
Diana Julie Leeming ◽  
Signe Holm Nielsen ◽  
Roslyn Vongsuvanh ◽  
Pruthviraj Uchila ◽  
Mette Juul Nielsen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Progression Free Survival ◽  
Healthy Controls ◽  
Type Vi Collagen ◽  
Free Survival ◽  
Nonalcoholic Fatty Liver ◽  
Collagen Remodeling ◽  
Cancer Types ◽  
Cirrhotic Patients ◽  
Specific Fragment

Aim: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer types with a high amount of fibrosis activity, namely for outcome in hepatocellular carcinoma (HCC) cirrhotic patients. Patients & methods: Plasma C6M, PRO-C6 and alphafeto-protein (AFP) were assessed in 309 patients with mixed etiologies (hepatitis C, hepatitis B, alcohol and nonalcoholic fatty liver) diagnosed as cirrhotics, cirrhotics with HCC, noncirrhotics and healthy controls. Progression-free survival and overall survival (OS) data were collected up to 6120 days after diagnosis. The ability of each marker to predict survival was investigated. Results & conclusion: The level of endotrophin assessed by PRO-C6 was able to separate healthy controls, noncirrhotics and cirrhotics from HCC (p < 0.05–0.0001). Both endotrophin and C6M provided value in the prediction of OS in cirrhotic patients with HCC. In the multivariate analysis for identifying HCC, in patients with high endotrophin (highest quartile) and that were positive for AFP (≥20 IU/ml), the hazard ratio for predicting OS was increased from 3.7 (p = 0.0006) to 14.4 (p = 0.0001) when comparing with AFP positive as a stand-alone marker. In conclusion, plasma levels for markers of Type VI collagen remodeling were associated with survival in cirrhotic patients with HCC. A combination of AFP with endotrophin improved the prognostic value compared with AFP alone for predicting OS in cirrhotic patients with HCC.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

scholarly journals Efficacy of lenvatinib for unresectable hepatocellular carcinoma based on background liver disease etiology: multi-center retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Hiraoka ◽  
Takashi Kumada ◽  
Toshifumi Tada ◽  
Joji Tani ◽  
Kazuya Kariyama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Hazard Analysis ◽  
Progression Free Survival ◽  
Significant Prognostic Factor ◽  
Disease Etiology ◽  
Alcoholic Fatty Liver ◽  
Free Survival ◽  
Significant Difference

AbstractIt was recently reported that hepatocellular carcinoma (HCC) patients with non-alcoholic steatohepatitis (NASH) are not responsive to immune-checkpoint inhibitor (ICI) treatment. The present study aimed to evaluate the therapeutic efficacy of lenvatinib in patients with non-alcoholic fatty liver disease (NAFLD)/NASH-related unresectable-HCC (u-HCC). Five hundred thirty u-HCC patients with Child–Pugh A were enrolled, and divided into the NAFLD/NASH (n = 103) and Viral/Alcohol (n = 427) groups. Clinical features were compared in a retrospective manner. Progression-free survival (PFS) was better in the NAFLD/NASH than the Viral/Alcohol group (median 9.3 vs. 7.5 months, P = 0.012), while there was no significant difference in overall survival (OS) (20.5 vs. 16.9 months, P = 0.057). In Cox-hazard analysis of prognostic factors for PFS, elevated ALT (≥ 30 U/L) (HR 1.247, P = 0.029), modified ALBI grade 2b (HR 1.236, P = 0.047), elevated AFP (≥ 400 ng/mL) (HR 1.294, P = 0.014), and NAFLD/NASH etiology (HR 0.763, P = 0.036) were significant prognostic factors. NAFLD/NASH etiology was not a significant prognostic factor in Cox-hazard analysis for OS (HR0.758, P = 0.092), whereas AFP (≥ 400 ng/mL) (HR 1.402, P = 0.009), BCLC C stage (HR 1.297, P = 0.035), later line use (HR 0.737, P = 0.014), and modified ALBI grade 2b (HR 1.875, P < 0.001) were significant. Lenvatinib can improve the prognosis of patients affected by u-HCC irrespective of HCC etiology or its line of treatment.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Kensuke Naruto ◽  
Tomokazu Kawaoka ◽  
Kei Amioka ◽  
Yutaro Ogawa ◽  
Kikukawa Chihiro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Median Overall Survival ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Introduction:</i></b> This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. <b><i>Methods:</i></b> In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. <b><i>Results:</i></b> There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. <b><i>Conclusion:</i></b> Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

scholarly journals Transarterial Radioembolization of Hepatocellular Carcinoma, Liver-Dominant Hepatic Colorectal Cancer Metastases, and Cholangiocarcinoma Using Yttrium90 Microspheres: Eight-Year Single-Center Real-Life Experience

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Julie Pellegrinelli ◽  
Olivier Chevallier ◽  
Sylvain Manfredi ◽  
Inna Dygai-Cochet ◽  
Claire Tabouret-Viaud ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Progression Free Survival ◽  
Single Center ◽  
Free Survival ◽  
Risk Of Death ◽  
Transarterial Radioembolization ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

scholarly journals Combination Therapy after TACE for Hepatocellular Carcinoma with Macroscopic Vascular Invasion: Stereotactic Body Radiotherapy versus Sorafenib

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 516 ◽  
Author(s):  
Lujun Shen ◽  
Mian Xi ◽  
Lei Zhao ◽  
Xuhui Zhang ◽  
Xiuchen Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stereotactic Body Radiotherapy ◽  
Vascular Invasion ◽  
Progression Free Survival ◽  
Sorafenib Treatment ◽  
Free Survival ◽  
Sorafenib Group ◽  
Treatment Responses ◽  
Hepatic Lesions ◽  
Macroscopic Vascular Invasion

Stereotactic body radiotherapy (SBRT) has shown promising results in the control of macroscopic vascular invasion in patients with hepatocellular carcinoma (HCC); however, its efficacy in comparison to sorafenib when combined with transarterial chemoembolization (TACE) remains to be determined. Between 2009 and 2017, 77 HCC patients with macroscopic vascular invasion receiving TACE–SBRT or TACE–sorafenib combination therapies were enrolled. The best treatment responses, overall survival (OS), and progression-free survival (PFS) of the two treatment arms were compared. Of the patients enrolled, 26 patients (33.8%) received TACE–SBRT treatment, and 51 (66.2%) received TACE–sorafenib treatment. The patients in the TACE–SBRT group were more frequently classified as elder in age (p = 0.012), having recurrent disease (p = 0.026), and showing lower rates of multiple hepatic lesions (p = 0.005) than patients in TACE–sorafenib group. After propensity score matching (PSM), 26 pairs of well-matched HCC patients were selected; patients in the TACE–SBRT group showed better overall response rates in trend compared to those in the TACE–sorafenib group. The hazard ratio (HR) of OS to PFS for the TACE–SBRT approach and the TACE–sorafenib approach was 0.36 (95% CI, 0.17–0.75; p = 0.007) and 0.35 (95% CI, 0.20–0.62; p < 0.001), respectively. For HCC patients with macrovascular invasion, TACE plus SBRT could provide improved OS and PFS compared to TACE–sorafenib therapy.

scholarly journals Prognostic Value of Lactate Dehydrogenase in Patients with Hepatocellular Carcinoma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Weihao Kong ◽  
Xiaomin Zuo ◽  
Hao Liang ◽  
Jingxiong Hu ◽  
Huabing Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sensitivity Analysis ◽  
Lactate Dehydrogenase ◽  
Publication Bias ◽  
Subgroup Analysis ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Free Survival

Background. Previous studies have shown the prognostic value of lactate dehydrogenase (LDH) in hepatocellular carcinoma (HCC), but the results are not persuasive. Therefore, the purpose of our study was to quantitatively explore the prognostic value of LDH in hepatocellular carcinoma.Methods. We searched the Web of Science, Embase, PubMed, and the Cochrane Library for literature published before October 2018 on the prognostic value of LDH in patients with hepatocellular carcinoma. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to assess the prognostic value of LDH in overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) of HCC. Subgroup analysis, sensitivity analysis, and metaregression were used to explore the source of heterogeneity. Funnel plots with Begg’s test and Egger’s test were used to detect potential publication biases. Furthermore, combined odds ratios (ORs) were utilized to assess the correlation between LDH and clinicopathological features.Results. A total of 10 nonrandomized controlled studies were included in this meta-analysis. The combined effects of LDH on HCC patients’ OS, RFS/DFS, and PFS were HR = 2.07, 95% CI: 1.63-2.62, P < 0.001; HR = 1.62, 95% CI: 1.37-1.90, P < 0.001; and HR = 1.96, 95% CI: 1.14-3.36, P = 0.014, respectively. Subgroup analysis and sensitivity analysis showed that the outcome was stable, and the results of the metaregression also identified statistical models as an important source of heterogeneity. Potential publication bias was detected in the OS studies, so the trim-and-fill method was used to explore publication bias, and the results showed stability. Furthermore, the combined OR suggests that LDH was significantly correlated with gender, Child-Pugh grade, alpha-fetoprotein, vascular invasion, and tumor size.Conclusions. Preoperative LDH elevation is significantly associated with poor prognosis in patients with HCC, which may be a promising factor in assessing the prognosis of patients with HCC.

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