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Tian H, Wan C. Comparative efficacy and safety of transarterial chemoembolization combined with tyrosine kinase inhibitors and immune checkpoint inhibitors versus tyrosine kinase inhibitors and immune checkpoint inhibitors alone in advanced hepatocellular carcinoma: a systematic review and meta-analysis. World J Surg Oncol 2025; 23:126. [PMID: 40197348 PMCID: PMC11974228 DOI: 10.1186/s12957-025-03788-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 03/29/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and advanced-stage disease presents significant therapeutic challenges. Combining transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has emerged as a promising strategy to enhance treatment efficacy. This meta-analysis evaluates efficacy and safety of TACE + TKIs + ICIs compared to TKIs + ICIs alone in patients with HCC. METHODS A systematic search was conducted across "PubMed", "Web of Science", "Cochrane Library", "Scopus", "Google Scholar", and "Embase" to screen studies up to November 2024. Studies comparing TACE + TKIs + ICIs with TKIs + ICIs alone in advanced HCC were included. Outcomes of interest included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events. Results were reported as relative risk (RR) or hazard ratios (HR) with 95% confidence intervals (CI). Funnel plots was used to assess publication bias. RESULTS Ten studies comprising 1999 patients were included. The combination of TACE + TKIs + ICIs marked improved ORR (RR = 1.81, 95%CI:1.57-2.09, P < 0.00001) and DCR (RR = 1.32, 95%CI: 1.19-1.46, P < 0.00001) comparing with TKIs + ICIs alone. OS and PFS were also significantly prolonged in combination group, with HR of 0.55 (95%CI:0.48-0.63, P < 0.00001) and 0.73 (95%CI:0.65-0.82, P < 0.00001), respectively. Adverse events such as pain (RR = 3.94, 95%CI:2.40-6.47, P < 0.001) and nausea/vomiting (RR = 2.28, 95% CI:1.56-3.33, P < 0.001) were more frequent in the TACE + TKIs + ICIs group, though rates of hypertension, diarrhea, and rash were similar between groups. Funnel plots indicated minimal publication bias for primary outcomes. CONCLUSIONS The combination of TACE, TKIs, and ICIs significantly improves ORR, DCR, OS, and PFS compared to TKIs and ICIs alone, demonstrating superior efficacy with an acceptable safety profile. These findings provide evidence for the integration of TACE with systemic therapies in the management of HCC.
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Affiliation(s)
- Hengyu Tian
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, No, China
| | - Chidan Wan
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, No, China.
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Qiu F, Yu G, Li M, Li Z, Zhang Q, Mu X, Cheng Y, Zhai P, Liu Q. Identification and Verification of a Glycolysis-Related lncRNA Prognostic Signature for Hepatocellular Carcinoma. Horm Metab Res 2024; 56:827-834. [PMID: 38772393 DOI: 10.1055/a-2314-0988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/23/2024]
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. The search for a new biomarker could help the prognosis of HCC patients. We identified the glycolytic gene set associated with HCC and the glycolytic lncRNA based on TCGA and MsigDB databases. According to these lncRNAs, K-means clustering, and regression analysis were performed on the patients. Two groups of HCC patients with different lncRNA expression levels were obtained based on K-means clustering results. The results of difference analysis and enrichment analysis showed that DEmRNA in the two HCC populations with significant survival differences was mainly enriched in transmembrane transporter complex, RNA polymerase II specificity, cAMP signaling pathway, and calcium signaling pathway. In addition, a prognostic model of HCC with 4 DElncRNAs was constructed based on regression analysis. ROC curve analysis showed that the model had good predictive performance. Drug predictionresults showed that the efficacy of JQ1, niraparib, and teniposide was higher in the low-risk group than in the high-risk group. In conclusion, this study preliminarily identified glycolytic-related prognostic features of lncRNAs in HCC and constructed a risk assessment model. The results of this study are expected to guide the prognosis assessment of clinical HCC patients.
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MESH Headings
- Warburg Effect, Oncologic
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/pathology
- Liver Neoplasms/drug therapy
- Liver Neoplasms/genetics
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- RNA, Long Noncoding/analysis
- RNA, Long Noncoding/metabolism
- Prognosis
- Risk Assessment/methods
- Databases, Genetic
- Gene Expression Regulation, Neoplastic
- ROC Curve
- Regression Analysis
- Drug Resistance, Neoplasm/genetics
- Poly(ADP-ribose) Polymerase Inhibitors
- Topoisomerase II Inhibitors
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use
- Treatment Outcome
- Liver/pathology
- Kaplan-Meier Estimate
- Survival Rate
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/metabolism
- Gene Expression Profiling
- Humans
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Affiliation(s)
- Fakai Qiu
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Guozheng Yu
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Mei Li
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Zhubin Li
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Qinyang Zhang
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Xudong Mu
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Yuan Cheng
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Pengtao Zhai
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Qunyi Liu
- Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi'an, China
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Zheng Y, Xiang Y, Shi H, Lin Z, Cheng S, Zhu J. Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab versus Transarterial Chemoembolization Alone in Intermediate-stage Hepatocellular Carcinoma: A Multicenter Retrospective Study. J Hepatocell Carcinoma 2024; 11:1079-1093. [PMID: 38882440 PMCID: PMC11180435 DOI: 10.2147/jhc.s461630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 06/06/2024] [Indexed: 06/18/2024] Open
Abstract
Purpose Combining transarterial chemoembolization (TACE) with systemic therapy has shown significant efficacy for intermediate-stage hepatocellular carcinoma (HCC) patients. This study aimed to validate the therapeutic efficacy of TACE combined with atezolizumab and bevacizumab (TACE + Atez/Bev) compared to TACE alone. Methods A retrospective study was conducted across three centers in China, encompassing 155 patients at the intermediate-stage of HCC. Propensity Score Matching (PSM) was used to minimize selection bias, with a ratio of 1:1. Primary outcomes were TACE-specific Progression-Free Survival (PFS) and Overall Survival (OS). Objective Response Rate (ORR) and Disease Control Rate (DCR) were assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Adverse events (AEs) related to treatment were analyzed to evaluate safety. Results Before PSM, the TACE + Atez/Bev group demonstrated extended median OS (not reached vs 20.3 months, P = 0.004) and PFS (20.0 months vs 9.8 months, P = 0.029) compared to the TACE-alone group. The TACE + Atez/Bev group also had a higher ORR (60.9% vs 41.3%, P = 0.026) and DCR (89.1% vs 58.7%, P < 0.001) than the TACE-alone group. After applying the PSM, the study included 42 pairs of patients. Compared to the TACE-alone group, the combination therapy group also showed significantly longer median OS (not reached vs 21.4 months, P = 0.008) and PFS (21.7 vs 9.7 months, P = 0.009). The combination therapy group also had a higher ORR (66.7% vs 38.1%, P = 0.009) and DCR (92.9% vs 57.1%, P < 0.001). AEs in the combination therapy group were mostly manageable, with the most common being elevated liver transaminase. Conclusion In treating intermediate-stage HCC, the survival benefit of combining TACE with atezolizumab and bevacizumab was significantly higher than TACE alone, and the treatment was well-tolerated.
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Affiliation(s)
- Yitao Zheng
- Department of Pancreatic and Gastrointestinal Surgery Division, Ningbo No.2 Hospital, Ningbo, People's Republic of China
- Department of Hepatological Surgery, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Yanjun Xiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People's Republic of China
| | - Hongqi Shi
- Department of Hepatological Surgery, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Zhuoqun Lin
- Department of Hepatological Surgery, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People's Republic of China
| | - Jiuting Zhu
- Department of Pancreatic and Gastrointestinal Surgery Division, Ningbo No.2 Hospital, Ningbo, People's Republic of China
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Li M, Wu L, Luo S, Liu Y, Sun C, Li E, Wang J, Li B, Huang Z, Ge J, Lei J, Zhou F, Liao W. Validation of a supplementary condition of eighth AJCC staging system for stage II hepatocellular carcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1217-1225. [PMID: 36690533 DOI: 10.1016/j.ejso.2023.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 01/09/2023] [Accepted: 01/16/2023] [Indexed: 01/19/2023]
Abstract
INTRODUCTION The eighth American Joint Committee on Cancer (AJCC) staging system was flawed regarding the prognosis of stage II hepatocellular carcinoma (HCC). The aims of this study were to reveal the defect and make updates. METHODS Clinical and survival data of HCC patients from the Surveillance, Epidemiology, and End Results database were used. We re-classified stage II into T2aN0M0 (tumors >2 cm with vascular invasion) and T2bN0M0 (multiple tumors ≤5 cm). The Kaplan-Meier method and log-rank test were used to estimate differences in overall survival (OS). Three propensity score matching analyses without (PSM1) or with (PSM2 and PSM3) consideration of surgical treatment were performed. Cox regression was used to reveal risk factors. RESULTS HCC patients identified as T1bN0M0, T2aN0M0, T2bN0M0, and T3N0M0 were recruited. OS in T2N0M0 was consistent with the eighth AJCC staging system after PSM1. T2bN0M0 had increased OS compared with T2aN0M0 after PSM2 (hazard ratio [HR] = 1.36; 95% confidence interval [CI] = 1.06-1.73; P = 0.0141) or PSM3 (HR = 1.18; 95%CI = 1.01-1.37; P = 0.0283). No survival benefit existed between T1bN0M0 and T2bN0M0 after PSM2 (HR = 0.92; 95%CI = 0.80-1.05; P = 0.2171) or PSM3 (HR = 0.92; 95%CI = 0.84-1.01; P = 0.0888). Compared with T2aN0M0, T3N0M0 had shorter OS after PSM2 (HR = 0.64; 95%CI = 0.50-0.82; P = 0.0003) or PSM3 (HR = 0.63; 95%CI = 0.54-0.73; P < 0.0001). Cox regression analysis revealed that surgical treatment was associated with better prognosis (HR = 0.3; 95%CI = 0.3-0.4; P < 0.001). CONCLUSIONS The current staging for T2N0M0 is imprecise because surgical treatment is not adequately evaluated and would be ineffective if the proportion of T2bN0M0 patients with surgical treatment was increased.
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Affiliation(s)
- Min Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Linquan Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Shuaiwu Luo
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Yaran Liu
- Department of Pharmacy, Nanchang University, No.999, University Avenue, Nanchang, 330006, China
| | - Chi Sun
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Enliang Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Jiakun Wang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Bowen Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Zhihao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Jin Ge
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Jun Lei
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Fan Zhou
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Wenjun Liao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China.
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Wang XH, Duan WB, Liang W, Li H, Xie XY, Li SQ, Chen MS, Liang P, Mao XH, Zhou QF. Efficacy of radiofrequency ablation following transarterial chemoembolisation combined with sorafenib for intermediate stage recurrent hepatocellular carcinoma: a retrospective, multicentre, cohort study. EClinicalMedicine 2023; 56:101816. [PMID: 36703645 PMCID: PMC9871741 DOI: 10.1016/j.eclinm.2022.101816] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND The evidence of radiofrequency ablation (RFA) following transarterial chemoembolisation (TACE) combined with sorafenib for intermediate-stage recurrent hepatocellular carcinoma (RHCC) is limited. Patient responses to this treatment vary because of the heterogeneous nature of RHCC, making it important to identify patients who are most likely to benefit from this combination therapy. The aim of this study was to evaluate the efficacy of RFA following TACE and sorafenib for the intermediate-stage RHCC. METHODS This retrospective, multicentre, cohort study included 363 patients with intermediate-stage RHCC underwent TACE combined with sorafenib (TACE-sorafenib group) or RFA following TACE and sorafenib (TACE-sorafenib + RFA group) between January 01, 2009 to December 31, 2015 from four institutions in China. Overall survival (OS), progression-free survival (PFS) and efficacy of patients were compared between the two groups by propensity score-matching (PSM). FINDINGS The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% in TACE-sorafenib + RFA group, and 93.3%, 57.0%, 32.7% in TACE-sorafenib group. The 1-, 2-, and 3-year PFS rates were 85.3%, 58.0%, 26.9% in TACE-sorafenib + RFA group, and 55.3%, 30.7%, 15.3% in TACE-sorafenib group. Compared with the TACE-sorafenib group, the TACE-sorafenib + RFA group had significantly longer OS (HR, 0.54; 95%CI, 0.40-0.73; P < 0.001) and PFS (HR, 0.52; 95% CI, 0.41-0.66; P < 0.001). Subgroup analysis was conducted to precisely screen out the beneficial population from RFA treatment. INTERPRETATION Our findings suggest that addition of RFA following TACE and sorafenib combination was superior to TACE combined with sorafenib for intermediate-stage RHCC, resulting in longer OS and PFS. Patients who had good response to TACE and achieved downstaging successfully could not benefit from the RFA therapy. FUNDING This research was funded by National Natural Science Foundation of China (No. 81627803), Chen Xiao-Ping Science and Technology Development Fund (CXPJJH1200009-06).
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Affiliation(s)
- Xiao-Hui Wang
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
| | - Wen-Bin Duan
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
| | - Wei Liang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
| | - Hui Li
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510060, China
| | - Shao-Qiang Li
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 510060, China
| | - Min-Shan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
- Corresponding author.
| | - Xian-Hai Mao
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
- Corresponding author.
| | - Qun-Fang Zhou
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
- Corresponding author.
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Zhou Y, Lei D, Hu G, Luo F. A Cell Cycle-Related 13-mRNA Signature to Predict Prognosis in Hepatocellular Carcinoma. Front Oncol 2022; 12:760190. [PMID: 35419294 PMCID: PMC8995863 DOI: 10.3389/fonc.2022.760190] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 02/17/2022] [Indexed: 12/02/2022] Open
Abstract
We aimed to propose a cell cycle-related multi/mRNA signature (CCS) for prognosis prediction and uncover new tumor-driver genes for hepatocellular carcinoma (HCC). Cell cycle-related gene sets and HCC samples with mRNA-Seq data were retrieved from public sources. The genes differentially expressed in HCCs relative to normal peritumoral tissues were extracted through statistical analysis. The CCS was constructed by Cox regression analyses. Predictive capacity and clinical practicality of the signature were evaluated and validated. The expression of the function-unknown genes in the CCS was determined by RT-qPCR. Candidate gene TICRR was selected for subsequent validation through functional experiments. A cell cycle-related 13-mRNA signature was generated from the exploratory cohort [The Cancer Genome Atlas (TCGA), n = 371)]. HCC cases were classified as high- vs. low-risk groups per overall survival (OS) [hazard ratio (HR) = 2.699]. Significantly, the CCS exhibited great predictive value for prognosis in three independent cohorts, particularly in GSE76427 cohort [area under the curve (AUC) = 0.835/0.822/0.808/0.821/0.826 at 1/2/3/4/5 years]. The nomogram constructed by integrating clinicopathological features with the CCS indicated high accuracy and practicability. Significant enrichment of tumorigenesis-associated pathways was observed in the high-risk patients by Gene Set Enrichment Analysis (GSEA). RT-qPCR revealed that TICRR was overexpressed in HCC samples. Increased TICRR expression implied poor prognosis in HCC patients. Furthermore, depletion of TICRR in HCC cells decreased cell proliferation and the G1/S transition. In conclusion, the established 13-CCS had efficacy in prognostic prediction of HCC patients. Additionally, TICRR was demonstrated as a tumor-driver gene for this deadly disease.
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Affiliation(s)
- Yang Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dengliang Lei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Gangli Hu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fang Luo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Xia D, Wang Q, Bai W, Wang E, Wang Z, Mu W, Sun J, Huang M, Yin G, Li H, Zhao H, Zhang C, Li J, Wu J, Zhu X, Yang S, Pan X, Li J, Li Z, Xu G, Shi H, Zhang H, Zhang Y, Ding R, Yu H, Zheng L, Yang X, Wang G, You N, Feng L, Zhang S, Huang W, Xu T, Fan W, Li X, Yang X, Zhou W, Wang W, Li X, Wang Z, Luo B, Niu J, Yuan J, Lv Y, Li K, Guo W, Yin Z, Fan D, Xia J, Han G. Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization. Eur Radiol 2022; 32:5799-5810. [PMID: 35381853 DOI: 10.1007/s00330-022-08716-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 02/08/2022] [Accepted: 03/05/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. METHODS A total of 1549 eligible treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score ≤ 7, and performance status score ≤ 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on "six-and-twelve" criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was ≤ 6, > 6 but ≤ 12, and > 12, respectively. RESULTS Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). CONCLUSIONS ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden. KEY POINTS • This is the first study utilizing individual patient data to comprehensively analyze the surrogacy of ORR with a long follow-up period. • Optimal timing of ORR assessment for predicting survival should be tailored according to tumor burden. • For patients with low and intermediate tumor burden, initial ORR is optimal for its timeliness upon similar sensitivity with best ORR. For patients with high tumor burden, best ORR has optimal sensitivity.
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Affiliation(s)
- Dongdong Xia
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Qiuhe Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wei Bai
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,Department of Medical Affairs, Air Force Hospital of Western Theater Command, Chengdu, Sichuan Province, China
| | - Zhexuan Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wei Mu
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Junhui Sun
- Department of Hepatobiliary and Pancreatic Interventional Cancer, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ming Huang
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Guowen Yin
- Department of Interventional Radiology, Jiangsu Provincial Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Hailiang Li
- Department of Interventional Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Hui Zhao
- Department of Interventional Radiology, The Affiliated Hospital of Nantong University, Nantong, China
| | - Chunqing Zhang
- Department of Gastroenterology and Hepatology, Shandong Province Hospital Affiliated to Shandong University, Jinan, China
| | - Jing Li
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Jianbing Wu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaoli Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Shufa Yang
- Department of Interventional Radiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
| | - Xingnan Pan
- Clinical Liver Diseases Research Center, Nanjing Military Command, 180th Hospital of PLA, Quanzhou, China
| | - Jiaping Li
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zixiang Li
- Interventional Medical Center of The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Guohui Xu
- Department of Interventional Radiology, Sichuan Cancer Hospital & Institute, Chengdu, China
| | - Haibin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Zhang
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Yuelin Zhang
- Department of Hepatobiliary and Pancreatic Interventional Cancer, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Rong Ding
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Hui Yu
- Department of Interventional Radiology, Jiangsu Provincial Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Lin Zheng
- Department of Interventional Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiaohu Yang
- Department of Interventional Radiology, The Affiliated Hospital of Nantong University, Nantong, China
| | - Guangchuan Wang
- Department of Gastroenterology and Hepatology, Shandong Province Hospital Affiliated to Shandong University, Jinan, China
| | - Nan You
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Long Feng
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shuai Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Wukui Huang
- Department of Interventional Radiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
| | - Tao Xu
- Clinical Liver Diseases Research Center, Nanjing Military Command, 180th Hospital of PLA, Quanzhou, China
| | - Wenzhe Fan
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xueda Li
- Interventional Medical Center of The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xuegang Yang
- Department of Interventional Radiology, Sichuan Cancer Hospital & Institute, Chengdu, China
| | - Weizhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Xiaomei Li
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhengyu Wang
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Bohan Luo
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jie Yuan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Yong Lv
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Kai Li
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Wengang Guo
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhanxin Yin
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Jielai Xia
- Department of Health Statistics, Fourth Military Medical University, Xi'an, China
| | - Guohong Han
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China. .,Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
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8
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[Transarterial chemoembolization of hepatocellular carcinoma]. Radiologe 2022; 62:225-233. [PMID: 35171312 DOI: 10.1007/s00117-022-00972-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2022] [Indexed: 10/19/2022]
Abstract
Transarterial chemoembolization (TACE) is used as palliative and neoadjuvant treatment for patients with hepatocellular carcinoma (HCC). TACE should be offered as palliative treatment to patients with intermediate stage large or multinodular HCC if no curative treatment option is available by resection or thermoablation and if extrahepatic metastases and tumor infiltration of main portal and systemic veins has been excluded. TACE is possible only in patients with preserved liver function (Child-Pugh A-B, best up to 7 points) and with good performance status (ECOG 0). TACE can be used for bridging and for downstaging prior to liver transplantation with the intention to maintain or reach limited intrahepatic tumor load defined by Milan criteria. TACE should be adapted to the vascularization pattern of the HCC nodules and performed as selective as possible and repetetively if necessary with the goal of complete devascularization of the tumor tissue. Conventional TACE (cytotoxic drugs, iodized oil and embolic particles) and drug-eluting TACE (anthracycline preloaded in microspheres) can be used in a comparable way. During drug-eluting TACE, peripheral concentration of cytotoxic drugs is lower. Using conventional TACE in a palliative setting, survival benefit for patients was 8-11 months compared to best supportive care; however, this requires that all known contraindications and other criteria in terms of tumor and liver disease, respectively, associated with negative prognosis be taken into consideration. Better local response is achieved by drug-eluting TACE; however, no related survival benefit was shown compared to conventional TACE so far. Response to neoadjuvant local treatment is associated with improved prognosis after liver transplantation.
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9
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Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
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Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
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10
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Hiraoka A, Kumada T, Kariyama K, Toyoda H, Yasuda S, Tsuji K, Hatanaka T, Kakizaki S, Naganuma A, Ishikawa T, Tada T, Takaguchi K, Itobayashi E, Shimada N, Shibata H, Tanaka T, Tsutsui A, Nagano T, Imai M, Nakamura S, Nouso K. Simple Scoring System for Predicting TACE Unsuitable among Intermediate-Stage Hepatocellular Carcinoma Patients in the Multiple Systemic Treatment Era. Oncology 2021; 100:65-73. [PMID: 34844247 PMCID: PMC8820430 DOI: 10.1159/000520292] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 10/14/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIM With the development of systemic treatment methods for unresectable hepatocellular carcinoma (uHCC), the concept of unsuitable for transcatheter arterial chemoembolization (TACE) has become important. This study aimed to establish a simple predictive scoring system for determining TACE unsuitable status. MATERIALS/METHODS From 1998 to 2015, 196 patients with intermediate-stage uHCC with Child-Pugh A (score 5:6 = 108:88) and given TACE as the initial treatment were enrolled. At the baseline, tumor burden (Milan criteria-out, up-to-7 in/out, and up-to-11 in/out: 0-2 points) and modified albumin-bilirubin grade 1/2a or 2b (0-1 point) were added to determine the score for TACE unsuitable (CITRUS-MICAN score; low <2 and high ≥2). In addition, a previously reported tumor marker (TM) score, in which alpha-fetoprotein (AFP) was ≥100 ng/mL, fucosylated AFP ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL (each 1 point) (total 0, 1, or ≥2 points), was used for additionally evaluating tumor malignancy potential. Prognosis was retrospectively evaluated based on those scores. RESULTS Median survival time (MST) was better for low compared to high CITRUS-MICAN score (42.0 vs. 26.4 months) (p = 0.002). A 2-step evaluation using the combination of CITRUS-MICAN and TM scores showed an MST of 43.2 months for low CITRUS-MICAN/TM score 0/1 (rank-A) and 39.6 months for low CITRUS-MICAN/TM score ≥2 (rank-B2), while it was 46.8 months for high CITRUS-MICAN/TM score 0 (rank-B1), 28.8 months for high CITRUS-MICAN/TM score 1 (rank-B2), and 22.8 months for high CITRUS-MICAN/TM score ≥2 (rank-C). For rank-A cases (n = 51), MST was 43.2 months, while it was 46.8 months for rank-B1 (n = 12), 31.2 months for rank-B2 (n = 82), and 22.8 months for rank-C (n = 51) (p = 0.001). CONCLUSION The results showed that rank-C indicates absolute TACE unsuitable status. For rank-A patients, good prognosis with TACE can be expected, while TACE refractoriness status during the clinical course should be carefully evaluated so as to anticipate the appropriate timing for switching to systemic treatment in rank-B1 and -B2 patients.
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Affiliation(s)
- Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Takashi Kumada
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Kazuya Kariyama
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Hidenori Toyoda
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kunihiko Tsuji
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Takeshi Hatanaka
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Gunma, Japan
| | - Satoru Kakizaki
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Atsushi Naganuma
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Toru Ishikawa
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Toshifumi Tada
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Koichi Takaguchi
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Ei Itobayashi
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Noritomo Shimada
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Hiroshi Shibata
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Takaaki Tanaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Akemi Tsutsui
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Takuya Nagano
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | - Michitaka Imai
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
| | | | - Kazuhiro Nouso
- Real-life Practice Experts for HCC (RELPEC) Study Group, Matsuyama, Japan
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
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11
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Jiang X, Zhang W, Li L, Xie S. Integrated Transcriptomic Analysis Revealed Hub Genes and Pathways Involved in Sorafenib Resistance in Hepatocellular Carcinoma. Pathol Oncol Res 2021; 27:1609985. [PMID: 34737677 PMCID: PMC8560649 DOI: 10.3389/pore.2021.1609985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/28/2021] [Indexed: 12/31/2022]
Abstract
Hepatocellular carcinoma (HCC), a high mortality malignancy, has become a worldwide public health concern. Acquired resistance to the multikinase inhibitor sorafenib challenges its clinical efficacy and the survival benefits it provides to patients with advanced HCC. This study aimed to identify critical genes and pathways associated with sorafenib resistance in HCC using integrated bioinformatics analysis. Differentially expressed genes (DEGs) were identified using four HCC gene expression profiles (including 34 sorafenib-resistant and 29 sorafenib-sensitive samples) based on the robust rank aggregation method and R software. Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING), and small molecules reversing sorafenib resistance were searched for using the connectivity map (CMAP) database. Pearson correlation and survival analyses of hub genes were performed using cBioPortal and Gene Expression Profiling and Interactive Analysis (GEPIA). Finally, the expression levels of hub genes in sorafenib-resistant HCC cells were verified using quantitative polymerase chain reaction (q-PCR). A total of 165 integrated DEGs (66 upregulated and 99 downregulated in sorafenib resistant samples compared sorafenib sensitive ones) primarily enriched in negative regulation of endopeptidase activity, extracellular exosome, and protease binding were identified. Some pathways were commonly shared between the integrated DEGs. Seven promising therapeutic agents and 13 hub genes were identified. These findings provide a strategy and theoretical basis for overcoming sorafenib resistance in HCC patients.
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Affiliation(s)
- Xili Jiang
- Department of Radiology, The Second People's Hospital of Hunan Province/Brain Hospital of Hunan Province, Changsha, China
| | - Wei Zhang
- Department of Radiology, The Second People's Hospital of Hunan Province/Brain Hospital of Hunan Province, Changsha, China
| | - Lifeng Li
- Department of Radiology, Changsha Central Hospital, Changsha, China
| | - Shucai Xie
- Department of Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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12
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Pan Y, Mei J, Chen J, Zhang D, Wang J, Wang X, Yi M, Zhou Z, Zhang Y, Chen M, Guo R, Xu L. Comparison Between Portal Vein Perfusion Chemotherapy and Neoadjuvant Hepatic Arterial Infusion Chemotherapy for Resectable Intermediate to Advanced Stage Hepatocellular Carcinoma. Ann Surg Oncol 2021; 29:2016-2029. [PMID: 34637058 DOI: 10.1245/s10434-021-10903-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/19/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively. OBJECTIVE This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC. METHODS A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes. RESULTS Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p = 0.364), sex (male: 25/28 vs. 35/36; p = 0.435), and tumor size (median 9.55 vs. 8.10 cm; p = 0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p = 0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p = 0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p = 0.007) and OS (HR 0.095; p = 0.007) for BCLC stage B/C HCC patients who received hepatectomy. CONCLUSIONS Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.
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Affiliation(s)
- Yangxun Pan
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden
| | - Jie Mei
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Jinbin Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Deyao Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Juncheng Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Xiaohui Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Minjiang Yi
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Rongping Guo
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. .,State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
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13
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Zhang L, Wang Z, Li M, Sun P, Bai T, Wang W, Bai H, Gou J, Wang Z. HCG18 Participates in Vascular Invasion of Hepatocellular Carcinoma by Regulating Macrophages and Tumor Stem Cells. Front Cell Dev Biol 2021; 9:707073. [PMID: 34527669 PMCID: PMC8435853 DOI: 10.3389/fcell.2021.707073] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022] Open
Abstract
Objectives To identify key genes involved in vascular invasion in hepatocellular carcinoma (HCC), to describe their regulatory mechanisms, and to explore the immune microenvironment of HCC. Methodology In this study, the genome, transcriptome, and immune microenvironment of HCC were assessed by using multi-platform data from The Cancer Genome Atlas (n = 373) and GEO data (GSE149614). The key regulatory networks, transcription factors and core genes related to vascular invasion and prognosis were explored based on the CE mechanism. Survival analysis and gene set enrichment were used to explore pathways related to vascular invasion. Combined with single-cell transcriptome data, the distribution of core gene expression in various cells was observed. Cellular communication analysis was used to identify key cells associated with vascular invasion. Pseudo-temporal locus analysis was used to explore the regulation of core genes in key cell phenotypes. The influence of core genes on current immune checkpoint therapy was evaluated and correlations with tumor stem cell scores were explored. Results We obtained a network containing 1,249 pairs of CE regulatory relationships, including 579 differential proteins, 28 non-coding RNAs, and 37 miRNAs. Three key transcription factors, ILF2, YBX1, and HMGA1, were identified, all regulated by HCG18 lncRNA. ScRNAseq showed that HCG18 co-localized with macrophages and stem cells. CIBERSORTx assessed 22 types of immune cells in HCC and found that HCG18 was positively correlated with M0 macrophages, while being negatively correlated with M1 and M2 macrophages, monocytes, and dendritic cells. Cluster analysis based on patient prognosis suggested that regulating phenotypic transformation of macrophages could be an effective intervention for treating HCC. At the same time, higher expression of HCG18, HMGA1, ILF2, and YBX1 was associated with a higher stem cell score and less tumor differentiation. Pan cancer analysis indicated that high expression of HCG18 implies high sensitivity to immune checkpoint therapy. Conclusion HCG18 participates in vascular invasion of HCC by regulating macrophages and tumor stem cells through three key transcription factors, YBX1, ILF2, and HMGA1.
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Affiliation(s)
- Liwei Zhang
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, Zhengzhou, China
| | - Zhiwei Wang
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mingxing Li
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Peng Sun
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tao Bai
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wang Wang
- Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, Zhengzhou, China.,Department of Physiology, Medical School of Zhengzhou University, Zhengzhou, China
| | - Hualong Bai
- Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, Zhengzhou, China
| | - Jianjun Gou
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhiju Wang
- Department of Physiology, Medical School of Zhengzhou University, Zhengzhou, China
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14
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Yang Y, Wu G, Li Q, Zheng Y, Liu M, Zhou L, Chen Z, Wang Y, Guo Q, Ji R, Zhou Y. Angiogenesis-Related Immune Signatures Correlate With Prognosis, Tumor Microenvironment, and Therapeutic Sensitivity in Hepatocellular Carcinoma. Front Mol Biosci 2021; 8:690206. [PMID: 34262941 PMCID: PMC8273615 DOI: 10.3389/fmolb.2021.690206] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 06/01/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the highly heterogeneous cancers that lacks an effective risk model for prognosis prediction. Therefore, we searched for angiogenesis-related immune genes that affected the prognosis of HCC to construct a risk model and studied the role of this model in HCC. Methods: In this study, we collected the transcriptome data of HCC from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. Pearson correlation analysis was performed to identify the association between immune genes and angiogenesis-related genes. Consensus clustering was applied to divide patients into clusters A and B. Subsequently, we studied the differentially expressed angiogenesis-related immune genes (DEari-genes) that affected the prognosis of HCC. The most significant features were identified by least absolute shrinkage and selection operator (LASSO) regression, and a risk model was constructed. The reliability of the risk model was evaluated in the TCGA discovery cohort and the ICGC validation cohort. In addition, we compared the novel risk model to the previous models based on ROC analysis. ssGSEA analysis was used for function evaluation, and pRRophetic was utilized to predict the sensitivity of administering chemotherapeutic agents. Results: Cluster A patients had favorable survival rates. A total of 23 DEari-genes were correlated with the prognosis of HCC. A five-gene (including BIRC5, KITLG, PGF, SPP1, and SHC1) signature-based risk model was constructed. After regrouping the HCC patients by the median score, we could effectively discriminate between them based on the adverse survival outcome, the unique tumor immune microenvironment, and low chemosensitivity. Conclusion: The five-gene signature-based risk score established by ari-genes showed a promising clinical prediction value.
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Affiliation(s)
- Yuan Yang
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.,Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Guozhi Wu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.,Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Qiang Li
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Ya Zheng
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Min Liu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Lingshan Zhou
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.,Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Zhaofeng Chen
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Qinghong Guo
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Rui Ji
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
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15
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Bai Y, Lin H, Chen J, Wu Y, Yu S. Identification of Prognostic Glycolysis-Related lncRNA Signature in Tumor Immune Microenvironment of Hepatocellular Carcinoma. Front Mol Biosci 2021; 8:645084. [PMID: 33968985 PMCID: PMC8100457 DOI: 10.3389/fmolb.2021.645084] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/19/2021] [Indexed: 12/13/2022] Open
Abstract
Purpose: The purpose of this study was to construct a novel risk scoring model with prognostic value that could elucidate tumor immune microenvironment of hepatocellular carcinoma (HCC). Samples and methods: Data were obtained through The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were carried out to screen for glycolysis-related long noncoding RNAs (lncRNAs) that could provide prognostic value. Finally, we established a risk score model to describe the characteristics of the model and verify its prediction accuracy. The receiver operating characteristic (ROC) curves of 1, 3, and 5 years of overall survival (OS) were depicted with risk score and some clinical features. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the characteristics of tumor immune microenvironment in HCC. The nomogram was drawn by screening indicators with high prognostic accuracy. The correlation of risk signature with immune infiltration and immune checkpoint blockade (ICB) therapy was analyzed. After enrichment of related genes, active behaviors and pathways in high-risk groups were identified and lncRNAs related to poor prognosis were validated in vitro. Finally, the impact of MIR4435-2HG upon ICB treatment was uncovered. Results: After screening through multiple steps, four glycolysis-related lncRNAs were obtained. The risk score constructed with the four lncRNAs was found to significantly correlate with prognosis of samples. From the ROC curve of samples with 1, 3, and 5 years of OS, two indicators were identified with high prognostic accuracy and were used to draw a nomogram. Besides, the risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e. B cells, etc.), and ICB key molecules (i.e. CTLA4,etc.). Gene enrichment analysis indicated that multiple biological behaviors and pathways were active in the high-risk group. In vitro validation results showed that MIR4435-2HG was highly expressed in the two cell lines, which had a significant impact on the OS of samples. Finally, we corroborated that MIR4435-2HG had intimate relationship with ICB therapy in hepatocellular carcinoma. Conclusion: We elucidated the crucial role of risk signature in immune cell infiltration and immunotherapy, which might contribute to clinical strategies and clinical outcome prediction of HCC.
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Affiliation(s)
- Yang Bai
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.,Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haiping Lin
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Jiaqi Chen
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, China
| | - Yulian Wu
- Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shi'an Yu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
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16
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Lim JY, Lee M, Kim TH. Is Transarterial Chemoembolization Only Treatment Option in Patients with Intermediate Stage of Hepatocellular Carcinoma?: in Perspectives of Surgery. JOURNAL OF LIVER CANCER 2020; 20:113-119. [PMID: 37384321 PMCID: PMC10035680 DOI: 10.17998/jlc.20.2.113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 07/30/2020] [Accepted: 07/31/2020] [Indexed: 06/30/2023]
Abstract
In the Barcelona Clinic Liver Cancer staging system, intermediate stage hepatocellular carcinoma (HCC) is defined as large multinodular tumors without vascular invasion or extrahepatic spread in an asymptomatic patient with good performance status. Intermediate stage HCC includes various subgroups and it is characterized by extensive heterogeneity. Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment modality for patients with intermediate stage HCC. Although TACE provides improved survival benefits compared with supportive care for patients with intermediate stage HCC, all of them are not good candidates for TACE. TACE refractoriness is another obstacle to effective treatment of patients with intermediate stage HCC. Given that many studies recently reported improved survival in patients treated with hepatic resection over TACE, we reviewed the survival outcomes of TACE and hepatic resection as a treatment strategy of intermediate stage HCC.
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Affiliation(s)
- Ji Young Lim
- Department of Health Promotion Center, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Tae Hun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
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17
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Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE. Eur Radiol 2020; 30:5663-5673. [PMID: 32424595 DOI: 10.1007/s00330-020-06931-5] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 03/15/2020] [Accepted: 04/30/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To investigate the predictive value of quantifiable imaging and inflammatory biomarkers in patients with hepatocellular carcinoma (HCC) for the clinical outcome after drug-eluting bead transarterial chemoembolization (DEB-TACE) measured as volumetric tumor response and progression-free survival (PFS). METHODS This retrospective study included 46 patients with treatment-naïve HCC who received DEB-TACE. Laboratory work-up prior to treatment included complete and differential blood count, liver function, and alpha-fetoprotein levels. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were correlated with radiomic features extracted from pretreatment contrast-enhanced magnetic resonance imaging (MRI) and with tumor response according to quantitative European Association for the Study of the Liver (qEASL) criteria and progression-free survival (PFS) after DEB-TACE. Radiomic features included single nodular tumor growth measured as sphericity, dynamic contrast uptake behavior, arterial hyperenhancement, and homogeneity of contrast uptake. Statistics included univariate and multivariate linear regression, Cox regression, and Kaplan-Meier analysis. RESULTS Accounting for laboratory and clinical parameters, high baseline NLR and PLR were predictive of poorer tumor response (p = 0.014 and p = 0.004) and shorter PFS (p = 0.002 and p < 0.001). When compared to baseline imaging, high NLR and PLR correlated with non-spherical tumor growth (p = 0.001 and p < 0.001). CONCLUSIONS This study establishes the prognostic value of quantitative inflammatory biomarkers associated with aggressive non-spherical tumor growth and predictive of poorer tumor response and shorter PFS after DEB-TACE. KEY POINTS • In treatment-naïve hepatocellular carcinoma (HCC), high baseline platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with non-nodular tumor growth measured as low tumor sphericity. • High PLR and NLR are predictive of poorer volumetric enhancement-based tumor response and PFS after DEB-TACE in HCC. • This set of readily available, quantitative immunologic biomarkers can easily be implemented in clinical guidelines providing a paradigm to guide and monitor the personalized application of loco-regional therapies in HCC.
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18
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Yan J, Man Z, Lu Q, Ma K. Long-Term Survival in Patients Receiving Combination Therapy with Resection and Radiofrequency Ablation for Multi-Focal Hepatocellular Carcinoma Classified as Barcelona Clinic Liver Cancer Stage B: A Retrospective Controlled Study. Cancer Manag Res 2020; 12:2613-2621. [PMID: 32368139 PMCID: PMC7173838 DOI: 10.2147/cmar.s237635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 03/18/2020] [Indexed: 01/08/2023] Open
Abstract
Objective To evaluate the survival outcomes of combined liver resection (LR) and radiofrequency ablation (RFA) on multi-focal hepatocellular carcinoma (HCC) in patients with Barcelona clinic liver cancer (BCLC) stage B. Methods A total of 210 cases of HCC were included in this study. In 42 cases, patients were treated with combination therapy using LR and RFA (LRCRFA). In 84 cases, patients underwent transarterial chemoembolization (TACE), and in another 84 cases, patients underwent LR; both the TACE and LR groups served as controls. It both categorized as BCLC stage B for LRCRFA and TACE groups but as BCLC stage A for LR group. Results The overall survival (OS) rate of the LRCRFA group was significantly higher than that of the TACE group (P<0.001) but was not significantly different when compared with the LR group (P=0.544). The disease-free survival (DFS) rate of the LRCRFA group was significantly lower than that of the LR group (P=0.029). Patients with ≤4 tumors or those with ≤5 tumors no larger than 6 cm in diameter experienced better long-term outcomes than other patients in the same LRCRFA group. The OS rates and DFS rates were not significantly different from those of patients in the LR group (P>0.05). Having more than 2 existing tumors was an independent risk factor for OS rate. Conclusion Combination therapy using LR and RFA can more effectively improve the prognosis of these patients than TACE. Patients with BCLC stage B HCC with ≤4 tumors or ≤5 tumors smaller than 6 cm in diameter are the ideal candidates for the application of LRCRFA.
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Affiliation(s)
- Jun Yan
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing, People's Republic of China.,The Institute of Hepatobiliary Surgery, The First Hospital Affiliated of Army Medical University, Chongqing, People's Republic of China.,Center of Hepatobiliary Pancreatic Disease, Xuzhou Central Hospital, Jiangsu, People's Republic of China
| | - Zhongsong Man
- Center of Hepatobiliary Pancreatic Disease, Xuzhou Central Hospital, Jiangsu, People's Republic of China
| | - Qian Lu
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing, People's Republic of China
| | - Kuansheng Ma
- The Institute of Hepatobiliary Surgery, The First Hospital Affiliated of Army Medical University, Chongqing, People's Republic of China
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19
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Abdel Ghafar MT, Morad MA, El-Zamarany EA, Ziada D, Soliman H, Abd-Elsalam S, Salama M. Autologous dendritic cells pulsed with lysate from an allogeneic hepatic cancer cell line as a treatment for patients with advanced hepatocellular carcinoma: A pilot study. Int Immunopharmacol 2020; 82:106375. [PMID: 32169808 DOI: 10.1016/j.intimp.2020.106375] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 02/14/2020] [Accepted: 03/03/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES This is a randomized trial adopted to evaluate the safety and efficacy of immunization with specific anti-hepatocellular carcinoma dendritic cells (DCs) in Egyptian patients with advanced hepatocellular carcinoma (HCC) as a treatment or adjuvant therapy in comparison with the traditional therapy. METHODS This study was conducted on 20 HCC patients who were assigned to four groups according to BCLC staging; group I: HCC patients (stage B) received trans-arterial chemoembolization (TACE) and DCs as an adjuvant therapy; group II: HCC patients (stage B) received TACE only; group III: advanced HCC patients (stage D) received DCs vaccine; group IV: advanced HCC patients (stage D) received supportive treatment. DCs were generated from peripheral blood monocytes and pulsed with a lysate of an allogeneic hepatic cancer cell line (HepG2). Toxicity and immunological response were reported as primary outcomes whereas clinical biochemical and radiological responses were reported as secondary outcomes. RESULTS Our study detected that patients who received DCs vaccine (group III) showed mild decrease in Child-Pugh score as well as AFP and PIVKA II levels and developed 20% partial response [PR] 40% stable disease [SD] and 40% progressive disease [PD] compared to the patients of group IV on supportive treatment who developed 100% PD. Although group I patients developed PR (60%) SD (20%) and PD (20%) no significant difference was detected in the clinical biochemical or radiological response between group I and group II patients. DCs vaccine had minimal adverse effects with no autoimmunity and elicited a better immunological response such as increased CD8 cells percentage and number as well as decreased TGFβ levels in the vaccinated patients. CONCLUSION DCs vaccine is safe as it is not associated with significant toxicity. However due to the small number of included patients the efficacy and immune response of using DCs vaccine in the treatment of advanced HCC patients need to be justified by testing of a large cohort.
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Affiliation(s)
| | - Morad Ahmed Morad
- Clinical Pathology Department Faculty of Medicine, Tanta University, Egypt
| | - Enas A El-Zamarany
- Clinical Pathology Department Faculty of Medicine, Tanta University, Egypt
| | - Dina Ziada
- Tropical Medicine Department Faculty of Medicine, Tanta University, Egypt
| | - Hanan Soliman
- Tropical Medicine Department Faculty of Medicine, Tanta University, Egypt
| | | | - Marwa Salama
- Tropical Medicine Department Faculty of Medicine, Tanta University, Egypt
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20
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Ni JY, Fang ZT, Sun HL, An C, Huang ZM, Zhang TQ, Jiang XY, Chen YT, Xu LF, Huang JH. A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation. Eur Radiol 2020; 30:2377-2390. [PMID: 31900694 DOI: 10.1007/s00330-019-06438-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 06/30/2019] [Accepted: 09/04/2019] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.
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Affiliation(s)
- Jia-Yan Ni
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong Province, People's Republic of China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang Road West, Guangzhou, 510120, Guangdong Province, People's Republic of China
| | - Zhu-Ting Fang
- Department of Interventional Radiology, Fujian Provincial Hospital, Provincial Clinic College of Fujian Medical University, Fuzhou, People's Republic of China
| | - Hong-Liang Sun
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang Road West, Guangzhou, 510120, Guangdong Province, People's Republic of China
| | - Chao An
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong Province, People's Republic of China
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Zhi-Mei Huang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong Province, People's Republic of China
| | - Tian-Qi Zhang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong Province, People's Republic of China
| | - Xiong-Ying Jiang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang Road West, Guangzhou, 510120, Guangdong Province, People's Republic of China
| | - Yao-Ting Chen
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang Road West, Guangzhou, 510120, Guangdong Province, People's Republic of China
| | - Lin-Feng Xu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang Road West, Guangzhou, 510120, Guangdong Province, People's Republic of China.
| | - Jin-Hua Huang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Cancer for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong Province, People's Republic of China.
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21
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Hiraoka A, Michitaka K, Kumada T, Izumi N, Kadoya M, Kokudo N, Kubo S, Matsuyama Y, Nakashima O, Sakamoto M, Takayama T, Kokudo T, Kashiwabara K, Eguchi S, Yamashita T, Kudo M. Prediction of Prognosis of Intermediate-Stage HCC Patients: Validation of the Tumor Marker Score in a Nationwide Database in Japan. Liver Cancer 2019; 8:403-411. [PMID: 31768348 PMCID: PMC6873098 DOI: 10.1159/000495944] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 12/03/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND/AIM Adequate assessment of transcatheter arterial chemoembolization (TACE)-refractory status has become more important for switching treatment in intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) patients treated with TACE. The usefulness of a previously proposed tumor marker score for predicting prognosis of BCLC-B HCC patients treated with TACE was investigated. METHODS Using a nationwide database, we examined the records of 1,306 naïve BCLC-B HCC with Child-Pugh A who were treated from 2001 to 2007, after excluding those with missing data (hepatic function or tumor markers) or cases with a single large tumor. Alpha-fetoprotein (AFP) ≥100 ng/mL, fucosylated AFP (AFP-L3) ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL were markers used to define positive cases. The number of positive tumor markers was used as a prognostic score, and its predictive value was evaluated in a retrospective manner. RESULTS Median survival time became shorter along with increased score (0, 1, ≥2 = 4.8, 3.8, 3.2 years, respectively; p < 0.01). Tumor marker score (≥2; hazard ratio [HR] 1.675, 95% confidence interval [CI] 1.372-2.044, p < 0.001), serum levels of albumin (≥3.5 g/dL; HR 0.726, 95% CI 0.528-0.997, p = 0.048), and up-to-7 criteria (HR 1.673, 95% CI 1.400-2.000, p < 0.001) were significant prognostic factors for death in the Cox hazard multivariate analysis. CONCLUSION Tumor marker score had a useful predictive prognostic value in BCLC-B HCC treated with TACE. Especially in patients with a tumor marker score of 2 or greater, a poor therapeutic response should be expected, and appropriate judgement of TACE-refractory status is necessary.
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Affiliation(s)
- Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masumi Kadoya
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kosuke Kashiwabara
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tatsuya Yamashita
- Advanced Preventive Medical Research Center, Kanazawa University, Kanazawa, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan
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22
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Inchingolo R, Posa A, Mariappan M, Spiliopoulos S. Locoregional treatments for hepatocellular carcinoma: Current evidence and future directions. World J Gastroenterol 2019; 25:4614-4628. [PMID: 31528090 PMCID: PMC6718039 DOI: 10.3748/wjg.v25.i32.4614] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 07/12/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Liver cancers are the second most frequent cause of global cancer-related mortality of which 90% are attributable to hepatocellular carcinoma (HCC). Despite the advent of screening programmes for patients with known risk factors, a substantial number of patients are ineligible for curative surgery at presentation with limited outcomes achievable with systemic chemotherapy/external radiotherapy. This has led to the advent of numerous minimally invasive options including but not limited to trans-arterial chemoembolization, radiofrequency/microwave ablation and more recently selective internal radiation therapy many of which are often the first-line treatment for select stages of HCC or serve as a conduit to liver transplant. The authors aim to provide a comprehensive overview of these various image guided minimally invasive therapies with a brief focus on the technical aspects accompanied by a critical analysis of the literature to assess the most up-to-date evidence from comparative systematic reviews and meta-analyses finishing with an assessment of novel combination regimens and future directions of travel.
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Affiliation(s)
- Riccardo Inchingolo
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
- Department of Radiology, King´s College Hospital, London SE5 9RS, United Kingdom
| | - Alessandro Posa
- Department of Radiology, IRCSS Fatebenefratelli Hospital, Roma 00186, Italy
| | - Martin Mariappan
- Interventional Radiology Department, Aberdeen Royal Infirmary Hospital, Aberdeen AB25 2ZN, United Kingdom
| | - Stavros Spiliopoulos
- 2nd Radiology Department, School of Medicine; National and Kapodistrian University of Athens, Chaidari Athens 12461, Greece
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23
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Du J, Chen M, Liu J, Hu P, Guan H, Jiao X. LncRNA F11‐AS1 suppresses liver hepatocellular carcinoma progression by competitively binding with miR‐3146 to regulate PTEN expression. J Cell Biochem 2019; 120:18457-18464. [PMID: 31168823 DOI: 10.1002/jcb.29163] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 05/22/2019] [Accepted: 05/23/2019] [Indexed: 02/03/2023]
Affiliation(s)
- Junkai Du
- Department of Emergency The First Affiliated Hospital of Xi’an JiaoTong University Xi’an Shaanxi China
| | - Mingyue Chen
- Department of Emergency The First Affiliated Hospital of Xi’an JiaoTong University Xi’an Shaanxi China
| | - Jianfei Liu
- Department of Emergency The First Affiliated Hospital of Xi’an JiaoTong University Xi’an Shaanxi China
| | - Pan Hu
- Department of Emergency The First Affiliated Hospital of Xi’an JiaoTong University Xi’an Shaanxi China
| | - Hong Guan
- Department of Emergency Xi’an Gaoxin Hospital Xi’an Shaanxi China
| | - Xiaoqin Jiao
- Department of Emergency The First Affiliated Hospital of Xi’an JiaoTong University Xi’an Shaanxi China
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24
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Huang CY, Hsieh FS, Wang CY, Chen LJ, Chang SS, Tsai MH, Hung MH, Kuo CW, Shih CT, Chao TI, Chen KF. Palbociclib enhances radiosensitivity of hepatocellular carcinoma and cholangiocarcinoma via inhibiting ataxia telangiectasia-mutated kinase-mediated DNA damage response. Eur J Cancer 2018; 102:10-22. [PMID: 30103095 DOI: 10.1016/j.ejca.2018.07.010] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 07/12/2018] [Accepted: 07/13/2018] [Indexed: 12/15/2022]
Abstract
AIM Palbociclib is an oral cyclin-dependent kinase 4/6 inhibitor, which is efficacious in treating breast cancer. Currently, there are numerous active clinical trials testing palbociclib alone or in combination with other medications for treating various types of malignancies. Here, we evaluated the anti-cancer effect of palbociclib in combination with radiation therapy (RT) for treating human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) and addressed the molecular mechanism behind the combination therapy. METHODS Immunofluorescence staining of γH2AX or 53BP1 was used to determine the effect of palbociclib on double-strand break (DSB) repair. Clonogenic assays, sphere formation and cell death ELISA were performed to study the sensitising effect of palbociclib on radiation-induced cytotoxicity. Signal alteration in DSB repair pathways was examined by Western blot analysis. Finally, we evaluated the in vivo anti-cancer activity and the associated molecular events of the combination therapy in a preclinical HCC xenograft model. RESULTS Palbociclib affected the kinetics of DNA repair and enhanced the radiation sensitivity of HCC and CCA cells. Importantly, we found that palbociclib inhibits ataxia telangiectasia-mutated (ATM) kinase, the key upstream kinase responding to RT-induced DSBs. Furthermore, we showed that the inhibitory effect of palbociclib on RT-induced ATM kinase activation is mediated by protein phosphatase 5 (PP5). Both in vitro and in vivo investigations revealed that the inhibition of the PP5-ATM axis by palbociclib after DNA damage is responsible for the synergism between palbociclib and RT. CONCLUSION Our findings provide a novel combination strategy against liver cancer cells. Clinical trials using palbociclib as an adjuvant in RT are warranted.
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Affiliation(s)
- Chao-Yuan Huang
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Imaging and Radiological Technology, Yuanpei University, Hsinchu, Taiwan
| | - Feng-Shu Hsieh
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
| | - Cheng-Yi Wang
- Department of Internal Medicine, Cardinal Tien Hospital, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Li-Ju Chen
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Shin Chang
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Hsien Tsai
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Man-Hsin Hung
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chiung-Wen Kuo
- Department of Medical Imaging and Radiological Technology, Yuanpei University, Hsinchu, Taiwan
| | - Chi-Ting Shih
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan
| | | | - Kuen-Feng Chen
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan.
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25
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Sangro B, Maini CL, Ettorre GM, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Van Buskirk M, Bilbao JI, Salvatori R, Giampalma E, Geatti O, Wilhelm K, Hoffmann RT, Izzo F, Iñarrairaegui M, Urigo C, Cappelli A, Vit A, Ahmadzadehfar H, Jakobs TF, Sciuto R, Pizzi G, Lastoria S. Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies. Eur J Nucl Med Mol Imaging 2018. [PMID: 29516130 PMCID: PMC6097757 DOI: 10.1007/s00259-018-3968-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Purpose Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. Methods This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. Results Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1–45.9) versus 30.9 months (19.6–46.8); p = 0.243); stage B: 18.4 months (11.2–19.4) versus 22.8 months (10.9–34.2); p = 0.815; and stage C: 8.8 months (7.1–10.8) versus 10.8 months (7.7–12.6); p = 0.976. Conclusions Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.
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Affiliation(s)
- Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra, and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Avda. Pio XII, 36, 31008, Pamplona, Spain.
| | | | | | - Roberto Cianni
- Interventional Radiology, Ospedale S.M.Goretti, Latina, Italy
| | - Rita Golfieri
- Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Daniele Gasparini
- Diagnostic and Interventional Radiology, Azienda Ospedaliera S. M. della Misericordia, Udine, Italy
| | - Samer Ezziddin
- Nuclear Medicine, Universitätsklinik Bonn, Bonn, Germany
| | - Philipp M Paprottka
- Interventional Radiology, LMU Klinikum der Universität München, Munich, Germany
| | - Francesco Fiore
- Onco Interventional Radiology, Istituto Tumori Pascale, Naples, Italy
| | | | | | | | | | - Onelio Geatti
- Nuclear Medicine, Azienda Ospedaliera S. M. della Misericordia, Udine, Italy
| | - Kai Wilhelm
- Department of Radiology, University of Bonn, Bonn, Germany
| | | | - Francesco Izzo
- Hepatobiliary Surgery, Istituto Tumori Pascale, Naples, Italy
| | - Mercedes Iñarrairaegui
- Liver Unit, Clinica Universidad de Navarra, and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Avda. Pio XII, 36, 31008, Pamplona, Spain
| | - Carlo Urigo
- Interventional Radiology, Ospedale S.M.Goretti, Latina, Italy
| | | | - Alessandro Vit
- Interventional Radiology, IFO Regina Elena National Cancer Institute, Rome, Italy
| | | | - Tobias Franz Jakobs
- Interventional Radiology, LMU Klinikum der Universität München, Munich, Germany
| | - Rosa Sciuto
- Nuclear Medicine, IFO Regina Elena National Cancer Institute, Rome, Italy
| | - Giuseppe Pizzi
- Interventional Radiology, IFO Regina Elena National Cancer Institute, Rome, Italy
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26
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Piscaglia F, Ogasawara S. Patient Selection for Transarterial Chemoembolization in Hepatocellular Carcinoma: Importance of Benefit/Risk Assessment. Liver Cancer 2018; 7:104-119. [PMID: 29662837 PMCID: PMC5892363 DOI: 10.1159/000485471] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Liver cancer is the second most common cause of cancer-related death, with hepatocellular carcinoma (HCC) accounting for most primary liver cancers and most commonly arising from a history of advanced chronic liver disease. Among the available therapies, transarterial chemoembolization (TACE) is the most widely utilized and is considered the first-line treatment recommended for patients staged as intermediate HCC (Barcelona Clinic Liver Cancer stage B). If applied correctly, TACE can produce survival benefits without adversely affecting hepatic functional reserve. SUMMARY The aim of this nonsystematic review is to evaluate the evidence supporting TACE, with a special interest in intermediate HCC, for which this treatment is recommended in first line. However, intermediate HCC represents a broad and heterogeneous group of patients, not all of whom will benefit from TACE. This review highlights the importance of appropriate patient selection for initial TACE and for retreatment. It also evaluates evidence for the treatment of patients who become refractory to TACE. Some patients may, in fact, benefit from early switch (i.e., after 1 or 2 TACE treatments) to systemic therapies rather than continuing retreatments with TACE in order to preserve liver function, thus allowing sequential first- and second-line drug therapies. KEY MESSAGES Careful assessment of an individual patient's benefit/risk ratio is recommended before any TACE session is considered to ensure optimal long-term outcomes in intermediate HCC.
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Affiliation(s)
- Fabio Piscaglia
- Unit of Internal Medicine, Department of Medicinal and Surgical Sciences, University of Bologna, S. Orsola Malpighi Hospital, Bologna, Italy
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
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27
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Zhaohui Z, Shunli S, Bin C, Shaoqiang L, Yunpeng H, Ming K, Lijian L, Gang PB. Hepatic Resection Provides Survival Benefit for Selected Intermediate-Stage (BCLC-B) Hepatocellular Carcinoma Patients. Cancer Res Treat 2018; 51:65-72. [PMID: 29510616 PMCID: PMC6333972 DOI: 10.4143/crt.2018.038] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/20/2018] [Indexed: 01/27/2023] Open
Abstract
PURPOSE The intermediate stage of hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B) comprises a highly heterogeneous population, and the treatment strategy is still controversial. Because of the heterogeneity, a subclassification of intermediate-stage HCCs was put forward by Bolondi according to the 'beyond Milan and within up-to-7' criteria and Child-Pugh score. In this study, we aim to analyze the prognosis of BCLC-B stage HCC patients who received hepatic resection according to the Bolondi's subclassification. Materials and Methods One thousand and one hundred three patients diagnosedwith HCC and treatedwith hepatic resectionwere enrolled in our hospital between 2006 and 2012. According to Bolondi's subclassification, the BCLC-B patients were divided into four groups. Recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS According to Bolondi's subclassification, the BCLC-B patients were divided into four groups: B1 (n=41, 18.7%), B2 (n=160, 73.1%), B3 (n=11, 5.0%), and B4 (n=7, 3.2%). Significant difference was observed between B1 and other groups (B1 vs. B2, p=0.022; B1 vs. B3, p < 0.001; B1 vs. B4, p < 0.001), but no difference for B2 vs. B4 (p=0.542) and B3 vs. B4 (p=0.542). In addition, no significant differences were observed between BCLC-A and BCLC-B1 group for both RFS (p=0.087) and OS (p=0.643). In multivariate analysis, BCLC-B subclassification was not a risk factor for both OS (p=0.263) and RFS (p=0.892). CONCLUSION In our study, HCC patients at B1 stagewere benefited from hepatic resection and had similar survival to BCLC-A stage patients. Our study provided rationality of hepatic resection for selected BCLC-B stage HCC patients instead of routine transarterial chemoembolization.
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Affiliation(s)
- Zhang Zhaohui
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shen Shunli
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chen Bin
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Li Shaoqiang
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Hua Yunpeng
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Kuang Ming
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Liang Lijian
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Peng Bao Gang
- Department of Hepatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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28
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Pinato DJ, Pai M, Reccia I, Patel M, Giakoustidis A, Karamanakos G, Rushd A, Jamshaid S, Oldani A, Grossi G, Pirisi M, Tait P, Sharma R. Preliminary qualification of a novel, hypoxic-based radiologic signature for trans-arterial chemoembolization in hepatocellular carcinoma. BMC Cancer 2018; 18:211. [PMID: 29463228 PMCID: PMC5819666 DOI: 10.1186/s12885-018-4120-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 02/12/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Survival advantage following trans-arterial chemoembolization (TACE) is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE radiologic features to derive a novel prognostic signature in HCC. METHODS A multi-institutional dataset of 98 patients was generated from two retrospective cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a number baseline imaging parameters was assessed and factors significant on univariate analysis were combined to create a novel radiologic signature on multivariable analyses predictive of overall survival (OS) following TACE. RESULTS Median OS was 15.4 months. Tumour size > 7 cm (p < 0.001), intra-tumour necrosis (ITN) (p = 0.02) and arterial ectatic neovascularisation (AEN) (p = 0.03) emerged as individual prognostic factors together with radiologic response (p < 0.001) and elevated alpha-fetoprotein (AFP) (p = 0.01). Combination of tumour size > 7 cm, ITN and AEN identified patients with poor prognosis (p < 0.001). CONCLUSIONS We identified a coherent signature based on commonly available imaging biomarkers likely to be reflective of differential patterns of relative hypoxia and neovascularisation. Large tumours displaying AEN and ITN are characterised by a shorter survival after TACE.
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Affiliation(s)
- David J Pinato
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Madhava Pai
- Department of Hepatobiliary Surgery, Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Isabella Reccia
- Department of Hepatobiliary Surgery, Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Markand Patel
- Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Alexandros Giakoustidis
- Division of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Georgios Karamanakos
- Department of Hepatobiliary Surgery, Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Azelea Rushd
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Shiraz Jamshaid
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Alberto Oldani
- Department of Health Sciences, Università degli Studi del Piemonte Orientale "A.Avogadro", via Solaroli 17, 28100, Novara, Italy
| | - Glenda Grossi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy.,Interdisciplinary Research Center of Autoimmune Diseases, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy
| | - Paul Tait
- Department of Radiology, Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, London, W120HS, UK
| | - Rohini Sharma
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W120HS, UK.
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Sacco R, Tapete G, Simonetti N, Sellitri R, Natali V, Melissari S, Cabibbo G, Biscaglia L, Bresci G, Giacomelli L. Transarterial chemoembolization for the treatment of hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2017; 4:105-110. [PMID: 28795053 PMCID: PMC5538681 DOI: 10.2147/jhc.s103661] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
According to the current European Association for the Study of Liver guidelines, transarterial chemoembolization (TACE) is the recommended first-line therapy for patients with intermediate-stage (Barcelona Clinic Liver Cancer-B class) hepatocellular carcinoma (HCC). The efficacy of this therapy is supported by robust evidence; however, there is still a lack of standardization in treatment methodology, and TACE protocols are widely variable. Moreover, TACE can be associated with a number of contraindications. Despite these limitations, research on TACE is still ongoing with the aim of optimizing the use of this methodology in the current management of HCC. In particular, TACE represents a control in comparative studies, and it is currently being investigated in combination schemes, for example, with sorafenib. In this review, we briefly describe the current scenario and the clinical innovations regarding TACE for the treatment of HCC.
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Affiliation(s)
- Rodolfo Sacco
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | - Gherardo Tapete
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | | | | | - Veronica Natali
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | - Sara Melissari
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | | | - Lilia Biscaglia
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
| | | | - Luca Giacomelli
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
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30
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Galle PR, Tovoli F, Foerster F, Wörns MA, Cucchetti A, Bolondi L. The treatment of intermediate stage tumours beyond TACE: From surgery to systemic therapy. J Hepatol 2017; 67:173-183. [PMID: 28323121 DOI: 10.1016/j.jhep.2017.03.007] [Citation(s) in RCA: 178] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 03/01/2017] [Accepted: 03/09/2017] [Indexed: 02/07/2023]
Abstract
Treatment of hepatocellular carcinoma (HCC) is dependent on the stage of the disease. Intermediate stage HCC encompasses the largest subgroup of patients with the disease, and is characterized by substantial heterogeneity. The standard therapeutic approach, transarterial chemoembolization (TACE), is probably over-used and may not be appropriate for all patients with intermediate stage HCC. In patients with extensive tumour bulk, multi-nodular spread or impaired liver function, TACE may not be optimal and other treatments can be considered as a first-line treatment. These include surgery, percutaneous ablation, radioembolization or systemic treatment. In addition, patients who do not achieve complete or partial necrosis (TACE failure) and patients with early recurrence after TACE, should be managed individually, considering systemic treatments usually reserved for advanced disease. In selected cases and in patients who achieve downstaging, radical approaches such as hepatic resection or even liver transplantation can be considered. In this review, we evaluate the current literature for the treatment strategies for patients with intermediate Barcelona Clinic Liver Cancer (BCLC) B stage HCC.
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Affiliation(s)
- Peter R Galle
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany.
| | - Francesco Tovoli
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Medicina Interna, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Friedrich Foerster
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany
| | - Marcus A Wörns
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany
| | - Alessandro Cucchetti
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Chirurgia generale e Trapianti, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Luigi Bolondi
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Medicina Interna, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
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Lv D, Wang Y, Zhang Y, Cui P, Xu Y. Downregulated long non-coding RNA DREH promotes cell proliferation in hepatitis B virus-associated hepatocellular carcinoma. Oncol Lett 2017; 14:2025-2032. [PMID: 28789433 PMCID: PMC5530050 DOI: 10.3892/ol.2017.6436] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Accepted: 03/23/2017] [Indexed: 02/06/2023] Open
Abstract
The hepatitis B virus X (HBx) protein has been characterized as an oncogene involved in epigenetic modifications during hepatocarcinogenesis; however, the underlying mechanisms are not entirely clear. Long non-coding RNAs (lncRNAs), a type of epigenetic regulator molecules, have also been demonstrated to serve crucial roles in carcinogenesis, including hepatocellular carcinoma (HCC). In the present study, a human lncRNA DREH was identified, which inhibits cell proliferation in vitro and in vivo, and acts as a tumor suppressor in HBx-mediated hepatocarcinogenesis. The study revealed that the expression of DREH was frequently downregulated in hepatitis B virus (HBV)-associated HCC tissues in comparison with adjacent non-cancerous hepatic tissues, and was inversely correlated with HBx mRNA expression in HBV-associated HCC. In addition, the levels of DREH were inversely correlated with hepatitis B surface antigen and tumor size in HCC tissues. The forced expression of HBx in liver cell lines resulted in a significant decrease in the expression of DREH. Furthermore, suppression of DREH expression promotes the proliferation of HCC cells in vitro and in vivo. In conclusion, the present findings support the role of HBx-downregulated lncRNA DREH in tumor suppression in HBV-associated HCC patients. This contributes to a better understanding of epigenetic aberration of deregulated lncRNAs by HBx and the potential development of lncRNA-based targeted approaches for the treatment of HBV-associated HCC.
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Affiliation(s)
- Dong Lv
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Yuan Wang
- Third Department of General Surgery, Peking University People's Hospital, Beijing 100044, P.R. China
| | - Ying Zhang
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Peilin Cui
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
| | - Youqing Xu
- Gastroenterology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
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Niu H, Du T, Xiao Q, Hu X, Li D, Wang C, Gao W, Xing T, Xu X. Application of embolization microspheres in interventional therapy of malignant non-hypervascular tumor of liver. Oncotarget 2017; 8:55593-55599. [PMID: 28903446 PMCID: PMC5589685 DOI: 10.18632/oncotarget.16286] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 03/09/2017] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To investigate the efficacy and safety of transarterial embolization (TAE) using embolization microspheres in the treatment of non-hypervascular malignant liver tumors. METHODS Patients with malignant non-hypervascular liver tumors, who were treated with TAE using embolization microspheres, were selected and analyzed retrospectively. The technical success rate, tumor response, and complications were assessed. RESULTS Six patients were included in the study: 1 patient each with hepatocellular-cholangiocarcinoma, intrahepatic cholangiocarcinoma, hepatic metastasis after resection of common bile duct carcinoma, liver metastasis from colon cancer, liver metastasis from esophageal cancer, and liver metastasis from pancreatic cancer. The technical success rate was 100%. At 1 and 3 months after TAE, tumor local reactions were seen in 6/6 and 2/6 patients, respectively, and the tumor necrosis rates were 48%-73% and 22%-68%, respectively. The main complications were those related to the embolization syndrome, including 1 case of liver abscess and 1 case of severe pain on the first day after embolization. CONCLUSION TAE with embolization microspheres is safe and effective in non-hypervascular liver tumors. It is a feasible option for palliative therapy of these tumors.
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Affiliation(s)
- Huanzhang Niu
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Tingwei Du
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Quanping Xiao
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Xin Hu
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Dongmin Li
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Chao Wang
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Wanqin Gao
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Taohong Xing
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Xiangmei Xu
- Department of Interventional Radiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
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Pinato DJ, Sharma R, Allara E, Yen C, Arizumi T, Kubota K, Bettinger D, Jang JW, Smirne C, Kim YW, Kudo M, Howell J, Ramaswami R, Burlone ME, Guerra V, Thimme R, Ishizuka M, Stebbing J, Pirisi M, Carr BI. The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma. J Hepatol 2017; 66:338-346. [PMID: 27677714 DOI: 10.1016/j.jhep.2016.09.008] [Citation(s) in RCA: 309] [Impact Index Per Article: 38.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 08/22/2016] [Accepted: 09/08/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC.
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Affiliation(s)
- David J Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK.
| | - Rohini Sharma
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK
| | - Elias Allara
- NIHR Blood and Transplant Research Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
| | - Clarence Yen
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK
| | - Tadaaki Arizumi
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
| | - Keiichi Kubota
- Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan
| | - Dominik Bettinger
- Department of Medicine II, University Hospital Freiburg, Freiburg, Germany
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Seoul, Republic of Korea
| | - Carlo Smirne
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, Novara, Italy
| | - Young Woon Kim
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Seoul, Republic of Korea
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
| | - Jessica Howell
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK
| | - Ramya Ramaswami
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK
| | - Michela E Burlone
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, Novara, Italy
| | - Vito Guerra
- IRCCS De Bellis, National Institute for Digestive Diseases, Castellana Grotte, Italy
| | - Robert Thimme
- Department of Medicine II, University Hospital Freiburg, Freiburg, Germany
| | - Mitsuru Ishizuka
- Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan
| | - Justin Stebbing
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK
| | - Mario Pirisi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, Novara, Italy
| | - Brian I Carr
- Izmir Biomedicine and Genome Centre, Dokuz Eylul University, Izmir, Turkey
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Hiraoka A, Kumada T, Nouso K, Tsuji K, Itobayashi E, Hirooka M, Kariyama K, Ishikawa T, Toyoda H, Tada T, Hiasa Y, Michitaka K. Simple method with tumor markers for predicting prognosis following transcatheter arterial chemo-embolization for switching to next therapy in intermediate hepatocellular carcinoma: multi-center analysis. KANZO 2017; 58:329-337. [DOI: 10.2957/kanzo.58.329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Affiliation(s)
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital
| | - Kazuhiro Nouso
- Department of Liver Disease Center, Okayama City Hospital
| | | | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
| | | | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Daini Hospital
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital
| | - Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
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Pinato DJ, Arizumi T, Jang JW, Allara E, Suppiah PI, Smirne C, Tait P, Pai M, Grossi G, Kim YW, Pirisi M, Kudo M, Sharma R. Combined sequential use of HAP and ART scores to predict survival outcome and treatment failure following chemoembolization in hepatocellular carcinoma: a multi-center comparative study. Oncotarget 2016; 7:44705-44718. [PMID: 27244889 PMCID: PMC5190130 DOI: 10.18632/oncotarget.9604] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 04/26/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is variable, despite a myriad of prognostic markers. We compared and integrated the established prognostic models, HAP and ART scores, for their accuracy of overall survival (OS) prediction. RESULTS In both training and validation sets, HAP and ART scores emerged as independent predictors of OS (p<0.01) with HAP achieving better prognostic accuracy (c-index: 0.68) over ART (0.57). We tested both scores in combination to evaluate their combined ability to predict OS. Subgroup analysis of BCLC-C patients revealed favorable HAP stage (p<0.001) and radiological response after initial TACE (p<0.001) as positive prognostic factors. PATIENTS AND METHODS Prognostic scores were studied using multivariable Cox regression and c-index analysis in 83 subjects with Barcelona Clinic Liver Cancer (BCLC) A/B stage from UK and Italy (training set), and 660 from Korea and Japan (validation set), all treated with conventional TACE. Scores were further validated in an separate analysis of patients with BCLC-C stage disease (n=63) receiving initial TACE. CONCLUSION ART and HAP scores are validated indices in patients with intermediate stage HCC undergoing TACE. The HAP score is best suited for screening patients prior to initial TACE, whilst sequential ART assessment improves early detection of chemoembolization failure. BCLC-C patients with low HAP stage may be a subgroup where TACE should be explored in clinical studies.
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Affiliation(s)
- David J Pinato
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Tadaaki Arizumi
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Seoul, Republic of Korea
| | - Elias Allara
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy
- School of Public Health, Università degli Studi di Torino, Torino, Italy
| | - Puvan I Suppiah
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Carlo Smirne
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy
| | - Paul Tait
- Department of Radiology, Imperial College NHS Trust, Hammersmith Hospital, London, UK
| | - Madhava Pai
- Department of Surgery, Imperial College NHS Trust, Hammersmith Hospital, London, UK
| | - Glenda Grossi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy
| | - Young Woon Kim
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Seoul, Republic of Korea
| | - Mario Pirisi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy
- Interdisciplinary Research Center of Autoimmune Diseases, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
| | - Rohini Sharma
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
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Hiraoka A, Kumada T, Nouso K, Tsuji K, Itobayashi E, Hirooka M, Kariyama K, Ishikawa T, Tada T, Toyoda H, Kawasaki H, Hiasa Y, Michitaka K. Proposed New Sub-Grouping for Intermediate-Stage Hepatocellular Carcinoma Using Albumin-Bilirubin Grade. Oncology 2016; 91:153-161. [PMID: 27362669 DOI: 10.1159/000447061] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 05/20/2016] [Indexed: 01/27/2023]
Abstract
AIM We retrospectively evaluated the efficacy of albumin-bilirubin (ALBI) grade, which has been proposed as a new classification for hepatic function, for evaluation of the prognosis of intermediate-stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer criteria stage B, BCLC-B). PATIENTS AND METHODS We enrolled 754 naïve BCLC-B patients (multiple tumors) and retrospectively analyzed their clinical features [surgical resection (hepatectomy), n = 170; radiofrequency ablation (RFA), n = 110; percutaneous ethanol injection, n = 7; transcatheter arterial chemoembolization, n = 396; others, n = 25; best supportive care, n = 46]. Four sub-groups were defined for the Modified Intermediate Stage of Liver Cancer (MICAN) criteria as follows: B1 (ALBI-1/within up-to-7 criteria), B2 (ALBI-2/within up-to-7 criteria), B3 (ALBI-1 and ALBI-2/multiple and beyond up-to-7 criteria), and B4 (ALBI-3/any). RESULTS The median survival time of patients classified as B1 (n = 94), B2 (n = 175), B3 (n = 452), and B4 (n = 33) was 65.1, 48.1, 29.6, and 14.6 months, respectively (p < 0.01 for each). Those in B1 treated with hepatectomy and RFA comprised 67.0%, while that ratio was 51.4% in B2, 28.3% in B3, and 12.1% in B4. CONCLUSION The MICAN criteria based on ALBI grade are simple and useful for prediction of prognosis and therapy decision-making in the heterogeneous population of BCLC-B patients.
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Affiliation(s)
- Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
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Ingle PV, Samsudin SZ, Chan PQ, Ng MK, Heng LX, Yap SC, Chai ASH, Wong ASY. Development and novel therapeutics in hepatocellular carcinoma: a review. Ther Clin Risk Manag 2016; 12:445-55. [PMID: 27042086 PMCID: PMC4801152 DOI: 10.2147/tcrm.s92377] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions.
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Affiliation(s)
| | - Sarah Zakiah Samsudin
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Pei Qi Chan
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Mei Kei Ng
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Li Xuan Heng
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Siu Ching Yap
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Amy Siaw Hui Chai
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Audrey San Ying Wong
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
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Zhou X, Zhu HQ, Ma CQ, Li HG, Liu FF, Chang H, Lu J. MiR-1180 promoted the proliferation of hepatocellular carcinoma cells by repressing TNIP2 expression. Biomed Pharmacother 2016; 79:315-20. [PMID: 27044843 DOI: 10.1016/j.biopha.2016.02.025] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Revised: 02/22/2016] [Accepted: 02/22/2016] [Indexed: 12/29/2022] Open
Abstract
MicroRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory function, playing crucial roles in cancer development and progression of hepatocellular carcinoma (HCC). Previous studies have indicated that miR-1180 was implicated in diverse biological processes. However, the underlying mechanism of miR-1180 in HCC has not been intensively investigated. In this study, we aimed to investigate the role of miR-1180 and its target genes in HCC. We found that miR-1180 expression was significantly increased in HCC cells and clinical tissues compared with their corresponding controls. Overexpression of miR-1180 promoted cell proliferation in HCC cell line HepG2. TNFAIP3 interacting protein 2 (TNIP2), a potential target gene of miR-1180, and were validated by a luciferase assay. Further studies revealed that miR-1180 regulated cell proliferation of HCC by directly suppressing TNIP2 expression and the knockdown of TNIP2 expression reversed the effect of miR-1180-in on HCC cell proliferation. In summary, our data indicated that miR-1180 might act as a tumor promoter by targeting TNIP2 during development of HCC.
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Affiliation(s)
- Xu Zhou
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, East District, Jinan 250014, Shandong Province, China
| | - Hua-Qiang Zhu
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, East District, Jinan 250014, Shandong Province, China
| | - Chao-Qun Ma
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, East District, Jinan 250014, Shandong Province, China
| | - Hong-Guang Li
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, East District, Jinan 250014, Shandong Province, China
| | - Fang-Feng Liu
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, East District, Jinan 250014, Shandong Province, China
| | - Hong Chang
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, East District, Jinan 250014, Shandong Province, China
| | - Jun Lu
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, East District, Jinan 250014, Shandong Province, China.
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Xu XS, Chen W, Miao RC, Zhou YY, Wang ZX, Zhang LQ, Qu K, Pang Q, Wang RT, Liu C. Survival Analysis of Hepatocellular Carcinoma: A Comparison Between Young Patients and Aged Patients. Chin Med J (Engl) 2016; 128:1793-800. [PMID: 26112722 PMCID: PMC4733704 DOI: 10.4103/0366-6999.159356] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background: To compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma (HCC). Methods: We analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients’ survival were evaluated by multivariate analysis, respectively. Results: The patients who were older than 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver functional reserve but more aggressive tumor factors than aged patients. Cox regression analysis showed that the elevated levels of aspartate aminotransferase (AST) (Wald χ2 = 3.963, P = 0.047, hazard ratio [HR] =1.453, 95% confidence interval [CI]: 1.006–2.098), lower albumin (Wald χ2 = 12.213, P < 0.001, HR = 1.982, 95% CI: 1.351–2.910), tumor size (Wald χ2 = 8.179, P = 0.004, HR = 1.841, 95% CI: 1.212–2.797), and higher alpha-fetoprotein level (Wald χ2 = 4.044, P = 0.044, HR = 1.465, 95% CI: 1.010–2.126) were independent prognostic factors for aged patients, while only elevated levels of AST (Wald χ2 = 14.491, P < 0.001, HR = 2.285, 95% CI: 1.493–3.496) and tumor size (Wald χ2 = 21.662, P < 0.001, HR = 2.928, 95% CI: 1.863–4.604) were independent prognostic factors for younger patients. Conclusions: Age is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver functional reserve are still encouraged to receive curative therapy.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Chang Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shannxi 710061, China
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Validation and reappraisal of the assessment for retreatment with transarterial chemoembolization score for unresectable non-metastatic hepatocellular carcinoma in a hepatitis b virus-endemic region. Eur Radiol 2016; 26:3510-8. [PMID: 26747261 DOI: 10.1007/s00330-015-4185-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 12/17/2015] [Accepted: 12/21/2015] [Indexed: 01/25/2023]
Abstract
OBJECTIVES To validate and reappraise the Assessment for Retreatment with Transarterial chemoembolization (ART) score comprising three parameters (>25 % increase in aspartate aminotransferase [AST], increase in Child-Pugh score and tumour response), determined prior to subsequent transarterial chemoembolization (TACE). METHODS Enrolled patients were diagnosed with unresectable non-metastatic hepatocellular carcinoma and underwent multiple TACEs between June 2006 and December 2007 (N = 153). Subgroupings were classified according to the established cut-off (≤1.5 vs. ≥2.5). Survival analysis using the Kaplan-Meier curve was performed. RESULTS The original ART score dichotomized patients according to their overall survival (P = 0.004). We found several patients who actually survived longer than others were assigned to a poor prognostic group due to the AST component. Parameter estimates for AST obtained from our analysis were much lower than the original version (0.5 vs. 2.1). We adjusted the component according to the value of our parameter estimates, and patients with >25 % AST increase received 1.0 point. After this modification, patients assigned to the favourable prognostic group were more likely to have a better survival outcome (median 23.9 vs. 12.2 months, P < 0.001). CONCLUSIONS In hepatitis B virus-endemic regions, the ART score is valid and can better predict post-TACE survival after the AST component is modified. KEY POINTS • The ART score was validated in a HBV-endemic region. • The modified ART score improved prognostic performance by reappraising the AST component. • The modified ART score helps physicians make decisions for further TACE.
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Shiozawa S, Usui T, Kuhara K, Tsuchiya A, Miyauchi T, Kono T, Asaka S, Yamaguchi K, Yokomizo H, Shimakawa T, Yoshimatsu K, Katsube T, Naritaka Y. Impact of Branched-Chain Amino Acid-Enriched Nutrient on liver Cirrhosis with Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization in Barcelona Clinic Liver Cancer Stage B: A Prospective Study. J NIPPON MED SCH 2016; 83:248-256. [PMID: 28133005 DOI: 10.1272/jnms.83.248] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND In decompensated liver cirrhosis, hypoalbuminemia still persists even after they have been treated with branched-chain amino acid (BCAA) granules. We prospectively evaluated whether BCAA enriched nutrient switched from BCAA granules would increase the serum albumin level, and consequently extend the survival time after hepatocellular carcinoma (HCC) treatment. METHODS This study included 77 patients treated for liver cirrhosis with HCC. After the nutritional assessment, all patients initially received BCAA granules. In patients with unchanged or decreased serum albumin levels, BCAA granules were discontinued and BCAA enriched nutrient was started. Transcatheter arterial chemembolization (TACE) for HCC were performed in those with an improved Child-Pugh score. RESULTS TACE were performed following the aggressive intervention with BCAA nutritional education in 54 of 77 (70.1%) patients. Finally, survival time was significantly extended in the TACE group (P<0.0001). CONCLUSION Timely aggressive nutritional intervention in Barcelona Clinic Liver Cancer stage B HCC, namely, early partial replacement with BCAA enriched nutrient may consequently improve the treatment outcome of HCC.
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Affiliation(s)
- Shunichi Shiozawa
- Department of Surgery, Tokyo Women's Medical University Medical Center East
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42
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Ciria R, López-Cillero P, Gallardo AB, Cabrera J, Pleguezuelo M, Ayllón MD, Luque A, Zurera L, Espejo JJ, Rodríguez-Perálvarez M, Montero JL, de la Mata M, Briceño J. Optimizing the management of patients with BCLC stage-B hepatocellular carcinoma: Modern surgical resection as a feasible alternative to transarterial chemoemolization. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2015; 41:1153-1161. [PMID: 26118317 DOI: 10.1016/j.ejso.2015.05.023] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Revised: 05/06/2015] [Accepted: 05/31/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To analyse the impact of liver resection (LR) in patients with Hepatocellular Carcinoma (HCC) within the Barcelona-Clinic-Liver-Cancer (BCLC)-B stage. METHODS Analysis of patients with BCLC-B HCC treated with LR or transarterial chemoembolization (TACE) between 2007 and 2012 in our hospital. Survival/recurrence analyses were performed by log-rank tests and Cox multivariate models. Further analyses were specifically obtained for the HCC subclassification (B1-2-3-4) proposed recently. RESULTS Eighty patients were treated (44-TACE/36-LR). Number of nodules was [1.8(1.1)], being multinodular in 50% of cases. Although resected patients had a higher hospital stay than those who underwent TACE (14 ± 13 vs 7 ± 6; P = 0.004), the rate and severity of complications was lower measured by Dindo-Clavien scale (P < 0.05). Overall survival was 40% with a median follow-up of 29.5 months (0.07-96.9). Five-years survival rates were 62.9%, 28.1% and 15.4%, respectively (P = 0.004) for B1, B2 and B3-4 stages. Cox model showed that only total bilirubin [OR = 2.055(1.23-3.44)] and BCLC subclassification B3-4 [OR = 2.439(1.04-5.7)] and B2 [OR = 2.79(1.35-5.77)] vs B1 were independent predictors of 5-years-survival. In B1 patients, surgical approach led a significant decrease in 5-years recurrence-rate (25% vs 60%; P = 0.018). In the surgical subgroup analysis, better results were observed if well/moderate differentiation combined with no microvascular-invasion (VI) in 5-years-survival (84.6%; P = 0.001) and -recurrence (23.1%; P = 0.041), respectively. These survival and recurrence trends were remarkable in B1 stages. CONCLUSIONS Management of Intermediate BCLC-B HCC stage should be more complex and include updated criteria regarding B-stage subclassifications, VI and tumour differentiation. Modern surgical resection would offer improved survival benefit with acceptable safety in selected BCLC-B stage patients.
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Affiliation(s)
- R Ciria
- Unit of Hepatobiliary Surgery and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofía, Cordoba, Spain.
| | - P López-Cillero
- Unit of Hepatobiliary Surgery and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofía, Cordoba, Spain
| | - A-B Gallardo
- Unit of Hepatobiliary Surgery and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofía, Cordoba, Spain
| | - J Cabrera
- Unit of Hepatobiliary Surgery and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofía, Cordoba, Spain
| | - M Pleguezuelo
- Unit of Hepatology and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| | - M-D Ayllón
- Unit of Hepatobiliary Surgery and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofía, Cordoba, Spain
| | - A Luque
- Unit of Hepatobiliary Surgery and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofía, Cordoba, Spain
| | - L Zurera
- Unit of Vascular and Interventional Radiology, University Hospital Reina Sofía, Cordoba, Spain
| | - J-J Espejo
- Unit of Vascular and Interventional Radiology, University Hospital Reina Sofía, Cordoba, Spain
| | - M Rodríguez-Perálvarez
- Unit of Hepatology and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| | - J-L Montero
- Unit of Hepatology and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| | - M de la Mata
- Unit of Hepatology and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofia, Cordoba, Spain
| | - J Briceño
- Unit of Hepatobiliary Surgery and Liver Transplantation, CIBERehd, IMIBIC, University Hospital Reina Sofía, Cordoba, Spain
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Poursaid A, Price R, Tiede A, Olson E, Huo E, McGill L, Ghandehari H, Cappello J. In situ gelling silk-elastinlike protein polymer for transarterial chemoembolization. Biomaterials 2015; 57:142-52. [PMID: 25916502 PMCID: PMC4429515 DOI: 10.1016/j.biomaterials.2015.04.015] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 04/03/2015] [Accepted: 04/08/2015] [Indexed: 12/23/2022]
Abstract
Hepatocellular carcinoma annually affects over 700,000 people worldwide and trends indicate increasing prevalence. Patients ineligible for surgery undergo loco-regional treatments such as transarterial chemoembolization (TACE) to selectively target tumoral blood supply. Using a microcatheter, chemotherapeutics are infused followed by an embolic agent, or the drug is encapsulated by the embolic moiety; simultaneously inducing stasis while delivering localized chemotherapy. Presently, several products are used, but no universally accepted system is promoted because very disparate limitations exist. The goal of this investigation was to design and develop in situ gelling recombinant silk-elastinlike protein polymers (SELPs) for TACE. Two SELP compositions, SELP-47K and SELP-815K, with varying lengths of silk and elastin blocks, were investigated to formulate a new embolic that was injectable through commercially available microcatheters. The goal was to develop a composition providing maximal permeation of tumor vasculature while exhibiting effective embolic activity. The SELPs evaluated remain soluble until reaching 37 °C, when irreversible transition ensues forming a solid hydrogel network. SELP-815K formulated at 12% w/w with shear processing demonstrated acceptable rheological properties and clear embolic capability under flow conditions in vitro. A rabbit model showed feasibility of embolization in vivo allowing selective occlusion of lobar hepatic arterial branches.
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Affiliation(s)
- Azadeh Poursaid
- Department of Bioengineering, University of Utah, 36 S. Wasatch Dr., Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA
| | - Robert Price
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA
| | - Andrea Tiede
- Department of Bioengineering, University of Utah, 36 S. Wasatch Dr., Salt Lake City, UT 84112, USA
| | - Erik Olson
- Department of Bioengineering, University of Utah, 36 S. Wasatch Dr., Salt Lake City, UT 84112, USA
| | - Eugene Huo
- Veterans Affairs Hospital, Salt Lake City, UT 84108, USA
| | - Lawrence McGill
- Associated Regional and University Pathologists, Salt Lake City, UT 84107, USA
| | - Hamidreza Ghandehari
- Department of Bioengineering, University of Utah, 36 S. Wasatch Dr., Salt Lake City, UT 84112, USA; Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT 84112, USA.
| | - Joseph Cappello
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA
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Kolligs FT, Bilbao JI, Jakobs T, Iñarrairaegui M, Nagel JM, Rodriguez M, Haug A, D'Avola D, op den Winkel M, Martinez-Cuesta A, Trumm C, Benito A, Tatsch K, Zech CJ, Hoffmann RT, Sangro B. Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma. Liver Int 2015; 35:1715-21. [PMID: 25443863 DOI: 10.1111/liv.12750] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 11/19/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard-of-care for intermediate-stage unresectable, hepatocellular carcinoma (HCC), as first-line treatment. METHODS SIRTACE was an open-label multicenter randomized-controlled pilot study, which prospectively compared primarily safety and health-related quality of life (HRQoL) changes following TACE and SIRT. Patients with unresectable HCC, Child-Pugh ≤B7, ECOG performance status ≤2 and ≤5 liver lesions (≤20 cm total maximum diameter) without extrahepatic spread were randomized to receive either TACE (at 6-weekly intervals until tumour enhancement was not observed on MRI or disease progression) or single-session SIRT (yttrium-90 resin microspheres). RESULTS Twenty-eight patients with BCLC stage A (32.1%), B (46.4%) or C (21.4%) received either a mean of 3.4 (median 2) TACE interventions (N = 15) or single SIRT (N = 13). Both treatments were well tolerated. Despite SIRT patients having significantly worse physical functioning at baseline, at week-12, neither treatment had a significantly different impact on HRQoL as measured by Functional Assessment of Cancer Therapy-Hepatobiliary total or its subscales. Both TACE and SIRT were effective for the local control of liver tumours. Best overall response-rate (RECIST 1.0) of target lesions were 13.3% and 30.8%, disease control rates were 73.3% and 76.9% for TACE and SIRT, respectively. Two patients in each group were down-staged for liver transplantation (N = 3) or radiofrequency ablation (N = 1). CONCLUSIONS Single-session SIRT appeared to be as safe and had a similar impact on HRQoL as multiple sessions of TACE, suggesting that SIRT might be an alternative option for patients eligible for TACE.
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Affiliation(s)
- Frank T Kolligs
- Department of Internal Medicine II, University of Munich, Munich, Germany
| | - Jose I Bilbao
- Interventional Radiology, Clinica Universidad de Navarra and Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, Spain
| | - Tobias Jakobs
- Institute of Radiology, Krankenhaus der Barmherzigen Brüder, Munich, Germany
| | | | - Jutta M Nagel
- Department of Internal Medicine II, University of Munich, Munich, Germany
| | | | - Alexander Haug
- Department of Nuclear Medicine, University of Munich, Munich, Germany
| | - Delia D'Avola
- Liver Unit, Clinica Universidad de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA) and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Pamplona, Spain
| | - Mark op den Winkel
- Department of Internal Medicine II, University of Munich, Munich, Germany
| | | | - Christoph Trumm
- Institute of Radiology, University of Munich, Munich, Germany
| | - Alberto Benito
- Department of Radiology, Clinica Universidad de Navarra, Pamplona, Spain
| | - Klaus Tatsch
- Department of Nuclear Medicine, Municipal Hospital Karlsruhe Inc., Karlsruhe, Germany
| | - Christoph J Zech
- Clinic of Radiology and Nuclear Medicine, University of Basel, Basel, Switzerland
| | - Ralf-Thorsten Hoffmann
- Institute and Policlinic of Radiology, University Hospital at the Technische Universitaet Dresden, Dresden, Germany
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA) and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Pamplona, Spain
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Hiraoka A, Ishimaru Y, Kawasaki H, Aibiki T, Okudaira T, Toshimori A, Kawamura T, Yamago H, Nakahara H, Suga Y, Azemoto N, Miyata H, Miyamoto Y, Ninomiya T, Hirooka M, Abe M, Matsuura B, Hiasa Y, Michitaka K. Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization. Oncology 2015; 89:167-74. [DOI: 10.1159/000381808] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2015] [Accepted: 03/18/2015] [Indexed: 01/12/2023]
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Kim MJ, Kim YS, Cho YH, Jang HY, Song JY, Lee SH, Jeong SW, Kim SG, Jang JY, Kim HS, Kim BS, Lee WH, Park JM, Lee JM, Lee MH, Choi DL. Use of (18)F-FDG PET to predict tumor progression and survival in patients with intermediate hepatocellular carcinoma treated by transarterial chemoembolization. Korean J Intern Med 2015; 30:308-15. [PMID: 25995661 PMCID: PMC4438285 DOI: 10.3904/kjim.2015.30.3.308] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Revised: 06/27/2014] [Accepted: 08/25/2014] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND/AIMS (18)F-Fluorodeoxyglucose positron-emission tomography ((18)F-FDG PET) has been used to assess the biological behavior of hepatocellular carcinoma (HCC). In this study, we investigated the usefulness of (18)F-FDG PET for predicting tumor progression and survival in patients with intermediate Barcelona Clinic Liver Cancer (BCLC) intermediate-stage HCC treated by transarterial chemoembolization (TACE). METHODS From February 2006 to March 2013, 210 patients treated with TACE, including 77 patients with BCLC intermediate-stage HCC, underwent examination by (18)F-FDG PET. (18)F-FDG uptake was calculated based on the tumor maximum (Tmax) standardized uptake value (SUV), the liver mean (Lmean) SUV, and the ratio of the Tmax SUV to the Lmean SUV (Tmax/Lmean). RESULTS The mean follow-up period for the 77 patients (52 males, 25 females; average age, 63.3 years) was 22.2 months. The median time to progression of HCC in patients with a low Tmax/Lmean (< 1.83) and high Tmax/Lmean (≥ 1.83) was 17 and 6 months, respectively (p < 0.001). The median overall survival time of patients with a low and high Tmax/Lmean was 44 and 14 months, respectively (p = 0.003). Multivariate analysis revealed that the Tmax/Lmean was an independent predictor of overall survival (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.210 to 3.156; p = 0.006) and tumor progression (HR, 2.05; 95% CI, 1.264 to 3.308; p = 0.004). CONCLUSIONS (18)F-FDG uptake calculated by the Tmax/Lmean using PET predicted tumor progression and survival in patients with BCLC intermediate-stage HCC treated by TACE.
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Affiliation(s)
- Min Jin Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Young Seok Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Youn Hee Cho
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Hee Yoon Jang
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Jeong-Yeop Song
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Sae Hwan Lee
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Soung Won Jeong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Sang Gyune Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Jae Young Jang
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Hong Su Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Boo Sung Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Hyung Lee
- Department of Nuclear Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Jung Mi Park
- Department of Nuclear Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Jae Myung Lee
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Min Hee Lee
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Deuk Lin Choi
- Department of Radiology, Soonchunhyang University Hospital, Seoul, Korea
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Li JH, Xie XY, Zhang L, Le F, Ge NL, Li LX, Gan YH, Chen Y, Zhang JB, Xue TC, Chen RX, Xia JL, Zhang BH, Ye SL, Wang YH, Ren ZG. Oxaliplatin and 5-fluorouracil hepatic infusion with lipiodolized chemoembolization in large hepatocellular carcinoma. World J Gastroenterol 2015; 21:3970-3977. [PMID: 25852283 PMCID: PMC4385545 DOI: 10.3748/wjg.v21.i13.3970] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 11/02/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate transarterial chemoembolization (TACE) with hepatic infusion of oxaliplatin and 5-fluorouracil and Lipiodol chemoembolization in large hepatocellular carcinoma (HCC).
METHODS: In this retrospective study, 132 patients with unresectable HCCs larger than 10 cm were treated with hepatic infusion of oxaliplatin and 5-fluorouracil followed by Lipiodol chemoembolization. The primary endpoint was overall survival (OS). Sixteen-week disease-control rate, time to progression (TTP), and major complications were also studied. Univariate and multivariate analyses were performed to identify prognostic factors affecting OS and TTP.
RESULTS: A total of 319 procedures were performed in the 132 patients. Eleven (8.3%) patients received radical resection following TACE treatment (median time to initial TACE 4.3 ± 2.3 mo). The median OS and TTP were 10.3 and 3.0 mo respectively, with a 50.0% 16-wk disease-control rate. Major complications were encountered in 6.0% (8/132) of patients following TACE and included serious jaundice in 1.5% (2/132) patients, aleukia in 1.5% (2/132), and hepatic failure in 3.0% (4/132). One patient died within one month due to serious hepatic failure and severe sepsis after receiving the second TACE. The risk factor associated with TTP was baseline alpha-fetoprotein level, and vascular invasion was an independent factor related to OS.
CONCLUSION: Hepatic infusion of oxaliplatin and 5-fluorouracil followed by lipiodolized-chemoembolization is a safe and promising treatment for patients with HCCs larger than 10 cm in diameter.
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Kinoshita A, Onoda H, Fushiya N, Koike K, Nishino H, Tajiri H. Staging systems for hepatocellular carcinoma: Current status and future perspectives. World J Hepatol 2015; 7:406-424. [PMID: 25848467 PMCID: PMC4381166 DOI: 10.4254/wjh.v7.i3.406] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 11/08/2014] [Accepted: 12/10/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major health concern worldwide and the third cause of cancer-related death. Despite advances in treatment as well as careful surveillance programs, the mortality rates in most countries are very high. In contrast to other cancers, the prognosis and treatment of HCC depend on the tumor burden in addition to patient’s underlying liver disease and liver functional reserve. Moreover, there is considerable geographic and institutional variation in both risk factors attributable to the underlying liver diseases and the management of HCC. Therefore, although many staging and/or scoring systems have been proposed, there is currently no globally accepted system for HCC due to the extreme heterogeneity of the disease. The aim of this review is to focus on currently available staging systems as well as those newly reported in the literatures since 2012. Moreover, we describe problems with currently available staging systems and attempts to modify and/or add variables to existing staging systems.
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50
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Peña AM, Núñez-Martínez Ó, Díaz-Sánchez A, Pons-Renedo F, Gómez-Rubio M, Polo-Lorduy B, Lledó-Navarro JL, Trapero-Marugán M, Ladero-Quesada JM, Poves-Martínez E, Ibáñez-Pinto A, Martín-Algívez AM, Lozano-Maya M, González-Alonso R, Piqueras-Alcol B, González-Moreno L, Fernández-Rodríguez C, Gea-Rodríguez F. Transarterial chemoembolisation in intermediate-stage hepatocellular carcinoma. Survey on clinical practice in hospitals in the Madrid Region. Ann Hepatol 2015; 14:207-217. [PMID: 25671830 DOI: 10.1016/s1665-2681(19)30783-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2025]
Abstract
BACKGROUND Transarterial chemoembolisation (TACE), having demonstrated survival benefits, is the treatmentof choice in intermediate-stage hepatocellular carcinoma, although there is great heterogeneity in its clinical application. MATERIAL AND METHODS A survey was sent to the Madrid Regional hospitals to assess applicability, indications and treatment protocols. The assessment was made overall and according to the type of hospital (groups A vs. B and C). RESULTS Seventeen out of 22 hospitals responded (8/8 group A, 9/ 14 group B-C). All do/indicate transarterial chemoembolisation, 13/17 at their own facilities. Eight of the 17 hospitals have multidisciplinary groups (5/8 A, 3/9 B-C). Nine hospitals perform > 20 procedures/year (7 group A), and 6 from group B-C request/perform < 10/year. It is performed on an "on-demand" basis in 12/17. In 5 hospitals, all the procedures use drug-eluting beads loaded with doxorubicin. The average number of procedures per patient is 2. The mean time from diagnosis of hepatocellular carcinoma to transarterial chemoembolisation is ≤ 2 months in 16 hospitals. In 11/17 hospitals, response is assessed by computed tomography. Radiological response is measured without specific criteria in 12/17 and the other five hospitals (4 group A) assessed using standardised criteria. CONCLUSION Uniformity among the Madrid Regional hospitals was found in the indication and treatment regimen. The use of DEB-TACE has become the preferred form of TACE in clinical practice. The differentiating factors for the more specialised hospitals are a larger volume of procedures, decision-making by multidisciplinary committees and assessment of radiological response more likely to be standardised.
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Affiliation(s)
- Ana Matilla Peña
- Department of Gastroenterology, Sección de Hepatología, Hospital General Universitario Gregorio Marañón, Madrid. Spain
| | - Óscar Núñez-Martínez
- Gastroenterology Unit, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain
| | - Antonio Díaz-Sánchez
- Gastroenterology Unit, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain
| | - Fernando Pons-Renedo
- Department of Gastroenterology, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - Mariano Gómez-Rubio
- Department of Gastroenterology, Hospital Universitario de Getafe, Getafe, Madrid, Spain
| | | | - José L Lledó-Navarro
- Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - María Trapero-Marugán
- Department of Gastroenterology, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | | | - Elvira Poves-Martínez
- Department of Gastroenterology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | - Alberto Ibáñez-Pinto
- Gastroenterology Unit, Hospital Universitario del Henares, Coslada, Madrid, Spain
| | | | - Mar Lozano-Maya
- Gastroenterology Unit, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Raquel González-Alonso
- Department of Gastroenterology, Hospital Universitario de Móstoles, Móstoles, Madrid, Spain
| | - Belén Piqueras-Alcol
- Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain
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