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Quan W, Fazlin Zulkifli H, Saari N, Shueb RH, Mustaffa N. Comparison of efficacy and safety of adjuvant therapies versus sorafenib in hepatocellular carcinoma: a systematic review and network meta-analysis. Front Pharmacol 2025; 16:1502931. [PMID: 40098625 PMCID: PMC11911332 DOI: 10.3389/fphar.2025.1502931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 02/14/2025] [Indexed: 03/19/2025] Open
Abstract
Purpose Diverse novel therapeutic options for hepatocellular carcinoma (HCC) have surfaced in recent years. However, it is increasingly difficult to select the optimal medication. This research aims to assess overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and severe adverse events (SAEs) in HCC patients receiving adjuvant therapies compared to those receiving sorafenib. Methods Four databases were used to search articles. Only randomized controlled trials were included. Indicators such as OS, PFS, DCR, ORR, AEs and SAEs were used as outcomes. The protocol for this meta-analysis was registered with PROSPERO (Registration ID: CRD42024544394). Results Forty trials were included in this meta-analysis. The Oxaliplatin, Fluorouracil, and Leucovorin (OFL) + sorafenib group and the sintilimab + bevacizumab biosimilar group decreased the risk of death and increased PFS, ORR, and DCR. Yet, they also yielded remarkable adverse effects and severe adverse effects. To sum up, the atezolizumab + bevacizumab combination and tepotinib were recommended due to their favorable performance on all indexes. Conclusion This study further substantiates the efficacy of combination therapies in HCC, while they cause more toxicity in general. It is pressingly urgent to develop new drugs for liver cancer and find rational strategies to alleviate AEs. Systematic Review Registration PROSPERO, identifier CRD42024544394.
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Affiliation(s)
- Wenjun Quan
- Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | | | - Norhafizah Saari
- IC-Innovation in Advanced Material and Photonics, Advanced Materials Research Centre (AMREC), SIRIM Berhad, Kulim, Kedah, Malaysia
| | - Rafidah Hanim Shueb
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, University Sains Malaysia, Kelantan, Malaysia
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nazri Mustaffa
- Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Department of Medicine, Hospital University Sains Malaysia, Kelantan, Malaysia
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Meng W, Luo Y, Zhao L, Zhang Y, Liu J, Li S, Du Y, Li H. Bibliometric study on the utilization of sorafenib in hepatocellular carcinoma. Front Oncol 2024; 14:1507608. [PMID: 39759148 PMCID: PMC11695192 DOI: 10.3389/fonc.2024.1507608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 12/09/2024] [Indexed: 01/07/2025] Open
Abstract
Background Although the number of studies on sorafenib for hepatocellular carcinoma (HCC) is increasing during the past two decades, no detailed scientometric examination of its knowledge framework has been undertaken. Therefore, we performed a bibliometric analysis on this topic. Methods VOSviewer and CiteSpace were utilized to analyze the articles regarding sorafenib for HCC from 2005 to 2024, which were retrieved from the Web of Science Core Collection (WoSCC) database. Results There were 7,667 articles related to sorafenib in HCC were retrieved from the WoSCC database, and they covered 99 countries/regions, 5,640 institutions, and 30,450 authors. The most published literature of countries and institutions were China and Sun Yat-sen University, respectively. Cancers is the journal with the most papers published in this field, and the journal with the most co-citations is N Engl J Med. Among authors, Masatoshi Kudo has published the most research papers, and the most co-citations go to JM Llovet. The keywords "survival", "apoptosis", "efficacy", "transarterial chemoembolization", "lenvatinib", etc. represent the current hotspots in this field. Conclusions We identified current hotspots and trends by bibliometric analysis in sorafenib-HCC field, which might provide valuable guidance for future researches. Further explorations are supposed to conduct the continued study of HCC apoptosis, large-scaled clinical trials with international cooperations, and comprehensive treatments including multiple systemic or locoregional approaches in patients with HCC.
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Affiliation(s)
- Wenjun Meng
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yihang Luo
- Department of Urology, The General Hospital of Western Theater Command, Chengdu, China
| | - Lu Zhao
- Department of Urology, The General Hospital of Western Theater Command, Chengdu, China
| | - Yaoyu Zhang
- Department of Urology, The General Hospital of Western Theater Command, Chengdu, China
| | - Jiyan Liu
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Shadan Li
- Department of Urology, The General Hospital of Western Theater Command, Chengdu, China
| | - Yang Du
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Hongshuai Li
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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Yang Y, Sun J, Cai J, Chen M, Dai C, Wen T, Xia J, Ying M, Zhang Z, Zhang X, Fang C, Shen F, An P, Cai Q, Cao J, Zeng Z, Chen G, Chen J, Chen P, Chen Y, Shan Y, Dang S, Guo WX, He J, Hu H, Huang B, Jia W, Jiang K, Jin Y, Jin Y, Jin Y, Li G, Liang Y, Liu E, Liu H, Peng W, Peng Z, Peng Z, Qian Y, Ren W, Shi J, Song Y, Tao M, Tie J, Wan X, Wang B, Wang J, Wang K, Wang K, Wang X, Wei W, Wu FX, Xiang B, Xie L, Xu J, Yan ML, Ye Y, Yue J, Zhang X, Zhang Y, Zhang A, Zhao H, Zhao W, Zheng X, Zhou H, Zhou H, Zhou J, Zhou X, Cheng SQ, Li Q, on behalf of Chinese Association of Liver Cancer and Chinese Medical Doctor Association. Chinese Expert Consensus on the Whole-Course Management of Hepatocellular Carcinoma (2023 Edition). Liver Cancer 2024:1-23. [DOI: 10.1159/000541622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complications of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment, and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient’s general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements, and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.
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Abdelhamed W, Shousha H, El-Kassas M. Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end? LIVER RESEARCH (BEIJING, CHINA) 2024; 8:141-151. [PMID: 39957750 PMCID: PMC11771265 DOI: 10.1016/j.livres.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 08/01/2024] [Accepted: 09/05/2024] [Indexed: 01/03/2025]
Abstract
Hepatocellular carcinoma (HCC) is the sixth most prevalent form of cancer globally and the third leading cause of cancer-related mortality. The incidence of portal vein tumor thrombosis (PVTT) in HCC patients is 21% at one year and 46% at three years. The presence of PVTT has consistently been associated with a poor prognosis for HCC patients over the past decades. Notably, HCC prognosis is influenced not only by the presence of PVTT but also by the degree or extent of PVTT. Currently, there is a lack of global consensus or established protocols regarding the optimal management of HCC with associated PVTT. The Barcelona Clinic for Liver Cancer classifies HCC patients with PVTT as stage C, indicating an advanced stage, and limiting treatment recommendations for these patients to systemic therapy. In recent years, there has been an increase in the availability of therapeutic options for HCC patients with PVTT. Treatment modalities include systemic therapy, transarterial chemoembolization, surgical resection, stereotactic body radiotherapy, transarterial radioembolization, and liver transplantation. An ideal therapy for each patient necessitates a multidisciplinary approach. This review article presents the latest updates in managing HCC patients with PVTT.
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Affiliation(s)
| | - Hend Shousha
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Tustumi F, Coelho FF, de Paiva Magalhães D, Júnior SS, Jeismann VB, Fonseca GM, Kruger JAP, D'Albuquerque LAC, Herman P. Treatment of hepatocellular carcinoma with macroscopic vascular invasion: A systematic review and network meta-analysis. Transplant Rev (Orlando) 2023; 37:100763. [PMID: 37393656 DOI: 10.1016/j.trre.2023.100763] [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: 04/10/2023] [Revised: 05/11/2023] [Accepted: 05/14/2023] [Indexed: 07/04/2023]
Abstract
BACKGROUND This study aimed to evaluate the outcomes of different treatments for patients with hepatocellular carcinoma (HCC) and macroscopic vascular invasion. METHODS A systematic review and meta-analysis of comparative studies was performed to evaluate various treatment modalities for HCC with macroscopic vascular invasion, including liver resection (LR), liver transplantation (LT), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), radiotherapy (RT), radiofrequency ablation (RFA), and antineoplastic systemic therapy (AnST). RESULTS After applying the selection criteria, 31 studies were included. The surgical resection (SR) group (including LR and LT) had a similar mortality rate to the non-surgical resection (NS) group (RD = -0.01; 95% CI -0.05 to 0.03). The SR group had a higher rate of complications (RD = 0.06; 95% CI 0.00 to 0.12) but a higher 3-year overall survival (OS) rate than the NS group (RD = 0.12; 95% CI 0.05 to 0.20). The network analysis revealed that the overall survival was lower in the AnST group. LT and LR had similar survival benefits. The meta-regression suggested that SR has a greater impact on the survival of patients with impaired liver function. DISCUSSION Most likely, LT has a significant impact on long-term survival and consequently would be a better option for HCC with macroscopic vascular invasion in patients with impaired liver function. LT and LR offer a higher chance of long-term survival than NS alternatives, although LR and LR are associated with a higher risk of procedure-related complications.
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Affiliation(s)
- Francisco Tustumi
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
| | - Fabricio Ferreira Coelho
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Daniel de Paiva Magalhães
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Sérgio Silveira Júnior
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Vagner Birk Jeismann
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Gilton Marques Fonseca
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Jaime Arthur Pirola Kruger
- Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Luiz Augusto Carneiro D'Albuquerque
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Paulo Herman
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
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Tao ZW, Cheng BQ, Zhou T, Gao YJ. Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review. Hepatobiliary Pancreat Dis Int 2022; 21:134-144. [PMID: 34955380 DOI: 10.1016/j.hbpd.2021.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/05/2021] [Indexed: 02/09/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.
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Affiliation(s)
- Zi-Wen Tao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Bao-Quan Cheng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Tao Zhou
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yan-Jing Gao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
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Lee S, Song SK, Bae B, Park Y. Comparing efficacies of different treatment regimens in patients with hepatocellular carcinoma accompanied by portal vein tumor thrombus using network meta-analysis. Ann Surg Treat Res 2022; 103:280-289. [DOI: 10.4174/astr.2022.103.5.280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 09/12/2022] [Accepted: 09/17/2022] [Indexed: 11/12/2022] Open
Affiliation(s)
- Seungji Lee
- Department of Surgery, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Korea
| | - Sung Kyu Song
- Department of Surgery, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Korea
| | - Byungje Bae
- Department of Surgery, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Korea
| | - Yongkeun Park
- Department of Surgery, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Korea
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Combination Intensity-Modulated Radiotherapy and Sorafenib Improves Outcomes in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis. JOURNAL OF ONCOLOGY 2021; 2021:9943683. [PMID: 34899910 PMCID: PMC8664501 DOI: 10.1155/2021/9943683] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 11/05/2021] [Indexed: 12/29/2022]
Abstract
Purpose To compare the difference in outcome of hepatocellular carcinoma (HCC) with portal vein thrombosis (PVTT) between intensity-modulated radiotherapy (IMRT) concurrent with sorafenib and IMRT alone. Methods A total of 82 patients with PVTT from 2014 to 2019 were included. Of these, 36 received IMRT concurrent with sorafenib treatment (group A), while 46 underwent IMRT alone (group B). The dose of IMRT was 40.0–62.5 Gy/2–2.5 Gy/4–6 w, and patients received orally administered sorafenib 400 mg twice a day in combination with IMRT. Overall survival (OS), progression-free survival (PFS), and median distant metastasis-free survival (DMFS) were evaluated by using LIFETEST procedure of SAS. Results The median survival time was 11.0 months in group A versus 9.0 months in group B. The 1- and 2-year OS in group A were 44.9% and 3.8% versus 28.6% and 2.6% in group B (P=0.036), respectively. The median PFS was 6.0 months in group A versus 3.0 months in group B. The 1- and 2-year PFS in group A were 20.7% and 6.9% versus 2.7% and 0.0% in group B (P=0.012), respectively. The 1- and 2-year DMFS in group A were 38.0% and 7.9% versus 16.7% and 0.0% in group B (P=0.019), respectively. Multivariate analysis showed that Child–Pugh classification, AFP response, and overall response were independent risk factors for OS (P < 0.05). There were no significant differences in adverse events except fatigue and skin reactions between the two groups. Conclusion Compared with IMRT alone, IMRT concurrent with sorafenib can improve the long-term efficacy of HCC patients with PVTT, without increasing adverse reactions. The patients with Child–Pugh A, overall response, and AFP response obtained better OS.
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Blaise L, Pereira H, Vilgrain V, Sutter O, Gigante E, Walter A, Ganne-Carrié N, Nahon P, Bouattour M, Dioguardi Burgio M, Grando V, Nkontchou G, Seror O, Nault JC. Percutaneous ablation for locally advanced hepatocellular carcinoma with tumor portal invasion. Clin Res Hepatol Gastroenterol 2021; 45:101731. [PMID: 34139320 DOI: 10.1016/j.clinre.2021.101731] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/27/2021] [Accepted: 06/10/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION We aim to assess the outcomes of percutaneous ablation of locally advanced HCC in a tertiary center, which is usually not indicated. We compared to sorafenib or trans-arterial radioembolization (TARE). METHODS We included 272 patients with HCC and tumor portal invasion treated by percutaneous ablation (n = 44) assessed retrospectively from one center compared to a control group from the SARAH trial including patients treated with sorafenib (n = 123) or TARE (n = 105). A propensity-score matching was performed in a subgroup of patients with similar baselines characteristics. RESULTS 84% of patients treated by ablation were male with a unique nodule (median size 50 mm) in 72.7% of the case. Complete tumor ablation was achieved in 75% of the patients with 20% Dindo-Clavien III-V adverse events including 6.8% of 90-days mortality. Sum of tumor size ≥70 mm was associated with incomplete ablation (p = 0.0239) and a higher risk of death (p = 0.0375). Patients in control group had a higher tumor burden, and more Vp3/4 compared to ablation group. Median overall survival was similar in the ablation and in the control group (16.4 and 14.0 months respectively, p = 0.48). The median progression-free survival was 6.6 months in ablation group compared to 4.2 months in the control group (p = 0.12). CONCLUSION Percutaneous ablation for locally advanced HCC was feasible and associated with similar long-term outcomes to sorafenib or TARE.
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Affiliation(s)
- Lorraine Blaise
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Helena Pereira
- Hôpital Européen Georges-Pompidou, Unité de Recherche Clinique, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM, Centre d'Investigation Clinique 1418 (CIC1418), Paris, France
| | - Valérie Vilgrain
- Service de Radiologie, Hôpital Beaujon, Hôpitaux Universitaires Paris Nord Val de Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France; Université de Paris et CRI, INSERM 1149, F-75018, Paris, France
| | - Olivier Sutter
- Unité de Radiologie Interventionnelle, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Elia Gigante
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Aurélie Walter
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Nathalie Ganne-Carrié
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France
| | - Pierre Nahon
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France
| | - Mohamed Bouattour
- Service d'Oncologie Digestive et Médicale, Hôpital Beaujon, Hôpitaux Universitaires Paris Nord Val de Seine, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Marco Dioguardi Burgio
- Service de Radiologie, Hôpital Beaujon, Hôpitaux Universitaires Paris Nord Val de Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France; Université de Paris et CRI, INSERM 1149, F-75018, Paris, France
| | - Véronique Grando
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Gisèle Nkontchou
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
| | - Olivier Seror
- Unité de Radiologie Interventionnelle, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France.
| | - Jean-Charles Nault
- Service d'Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors laboratory, F-75006, Paris, France.
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Kim GH, Kim JH, Kim PH, Chu HH, Gwon DI, Ko HK. Emerging Trends in the Treatment of Advanced Hepatocellular Carcinoma: A Radiological Perspective. Korean J Radiol 2021; 22:1822-1833. [PMID: 34431250 PMCID: PMC8546136 DOI: 10.3348/kjr.2021.0229] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/17/2021] [Accepted: 06/03/2021] [Indexed: 01/10/2023] Open
Abstract
This is a narrative review of various treatment modalities for advanced hepatocellular carcinoma (HCC), with a focus on recent updates in radiological treatments, as well as novel treatment concepts related to immune checkpoint inhibitors and combination therapies with locoregional treatments. Interventional radiologists have made efforts toward developing alternative and/or combination treatments for first-line systemic treatment of patients with advanced HCC. Locoregional treatments with or without systemic therapy may be considered in the selected patients. Various treatment modalities for advanced HCC are emerging, and several randomized controlled trials, including those of combination treatments with immunotherapy, are ongoing.
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Affiliation(s)
- Gun Ha Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
| | - Pyeong Hwa Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hee Ho Chu
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Heung-Kyu Ko
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Zane KE, Makary MS. Locoregional Therapies for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis. Cancers (Basel) 2021; 13:5430. [PMID: 34771593 PMCID: PMC8582519 DOI: 10.3390/cancers13215430] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 10/22/2021] [Accepted: 10/28/2021] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma is the fourth leading cause of cancer worldwide, and the fastest increasing cause of cancer mortality in the United States. Its propensity for vascular invasion leads to the presence of portal vein tumor thrombus in up to half of patients. PVTT results in a classification of advanced disease, given the risk recurrence secondary to intravascular spread, and formal guidelines recommend systemic therapy in these patients. However, recent advances in locoregional therapies including TACE, TARE, and ablation have demonstrated the potential to drastically improve overall survival in patients with HCC complicated by PVTT.
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Affiliation(s)
| | - Mina S. Makary
- Department of Radiology, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
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12
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Kim SJ, Kim JM. Liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis. JOURNAL OF LIVER CANCER 2021; 21:105-112. [PMID: 37383081 PMCID: PMC10035684 DOI: 10.17998/jlc.2021.03.17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/09/2021] [Accepted: 03/17/2021] [Indexed: 06/30/2023]
Abstract
Traditionally, liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis is not recommended. However, with recent developments in locoregional therapies for hepatocellular carcinoma, more aggressive treatments have been attempted for advanced hepatocellular carcinoma. Recently, various studies on locoregional therapies for downstaging followed by living donor liver transplantation reported inspiring overall survival and recurrence-free survival of patients. These downstaging procedures included three-dimensional conformal radiation therapy, trans-arterial chemoembolization, stereotactic body radiation therapy, trans-arterial radioembolization, hepatic arterial infusion chemotherapy and combinations of these therapies. Selection of the optimal downstaging protocol should depend on tumor location, biology and background liver status. The risk factors affecting outcome include pre-downstaging alpha-fetoprotein values, delta alpha-fetoprotein values, disappearance of portal vein tumor thrombosis on imaging and meeting the Milan criteria or not after downstaging. For hepatocellular carcinoma with portal vein tumor thrombosis, downstaging procedure with liver transplantation in mind would be helpful. If the reaction of the downstaged tumor is good, liver transplantation may be performed.
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Affiliation(s)
- Sang Jin Kim
- Division of Hepatobiliopancreas and Transplant Surgery, Korea University Ansan Hospital, Ansan, Korea
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Wang J, Li X, Wang F, Shi D, Zhang J. Anlotinib followed by transarterial chemoembolization and radiofrequency ablation is a safe and effective initial treatment for hepatocellular carcinoma patients with portal vein tumor thrombus: A retrospective case series study. J Cancer Res Ther 2021; 17:619-624. [PMID: 34269290 DOI: 10.4103/jcrt.jcrt_1253_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background Portal vein tumor thrombus (PVTT) remains a poor prognostic factor occurring in about 10%-40% of patients with hepatocellular carcinoma (HCC) for the optimal treatment is controversial. Anlotinib is an novel small molecule inhibitor that has a broad spectrum of inhibitory activities on tumor angiogenesis and growth. However, so far, no studies have reported the use of anlotinib in the treatment of HCC patients with PVTT. Here, we evaluated the safety and efficacy of anlotinib, followed by transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for the treatment of patients with HCC and PVTT. Materials and Methods A total of 145 consecutive HCC patients who underwent TACE in combination with RFA were enrolled in the retrospective study. Twenty-eight patients were diagnosed with PVTT and received anlotinib as basic treatment. The adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs Version 4.0. Time to tumor progression (TTP) and overall survival (OS) were calculated using the Kaplan-Meier method. Results The most common toxicities related to anlotinib were pharyngalgia (53.6%), fatigue (42.9%), and hand-foot skin reaction (39.3%). The median OS was 13 months (range: 3-18 months) with 1-year OS rate of 64.3%. The median TTP was 7 months (range: 1-12 months) with 6-month rate of 46.4%. Conclusion Anlotinib followed by TACE and RFA is a safe and effective initial treatment modality for HCC patients with PVTT. Anlotinib may be a promising therapeutic option for relieving and/or stabilizing HCC with PVTT.
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Affiliation(s)
- Jianpeng Wang
- Department of Oncology, First People's Hospital of Foshan, Foshan Hospital of Sun Yat-Sen University, Foshan, China
| | - Xishan Li
- Department of Interventional Radiology, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, China
| | - Fengjie Wang
- Department of Oncology, First People's Hospital of Foshan, Foshan Hospital of Sun Yat-Sen University, Foshan, China
| | - Degang Shi
- Department of Oncology, First People's Hospital of Foshan, Foshan Hospital of Sun Yat-Sen University, Foshan, China
| | - Jiren Zhang
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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Lock M, Meyers BM, Mujoomdar A. The addition of radiofrequency ablation for patients receiving sorafenib: new evidence for a new standard? ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:3. [PMID: 33553296 PMCID: PMC7859796 DOI: 10.21037/atm-20-7474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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15
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Ding X, Sun W, Chen J, Li W, Shen Y, Guo X, Teng Y, Liu X, Sun S, Wei J, Li W, Chen H, Liu B. Percutaneous Radiofrequency Ablation Combined With Transarterial Chemoembolization Plus Sorafenib for Large Hepatocellular Carcinoma Invading the Portal Venous System: A Prospective Randomized Study. Front Oncol 2020; 10:578633. [PMID: 33194699 PMCID: PMC7644860 DOI: 10.3389/fonc.2020.578633] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 09/28/2020] [Indexed: 01/27/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) portends a worse prognosis. The objective of this study was to compare the efficacy of percutaneous radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) plus sorafenib to that of the most commonly utilized regimen of TACE plus sorafenib in large HCCs with type I/II PVTT. Methods An open-label, single-center, prospective, randomized trial of participants with tumors ≥5 cm and type I/II PVTT was performed. Participants with previously untreated HCCs were divided into two groups: RFA + cTACE + sorafenib (study group, n = 40) and cTACE + sorafenib (control group, n = 40). The primary endpoint was the objective response rate (ORR), the secondary endpoints included the overall survival (OS); time to progression (TTP); and toxicity. Prognostic factors were analyzed using cox-regression analysis. Results 80 patients were enrolled into this study with integrated clinical data. Under a median follow-up of 506 days, the median age was 57.5 years (range: 28–80 years). The ORR of study group was higher than control group (70% vs 22.5%, p<0.001). Furthermore, the median OS of study group was superior to that of control group (468 days vs 219 days, HR: 0.44 [95% CI: 0.25–0.78], P = 0.005). Adverse events occurred with 100% probability in both groups (p>0.99), but no treatment-related deaths were recorded. Tumor encapsulation and attaining treatment response predict favorable OS in a multivariate Cox model. The rates of adverse events in both groups were 100% (p>0.99). There were no treatment-related deaths. Conclusions RFA combined with TACE plus sorafenib is a safe, well-tolerated three-modality treatment for large HCCs with types I/II PVTT, and it demonstrated better efficacy than TACE plus sorafenib alone.
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Affiliation(s)
- Xiaoyan Ding
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Sun
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jinglong Chen
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Li
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjun Shen
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaodi Guo
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Teng
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaomin Liu
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shasha Sun
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jianying Wei
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wendong Li
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hui Chen
- School of Biomedical Engineering, Capital Medical University, Beijing, China
| | - Bozhi Liu
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Tak KY, Nam HC, Choi JY, Yoon SK, Kim CW, Kim HY, Lee SW, Lee HL, Chang UI, Song DS, Yang JM, Kwon JH, Yoo SH, Sung PS, Choi SW, Song MJ, Kim SH, Jang JW. Effectiveness of sorafenib dose modifications on treatment outcome of hepatocellular carcinoma: Analysis in real-life settings. Int J Cancer 2020; 147:1970-1978. [PMID: 32167170 DOI: 10.1002/ijc.32964] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 02/28/2020] [Accepted: 03/03/2020] [Indexed: 12/22/2022]
Abstract
Controlling adverse events (AEs) through dose reduction can enhance drug adherence and treatment response. Currently, there is no guide for sorafenib dosing. The aim of this study was to evaluate whether sorafenib dosing could affect treatment outcomes. A total of 782 hepatocellular carcinoma (HCC) patients treated with sorafenib were evaluated for sorafenib dosing and its modifications via medical records at baseline and regular follow-up. Study outcomes included progression-free survival (PFS), overall survival (OS), sorafenib duration, cumulative dose, AEs and drug discontinuation. The median patient survival was 7.7 months. Overall, 242 (30.9%) patients underwent dose reduction and 121 (17.5%) discontinued sorafenib due to AEs. In multivariate analysis, dose reduction was identified to be independently predictive of PFS and OS. The 800-to-400 mg/day group provided significantly better PFS than the 800 mg/day-maintained group or the 800-to-600 mg/day group. Likewise, the 800-to-400 mg/day group resulted in a significantly better OS than other dosing. However, dose reduction to 200 mg/day led to significantly worse PFS and OS. Hand-foot skin reaction and drug discontinuation due to AEs were higher in the 800-to-600 mg/day group than the 800-to-400 mg/day group. The 800-to-400 mg/day group had significantly longer treatment duration and higher cumulative dose than the 800 mg/day-maintained group. Sorafenib dose reduction can improve HCC survival and increase patient tolerance and adherence coupled with longer duration and higher cumulative dose. Dose reduction from 800 to 400 mg/day than to 600 mg/day is recommended when clinically warranted. However, dose reduction to 200 mg/day is not recommendable.
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Affiliation(s)
- Kwon Yong Tak
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, Seoul, South Korea
| | - Hee Chul Nam
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, Seoul, South Korea
| | - Jong Young Choi
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, Seoul, South Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, Seoul, South Korea
| | | | - Hee Yeon Kim
- Uijeongbu St. Mary's Hospital, Seoul, South Korea
| | | | - Hae Lim Lee
- Bucheon St. Mary's Hospital, Seoul, South Korea
| | - U Im Chang
- St. Vincent's Hospital, Seoul, South Korea
| | | | - Jin Mo Yang
- Incheon St. Mary's Hospital, Seoul, South Korea
| | | | | | - Pil Soo Sung
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, Seoul, South Korea
| | | | | | | | - Jeong Won Jang
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, Seoul, South Korea
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17
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Zhang Y, Miao H, Xie W, Jiang S, Song Z, Huang G, Fan W, Wang Y, Li J, Chen Y. The PPRD score stratifies patients with hepatocellular carcinoma and portal vein tumor thrombus treated with sorafenib plus transarterial chemoembolization. Eur Radiol 2020; 31:232-243. [PMID: 32728770 DOI: 10.1007/s00330-020-07078-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/23/2020] [Accepted: 07/16/2020] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To identify clinical prognostic and predictive factors in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing sorafenib plus transarterial chemoembolization (TACE) and establish a prognostic score for these patients. METHODS Between January 2012 and December 2017, 184 consecutive patients with HCC and PVTT were concurrently treated with sorafenib and TACE. Univariate and multivariate analyses were performed to explore the clinical factors independently correlated with overall survival (OS). A prognostic score was then developed to identify different prognoses in an initial cohort and validated in an external cohort (n = 72). RESULTS In the multivariate analysis, performance status, extension of PVTT, initial radiological response, and sorafenib-related dermatologic toxicity were identified as predictors associated with OS. These factors were used to develop a prognostic score (PPRD score, range from 0 to 11). The median survival was found to decrease as the PPRD score increased, and patients were stratified into a favorable group (0 points), intermediate group (1-4 points), and dismal group (> 4 points). The median survival of patients in the three groups was 34.0 months, 20.0 months, and 7.0 months, respectively (p < 0.001). Additionally, the time to progression (TTP) (p < 0.001) was stratified along the same prognostic groups. The external validation cohort confirmed the prognostic scores. CONCLUSIONS The proposed score system can accurately stratify the outcomes of patients with HCC and PVTT treated with sorafenib plus TACE to help identify which group of patients may benefit from treatment. KEY POINTS • The survival benefits of patients with advanced HCC treated with sorafenib plus TACE remains controversial. • The independent factors associated with survival were identified to develop a prognostic score, called the PPRD score (standing for performance status, PVTT grade, radiological response, and sorafenib-related dermatologic toxicity); the median survival decreases as the score increases. • The scoring system can accurately stratify the survival benefits of patients with HCC and PVTT treated with combination therapy and help to identify which group of patients may benefit from the treatment. Graphical abstract.
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Affiliation(s)
- Yingqiang Zhang
- Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, People's Republic of China
- Department of Interventional Radiology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Hongfei Miao
- Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, People's Republic of China
| | - Wenlin Xie
- Department of Pathology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Suxiang Jiang
- Department of Radiology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Ze Song
- Department of Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Guihua Huang
- Digestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China
| | - Yu Wang
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China.
| | - Yong Chen
- Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, People's Republic of China.
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18
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Liu L, Zhang Q, Geng J, Li S, Zhao S, Zhang X, Hu J, Feng D. Comparison of radiofrequency ablation combined with sorafenib or sorafenib alone in patients with ECOG performance score 1: identifying optimal candidates. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:583. [PMID: 32566610 PMCID: PMC7290551 DOI: 10.21037/atm.2020.03.71] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background Sorafenib has been recommended as the first-line treatment and shown to prolong the median overall survival (OS) of patients with advanced unresectable hepatocellular carcinoma (HCC). Recently, a growing number of earlier studies showed the application of radiofrequency ablation (RFA) plus sorafenib in patients diagnosed at the advanced-stage HCC. This study aimed to compare the outcomes of RFA plus sorafenib versus sorafenib alone and identify prognostic factors related to OS for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread. Methods A total of 276 consecutive patients in BCLC stage C with PS 1 but without vascular invasion or extrahepatic spread were enrolled in this retrospective study. Survival analyses were performed using the Kaplan-Meier analysis, and the log-rank test examined the statistical differences between the transarterial chemoembolization (TACE) and sorafenib groups. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS. Results Based on the Kaplan-Meier curves, patients treated with RFA plus sorafenib showed better OS than those undergoing sorafenib, with respective OS at 1, 3 and 5 years (84.0%, 43.1%, 22.8% vs. 55.6%, 29.6%, 4.8%, Log-rank P<0.001). The univariate analysis and multivariate analysis showed that tumor size, tumor number, treatment method, albumin, bilirubin, and the Child-Pugh score were associated with OS. According to the subgroups analyses based on the tumor size and tumor number, there were significant differences in OS among overall subsets except in patients with tumor number ≥4 between RFA plus sorafenib and sorafenib therapy. Conclusions RFA plus sorafenib provided better prognostic performance than sorafenib, which should be suggested as an alternative treatment modality compared with sorafenib for BCLC stage C patients with PS 1 but without vascular invasion or extrahepatic spread.
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Affiliation(s)
- Lei Liu
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Qian Zhang
- Division of Medical Affairs, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Jie Geng
- Teaching and research section of Surgery, Tangdu Hospital, Xi'an 710038, China
| | - Songlun Li
- Department of Blood Transfusion, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Shoujie Zhao
- Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Xiangnan Zhang
- Division of Scientific Research, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Jie Hu
- Department of Clinical Laboratory, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Dayun Feng
- Department of Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China
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Renzulli M, Tovoli F, Clemente A, Ierardi AM, Pettinari I, Peta G, Marasco G, Festi D, Piscaglia F, Cappabianca S, Carrafiello G, Golfieri R. Ablation for hepatocellular carcinoma: beyond the standard indications. Med Oncol 2020; 37:23. [PMID: 32166482 DOI: 10.1007/s12032-020-01348-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 02/20/2020] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC), the most common primary liver neoplasia, represents the fifth most common malignant disease in men. Percutaneous ablation treatment is recommended among the treatments suggested for HCC patients in the very early/early stage. In the last decade, very important results in terms of survival benefits have been obtained with local ablative therapies, also outside the standard indications, thanks to many technical innovations. In particular, important results of ablation as a safe and effective technique have been obtained in the treatment of intermediate- or advanced-stage patients with HCC, and in the treatment of unfavourable tumour locations. Moreover, awareness is growing regarding the necessity of overcoming the rigidity of traditional guidelines in the treatment of HCC due to the complexity of patients with HCC, focusing on Precision Medicine. In this context, it is important to know the standard and non-standard indications of ablation in the treatment of HCC in order to offer the best therapeutic option tailored for each patient. The aim of this study was to analyse the possible clinical applications of ablative therapies for HCC patients, beyond the traditional indications recommended in the most widespread clinical practice guidelines for the management of HCC.
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Affiliation(s)
- Matteo Renzulli
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy.
| | - Francesco Tovoli
- Unit of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Alfredo Clemente
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Anna Maria Ierardi
- Diagnostic and Interventional Radiology Department, ASST Santi Paolo e Carlo, San Paolo Hospital, University of Milan, Milan, Italy
| | - Irene Pettinari
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy
| | - Giuliano Peta
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Fabio Piscaglia
- Unit of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Salvatore Cappabianca
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Gianpaolo Carrafiello
- Diagnostic and Interventional Radiology Department, ASST Santi Paolo e Carlo, San Paolo Hospital, University of Milan, Milan, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy
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20
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Kumar A, Acharya SK, Singh SP, Arora A, Dhiman RK, Aggarwal R, Anand AC, Bhangui P, Chawla YK, Datta Gupta S, Dixit VK, Duseja A, Kalra N, Kar P, Kulkarni SS, Kumar R, Kumar M, Madhavan R, Mohan Prasad V, Mukund A, Nagral A, Panda D, Paul SB, Rao PN, Rela M, Sahu MK, Saraswat VA, Shah SR, Shalimar, Sharma P, Taneja S, Wadhawan M, The INASL Task-Force on Hepatocellular Carcinoma. 2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations. J Clin Exp Hepatol 2020; 10:43-80. [PMID: 32025166 PMCID: PMC6995891 DOI: 10.1016/j.jceh.2019.09.007] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/15/2019] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.
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Key Words
- AFP, alpha-fetoprotein
- AIH, autoimmune hepatitis
- ALT, alanine aminotransferase
- DAA, direct-acting antiviral
- DALY, disability-adjusted life-year
- DNA, deoxyribonucleic acid
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- Gd-BOPTA, gadolinium benzyloxypropionictetraacetate
- Gd-EOB-DTPA, gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid
- HBV, hepatitis B virus
- HBeAg, hepatitis B envelope antigen
- HCC, hepatocellular carcinoma
- HIV, human immunodeficiency virus
- IARC, International Agency for Research on Cancer
- IFN, interferon
- INASL, Indian National Association for Study of the Liver
- MiRNA, micro-RNA
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- PIVKA, protein induced by vitamin K absence
- RFA
- RNA, ribonucleic acid
- SVR, sustained virological response
- TACE
- TACE, trans-arterial chemoembolization
- TARE, transarterial radioembolization
- TNF, tumor necrosis factor
- WHO, World Health Organization
- liver cancer
- targeted therapy
- transplant
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Affiliation(s)
- Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Anil C. Anand
- Department of Gastroenterology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Siddhartha Datta Gupta
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Naveen Kalra
- Department of Radio Diagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Suyash S. Kulkarni
- Division of Interventional Radiology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, Maharashtra, 400 012, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Ram Madhavan
- Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita University, Peeliyadu Road, Ponekkara, Edappally, Kochi, Kerala, 682 041, India
| | - V.G. Mohan Prasad
- Department of Gastroenterology, VGM Gastro Centre, 2100, Trichy Road, Rajalakshmi Mills Stop, Singanallur, Coimbatore, Tamil Nadu, 641 005, India
| | - Amar Mukund
- Department of Radiology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Dipanjan Panda
- Department of Oncology, Institutes of Cancer, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, No. 6-3-661, Punjagutta Road, Somajiguda, Hyderabad, Telangana, 500 082, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600 100, India
| | - Manoj K. Sahu
- Department of Medical Gastroenterology, IMS & SUM Hospital, K8 Kalinga Nagar, Shampur, Bhubaneswar, Odisha 751 003, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Samir R. Shah
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Manav Wadhawan
- Liver & Digestive Diseases Institute, Institute of Liver & Digestive Diseases, BLK Super Specialty Hospital, Delhi, 110 005, India
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Zhou HQ, Liu MS, Deng TB, Xie PB, Wang W, Shao T, Wu Y, Zhang P. The TGF-β/Smad Pathway Inhibitor SB431542 Enhances The Antitumor Effect Of Radiofrequency Ablation On Bladder Cancer Cells. Onco Targets Ther 2019; 12:7809-7821. [PMID: 31576139 PMCID: PMC6765330 DOI: 10.2147/ott.s212596] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 09/09/2019] [Indexed: 12/12/2022] Open
Abstract
Background Despite progress achieved in bladder cancer (BC) treatment, the prognosis of patients with advanced BC (ie, metastasized from the bladder to other organs) is poor. Although mortality in cases of low-grade BC is rare, the treatment, such as a radical cystectomy, often has a serious impact on the quality of life. Thus, research is needed to identify more effective treatment strategies and this work is aiming to examine the potential application of combination of radiofrequency ablation (RFA) and SB435142, a inhibitor of transforming growth factor β (TGFβ)/Smad pathway. Methods BC cells were transplanted into nude mice (thymusdeficiency Bal B/c) to form subcutaneous tumors. The mice with subcutaneous tumors were then treated with RFA and oral administration of SB431542, an inhibitor of TGFβ/Smad signaling pathway. The antitumor effect of RFA was measured by tumor proliferation curves and micro-positron emission computed tomography (micro-PET). The effect of SB431542 on epithelial-mesenchymal transition (EMT) related regulators in subcutaneous tumor tissues formed by BC cells were examined by quantitative real-time polymerase chain reaction (qPCR) experiments. Results The SB431542 treatment enhanced the antitumor effect of RFA on subcutaneous growth of BCs. SB431542 also decreased EMT-related regulators in subcutaneous tumor tissues formed by BC cells in nude mice. Conclusion SB431542 enhances the effect of RFA on BC.
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Affiliation(s)
- Hong-Qing Zhou
- Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University , Qujing City 655000, Yunnan Province, People's Republic of China
| | - Ming-Sheng Liu
- Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University , Qujing City 655000, Yunnan Province, People's Republic of China
| | - Ti-Bin Deng
- Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University , Qujing City 655000, Yunnan Province, People's Republic of China
| | - Ping-Bo Xie
- Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University , Qujing City 655000, Yunnan Province, People's Republic of China
| | - Wei Wang
- Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University , Qujing City 655000, Yunnan Province, People's Republic of China
| | - Tao Shao
- Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University , Qujing City 655000, Yunnan Province, People's Republic of China
| | - Yao Wu
- Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University , Qujing City 655000, Yunnan Province, People's Republic of China
| | - Peng Zhang
- Department of Urology, State Key Laboratory of Kidney Diseases, Chinese People's Liberation Army (PLA) General Hospital/Chinese PLA Medical Academy, Beijing 100853, People's Republic of China
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22
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Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers. World J Gastroenterol 2019; 25:4360-4382. [PMID: 31496618 PMCID: PMC6710186 DOI: 10.3748/wjg.v25.i31.4360] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/24/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide: Portal vein tumor thrombosis (PVTT) occurs in about 35%-50% of patients and represents a strong negative prognostic factor, due to the increased risk of tumor spread into the bloodstream, leading to a high recurrence risk. For this reason, it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care, due to its antiangiogenetic action, although it can grant only a poor prolongation of life expectancy. Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition, including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement, tumor biological aggressiveness, complications caused by portal hypertension, patient's clinical features and tolerance to antineoplastic treatments. The median survival has been reported to range between 2.7 and 4 mo in absence of therapy, but it can vary from 5 mo to 5 years, thus depicting an extremely variable scenario. For this reason, it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.
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MESH Headings
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Carcinoma, Hepatocellular/complications
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/therapy
- Chemoembolization, Therapeutic/methods
- Contrast Media/administration & dosage
- Disease-Free Survival
- Hepatectomy
- Humans
- Hypertension, Portal/etiology
- Hypertension, Portal/mortality
- Hypertension, Portal/therapy
- Liver Neoplasms/complications
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- Liver Transplantation
- Neoadjuvant Therapy/methods
- Neoplasm Invasiveness/pathology
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/prevention & control
- Patient Selection
- Portal Vein/diagnostic imaging
- Portal Vein/pathology
- Prognosis
- Survival Analysis
- Thrombectomy
- Time Factors
- Ultrasonography/methods
- Venous Thrombosis/etiology
- Venous Thrombosis/mortality
- Venous Thrombosis/therapy
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Affiliation(s)
- Lucia Cerrito
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Brigida Eleonora Annicchiarico
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Roberto Iezzi
- Department of Bioimaging and Radiological Sciences, Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Maurizio Pompili
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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23
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Xiang X, Lau WY, Wu ZY, Zhao C, Ma YL, Xiang BD, Zhu JY, Zhong JH, Li LQ. Transarterial chemoembolization versus best supportive care for patients with hepatocellular carcinoma with portal vein tumor thrombus：a multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2019; 45:1460-1467. [PMID: 31005471 DOI: 10.1016/j.ejso.2019.03.042] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 03/08/2019] [Accepted: 03/28/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND This study aims to compare the efficacy and safety of treatment after transarterial chemoembolization(TACE) with best supportive care (BSC) in patients with hepatocellular carcinoma (HCC) with PVTT. METHODS This retrospective study was conducted on 1,040 patients with HCC with PVTT who were treated either with TACE (n = 675) or BSC (n = 365). BSC did not include sorafenib. The two groups of patients were compared with or without propensity score matching. A subgroup analysis was subsequently performed by stratifying patients according to the stages of PVTT in the Cheng's PVTT classification. RESULTS In PVTTtypes I-III, TACE was associated with significantly better overall survival (OS) thanBSC (P < 0.05). Within each type of PVTT for patients who received TACE or BSC, OS was significantly worse in patients with type IVPVTT than in any of the other three types of PVTT (all P < 0.05). TACE was associated with better long-termOS than BSC after propensity score matching or on stratification by the PVTT types. CONCLUSION TACE was associated with better OS than BSC in HCC patients with PVTT types I-III but not type IV. Patients with type IV PVTT showed the worst prognosis, regardless of whether TACE or BSC was used.
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Affiliation(s)
- Xiao Xiang
- Department of Hepatobilliary Surgery, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Peking University People's Hospital, Beijing, China; Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Wan-Yee Lau
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
| | - Zhen-Yu Wu
- Department of Hepatobilliary Surgery, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Peking University People's Hospital, Beijing, China; Department of Hepatobiliary Surgery, Beijing Aerospace Hospital, Beijing, China
| | - Chao Zhao
- Department of Invasive Technology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Yi-Long Ma
- Department of Invasive Technology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Ji-Ye Zhu
- Department of Hepatobilliary Surgery, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Peking University People's Hospital, Beijing, China.
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China.
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China.
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Neureiter D, Stintzing S, Kiesslich T, Ocker M. Hepatocellular carcinoma: Therapeutic advances in signaling, epigenetic and immune targets. World J Gastroenterol 2019; 25:3136-3150. [PMID: 31333307 PMCID: PMC6626722 DOI: 10.3748/wjg.v25.i25.3136] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 05/02/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases. Treatment of advanced disease stages is still unsatisfying. Besides first and second generation tyrosine kinase inhibitors, immune checkpoint inhibitors have become central for the treatment of HCC. New modalities like epigenetic therapy using histone deacetylase inhibitors (HDACi) and cell therapy approaches with chimeric antigen receptor T cells (CAR-T cells) are currently under investigation in clinical trials. Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers. The current status of treatment options for advanced HCC, emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here.
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Affiliation(s)
- Daniel Neureiter
- Institute of Pathology, Cancer Cluster Salzburg, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg 5020, Austria
| | - Sebastian Stintzing
- Medical Department, Division of Oncology and Hematology, Campus Charité Mitte, Charité University Medicine Berlin, Berlin 10117, Germany
| | - Tobias Kiesslich
- Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK) and Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg 5020, Austria
| | - Matthias Ocker
- Translational Medicine Oncology, Bayer AG, Berlin 13353, Germany
- Charité University Medicine Berlin, Berlin 10117, Germany
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Hsiao P, Hsieh KC, Chen YS, Hsu CC, Lo GH, Li YC, Hsieh PM, Lin HY, Wu TC, Yeh JH, Lin CW. Sorafenib with concurrent multiple-line therapies improves overall survival in advanced stage hepatocellular carcinoma. Medicine (Baltimore) 2019; 98:e16074. [PMID: 31232945 PMCID: PMC6636964 DOI: 10.1097/md.0000000000016074] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies.We analyzed the treatment and OS of 401 patients with Barcelona clinic liver cancer stage C HCC between 2012 and 2017. Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the Kaplan-Meier method.The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1-80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥5 cm, serum alpha-fetoprotein ≥200, and serum albumin ≥3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multiple-line treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan-Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib alone.Sorafenib with concurrent multiple-line therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.
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Affiliation(s)
- Pojen Hsiao
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital
| | | | - Yaw-Sen Chen
- Department of Surgery, E-Da Hospital, I-Shou University
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung
| | - Chia-Chang Hsu
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung
- Division of Gastroenterology and Hepatology, Department of Medicine
- Health Examination Center
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung
- Division of Gastroenterology and Hepatology, Department of Medicine
| | - Yu-Chan Li
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung
| | - Pei-Min Hsieh
- Department of Surgery, E-Da Hospital, I-Shou University
| | - Hung-Yu Lin
- Department of Surgery, E-Da Hospital, I-Shou University
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Tsung-Chin Wu
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital
| | - Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung
- Division of Gastroenterology and Hepatology, Department of Medicine
- Health Examination Center
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
- School of Chinese Medicine, College of Chinese Medicine, China Medical University
- Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
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Park JW, Kim YJ, Kim DY, Bae SH, Paik SW, Lee YJ, Kim HY, Lee HC, Han SY, Cheong JY, Kwon OS, Yeon JE, Kim BH, Hwang J. Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial. J Hepatol 2019; 70:684-691. [PMID: 30529387 DOI: 10.1016/j.jhep.2018.11.029] [Citation(s) in RCA: 143] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Revised: 11/08/2018] [Accepted: 11/27/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC. METHODS In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS). RESULTS For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006). CONCLUSION Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC. LAY SUMMARY For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.
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Affiliation(s)
| | | | | | - Si-Hyun Bae
- The Catholic University of Korea, South Korea; Seoul St. Mary's Hospital, South Korea
| | | | - Youn-Jae Lee
- Inje University Busan Paik Hospital, South Korea
| | | | - Han Chu Lee
- Asan Medical Center, University of Ulsan, South Korea
| | | | | | - Oh Sang Kwon
- Gachon University Gil Medical Center, South Korea
| | | | | | - Jaeseok Hwang
- Keimyung University Dongsan Medical Center, South Korea
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27
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Kim PH, Choi SH, Kim JH, Park SH. Comparison of Radioembolization and Sorafenib for the Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Systematic Review and Meta-Analysis of Safety and Efficacy. Korean J Radiol 2019; 20:385-398. [PMID: 30799569 PMCID: PMC6389804 DOI: 10.3348/kjr.2018.0496] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 11/02/2018] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To compare the safety and efficacy of radioembolization with that of sorafenib for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS MEDLINE, EMBASE, and Cochrane databases were searched for studies reporting outcomes in patients with HCC and PVTT treated with radioembolization or sorafenib. Meta-analyses of cumulative overall survival (OS) and Kaplan-Meier survival rates according to the time to progression (TTP) and incidence of adverse events (AEs) were performed. Subgroup analyses were conducted on 1-year OS data. RESULTS Seventeen studies were identified (four involving radioembolization, 10 involving sorafenib, and three comparing both). Pooled OS rates were higher in the radioembolization group, notably at 6 months {76% (95% confidence interval [CI], 64-85%) vs. 54% (95% CI, 45-62%)} and 1 year (47% [95% CI, 38-57%] vs. 24% [95% CI, 18-30%]); TTP was also longer with radioembolization. In patients undergoing radioembolization, the proportion of patients with Eastern Cooperative Oncology Group status 0 (p < 0.0001), Child-Pugh A (p < 0.0001), extrahepatic metastasis (p = 0.0012), and a history of cancer treatment (p = 0.0048) was identified as a significant source of heterogeneity for the 1-year OS. Radioembolization was associated with a lower incidence of grade 3/4 AEs than sorafenib (9% [95% CI, 3-27%] vs. 28% [95% CI, 17-43%]). CONCLUSION Compared with sorafenib, radioembolization is a safer and more effective treatment for HCC with PVTT and is associated with prolonged survival, delayed tumor progression, and fewer grade 3/4 AEs.
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Affiliation(s)
- Pyeong Hwa Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Seong Ho Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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28
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Fernandes EDSM, Rodrigues PD, Álvares-da-Silva MR, Scaffaro LA, Farenzena M, Teixeira UF, Waechter FL. Treatment strategies for locally advanced hepatocellular carcinoma. Transl Gastroenterol Hepatol 2019; 4:12. [PMID: 30976715 DOI: 10.21037/tgh.2019.01.02] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 01/04/2019] [Indexed: 01/27/2023] Open
Abstract
Liver cancer ranks fifth in incidence and fourth in overall cancer-related mortality, with approximately 854,000 new cases and 810,000 deaths per year worldwide. Hepatocellular carcinoma (HCC) accounts for 90% of these cases, and, over time, both the incidence and mortality of this cancer have been rising in many regions. Several staging systems are used to assess the extent of primary tumor, presence of metastasis, and underlying liver disease, and thereby aid in the definition of treatment strategies and prognosis for these patients. The consequence of this heterogeneity in HCC staging is that no consensual definition of advanced disease exists, and there is still ongoing debate on the optimal treatment for these patients. Patients with advanced tumors can be candidates for multiple therapies, ranging from potentially curative options such as transplantation and resection-to locoregional and systemic treatments; these should be evaluated on an individual basis by a multidisciplinary team. This paper provides an overview of treatment options for advanced stage HCC, based on a review of the latest relevant literature and the personal experience of the authors.
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Affiliation(s)
- Eduardo De Souza Martins Fernandes
- Department of Surgery, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Pablo Duarte Rodrigues
- Digestive Surgery Division, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Mário Reis Álvares-da-Silva
- Gastroenterology and Hepatology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.,School of Medicine, Universidade Federal do Rio Grande Do Sul (UFGRS), Porto Alegre, RS, Brazil
| | | | | | - Uirá Fernandes Teixeira
- Digestive Surgery Division, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Fábio Luiz Waechter
- Digestive Surgery Division, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
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Yuan Z, Wang Y, Hu C, Gao W, Zheng J, Li W. Efficacy of Percutaneous Thermal Ablation Combined With Transarterial Embolization for Recurrent Hepatocellular Carcinoma After Hepatectomy and a Prognostic Nomogram to Predict Survival. Technol Cancer Res Treat 2019; 17:1533033818801362. [PMID: 30244651 PMCID: PMC6153531 DOI: 10.1177/1533033818801362] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
AIM This study aimed to evaluate the efficacy of percutaneous thermal ablation combined with transarterial embolization for recurrent hepatocellular carcinoma after hepatectomy and establish a prognostic nomogram to predict survival. METHODS One hundred seventeen patients with recurrent hepatocellular carcinoma receiving ablation from 2009 to 2014 were included in primary cohort to establish a prognostic nomogram. Between 2014 and 2016, 51 patients with recurrent hepatocellular carcinoma treated by ablation were enrolled in the validation cohort to validate the predictive accuracy of the nomogram. All patients underwent locoregional ablation. Overall survival was the primary end point, and progression-free survival was the second end point. The performance of the nomogram was assessed through concordance index and calibration curve and compared with 5 conventional hepatocellular carcinoma staging systems. RESULTS The 1-, 3-, and 5-year overall survival rates of primary cohort were 88.4%, 70.7%, and 64.1%, respectively. The 1-, 3-, and 5-year progression-free survival rates of primary cohort were 44%, 14%, and 8.7%, respectively. The results of multivariate analysis showed that tumor size ( P = .0469; hazard ratio, 1.020; 95% confidence interval, 1.0004-1.040), preoperative extrahepatic disease ( P = .0675; hazard ratio, 2.604; 95% confidence interval, 0.933-7.264), and close to hepatic hilum <2 cm ( P = .0053; hazard ratio, 3.691; 95% confidence interval, 1.474-9.240) were predictive factors for overall survival. The study established a nomogram to predict survival (concordance index, 0.752; 95% confidence interval, 0.656-0.849). According to the predicted overall survival, patients with recurrent hepatocellular carcinoma were divided into 3 risk classes ( P < .05): low-risk group (total score <55; predicted 5-year overall survival rate, 82.9%), intermediate-risk group (55 ≤ total score < 99; predicted 5-year overall survival rate, 52.8%), and high-risk group (hazard ratio, total score ≥99; predicted 5-year overall survival rate, not available). CONCLUSION Percutaneous thermal ablation appears to be an effective procedure for the treatment of recurrent hepatocellular carcinoma after hepatectomy. The proposed nomogram provides a mechanism to accurately predict survival and could stratify risk among patients with recurrent hepatocellular carcinoma treated by ablation therapy.
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Affiliation(s)
- Zhuhui Yuan
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.,Zhuhui Yuan, Yang Wang, and Caixia Hu contributed equally to this work
| | - Yang Wang
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.,Zhuhui Yuan, Yang Wang, and Caixia Hu contributed equally to this work
| | - Caixia Hu
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.,Zhuhui Yuan, Yang Wang, and Caixia Hu contributed equally to this work
| | - Wenfeng Gao
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Jiasheng Zheng
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Wei Li
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China
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Zhu J, Yin T, Xu Y, Lu XJ. Therapeutics for advanced hepatocellular carcinoma: Recent advances, current dilemma, and future directions. J Cell Physiol 2019; 234:12122-12132. [PMID: 30644100 DOI: 10.1002/jcp.28048] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Accepted: 11/30/2018] [Indexed: 12/16/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a serious threat to people's health worldwide. The prognosis of advanced HCC is dim if left untreated. In the clinic, the treatment options for advanced HCC include surgery, radiotherapy, transcatheter arterial chemoembolization, and so forth. In recent years, molecular targeted therapy and immunotherapy have also made great progress, bringing new hope to patients with advanced HCC. In this study, therapeutic advances, current dilemma, and future directions of advanced HCC are reviewed, which might serve as a summary for clinicians and may stimulate future research.
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Affiliation(s)
- Jing Zhu
- Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, The Sparkfire Scientific Research Group of Nanjing Medical University, Nanjing, China
| | - Tailang Yin
- Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yong Xu
- Department of Nephrology, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China
| | - Xiao-Jie Lu
- Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, The Sparkfire Scientific Research Group of Nanjing Medical University, Nanjing, China
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31
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Wang JC, Xia AL, Xu Y, Lu XJ. Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis. J Cell Physiol 2018; 234:1062-1070. [PMID: 30256409 DOI: 10.1002/jcp.27324] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 08/03/2018] [Indexed: 12/31/2022]
Abstract
Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.
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Affiliation(s)
- Jin-Cheng Wang
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - An-Liang Xia
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yong Xu
- Department of Nephrology, Huai'an Second People' Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
| | - Xiao-Jie Lu
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Abstract
OBJECTIVE The purpose of this article is to discuss the use, comparative efficacy, and general technical considerations of percutaneous ablation, alone or in combination with other therapies, for the treatment of hepatocellular carcinoma (HCC). CONCLUSION Percutaneous ablation is a mainstay treatment for early-stage HCC, offering survival comparable to that of surgical resection for small lesions. It can act as a primary curative therapy or bridge therapy for patients waiting to undergo liver transplant. New ablation modalities and combining tumor ablation with other therapies, such as transarterial chemoembolization, can improve clinical outcomes and allow treatment of larger lesions. Combining thermal ablation with systemic chemotherapy, including immunotherapy, is an area of future development.
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Costentin CE, Ferrone CR, Arellano RS, Ganguli S, Hong TS, Zhu AX. Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy. Liver Cancer 2017; 6:360-374. [PMID: 29234639 PMCID: PMC5704715 DOI: 10.1159/000481315] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Tumoral macrovascular invasion (MVI) of hepatic and/or portal vein branches is a common phenomenon in hepatocellular carcinoma (HCC) and is associated with poorer prognosis when compared to HCC without MVI. SUMMARY Current international guidelines for the management of HCC recommend sorafenib as the only treatment option in case of MVI. Despite guideline recommendations, several alternative options have been tested to manage HCC with MVI: surgery, transarterial chemoembolization, external or internal radiation, hepatic arterial infusion chemotherapy, percutaneous treatment, cryotherapy, or the combination of two or more of these strategies, with or without sorafenib. Here we will provide a comprehensive state-of-the-art review for the management of this challenging clinical entity based on the most recent available data. KEY MESSAGES There is a growing body of evidence suggesting that alternative strategies to standard-of-care sorafenib might improve survival in patients with advanced HCC with MVI but the level of evidence remains weak. Randomized phase III trials are ongoing and will hopefully provide information leading towards a more personalized treatment algorithm.
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Affiliation(s)
- Charlotte E. Costentin
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Cristina R. Ferrone
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Ronald S. Arellano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Suvranu Ganguli
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Theodore S. Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Andrew X. Zhu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
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Yin J, Bo WT, Sun J, Xiang X, Lang JY, Zhong JH, Li LQ. New Evidence and Perspectives on the Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus. J Clin Transl Hepatol 2017; 5:169-176. [PMID: 28660155 PMCID: PMC5472938 DOI: 10.14218/jcth.2016.00071] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 03/02/2017] [Accepted: 03/04/2017] [Indexed: 02/06/2023] Open
Abstract
Portal vein tumor thrombosis (PVTT) is an intractable condition but common phenomenon in hepatocellular carcinoma (HCC). HCC patients with PVTT may have worse liver function, a higher chance of comorbidity related to portal hypertension, lower tolerance to treatment and poorer prognoses. In Western guidelines, patients are offered palliative treatment with sorafenib or other systemic agents because HCC with PVTT is grouped together with metastatic HCC during the planning of its management. In recent years, various treatment options have become available for patients with HCC and PVTT. Therapy has also shifted toward evidence-based treatment. However, policies for the management of HCC with PVTT have not been established. This comprehensive literature review aims to present current and available management options for patients with HCC and PVTT. Evidence is mainly based on studies published after 2010.
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Affiliation(s)
- Jun Yin
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Wen-Tao Bo
- Department of Hepatobiliary Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jian Sun
- Department of Medical Affairs, ZiBo Hospital of Integrated Traditional Chinese and Western Medicine, Zibo, China
| | - Xiao Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Jin-Yi Lang
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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Jiang JF, Lao YC, Yuan BH, Yin J, Liu X, Chen L, Zhong JH. Treatment of hepatocellular carcinoma with portal vein tumor thrombus: advances and challenges. Oncotarget 2017; 8:33911-33921. [PMID: 28430610 PMCID: PMC5464922 DOI: 10.18632/oncotarget.15411] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 02/02/2017] [Indexed: 02/06/2023] Open
Abstract
Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.
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Affiliation(s)
- Jin-Fang Jiang
- Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Yong-Cong Lao
- Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Bao-Hong Yuan
- Department of General Surgery, Yan’An Hospital Affiliated to Kunming Medical University, Kunming, China
| | - Jun Yin
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xin Liu
- Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Long Chen
- Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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