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1
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Li PJ, Tabrizian P, Daher D, Gaviria F, Ajmera V, Montalvan-Sanchez EE, Gutierrez JA, Zhou K, Delebecque F, Garcia N, Barrick B, Wong C, Nephew L, Holden J, Dave S, Schnickel GT, Rich NE, Florman SS, Sapisochin G, Yao F, Singal AG, Mehta N. A prospective multicenter validation of RETREAT for posttransplantation HCC recurrence prediction. Hepatology 2025:01515467-990000000-01196. [PMID: 40067686 DOI: 10.1097/hep.0000000000001297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 01/27/2025] [Indexed: 03/24/2025]
Abstract
BACKGROUND AND AIMS The RETREAT(Risk Estimation of Tumor REcurrence After Transplant) score is a simple risk stratification tool for postliver transplantation (LT) HCC recurrence that has been validated in retrospective cohort studies. A prospective, multicenter study is needed to further demonstrate accuracy especially given the evolving clinical demographics and HCC transplant practice. Our aim is to validate and compare the RETREAT score to other post-LT HCC recurrence risk scores in a contemporary, prospective cohort of patients. APPROACH AND RESULTS We prospectively enrolled patients with HCC who underwent LT from 8 centers between 2018 and 2022. The primary outcome was post-LT recurrence-free survival. Secondary outcomes included post-LT and post-recurrence survival. Model performance, determined using the concordance index, Akaike information criterion, integrated Brier score, and calibration, was compared to that of other established risk scores.We included 1166 patients with HCC who underwent LT, of which 78 (6.7%) had post-LT HCC recurrence after a median follow-up time of 2.2 years (IQR 1.2-3.2). The median RETREAT score was 4 (IQR 3-5) in patients with post-LT HCC recurrence and 1 (IQR 1 - 2) in patients without. Those with a RETREAT score of 0, 3, and 5+ had a 99.4%, 84.1%, and 55.6% recurrence-free survival, respectively, at 3 years post-LT. The RETREAT score was also able to stratify post-LT overall and postrecurrence survival. The RETREAT score's concordance index was 0.81 (95% CI: 0.77-0.85) and outperformed the MORAL and RELAPSE scores across multiple metrics. CONCLUSIONS The RETREAT score retains high accuracy for predicting post-LT HCC recurrence, further supporting RETREAT-guided post-LT HCC surveillance and care.
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Affiliation(s)
- P Jonathan Li
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA
| | - Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Darine Daher
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Felipe Gaviria
- Department of Surgery, HPB Surgical Oncology and Multi-Organ Transplant Program, University Health Network, University of Toronto, Ontario, Canada
| | - Veeral Ajmera
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California, USA
| | - Eleazar E Montalvan-Sanchez
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | | | - Kali Zhou
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Fanny Delebecque
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California, USA
| | - Nicole Garcia
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Bethany Barrick
- Scripps Center for Organ Transplantation, La Jolla, California, USA
| | - Christopher Wong
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Lauren Nephew
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - John Holden
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Shravan Dave
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California, USA
| | - Gabriel T Schnickel
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, University of California San Diego, San Diego, California, USA
| | - Nicole E Rich
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Sander S Florman
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Gonzalo Sapisochin
- Department of Surgery, HPB Surgical Oncology and Multi-Organ Transplant Program, University Health Network, University of Toronto, Ontario, Canada
| | - Francis Yao
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Neil Mehta
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA
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Hassanain H, Connor AA, Brombosz EW, Patel K, Elaileh A, Basra T, Kodali S, Victor DW, Simon CJ, Cheah YL, Hobeika MJ, Mobley CM, Saharia A, Dhingra S, Schwartz M, Maqsood A, Heyne K, Kaseb AO, Vauthey JN, Gaber AO, Abdelrahim M, Ghobrial RM. Sorafenib as Adjuvant Therapy Post-Liver Transplant: A Single-center Experience. Transplant Direct 2025; 11:e1746. [PMID: 39866680 PMCID: PMC11759322 DOI: 10.1097/txd.0000000000001746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/11/2024] [Accepted: 10/31/2024] [Indexed: 01/28/2025] Open
Abstract
Background Hepatocellular carcinoma (HCC) has a rising incidence and mortality in North America. Liver transplantation (LT) with adjunctive therapies offers excellent outcomes. However, HCC recurrences are associated with high mortality. We investigate whether adjuvant systemic therapy can reduce recurrence, as shown with other malignancies. Methods Medical records of patients undergoing LT for HCC at a single center between January 2016 and December 2022 were retrospectively reviewed. Patients were stratified into 3 groups: (1) recipients of adjuvant sorafenib, (2) nonrecipients at high recurrence risk, and (3) nonrecipients at low risk by explant pathology features. The outcomes were overall survival (OS) and recurrence-free survival (RFS). Adjuvant sorafenib recipients were also propensity score matched 1:2 to nonadjuvant recipients based on recurrence risk features. Results During the study period, 273 patients with HCC underwent LT and 16 (5.9%) received adjuvant sorafenib therapy. Adjuvant sorafenib recipients were demographically similar to nonrecipients and, on explant pathology, had greater tumor burden, lymphovascular invasion, and poorer differentiation (all P < 0.001). Adverse events were observed in 12 adjuvant sorafenib recipients (75%). OS was similar among the 3 groups (P = 0.2), and adjuvant sorafenib was not associated with OS in multivariable analysis (hazard ratio, 1.31; 95% confidence interval, 0.45-3.78; P = 0.62). RFS was significantly lower in sorafenib patients (hazard ratio, 6.99; 95% confidence interval, 2.12-23.05; P = 0.001). Following propensity matching, adjuvant sorafenib use was not associated with either OS (P = 0.24) or RFS rates (P = 0.65). Conclusions In this single-center analysis, adjuvant sorafenib was not associated with OS. Recipients were observed to have shorter RFS, likely due to the increased prevalence of high-risk features, and sorafenib use was associated with high frequencies of adverse events.
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Affiliation(s)
- Hala Hassanain
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ashton A. Connor
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | | | - Khush Patel
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Ahmed Elaileh
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Tamneet Basra
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Sudha Kodali
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - David W. Victor
- Department of Medicine, Houston Methodist Hospital, Houston, TX, USA
| | | | - Yee Lee Cheah
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Mark J. Hobeika
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | | | - Ashish Saharia
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Sadhna Dhingra
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Mary Schwartz
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Anaum Maqsood
- Dr. Mary and Ron Neal Cancer Center, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Kirk Heyne
- Dr. Mary and Ron Neal Cancer Center, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - Ahmed O. Kaseb
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX
| | - A. Osama Gaber
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Maen Abdelrahim
- Dr. Mary and Ron Neal Cancer Center, Department of Medicine, Houston Methodist Hospital, Houston, TX
| | - R. Mark Ghobrial
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
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Garcia KB, Hussein A, Satish S, Wehrle CJ, Karakaya O, Panconesi R, Sun K, Jiao C, Fernandes E, Pinna A, Hashimoto K, Miller C, Aucejo F, Schlegel A. Machine Perfusion as a Strategy to Decrease Ischemia-Reperfusion Injury and Lower Cancer Recurrence Following Liver Transplantation. Cancers (Basel) 2024; 16:3959. [PMID: 39682147 DOI: 10.3390/cancers16233959] [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: 08/05/2024] [Revised: 11/12/2024] [Accepted: 11/13/2024] [Indexed: 12/18/2024] Open
Abstract
Liver transplantation (LT) is a key treatment for primary and secondary liver cancers, reducing tumor burden with concurrent improvement of liver function. While significant improvement in survival is noted with LT, cancer recurrence rates remain high. Mitochondrial dysfunction caused by ischemia-reperfusion injury (IRI) is known to drive tumor recurrence by creating a favorable microenvironment rich in pro-inflammatory and angiogenic factors. Therefore, strategies that decrease reperfusion injury and mitochondrial dysfunction may also decrease cancer recurrence following LT. Machine perfusion techniques are increasingly used in routine clinical practice of LT with improved post-transplant outcomes and increased use of marginal grafts. Normothermic (NMP) and hypothermic oxygenated machine perfusion (HOPE) provide oxygen to ischemic tissues, and impact IRI and potential cancer recurrence through different mechanisms. This article discussed the link between IRI-associated inflammation and tumor recurrence after LT. The current literature was screened for the role of machine perfusion as a strategy to mitigate the risk of cancer recurrence. Upfront NMP ("ischemia free organ transplantation") and end-ischemic HOPE were shown to reduce hepatocellular carcinoma recurrence in retrospective studies. Three prospective randomized controlled trials are ongoing in Europe to provide robust evidence on the impact of HOPE on cancer recurrence in LT.
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Affiliation(s)
- Karla Bracho Garcia
- Department of Liver Transplantation, Cleveland Clinic Weston Hospital, Weston, FL 33331, USA
| | - Ahmed Hussein
- Department of Liver Transplantation, Cleveland Clinic Weston Hospital, Weston, FL 33331, USA
| | - Sangeeta Satish
- Transplantation Center, Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Chase J Wehrle
- Transplantation Center, Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Omer Karakaya
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Rebecca Panconesi
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Keyue Sun
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Chunbao Jiao
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Eduardo Fernandes
- Department of Liver Transplantation, Cleveland Clinic Weston Hospital, Weston, FL 33331, USA
| | - Antonio Pinna
- Department of Liver Transplantation, Cleveland Clinic Weston Hospital, Weston, FL 33331, USA
| | - Koji Hashimoto
- Transplantation Center, Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Charles Miller
- Transplantation Center, Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Federico Aucejo
- Transplantation Center, Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Andrea Schlegel
- Transplantation Center, Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
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Lu X, Zhu Q, Cai J, Yang Z, Gu G, Pang L, Su M, Zhang F, Lin H, Wu W, Xu L, Liu C. Pretransplant immunotherapy increases acute rejection yet improves survival outcome of HCC patients with MVI post-liver transplantation. Cancer Immunol Immunother 2024; 74:18. [PMID: 39527136 PMCID: PMC11554970 DOI: 10.1007/s00262-024-03853-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 10/01/2024] [Indexed: 11/16/2024]
Abstract
Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as the most promising strategy for hepatocellular carcinoma (HCC) downstaging prior to liver transplantation (LT). However, further evidence is required to assess the feasibility and safety of pretransplant ICI exposure. We retrospective analyzed 159 HCC patients who underwent LT at our institution from June 2019 to December 2023, and 39 recipients (39/159, 24.5%) received pretransplant ICI therapy. The perioperative acute rejection rate and rejection-related mortality rate in the ICI group were 23.1% (9/39) and 12.8% (5/39), respectively, which were significantly higher than those in the non-ICI group, at 5% (6/120, P = 0.002) and 0% (0/120, P = 0.001). There was no significant difference in the 90-day post-transplant overall survival (OS) (P = 0.447) and recurrence-free survival (RFS) (P = 0.723) between these two groups. We found 37.1% (59/159) recipients were found to have microvascular invasion (MVI), no matter whether the HCC tumor is within Milan criteria or not. Notably, though MVI was identified as a risk factor for the LT recipients, pretransplant ICI exposure appeared to be a protective factor for HCC patients with MVI which benefits its overall survival. Besides, the RFS and OS in the ICI exposure recipients with MVI were comparable to the non-ICI exposure recipients without MVI. However, no synergistic anti-tumor effects were observed with pretransplant ICI immunotherapy when combined with locoregional of TACE, HAIC, RFA and systematic of lenvatinib or sorafenib downstaging treatments, nor with post-transplant adjuvant of systematic or FOLFOX chemotherapy. Further comprehensive studies are needed to balance the dual natural effects of immunotherapy by optimizing downstaging protocols and patient selection to reduce acute rejection and improve long-term survival.
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Affiliation(s)
- Xinjun Lu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Qi Zhu
- Department of Pancreatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Junfeng Cai
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Zuozhong Yang
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Guangxiang Gu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Li Pang
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Mingye Su
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Fapeng Zhang
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Haoming Lin
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Wenrui Wu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Leibo Xu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Chao Liu
- Department of Pancreatic-Biliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
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Li PJ, Shah S, Mehta N. Recent Advances in Liver Transplantation for Hepatocellular Carcinoma. Curr Treat Options Oncol 2024; 25:1153-1162. [PMID: 39085572 PMCID: PMC11416390 DOI: 10.1007/s11864-024-01247-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2024] [Indexed: 08/02/2024]
Abstract
OPINION STATEMENT Liver transplantation for hepatocellular carcinoma (HCC) remains an evolving field. Major challenges HCC transplant patients face today include liver organ donor shortages and the need for both better pre-transplant bridging/downstaging therapies and post-transplant HCC recurrence treatment options. The advent of immunotherapy and the demonstrated efficacy of immune checkpoint inhibitors in multiple solid tumors including advanced/unresectable HCC hold promise in expanding both the neoadjuvant and adjuvant HCC transplant treatment regimen, though caution is needed with these immune modulating agents leading up to and following transplant. New options for pre-transplant HCC management will expand access to this curative option as well as ensure patients have adequate control of their HCC prior to transplant to maximize the utility of a liver donor. Machine perfusion has been an active area of investigation in recent years and could expand the organ donor pool, helping address current liver donor shortages. Finally, additional HCC biomarkers such as AFP-L3 and DCP have shown promise in improving risk stratification of HCC patients. Together, these three recent advancements will likely alter HCC transplant guidelines in the coming years.
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Affiliation(s)
- P Jonathan Li
- University of California San Francisco School of Medicine, 533 Parnassus Avenue, San Francisco, CA, 94143, USA.
| | - Sachin Shah
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
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Mukthinuthalapati VVPK, Gupta S. Growing need of adjuvant therapy and expanded access for liver transplant in hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2023; 11:32. [PMID: 36819559 PMCID: PMC9929753 DOI: 10.21037/atm-22-5875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 12/16/2022] [Indexed: 02/03/2023]
Affiliation(s)
| | - Shweta Gupta
- Department of Medicine Quality Council, John H Stroger Jr. Hospital of Cook County, Chicago, IL, USA
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Deng Y, Yang J, Chen Y, Wang J, Fu B, Zhang T, Yi S, Yang Y. Development of a Risk Classifier to Predict Tumor Recurrence and Lenvatinib Benefits in Hepatocellular Carcinoma After Liver Transplantation. Transplant Proc 2023; 55:153-163. [PMID: 36522222 DOI: 10.1016/j.transproceed.2022.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 10/22/2022] [Accepted: 11/16/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Current selection tools were not precise enough to predict recurrence of hepatocellular carcinoma (HCC) and benefit of adjuvant lenvatinib for patients who received liver transplant (LT) for HCC. Thus, we aim at developing a risk classifier to predict recurrence of HCC and benefit of adjuvant Lenvatinib for those who underwent LT for HCC. METHODS Cox regression model was applied to selected predictors and created the final model in a training cohort of 287 patients who underwent LT for HCC, which was tested in an internal validation cohort of 72 patients by using C-statistic and net classification index (NRI) compared with the following HCC selection criteria: the Milan criteria, the Up-to-7 criteria, and the University of California, San Francisco criteria. RESULTS We built a Risk Classifier of South China Cohort (RCOSC) based on 4 variables: the maximum diameter plus number of viable tumors, alpha-fetoprotein, microvascular invasion, and highest alanine aminotransferase in 7 days after LT. In validation analyses, our RCOSC showed good predictive performance (C-statistic, 0.866; 95% confidence interval [CI], 0.833-0.899) and had better prognostic value than Milan criteria (NRI, 0.406; P < .001), University of California, San Francisco (NRI, 0.497; P < .001), and Up-to-7 (NRI, 0.527; P < .001). By applying the RCOSC, we were able to accurately categorize patients into high-risk and low-risk groups. Further survival analysis revealed that the patients in the high-risk group might have a better therapeutic response to preventive regimen of lenvatinib after LT for HCC (hazard ratio, 0.38; 95% CI, 0.161-0.871, P = .018). CONCLUSIONS Our RCOSC presented favorable predictive performance for HCC recurrence. It might be capable of sifting out patients who benefit from adjuvant therapy after LT for HCC, providing a reliable tool for precise clinical decision-making of patients with HCC with LT.
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Affiliation(s)
- Yinan Deng
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jianming Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yewu Chen
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiangfeng Wang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Binsheng Fu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Tong Zhang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuhong Yi
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
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Zeng ZM, Mo N, Zeng J, Ma FC, Jiang YF, Huang HS, Liao XW, Zhu GZ, Ma J, Peng T. Advances in postoperative adjuvant therapy for primary liver cancer. World J Gastrointest Oncol 2022; 14:1604-1621. [PMID: 36187393 PMCID: PMC9516643 DOI: 10.4251/wjgo.v14.i9.1604] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 05/13/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.
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Affiliation(s)
- Zhi-Ming Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ning Mo
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yan-Feng Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hua-Sheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Sun Y, Zhang W, Bi X, Yang Z, Tang Y, Jiang L, Bi F, Chen M, Cheng S, Chi Y, Han Y, Huang J, Huang Z, Ji Y, Jia L, Jiang Z, Jin J, Jin Z, Li X, Li Z, Liang J, Liu L, Liu Y, Lu Y, Lu S, Meng Q, Niu Z, Pan H, Qin S, Qu W, Shao G, Shen F, Song T, Song Y, Tao K, Tian A, Wang J, Wang W, Wang Z, Wu L, Xia F, Xing B, Xu J, Xue H, Yan D, Yang L, Ying J, Yun J, Zeng Z, Zhang X, Zhang Y, Zhang Y, Zhao J, Zhou J, Zhu X, Zou Y, Dong J, Fan J, Lau WY, Sun Y, Yu J, Zhao H, Zhou A, Cai J. Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements. Liver Cancer 2022; 11:192-208. [PMID: 35949289 PMCID: PMC9218612 DOI: 10.1159/000521596] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 12/15/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. SUMMARY For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. KEY MESSAGES Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.
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Affiliation(s)
- Yongkun Sun
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhengqiang Yang
- Department of Interventional Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Tang
- Department of GCP Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Jiang
- Department of Diagnostic Imaging, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Bi
- Department of Medical Oncology, West China Hospital, Chengdu, China
| | - Minshan Chen
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shuqun Cheng
- The Six Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Yihebali Chi
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Han
- Department of Interventional Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Huang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Liqun Jia
- Department of Oncology of Integrative Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Zhichao Jiang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Jin
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhengyu Jin
- Department of Radiology, Peking Union Medical College Hospital, Beijing, China
| | - Xiao Li
- Department of Interventional Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhiyu Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, China
| | - Lianxin Liu
- Department of Hepatic Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Yunpeng Liu
- Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yinying Lu
- Department of Comprehensive Liver Cancer Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shichun Lu
- Department of Hepatobiliary Surgery, First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Chinese PLA Medical School, Beijing, China
| | - Qinghua Meng
- Department of Clinical Care Medicine of Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Zuoxing Niu
- Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan, China
| | - Hongming Pan
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Shukui Qin
- Department of Medical Oncology, PLA Cancer Centre of Nanjing Bayi Hospital, Nanjing, China
| | - Wang Qu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guoliang Shao
- Department of Interventional Radiology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
| | - Feng Shen
- Department of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Tianqiang Song
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yan Song
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Aiping Tian
- Department of Traditional Chinese Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianhua Wang
- Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Wenling Wang
- Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital, Guiyang, China
| | - Zhe Wang
- Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Liqun Wu
- Department of Hepatic Biliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Feng Xia
- Department of Hepatobiliary Surgery, The Southwest Hospital of AMU, Chongqing, China
| | - Baocai Xing
- Department of Hepatobiliary and Pancreatic Surgery Unit I, Beijing Cancer Hospital, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Huadan Xue
- Department of Radiology, Peking Union Medical College Hospital, Beijing, China
| | - Dong Yan
- Department of Interventional Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lin Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingping Yun
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhaochong Zeng
- Department of Radiology, Zhongshan Hospital Fudan University, Shanghai, China
| | - Xuewen Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, China
| | - Yanqiao Zhang
- Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yefan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Zhu
- Department of Interventional Radiology, Beijing Cancer Hospital, Beijing, China
| | - Yinghua Zou
- Department of Interventional Radiology, Peking University First Hospital, Beijing, China
| | - Jiahong Dong
- Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - Wan Yee Lau
- Department of Hepatic Biliary Pancreatic Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Yan Sun
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jinming Yu
- Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Taian, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Aiping Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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10
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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11
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Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managing recurrence for patients undergoing LT for HCC. AREAS COVERED In this review, we will provide an overview of methods of patient risk stratification in the post-transplant period, the data around surveillance for HCC recurrence, and the evidence for and against post-LT adjuvant treatment strategies. Finally, we will provide data regarding treatment options for patients with HCC recurrence after LT. Using an extensive search of original papers and society guidelines, this paper provides a comprehensive review of the data for assessing risk and managing recurrence for patients undergoing LT for HCC. EXPERT OPINION The development of multiple post-transplant prognostic scoring systems have allowed for improved assessment of recurrence risk and stratification of patients. However, the ability to translate this information into surveillance and therapeutic strategies that improve patient outcomes still have to be fully demonstrated. Post-LT immunosuppression strategies have been implemented in order to attempt to reduce this risk. Evidence-based strategies for managing recurrent HCC are evolving. We expect that with further understanding of individual patient characteristics will allow for optimal therapeutic selection.
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Affiliation(s)
- Daniel Hoffman
- Department of Surgery, University of California , San Francisco, CA, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California , San Francisco, CA, USA
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12
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Han B, Ding H, Zhao S, Zhang Y, Wang J, Zhang Y, Gu J. Potential Role of Adjuvant Lenvatinib in Improving Disease-Free Survival for Patients With High-Risk Hepatitis B Virus-Related Hepatocellular Carcinoma Following Liver Transplantation: A Retrospective, Case Control Study. Front Oncol 2020; 10:562103. [PMID: 33365268 PMCID: PMC7750628 DOI: 10.3389/fonc.2020.562103] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 11/04/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND AND AIM Although liver transplantation (LT) is one of the most effective treatments for the patients with hepatocellular carcinoma (HCC), the high-risk patients suffer from a high ratio of tumor recurrence after LT. Lenvatinib, as a novel targeted drug, has shown an excellent effect in the treatment of advanced HCC, but there is no study on its effect in preventing HCC recurrence in the patients undergoing transplantation. Therefore, this study was designed to evaluate the role of adjuvant lenvatinib in preventing recurrence of high-risk LT recipients with HBV-related HCC. METHODS We retrospectively analyzed 23 high-risk patients consisting of lenvatinib group (n=14) and control group (n=9) with HBV-related HCC who underwent LT in our center. Disease-free survival (DFS) and HCC recurrence of the two groups were compared. The adverse events (AEs) and drug tolerance of lenvatinib were evaluated. RESULTS The median DFS in lenvatinib group was 291 (95%CI 204-516) days, significantly longer than 182 (95%CI 56-537) days in control group (P=0.04). Three patients in lenvatinib group (21.4%) and five patients in control group (55.6%) had short-term HCC recurrence (P=0.11). All patients in lenvatinib group could tolerate oral lenvatinib for at least three cycles except six cases (42.9%) of dose reduction and 1 case of interruption (14.3%). Thirteen patients (92.9%) taking lenvatinib experienced AEs. The most common AEs were hypertension (64.3%) and proteinuria (42.9%), and the most serious AEs were Grade 3 for 4 cases (28.5%) according to common terminology criteria for adverse events (CTCAE) version 5.0. Additionally, no influence of lenvatinib on the dosage and blood concentration of FK506 was observed. CONCLUSIONS Adjuvant lenvatinib had a potential benefit on prolonging the DFS and reducing the recurrence of high-risk HBV-related HCC patients following liver transplantation with an acceptable drug safety and patient tolerance.
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Affiliation(s)
- Bing Han
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Han Ding
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuai Zhao
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yichi Zhang
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian Wang
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yue Zhang
- Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Jinyang Gu
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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13
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Verna EC, Patel YA, Aggarwal A, Desai AP, Frenette C, Pillai AA, Salgia R, Seetharam A, Sharma P, Sherman C, Tsoulfas G, Yao FY. Liver transplantation for hepatocellular carcinoma: Management after the transplant. Am J Transplant 2020; 20:333-347. [PMID: 31710773 DOI: 10.1111/ajt.15697] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/03/2019] [Accepted: 10/21/2019] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.
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Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University, New York, New York, USA
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Avin Aggarwal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tuscon, Arizona, USA
| | - Archita P Desai
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Catherine Frenette
- Scripps Center for Organ Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Anjana A Pillai
- Center for Liver Diseases, University of Chicago Medicine, Chicago, Illinois, USA
| | - Reena Salgia
- Department of Gastroenterology/Hepatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Anil Seetharam
- Transplant Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Pratima Sharma
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Courtney Sherman
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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14
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Wang D, Jia W, Wang Z, Wen T, Ding W, Xia F, Zhang L, Wu F, Peng T, Liu B, Zhou C, Zheng Q, Miao X, Peng J, Huang Z, Dou K. Retrospective analysis of sorafenib efficacy and safety in Chinese patients with high recurrence rate of post-hepatic carcinectomy. Onco Targets Ther 2019; 12:5779-5791. [PMID: 31410023 PMCID: PMC6643495 DOI: 10.2147/ott.s168447] [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] [Received: 03/16/2018] [Accepted: 01/17/2019] [Indexed: 02/05/2023] Open
Abstract
Background: There is no guideline recommendation for preventing hepatocellular carcinoma (HCC) recurrence after hepatic resection. Moreover, an unmet need exists on the effectiveness of sorafenib therapy in recurrent HCC. Purpose: We therefore assessed the efficacy and safety of sorafenib in Chinese HCC patients with high risk of recurrence. Patients and methods: Data were collected retrospectively from 15 Chinese research centers from January 1, 2012 to November 15, 2013, by chart reviews of patients with moderate-advanced HCC who received hepatic carcinectomy. The primary end point was recurrence-free survival rate at 1 year in patients with a high recurrence risk. Secondary end points included 1-year survival rate, time to recurrence and safety assessment. Results: A total of 209 high-risk patients (sorafenib, n=98; control, n=111) who underwent carcinectomy were analyzed. There was no significant difference in the proportion of patients with recurrence-free survival at 1 year between the sorafenib and control (70.43% vs 68.90%: χ2=0.007, P=0.934). One-year survival rate was significantly higher with sorafenib than observed with control (95.5% vs 83.35%; χ2=7.441, P=0.006). Time to recurrence between sorafenib and control groups was similar. Incidences of all the adverse events (AEs) were similar in both the groups and transaminase elevation was most common in both groups (20.37% vs 24.79%). Thrombocytopenia incidence was significantly lower with the sorafenib group than with control (1.85% vs 9.40%; P=0.015). Conclusion: Sorafenib may be considered as a feasible option in the treatment of HCC recurrence.
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Affiliation(s)
- Desheng Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, Shaanxi, China
| | - Weridong Jia
- Department of Hepatobiliary Surgery, Anhui Provincial Hospital, Hefei, China
| | - Zhiming Wang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Changsha, China
| | - Tianfu Wen
- Department of Hepatobiliary Surgery, West China Hospital, Chengdu, China
| | - Wei Ding
- Department of Hepatobiliary Surgery, Cancer Hospital of Xinjiang, Urumqi, China
| | - Feng Xia
- Department of Hepatobiliary Surgery, Southwest Hospital, Chongqing, China
| | - Ling Zhang
- Department of Hepatobiliary Surgery, Cancer Hospital of Henan, Zhengzhou, China
| | - Feixiang Wu
- Department of Hepatobiliary Surgery, Cancer Hospital of Guangxi Medical University, Nanning, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Bin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Cuncai Zhou
- Department of Hepatobiliary Surgery, Cancer Hospital of Jiangxi, Nanchang, China
| | - Qichang Zheng
- Department of Hepatobiliary Surgery, Wuhan Union Hospital, Wuhan, China
| | - Xiongying Miao
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xiangya, Changsha, China
| | - Junping Peng
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of Sichuan, Chengdu, China
| | - Zhiyong Huang
- Department of Hepatobiliary Surgery, Wuhan Tongji Hospital, Wuhan, China
| | - Kefeng Dou
- Department of Hepatobiliary Surgery, Xijing Hospital, Shaanxi, China
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15
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Chapman WC, Korenblat KM, Fowler KJ, Saad N, Khan AS, Subramanian V, Doyle MBM, Dageforde LA, Tan B, Grierson P, Lin Y, Xu M, Brunt EM. Hepatocellular carcinoma: Where are we in 2018? Curr Probl Surg 2018; 55:450-503. [PMID: 30526875 DOI: 10.1067/j.cpsurg.2018.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- William C Chapman
- Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO.
| | - Kevin M Korenblat
- Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO
| | | | - Nael Saad
- University of Rochester, Rochester, NY
| | - Adeel S Khan
- Division of Abdominal Transplant Surgery, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO
| | - Vijay Subramanian
- Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO
| | - Maria B Majella Doyle
- Barnes-Jewish Hospital, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO
| | - Leigh Anne Dageforde
- Harvard Medical School, Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA
| | - Benjamin Tan
- Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO
| | - Patrick Grierson
- Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO
| | - Yiing Lin
- Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO
| | - Min Xu
- Department of Surgery, Washington University School of Medicine, St. Louis, MO
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16
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Satapathy SK, Das K, Kocak M, Helmick RA, Eason JD, Nair SP, Vanatta JM. No apparent benefit of preemptive sorafenib therapy in liver transplant recipients with advanced hepatocellular carcinoma on explant. Clin Transplant 2018; 32:e13246. [PMID: 29577449 DOI: 10.1111/ctr.13246] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Sorafenib has shown survival benefits in patients with advanced HCC; however, limited data are available on its role in OLT recipients with advanced HCC in the explant. AIM Evaluate the role of preemptive sorafenib therapy on HCC recurrence and survival after OLT with advanced HCC on explant pathology. METHODS We retrospectively reviewed the outcome after OLT of all HCC recipients with advanced HCC in the explant pathology from 04/2006 to 12/2012 based on preemptive treatment with sorafenib. RESULTS During the observation period, 217 HCC recipients underwent OLT; 50 explants revealed advanced HCC. After exclusion of 5 patients who were lost to follow-up, 45 LT recipients were finally included for analysis. Recipients were grouped as sorafenib Gr (N = 25) and nonsorafenib Gr (N = 20). Both recurrence-free survival (RFS) (P = .67) and overall survival were similar between groups (P = .53) on Kaplan-Meier analysis. Additionally, sorafenib use was neither associated with HCC recurrence-free survival (HR 0.74, 95% CI [0.32-1.70]; P = .48) nor overall survival (HR 0.92, 95% CI [0.39-2.15], P = .84) on multivariate Cox proportional hazard model with sorafenib use as time-varying covariates. CONCLUSION Preemptive treatment with sorafenib in OLT recipients with high-risk features in explant does not improve HCC recurrence-free or overall survival.
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Affiliation(s)
- Sanjaya K Satapathy
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Kanak Das
- Division of Gastroenterology, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Mehmet Kocak
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Ryan A Helmick
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - James D Eason
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Satheesh P Nair
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Jason M Vanatta
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
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17
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Costentin CE, Amaddeo G, Decaens T, Boudjema K, Bachellier P, Muscari F, Salamé E, Bernard PH, Francoz C, Dharancy S, Vanlemmens C, Radenne S, Dumortier J, Hilleret MN, Chazouillères O, Pageaux GP, Calderaro J, Laurent A, Roudot-Thoraval F, Duvoux C. Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models. Liver Int 2017; 37:717-726. [PMID: 28199760 DOI: 10.1111/liv.13388] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 02/08/2017] [Indexed: 12/17/2022]
Abstract
AIM Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. METHODS Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. RESULTS Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17). CONCLUSION Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT.
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Affiliation(s)
| | | | - Thomas Decaens
- Service d'hépatologie, CHU Grenoble Alpes, Grenoble, France
| | - Karim Boudjema
- Service de Chirurgie digestive, Hôpital Pontchaillou, Rennes, France
| | | | - Fabrice Muscari
- Service de Chirurgie digestive, Hôpital Rangueil, Toulouse, France
| | - Ephrem Salamé
- Service de Chirurgie digestive, CHU de Tours, Chambray-lès-Tours, France
| | | | | | | | | | - Sylvie Radenne
- Service d'hépatologie, Hôpital Lyon Croix Rousse, Lyon, France
| | - Jérôme Dumortier
- Service d'hépatologie, Hospices Civiles de Lyon, Hôpital Edouard Herriot, Lyon, France
| | | | | | | | - Julien Calderaro
- Département de Pathologie, Hôpital Henri Mondor, Créteil, France
| | - Alexis Laurent
- Service de Chirurgie digestive, Hôpital Henri Mondor, Créteil, France
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18
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Kim SS, Kang TW, Song KD, Cho SK, Lee MW, Rhim H, Sinn DH, Jung SH. Radiofrequency ablation and transarterial chemoembolisation as first-line treatment for recurrent hepatocellular carcinoma or isolated intrahepatic recurrent hepatocellular carcinoma in transplanted livers. Clin Radiol 2016; 72:141-149. [PMID: 27742104 DOI: 10.1016/j.crad.2016.09.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 08/09/2016] [Accepted: 09/08/2016] [Indexed: 12/30/2022]
Abstract
AIM To evaluate the efficacy of radiofrequency ablation (RFA) and transarterial chemoembolisation (TACE) as a first-line treatment for isolated intrahepatic recurrent hepatocellular carcinoma (IIR-HCC) after liver transplantation (LT). MATERIALS AND METHODS This retrospective study was approved by the institutional review board. Between January 2005 and January 2015, 588 consecutive patients underwent LT for the treatment of HCC. Among them, 27 patients with IIR-HCCs after LT who were treated with RFA (n=6) or TACE (n=21) as a first-line treatment were retrospectively included in this study. Disease-free and overall survival rates were estimated using the Kaplan-Meier method. Risk factors affecting these outcomes were assessed with Cox regression models. RESULTS Except for the total number of recurrent tumours and time-to-tumour recurrence after LT, baseline characteristics were not significantly different between the groups. The 2-year disease-free survival rates for RFA and TACE (20% versus 14%, respectively; p=0.180) and 4-year overall survival rates (33% versus 25%, respectively; p=0.065) were not significantly different between groups. In addition, the types of treatment were not associated with disease-free or overall survival in multivariate analyses. CONCLUSION TACE may be an effective treatment comparable to RFA in patients with IIR-HCC after LT when RFA is not feasible.
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Affiliation(s)
- S S Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - T W Kang
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - K D Song
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - S K Cho
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - M W Lee
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - H Rhim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - D H Sinn
- Division of Hepatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - S-H Jung
- Biostatics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan Univeristy, Seoul, Republic of Korea
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19
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Gadaleta-Caldarola G, Infusino S, Divella R, Ferraro E, Mazzocca A, De Rose F, Filippelli G, Abbate I, Brandi M. Sorafenib: 10 years after the first pivotal trial. Future Oncol 2016; 11:1863-80. [PMID: 26161924 DOI: 10.2217/fon.15.85] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors.
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Affiliation(s)
- Gennaro Gadaleta-Caldarola
- Medical Oncology Unit, 'Mons. R Dimiccoli' Hospital, Viale Ippocrate, 15, 76121 Barletta, Asl BAT, Italy
| | - Stefania Infusino
- Medical Oncology Unit, 'S Francesco di Paola' Hospital, Via Promintesta, 87027 Paola, ASP, Cosenza, Italy
| | - Rosa Divella
- Laboratory of Clinical and Experimental Pathology - National Cancer Institute 'Giovanni Paolo II', Viale Orazio Flacco 65, 70124, Bari, Italy
| | - Emanuela Ferraro
- Department of Internal Medicine & Clinical Specialties, University of Rome 'La Sapienza', Policlinico Umberto I, Viale del Policlinico, 155, 00161 Roma, Italy
| | - Antonio Mazzocca
- Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G Cesare, 11,70124 Bari, Italy, National Institute for Digestive Diseases, IRCCS 'Saverio De Bellis', Via Turi 27, 70013, Castellana Grotte, Bari, Italy
| | | | - Gianfranco Filippelli
- Medical Oncology Unit, 'S Francesco di Paola' Hospital, Via Promintesta, 87027 Paola, ASP, Cosenza, Italy
| | - Ines Abbate
- Laboratory of Clinical and Experimental Pathology - National Cancer Institute 'Giovanni Paolo II', Viale Orazio Flacco 65, 70124, Bari, Italy
| | - Mario Brandi
- Medical Oncology Unit, 'Mons. R Dimiccoli' Hospital, Viale Ippocrate, 15, 76121 Barletta, Asl BAT, Italy
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20
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Khorsandi SE, Heaton N. Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence. Transl Gastroenterol Hepatol 2016; 1:25. [PMID: 28138592 DOI: 10.21037/tgh.2016.03.18] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Accepted: 02/01/2016] [Indexed: 12/12/2022] Open
Abstract
The introduction of liver transplant listing criteria for hepatocellular cancer (HCC) has significantly improved oncological outcomes and survival. But despite this HCC recurrence is still problematic. There is emerging evidence that the choice of immunosuppression (IS) after transplant for HCC can influence oncological survival and HCC recurrence. The following is a short summary of what has been published on HCC recurrence with the different classes of immunosuppressive agents in present use, concluding with the possible rationalization of the use of these immunosuppressive agents in the post-transplant patient at high risk of recurrence.
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Affiliation(s)
- Shirin Elizabeth Khorsandi
- Institute of Liver Studies, King's Healthcare Partners at Denmark Hill, King's College Hospital NHSFT, London, SE5 9RS, UK
| | - Nigel Heaton
- Institute of Liver Studies, King's Healthcare Partners at Denmark Hill, King's College Hospital NHSFT, London, SE5 9RS, UK
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21
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Zhang W. Sorafenib in adjuvant setting: call for precise and personalized therapy. Transl Gastroenterol Hepatol 2016; 1:13. [PMID: 28138580 DOI: 10.21037/tgh.2016.03.13] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 02/05/2016] [Indexed: 12/30/2022] Open
Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
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22
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Fahrner R, Dondorf F, Ardelt M, Dittmar Y, Settmacher U, Rauchfuß F. Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival. World J Gastroenterol 2015; 21:12071-12082. [PMID: 26576092 PMCID: PMC4641125 DOI: 10.3748/wjg.v21.i42.12071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 08/04/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.
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23
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Zhang W, Zhao G, Wei K, Zhang Q, Ma W, Song T, Wu Q, Zhang T, Kong D, Li Q. Adjuvant sorafenib reduced mortality and prolonged overall survival and post-recurrence survival in hepatocellular carcinoma patients after curative resection: a single-center experience. Biosci Trends 2015; 8:333-8. [PMID: 25641180 DOI: 10.5582/bst.2014.01120] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Adjuvant therapy after resection of hepatocellular carcinoma (HCC) is limited. Here, we evaluated the effects of postoperative sorafenib on recurrence and survival in HCC patients. Recurrence-free survival and overall survival were analyzed as the main endpoint, recurrence rate, and mortality rate were analyzed as second endpoint. Furthermore, post-recurrence survival was also analyzed. Clinicopathological factors were compared between sorafenib and control groups. Seventy-eight patients were eligible for final data analysis (46 in control group; 32 in sorafenib group). Sorafenib did not significantly prolong recurrence-free survival (11.0 months in the control group vs. 11.7 months in the sorafenib group, p = 0.702), but significantly prolonged overall survival (32.4 vs. 25.0 months, p = 0.046). Sorafenib did not reduce recurrence rate (67.7% vs. 78.3%, p = 0.737), but significantly reduced mortality rate (28.1% vs. 60.9%, p = 0.004). The increased post-recurrence survival (22.2 vs. 4.4 months, p = 0.003) may have contributed to the survival benefit after recurrence in the sorafenib group. Adjuvant sorafenib did not decrease tumor recurrence, but significantly reduced mortality and prolonged overall survival of HCC patients after curative resection, probably by inhibiting tumor growth after tumor recurrence.
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Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical ResearchCenter for Cancer and Key Laboratory of Cancer Prevention and Therapy
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24
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Kiroplastis K, Fouzas I, Katsiki E, Patsiaoura K, Daoudaki M, Komninou A, Xolongitas E, Katsika E, Kaidoglou K, Papanikolaou V. The effect of sorafenib on liver regeneration and angiogenesis after partial hepatectomy in rats. Hippokratia 2015; 19:249-255. [PMID: 27418785 PMCID: PMC4938473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
BACKGROUND Liver regeneration is vital for the survival of patients submitted to extensive liver resection as a treatment of hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor of angiogenesis and cell division, both of which are integral components of liver regeneration. We investigated the effect of preoperative treatment with sorafenib, a drug used for the treatment of HCC, on liver regeneration and angiogenesis in healthy rats, after two-thirds partial hepatectomy (PH2/3). METHODS In total 48 Wistar rats received intragastric injections of sorafenib (30 mg/kg/d) or vehicle, underwent PH2/3, and were sacrificed at 48, 96 or 168 hours after that. The regenerative index of the liver remnant was studied, as well as the mitotic index. DNA synthesis and angiogenesis were estimated by immunohistochemistry for the Ki-67 and CD34 antigens, respectively. RESULTS Sorafenib reduced significantly the regenerative index at all time points but not the mitotic index at 48, 96 or 168 hours. Deoxyribonucleic acid (DNA) synthesis and angiogenesis were not affected significantly either. CONCLUSIONS Sorafenib, when administered preoperatively, reduces incompletely and transiently the regeneration of the liver after PH2/3 in rats. This could mean that sorafenib can be used as neoadjuvant treatment of patients with HCC prior to liver resection, but further experimental and clinical studies are needed to establish the safety of this treatment. Hippokratia 2015; 19 (3): 249-255.
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Affiliation(s)
- K Kiroplastis
- 5 Surgical Department, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece
| | - I Fouzas
- Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece
| | - E Katsiki
- Department of Pathology, Hippokratio General Hospital, Thessaloniki, Greece
| | - K Patsiaoura
- Department of Pathology, Hippokratio General Hospital, Thessaloniki, Greece
| | - M Daoudaki
- Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece
| | - A Komninou
- School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - E Xolongitas
- Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece
| | - E Katsika
- Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece
| | - K Kaidoglou
- Department of Histology Embryology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - V Papanikolaou
- Division of Transplantation, Department of Surgery, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki, Greece
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25
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Lin HS, Wan RH, Gao LH, Li JF, Shan RF, Shi J. Adjuvant chemotherapy after liver transplantation for hepatocellular carcinoma: a systematic review and a meta-analysis. Hepatobiliary Pancreat Dis Int 2015; 14:236-45. [PMID: 26063023 DOI: 10.1016/s1499-3872(15)60373-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and liver transplantation (LT) is considered as the best therapeutic option for patients with HCC combined with cirrhosis. However, tumor recurrence after LT for HCC remains the major obstacle for long-term survival. The present study was to evaluate the efficacy and necessity of adjuvant chemotherapy in patients with HCC who had undergone LT. DATA SOURCES Several databases were searched to identify comparative studies fulfilling the predefined selection criteria before October 2014. Suitable studies were chosen and data extracted for meta-analysis. Three authors independently evaluated the bias of each study according to the Cochrane Handbook for Systematic Review of Intervention. Stata 12 was used for statistical analysis. Hazard ratio (HR) was considered as a summary statistic for overall survival, disease-free survival and recurrence rate. RESULTS Three prospective studies and 5 retrospective studies including 360 patients (166 in the adjuvant chemotherapy group, and 194 in the control group) were included. Compared with the control group, post-LT adjuvant chemotherapy conferred significant benefit for overall survival (HR: 0.34; 95% CI: 0.22-0.52; P=0.000). Meanwhile, the results showed an improvement for disease-free survival on favoring adjuvant chemotherapy (HR: 0.87; 95% CI: 0.78-0.95; P=0.004). However, no significant difference in HCC recurrence rate was observed between the two groups (HR: 1.26; 95% CI: 0.40-4.00; P=0.696). Descriptions of adverse events were of anecdotal nature and did not allow meta-analytic calculations. CONCLUSIONS Adjuvant chemotherapy after LT for HCC can significantly prolong patient's survival and delay the recurrence of HCC. For advanced HCC with poor differentiation, patients may perhaps benefit from the early implantation of adjuvant chemotherapy after LT.
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Affiliation(s)
- Hua-Shan Lin
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Nanchang University, Nanchang 330000, China. sj88692702@ sina.com
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26
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Guerrero-Misas M, Rodríguez-Perálvarez M, De la Mata M. Strategies to improve outcome of patients with hepatocellular carcinoma receiving a liver transplantation. World J Hepatol 2015; 7:649-661. [PMID: 25866602 PMCID: PMC4388993 DOI: 10.4254/wjh.v7.i4.649] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 12/15/2014] [Accepted: 01/15/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the only therapeutic option which allows to treat both, the hepatocellular carcinoma and the underlying liver disease. Indeed, liver transplantation is considered the standard of care for a subset of patients with cirrhosis and hepatocellular carcinoma. However, tumour recurrence rates are as high as 20%, and once the recurrence is established the therapeutic options are scarce and with little impact on prognosis. Strategies to minimize tumour recurrence and thus to improve outcome may be classified into 3 groups: (1) An adequate selection of candidates for liver transplantation by using the Milan criteria; (2) An optimized management within waiting list including prioritization of patients at high risk of tumour progression, and the implementation of bridging therapies, particularly when the expected length within the waiting list is longer than 6 mo; and (3) Tailored immunosuppression comprising reduced exposure to calcineurin inhibitors, particularly early after liver transplantation, and the addition of mammalian target of rapamycin inhibitors. In the present manuscript the available scientific evidence supporting these strategies is comprehensively reviewed, and future directions are provided for novel research approaches, which may contribute to the final target: to cure more patients with hepatocellular carcinoma and with an improved long term outcome.
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Affiliation(s)
- Marta Guerrero-Misas
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
| | - Manuel Rodríguez-Perálvarez
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
| | - Manuel De la Mata
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
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27
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Liver Transplantation for Hepatocellular Carcinoma. CURRENT TRANSPLANTATION REPORTS 2014. [DOI: 10.1007/s40472-014-0028-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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