|
1
|
Varma V, Nekarakanti PK, Agarwal S, Dey R, Gupta S. Role of Locoregional Therapy on Survival After Living Donor Liver Transplantation for Hepatocellular Carcinoma--Experience from a High-volume Center. J Clin Exp Hepatol 2025; 15:102490. [PMID: 39868008 PMCID: PMC11757764 DOI: 10.1016/j.jceh.2024.102490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 12/12/2024] [Indexed: 01/28/2025] Open
Abstract
Background Locoregional therapy (LRT) in patients with hepatocellular carcinoma (HCC) before liver transplantation (LT) has a role in improving the tumor biology and post-LT survival outcome apart from downstaging and bridging. We retrospectively analyzed our database of adult living donor liver transplants (LDLT) for HCC, to compare the survival outcomes in Group-1 (upfront-LT, HCC within Milan/UCSF/AFP<1000 ng/ml) and Group-2 (LT post-LRT, HCC beyond UCSF/irrespective of tumor burden with AFP>1000 ng/ml). We also explored the risk factors for recurrence on follow-up. Methods A study group (n = 506, Group-1-348, Group-2 = 158) of patients with HCC who underwent LDLT between July 2006 and December 2022, excluding incidental HCC (n = 42), patients with other histology (n = 13) and in-hospital mortality (n = 43), were analyzed. Study cohort (n = 341), after propensity score matching, was analyzed for survival outcomes (overall survival, OS and disease-free survival, DFS) and risk factors for recurrence between Group-1 (n = 156) and Group-2 (n = 158). Results Group-2 exhibited a trend towards better mean OS and DFS compared to Group-1 (OS-133 vs. 107-months, P = NS, DFS-118 vs. 102-months, P = NS). Long-term OS (10-year) for those within Milan and UCSF criteria was superior in Group-2, P = NS. Complete pathological response (cPR) after LRT (46.8%), significantly improved OS and DFS compared to those with partial response and stable disease; 152 vs. 94 vs. 49 months, P = 0.001, and 147 vs. 75 vs. 41 months, P = 0.006, respectively. Recipient age, size of tumor, and pre-LT serum alpha-fetoprotein (AFP) were independent predictors of cPR. Independent risk factors for recurrence included pre-LT AFP, tumors beyond UCSF, perineural invasion, and high-grade tumors. Conclusion Locoregional therapy in HCC offers significantly better OS and DFS in those who had a complete pathological response. Risk factors for recurrence post-LT were AFP level, beyond UCSF tumors, and high-grade HCC with PNI on histology.
Collapse
Affiliation(s)
- Vibha Varma
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Phani K. Nekarakanti
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Shaleen Agarwal
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Rajesh Dey
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Subash Gupta
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| |
Collapse
|
|
2
|
Goodsell KE, Tao AJ, Park JO. Neoadjuvant therapy for hepatocellular carcinoma-priming precision innovations to transform HCC treatment. Front Surg 2025; 12:1531852. [PMID: 40115081 PMCID: PMC11922951 DOI: 10.3389/fsurg.2025.1531852] [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: 11/21/2024] [Accepted: 02/18/2025] [Indexed: 03/23/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is increasing in prevalence globally, and cure remains limited with non-operative treatment. Surgical intervention, through resection or transplantation, offers a potential for cure for select patients. However, many patients present with advanced or unresectable disease, and recurrence rates remain high. Recent advances in systemic therapies, particularly immune checkpoint inhibitors, have demonstrated promise in treating unresectable HCC and as adjuvant therapy. Evidence from adjuvant trials highlights the synergistic potential of combined liver-directed and systemic therapies. These findings have ignited growing interest in neoadjuvant therapy across various scenarios: (1) as a bridging strategy while awaiting transplantation, (2) for downstaging disease to enable transplantation, (3) for converting unresectable disease to a resectable state, or (4) as neoadjuvant treatment in operable cases. Early-stage trials of neoadjuvant therapy in resectable HCC have reported promising outcomes. To realize the potential of neoadjuvant treatment for HCC, thoughtfully designed, adequately powered, multi-center clinical trials are essential.
Collapse
Affiliation(s)
- Kristin E Goodsell
- Department of Surgery, University of Washington, Seattle, WA, United States
| | - Alice J Tao
- Department of Surgery, University of Washington, Seattle, WA, United States
| | - James O Park
- Department of Surgery, University of Washington, Seattle, WA, United States
- Department of Surgery, Mount Sinai Hospital, New York, NY, United States
| |
Collapse
|
|
3
|
Bianchi V, Nure E, Nesci C, Pascale MM, Sganga G, Agnes S, Brisinda G. Bridge Therapy before Liver Transplant for Advanced Hepatocellular Carcinoma. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1010. [PMID: 38929627 PMCID: PMC11205611 DOI: 10.3390/medicina60061010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/17/2024] [Accepted: 06/19/2024] [Indexed: 06/28/2024]
Abstract
Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.
Collapse
Affiliation(s)
- Valentina Bianchi
- Emergency Surgery and Trauma Center, Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy; (V.B.); (C.N.); (G.S.)
| | - Erida Nure
- General and Transplant Surgery, Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy; (E.N.); (M.M.P.); (S.A.)
| | - Carmen Nesci
- Emergency Surgery and Trauma Center, Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy; (V.B.); (C.N.); (G.S.)
| | - Marco Maria Pascale
- General and Transplant Surgery, Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy; (E.N.); (M.M.P.); (S.A.)
| | - Gabriele Sganga
- Emergency Surgery and Trauma Center, Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy; (V.B.); (C.N.); (G.S.)
- Catholic School of Medicine “Agostino Gemelli”, 00168 Rome, Italy
| | - Salvatore Agnes
- General and Transplant Surgery, Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy; (E.N.); (M.M.P.); (S.A.)
- Catholic School of Medicine “Agostino Gemelli”, 00168 Rome, Italy
| | - Giuseppe Brisinda
- Emergency Surgery and Trauma Center, Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168 Rome, Italy; (V.B.); (C.N.); (G.S.)
- Catholic School of Medicine “Agostino Gemelli”, 00168 Rome, Italy
| |
Collapse
|
|
4
|
Lee VHF, Vardhanabhuti V, Wong TCL, Lam KO, Choi HCW, Chiu KWH, Ho PPY, Leung DKC, Szeto MHM, Choi KF, Chan SC, Leung TW, Khong PL, Lo CM. Stereotactic Body Radiotherapy and Liver Transplant for Liver Cancer: A Nonrandomized Controlled Trial. JAMA Netw Open 2024; 7:e2415998. [PMID: 38857045 PMCID: PMC11165380 DOI: 10.1001/jamanetworkopen.2024.15998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 04/09/2024] [Indexed: 06/11/2024] Open
Abstract
Importance Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.
Collapse
Affiliation(s)
- Victor Ho-Fun Lee
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Varut Vardhanabhuti
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tiffany Cho-Lam Wong
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Ka-On Lam
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Horace Cheuk-Wai Choi
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Keith Wan-Hang Chiu
- Department of Diagnostic Radiology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Patty Pui-Ying Ho
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | | | - Matthew Ho-Man Szeto
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Kwok-Fung Choi
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - See-Ching Chan
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - To-Wai Leung
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China
| | - Pek-Lan Khong
- Department of Diagnostic Radiology and Clinical Imaging Research Center, National University of Singapore, Singapore
| | - Chung-Mau Lo
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| |
Collapse
|
|
5
|
Yalcin S, Lacin S, Kaseb AO, Peynircioğlu B, Cantasdemir M, Çil BE, Hurmuz P, Doğrul AB, Bozkurt MF, Abali H, Akhan O, Şimşek H, Sahin B, Aykan FN, Yücel İ, Tellioğlu G, Selçukbiricik F, Philip PA. A Post-International Gastrointestinal Cancers' Conference (IGICC) Position Statements. J Hepatocell Carcinoma 2024; 11:953-974. [PMID: 38832120 PMCID: PMC11144653 DOI: 10.2147/jhc.s449540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 05/14/2024] [Indexed: 06/05/2024] Open
Abstract
Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40-50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient's medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.
Collapse
Affiliation(s)
- Suayib Yalcin
- Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Sahin Lacin
- Department of Medical Oncology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Ahmed Omar Kaseb
- Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Bora Peynircioğlu
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | | | - Barbaros Erhan Çil
- Department of Radiology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Pervin Hurmuz
- Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ahmet Bülent Doğrul
- Department of General Surgery, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Murat Fani Bozkurt
- Department of Nuclear Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Hüseyin Abali
- Department of Medical Oncology, Bahrain Oncology Center, Muharraq, Bahrain
| | - Okan Akhan
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Halis Şimşek
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Berksoy Sahin
- Department of Medical Oncology, Cukurova University Faculty of Medicine, Adana, Türkiye
| | - Faruk N Aykan
- Department of Medical Oncology, Istinye University Faculty of Medicine Bahçeşehir Liv Hospital, İstanbul, Turkey
| | - İdris Yücel
- Medicana International Hospital Samsun, Department of Medical Oncology, Samsun, Turkey
| | - Gürkan Tellioğlu
- Department of General Surgery, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Fatih Selçukbiricik
- Department of Medical Oncology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Philip A Philip
- Department of Medicine, Division of Hematology-Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| |
Collapse
|
|
6
|
Lim WX, Sim KS, Chen CL, Ou HY, Yu CY, Cheng YF. Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma: The Effectiveness of Different Particle Sizes in Downstaging and Bridging in Living Donor Liver Transplantation. Transplant Proc 2024; 56:596-601. [PMID: 38472083 DOI: 10.1016/j.transproceed.2024.01.062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 01/16/2024] [Indexed: 03/14/2024]
Abstract
AIM To compare the effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) with different particle sizes in bridging and downstaging in pretransplant hepatocellular carcinoma patients. Assess the recurrent and survival rates after living donor liver transplantation (LDLT). METHODS Retrospective review of 580 patients who underwent TACE using DEB from August 2012 to June 2020 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and post-TACE computed tomography scan images of the liver were reviewed, and treatment responses were assessed using modified Response Evaluation Criteria in Solid Tumors criteria. Patients were divided by who met the criteria (n = 342) or beyond (n = 238) the University of California San Francisco criteria for successful bridging and downstaging rate evaluation. Each group was divided into subgroups according to DEB particle sizes (group A: <100μm, group B: 100-300 μm, group C: 300-500 μm, and group D: 500-700 μm) to compare objective response rate and post-LDLT survival rate. RESULTS Overall successful bridging and downstaging rate is 97.1% and 58.4%, respectively, in the group of patients who meet the criteria (n = 332) and are beyond (n = 139) the University of California San Francisco criteria. Group B (100-300 μm) had a higher successful bridging rate (99.5%, P = .003) and downstaging rate (63.8%, P = .443). This subgroup also demonstrated a higher objective response rate in single (93.2%, P = .038) tumors, multiple (83.3%, P = .001) tumors, and tumors with size less than 5 cm (93.9%, P = .005). There are no significant differences in post-LDLT overall survival rate between different particle sizes. CONCLUSION TACE with 100 to 300 μm DEB particles is associated with a better chance of bridging and downstaging hepatocellular carcinoma patients to LDLT.
Collapse
Affiliation(s)
- Wei-Xiong Lim
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuan Siong Sim
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hsin-You Ou
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Yu
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| |
Collapse
|
|
7
|
Chen JJ, Jin ZC, Zhong BY, Fan W, Zhang WH, Luo B, Wang YQ, Teng GJ, Zhu HD. Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives. United European Gastroenterol J 2024; 12:226-239. [PMID: 38372444 PMCID: PMC10954431 DOI: 10.1002/ueg2.12554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 01/07/2024] [Indexed: 02/20/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.
Collapse
Affiliation(s)
- Jian-Jian Chen
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Zhi-Cheng Jin
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei-Hua Zhang
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Biao Luo
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Yu-Qing Wang
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Gao-Jun Teng
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Hai-Dong Zhu
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| |
Collapse
|
|
8
|
Matevish L, Patel MS, Vagefi PA. Downstaging Techniques for Hepatocellular Carcinoma in Candidates Awaiting Liver Transplantation. Surg Clin North Am 2024; 104:145-162. [PMID: 37953033 DOI: 10.1016/j.suc.2023.07.004] [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] [Indexed: 11/14/2023]
Abstract
During the last decade, downstaging for hepatocellular carcinoma has expanded the pool of patients eligible for liver transplantation. The literature is rife with attempts to elucidate best treatment strategies with novel locoregional and systemic therapies continuing to emerge. Several trials have confirmed the large-scale success of downstaging protocols, with equitable long-term survival and recurrence rates after liver transplant. We review the currently available techniques used for downstaging, including their indications, complications, and efficacies. New frontiers have focused on the potential role of immunotherapy in the neoadjuvant setting, although more research is needed to delineate its role in current treatment paradigms.
Collapse
Affiliation(s)
- Lauren Matevish
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Madhukar S Patel
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Parsia A Vagefi
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
| |
Collapse
|
|
9
|
Wang SY, Sun K, Jin S, Wang KY, Jiang N, Shan SQ, Lu Q, Lv GY, Dong JH. Predicting the outcomes of hepatocellular carcinoma downstaging with the use of clinical and radiomics features. BMC Cancer 2023; 23:858. [PMID: 37700255 PMCID: PMC10496191 DOI: 10.1186/s12885-023-11386-0] [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: 04/14/2023] [Accepted: 09/07/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.
Collapse
Affiliation(s)
- Si-Yuan Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Kai Sun
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
| | - Shuo Jin
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Kai-Yu Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Nan Jiang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Si-Qiao Shan
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Qian Lu
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Guo-Yue Lv
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Jia-Hong Dong
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China.
| |
Collapse
|
|
10
|
Giudicelli H, Roux C, Monsel A, Conti F, Scatton O, Allaire M. Successful advanced hepatocellular carcinoma downstaging with atezolizumab-Bevacizumab and radioembolization before liver transplantation. Clin Res Hepatol Gastroenterol 2023; 47:102167. [PMID: 37343767 DOI: 10.1016/j.clinre.2023.102167] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 06/19/2023] [Indexed: 06/23/2023]
Affiliation(s)
- Heloise Giudicelli
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Charles Roux
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de radiologie interventionnelle, Paris, France
| | - Antoine Monsel
- Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Sorbonne University, Paris, France; INSERM UMRS-959 Immunology-Immunopathology-Immunotherapy (I3), Sorbonne University, Paris, France
| | - Filomena Conti
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
| | - Olivier Scatton
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de chirurgie digestive, Paris, France; Sorbonne Université, INSERM, Centre de recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), F-75012 Paris, France
| | - Manon Allaire
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France; INSERM UMR 1138, Centre de recherche des Cordeliers, 75006 Paris, France.
| |
Collapse
|
|
11
|
Koh B, Tan DJH, Lim WH, Wong JSL, Ng CH, Chan KE, Wang M, Yong WP, Dan YY, Wang LZ, Tan N, Muthiah M, Kow A, Syn NL, Huang DQ, Yau T. Trial watch: immunotherapeutic strategies on the horizon for hepatocellular carcinoma. Oncoimmunology 2023; 12:2214478. [PMID: 37284696 PMCID: PMC10241000 DOI: 10.1080/2162402x.2023.2214478] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/10/2023] [Accepted: 05/11/2023] [Indexed: 06/08/2023] Open
Abstract
The use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25-30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation - which is a potentially curative strategy unique to HCC management - as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments.
Collapse
Affiliation(s)
- Benjamin Koh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Jeffrey S L Wong
- Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Region, China
- State Key Laboratory for Liver Disease, University of Hong Kong, Hong Kong, Special Administrative Region, China
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Meng Wang
- Division of Advanced Internal Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Wei Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Louis Z Wang
- SingHealth Internal Medicine Residency Programme, Singapore General Hospital, Singapore, Singapore
| | - Nigel Tan
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, Singapore, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Division of Advanced Internal Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Alfred Kow
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, Singapore, Singapore
| | - Nicholas L. Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
- Department of Pathology, National University Hospital, Singapore, Singapore
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Division of Advanced Internal Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Thomas Yau
- Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Region, China
- State Key Laboratory for Liver Disease, University of Hong Kong, Hong Kong, Special Administrative Region, China
| |
Collapse
|
|
12
|
Di Martino M, Ferraro D, Pisaniello D, Arenga G, Falaschi F, Terrone A, Maniscalco M, Galeota Lanza A, Esposito C, Vennarecci G. Bridging therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis on intention-to-treat outcomes. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:429-438. [PMID: 36207763 DOI: 10.1002/jhbp.1248] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/16/2022] [Accepted: 09/08/2022] [Indexed: 04/28/2023]
Abstract
INTRODUCTION Locoregional therapies are commonly used as bridging strategies to decrease the drop-out of patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The present paper aims to assess the outcomes of bridging therapies in patients with HCC considered for LT according to an intention-to-treat (ITT) survival analysis. MATERIAL AND METHODS Medline and Web of Science databases were searched for reports published before May 2021. Papers assessing adult patients with HCC considered for LT and reporting ITT survival outcomes were included. Two reviewers independently identified, extracted the data, and evaluated the papers according to Newcastle-Ottawa criteria. Outcomes analyzed were: drop-out rate; time on the waiting list; 1-, 3-, and 5-year survival after LT and based on an ITT analysis. RESULTS The search identified 3106 records; six papers (1043 patients) met the inclusion criteria. Patients with HCC, listed for LT and submitted to bridging therapies presented a longer waiting time before LT (MD 3.77, 95% CI 2.07-5.48) in comparison with the non-interventional group. However, they presented a raised post LT after 1-year (OR 2.00, 95% CI 1.18-3.41), 3-years (OR 1.47, 95% CI 1.01-2.15), and 5-years (OR 1.50, 95% CI 1.06-2.13) survival. CONCLUSION Patients submitted to bridging procedures, despite having a longer interval on the waiting list, presented better post-LT survival outcomes. Bridging therapies for selected patients at low risk of post-procedural complications and long expected intervals on the waiting list should be encouraged. However, further clinical trials should confirm the survival benefit of bridging therapies in patients with HCC listed for LT.
Collapse
Affiliation(s)
- Marcello Di Martino
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
- Division of Haepatology, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Daniele Ferraro
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Donatella Pisaniello
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Giuseppe Arenga
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Federica Falaschi
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Alfonso Terrone
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Marilisa Maniscalco
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Alfonso Galeota Lanza
- Division of Haepatology, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Ciro Esposito
- Liver Intesive Care Unit, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| | - Giovanni Vennarecci
- Division of Hepatobiliary and Liver Transplantation Surgery, Department of Transplantation Surgery, A.O.R.N. Cardarelli, Napoli, Italy
| |
Collapse
|
|
13
|
Minici R, Siciliano MA, Ammendola M, Santoro RC, Barbieri V, Ranieri G, Laganà D. Prognostic Role of Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR) and Lymphocyte-to-C Reactive Protein Ratio (LCR) in Patients with Hepatocellular Carcinoma (HCC) undergoing Chemoembolizations (TACE) of the Liver: The Unexplored Corner Linking Tumor Microenvironment, Biomarkers and Interventional Radiology. Cancers (Basel) 2022; 15:257. [PMID: 36612251 PMCID: PMC9818978 DOI: 10.3390/cancers15010257] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/04/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
TACE plays a pivotal role in hepatocellular carcinoma, from disease control to downstaging and bridging to liver transplant. Response to TACE is a surrogate marker of tumor aggressive biology, with manifold practical implications such as survival, the need for more aggressive treatments in the intermediate stage, the selection of patients on the transplant waiting list, the dropout rate from the transplant list and the post-transplant recurrence rate. Inflammation-based scores are biomarkers of the relationship between the tumor stromal microenvironment and the immune response. Investigating the connection among the tumor stromal microenvironment, biomarkers, and the response to TACE is crucial to recognize TACE refractoriness/failure, thus providing patients with tailored therapeutics. This review aims to provide a comprehensive overview of the prognostic roles of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the lymphocyte-to-C reactive protein ratio (LCR) in patients with HCC undergoing chemoembolization of the liver. Inflammation-based scores may be convenient, easily obtained, low-cost, and reliable biomarkers with prognostic significance for HCC undergoing TACE. Baseline cut-off values differ between various studies, thus increasing confusion about using of inflammation-based scores in clinical practice. Further investigations should be conducted to establish the optimal cut-off values for inflammation-based scores, consolidating their use in clinical practice.
Collapse
Affiliation(s)
- Roberto Minici
- Radiology Division, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | | | - Michele Ammendola
- Digestive Surgery Unit, Science of Health Department, Magna Graecia University, 88100 Catanzaro, Italy
| | - Rita Carlotta Santoro
- Haemophilia and Thrombosis Center, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | - Vito Barbieri
- Oncology Division, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | - Girolamo Ranieri
- Interventional and Medical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
| | - Domenico Laganà
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy
| |
Collapse
|
|
14
|
Hepatocellular Carcinoma, Alpha Fetoprotein, and Liver Allocation for Transplantation: Past, Present and Future. Curr Oncol 2022; 29:7537-7551. [PMID: 36290870 PMCID: PMC9600271 DOI: 10.3390/curroncol29100593] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/01/2022] [Accepted: 10/02/2022] [Indexed: 11/05/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation and has been the treatment of choice due to the oncologic benefit for patients with advanced chronic liver disease (AdvCLD) and small tumors for the last 25 years. For HCC patients undergoing liver transplantation, alpha fetoprotein (AFP) has increasingly been applied as an independent predictor for overall survival, disease free recurrence, and waitlist drop out. In addition to static AFP, newer studies evaluating the AFP dynamic response to downstaging therapy show enhanced prognostication compared to static AFP alone. While AFP has been utilized to select HCC patients for transplant, despite years of allocation policy changes, the US allocation system continues to take a uniform approach to HCC patients, without discriminating between those with favorable or unfavorable tumor biology. We aim to review the history of liver allocation for HCC in the US, the utility of AFP in liver transplantation, the implications of weaving AFP as a biomarker into policy. Based on this review, we encourage the US transplant community to revisit its HCC organ allocation model, to incorporate more precise oncologic principles for patient selection, and to adopt AFP dynamics to better stratify waitlist dropout risk.
Collapse
|
|
15
|
Ghosh A, Gupta V, Al Khalifah A, Akhter NM. Transradial versus transfemoral arterial access in DEB-TACE for hepatocellular carcinoma. J Clin Imaging Sci 2022; 12:38. [PMID: 36128344 PMCID: PMC9479582 DOI: 10.25259/jcis_47_2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/24/2022] [Indexed: 11/04/2022] Open
Abstract
Objectives
Transradial access has become increasingly popular in body interventional procedures but has not been ubiquitously adapted. This retrospective study compares the efficacy of this approach versus transfemoral access in hepatocellular carcinoma (HCC) patients who underwent drug-eluting bead transarterial chemoembolization (DEB-TACE).
Materials and Methods
A total of 130 HCC patients underwent 146 DEB-TACE procedures within our institution from June 2015 to May 2020. About 90 and 56 procedures were logged for the transradial and transfemoral cohorts, respectively. Peak skin dose, fluoroscopy time, administered contrast volume, total procedure time, and equipment cost data for each procedure were reviewed to evaluate for statistical differences between the two groups.
Results
All 146 cases were technically successful without major complications or access failures in either group. No statistical differences were present between the two access groups in regards to peak skin dose or fluoroscopy time. Transradial access recorded a significantly higher contrast volume (P < 0.05), and a significantly longer procedural time than transfemoral access (P < 0.01). However, transradial access also displayed a significantly lower procedural equipment cost (P < 0.01) between the two groups.
Conclusion
Transradial DEB-TACE has similar trends to transfemoral DEB-TACE in several pertinent radiation parameters and is also significantly more cost-efficacious. The results of this investigation suggest the consideration of transradial access whenever viable as an alternative to transfemoral access in the DEB-TACE treatment of HCC patients.
Collapse
Affiliation(s)
- Abheek Ghosh
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Vikash Gupta
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Abdullah Al Khalifah
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| | - Nabeel Mohsin Akhter
- Department of Interventional Radiology, University of Maryland, Baltimore, Maryland, United States,
| |
Collapse
|
|
16
|
Radiofrequency ablation versus trans-arterial chemoembolization in patients with HCC awaiting liver transplant: an analysis of the Scientific Registry of Transplant Recipients. J Vasc Interv Radiol 2022; 33:1222-1229.e1. [PMID: 35777619 DOI: 10.1016/j.jvir.2022.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 04/21/2022] [Accepted: 06/21/2022] [Indexed: 11/22/2022] Open
Abstract
PURPOSE To evaluate differences in waitlist mortality/dropout for liver transplant candidates with hepatocellular carcinoma (HCC) who undergo radiofrequency ablation (RFA) versus trans-arterial chemoembolization (TACE). MATERIAL AND METHODS From 2004-2013, 11,824 patients in the Scientific Registry of Transplant Recipients (SRTR) with HCC who underwent RFA or TACE. Patients were followed until December 31, 2019 or 5 years, whichever came first and stratified by Milan criteria. Competing risk and Cox regression analyses to compare waitlist mortality/dropout were performed with adjusted hazard ratios (asHR, reference group RFA). Regression models were adjusted for age, race, sex, calculated Model for End Stage Liver Disease (cMELD) score, tumor size, and number. RESULTS There was no difference in waitlist mortality/dropout for patients outside Milan criteria (N = 1,226) between TACE (19.2%) compared to RFA (19.0%) (asHR 0.91; 95% CI 0.79-1.03). There was also no difference for patients inside Milan criteria (N = 10,598) in waitlist mortality/dropout (TACE 13.4% vs. RFA 12.9%) (asHR 1.29; 95% CI 0.79-2.09). Subgroup analysis within Milan criteria demonstrated no evidence of difference in TACE compared to RFA in patients with single tumor ≤3 cm (asHR 0.92; 95% CI 0.77-1.10), single tumor > 3 cm (asHR 1.03; 95% CI 0.79-1.34), or with > 1 tumor (asHR 0.89; 95% CI 0.72-1.09). CONCLUSION Using national registry data, no difference was found in waitlist mortality/dropout for transplant candidates with HCC who received TACE vs. RFA.
Collapse
|
|
17
|
Benkö T, König J, Theysohn JM, Schotten C, Saner FH, Treckmann J, Radunz S. Bridging treatment prior to liver transplantation for hepatocellular carcinoma: radioembolization or transarterial chemoembolization? Eur J Med Res 2022; 27:74. [PMID: 35619164 PMCID: PMC9134704 DOI: 10.1186/s40001-022-00708-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 05/16/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment. METHODS We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival. RESULTS Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death. CONCLUSIONS Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.
Collapse
Affiliation(s)
- Tamás Benkö
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Julia König
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jens M Theysohn
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
| | - Clemens Schotten
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Fuat H Saner
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jürgen Treckmann
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Sonia Radunz
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany.
| |
Collapse
|
|
18
|
Vietti Violi N, Gnerre J, Law A, Hectors S, Bane O, Doucette J, Abboud G, Kim E, Schwartz M, Fiel MI, Taouli B. Assessment of HCC response to Yttrium-90 radioembolization with gadoxetate disodium MRI: correlation with histopathology. Eur Radiol 2022; 32:6493-6503. [PMID: 35380226 DOI: 10.1007/s00330-022-08732-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 02/19/2022] [Accepted: 03/11/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND AND AIMS Transarterial 90Y radioembolization (TARE) is increasingly being used for hepatocellular carcinoma (HCC) treatment. However, tumor response assessment after TARE may be challenging. We aimed to assess the diagnostic performance of gadoxetate disodium MRI for predicting complete pathologic necrosis (CPN) of HCC treated with TARE, using histopathology as the reference standard. METHODS This retrospective study included 48 patients (M/F: 36/12, mean age: 62 years) with HCC treated by TARE followed by surgery with gadoxetate disodium MRI within 90 days of surgery. Two radiologists evaluated tumor response using RECIST1.1, mRECIST, EASL, and LI-RADS-TR criteria and evaluated the percentage of necrosis on subtraction during late arterial, portal venous, and hepatobiliary phases (AP/PVP/HBP). Statistical analysis included inter-reader agreement, correlation between radiologic and pathologic percentage of necrosis, and prediction of CPN using logistic regression and ROC analyses. RESULTS Histopathology demonstrated 71 HCCs (2.8 ± 1.7 cm, range: 0.5-7.5 cm) including 42 with CPN, 22 with partial necrosis, and 7 without necrosis. EASL and percentage of tumor necrosis on subtraction at the AP/PVP were independent predictors of CPN (p = 0.02-0.03). Percentage of necrosis, mRECIST, EASL, and LI-RADS-TR had fair to good performance for diagnosing CPN (AUCs: 0.78 - 0.83), with a significant difference between subtraction and LI-RADS-TR for reader 2, and in specificity between subtraction and other criteria for both readers (p-range: 0.01-0.04). Radiologic percentage of necrosis was significantly correlated to histopathologic degree of tumor necrosis (r = 0.66 - 0.8, p < 0.001). CONCLUSIONS Percentage of tumor necrosis on subtraction and EASL criteria were significant independent predictors of CPN in HCC treated with TARE. Image subtraction should be considered for assessing HCC response to TARE when using MRI. KEY POINTS • Percentage of tumor necrosis on image subtraction and EASL criteria are significant independent predictors of complete pathologic necrosis in hepatocellular carcinoma treated with90Y radioembolization. • Subtraction, mRECIST, EASL, and LI-RADS-TR have fair to good performance for diagnosing complete pathologic necrosis in hepatocellular carcinoma treated with90Y radioembolization.
Collapse
Affiliation(s)
- Naik Vietti Violi
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine Mount Sinai, New York, NY, USA.,Department of Radiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Jeffrey Gnerre
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Amy Law
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Stefanie Hectors
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine Mount Sinai, New York, NY, USA
| | - Octavia Bane
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine Mount Sinai, New York, NY, USA
| | - John Doucette
- Department of Environmental Medicine & Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ghadi Abboud
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine Mount Sinai, New York, NY, USA
| | - Edward Kim
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Myron Schwartz
- The Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - M Isabel Fiel
- Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bachir Taouli
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine Mount Sinai, New York, NY, USA. .,Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA.
| |
Collapse
|
|
19
|
Precision Medicine for Hepatocellular Carcinoma: Clinical Perspective. J Pers Med 2022; 12:jpm12020149. [PMID: 35207638 PMCID: PMC8879044 DOI: 10.3390/jpm12020149] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major malignant diseases worldwide, characterized by growing incidence and high mortality rates despite apparent improvements in surveillance programs, diagnostic and treatment procedures, molecular therapies, and numerous research initiatives. Most HCCs occur in patients with liver cirrhosis, and the competing mortality risks from the tumor and the cirrhosis should be considered. Presently, previously identified risk factors, such as hepatitis virus infection, hepatic inflammation and fibrosis, and metabolic syndrome, may be used as chemoprevention targets. The application of precision medicine for HCC management challenges the one-size-fits-all concept; moreover, patients should no longer be treated entirely according to the histology of their tumor but based on molecular targets specific to their tumor biology. Next-generation sequencing emphasizes HCC molecular heterogeneity and aids our comprehension of possible vulnerabilities that can be exploited. Moreover, genetic sequencing as part of a precision medicine concept may work as a promising tool for postoperative cancer monitoring. The use of genetic and epigenetic markers to identify therapeutic vulnerability could change the diagnosis and treatment of HCC, which so far was based on Barcelona clinic liver cancer (BCLC) staging. In daily clinical practice, the shift from a stage-oriented to a therapeutic-oriented approach is needed to direct the choice of HCC treatment toward the potentially most effective option on an individual basis. The important factor in precision medicine is the promotion of patient management based on the individual approach, knowing that the final decision must be approved by a multidisciplinary expert team.
Collapse
|
|
20
|
Xu L, Chen L, Zhang W. Neoadjuvant treatment strategies for hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1550-1566. [PMID: 35070063 PMCID: PMC8727178 DOI: 10.4240/wjgs.v13.i12.1550] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/27/2021] [Accepted: 11/30/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) remains high globally. Surgical treatment is the best treatment for improving the prognosis of patients with HCC. Neoadjuvant therapy plays a key role in preventing tumor progression and even downstaging HCC. The liver transplantation rate and resectability rate have increased for neoadjuvant therapy. Neoadjuvant therapy is effective in different stages of HCC. In this review, we summarized the definition, methods, effects, indications and contraindications of neoadjuvant therapy in HCC, which have significance for guiding treatment.
Collapse
Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| |
Collapse
|
|
21
|
Wong TC, Lee VH, Law AL, Pang HH, Lam K, Lau V, Cui TY, Fong AS, Lee SW, Wong EC, Dai JW, Chan AC, Cheung T, Fung JY, Yeung RM, Luk M, Leung T, Lo C. Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant. Hepatology 2021; 74:2580-2594. [PMID: 34091914 PMCID: PMC9291538 DOI: 10.1002/hep.31992] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 05/26/2021] [Accepted: 05/30/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P < 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence-free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size <3 cm, listing alpha-fetoprotein <200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout. CONCLUSIONS SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.
Collapse
Affiliation(s)
- Tiffany Cho‐Lam Wong
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - Victor Ho‐Fun Lee
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - Ada Lai‐Yau Law
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Herbert H. Pang
- School of Public HealthThe University of Hong KongHong Kong S.A.R.
| | - Ka‐On Lam
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - Vince Lau
- Department of RadiologyQueen Mary HospitalHong Kong S.A.R.
| | | | | | - Sarah Wai‐Man Lee
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Edwin Chun‐Yin Wong
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Jeff Wing‐Chiu Dai
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - Albert Chi‐Yan Chan
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - Tan‐To Cheung
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| | - James Yan‐Yue Fung
- Department of MedicineThe University of Hong KongHong Kong S.A.R.,Department of MedicineQueen Mary HospitalHong Kong S.A.R.
| | - Rebecca Mei‐Wan Yeung
- Department of Clinical OncologyPamela Youde Nethersole Eastern HospitalHong Kong S.A.R.
| | - Mai‐Yee Luk
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - To‐Wai Leung
- Department of Clinical OncologyThe University of Hong KongHong Kong S.A.R.,Department of Clinical OncologyQueen Mary HospitalHong Kong S.A.R.
| | - Chung‐Mau Lo
- Department of SurgeryThe University of Hong KongHong Kong S.A.R.,Department of SurgeryQueen Mary HospitalHong Kong S.A.R.
| |
Collapse
|
|
22
|
Bucalau AM, Tancredi I, Verset G. In the Era of Systemic Therapy for Hepatocellular Carcinoma Is Transarterial Chemoembolization Still a Card to Play? Cancers (Basel) 2021; 13:5129. [PMID: 34680278 PMCID: PMC8533902 DOI: 10.3390/cancers13205129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/30/2021] [Accepted: 10/07/2021] [Indexed: 02/07/2023] Open
Abstract
Conventional transarterial embolization (cTACE) has been proven to be effective for intermediate stage hepatocellular carcinoma (HCC), with a recent systematic review showing an overall survival (OS) of 19.4 months. Nevertheless, due to the rapid development of the systemic therapeutic landscape, the place of TACE is becoming questionable. Is there still a niche for TACE in the era of immunotherapy and combination treatments such as atezolizumab-bevacizumab, which has shown an OS of 19.2 months with excellent tolerance? The development of drug-eluting microspheres (DEMs) has led to the standardization of the technique, and along with adequate selection, it showed an OS of 48 months in a retrospective study. In order to increase treatment selectivity, new catheters have also been added to the TACE arsenal as well as the use of cone-beam CT (CBCT), which provides three-dimensional volumetric images and guidance during procedures. Moreover, the TACE indications have also widened. It may serve as a "bridging therapy" for liver transplantation candidates while they are on the waiting list, and it represents a valuable downstaging tool to transplantation criteria. The aim of this review is to explore the current data on the advancements of TACE and its future place amongst the growing panel of treatments.
Collapse
Affiliation(s)
- Ana-Maria Bucalau
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium;
| | - Illario Tancredi
- Department of Interventional Radiology, Hôpital Erasme, 1070 Brussels, Belgium;
| | - Gontran Verset
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Erasme, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium;
| |
Collapse
|
|
23
|
Pinato DJ, Murray SM, Forner A, Kaneko T, Fessas P, Toniutto P, Mínguez B, Cacciato V, Avellini C, Diaz A, Boyton RJ, Altmann DM, Goldin RD, Akarca AU, Marafioti T, Mauri FA, Casagrande E, Grillo F, Giannini E, Bhoori S, Mazzaferro V. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer 2021; 9:e003311. [PMID: 34593621 PMCID: PMC8487214 DOI: 10.1136/jitc-2021-003311] [Citation(s) in RCA: 112] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. METHODS We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T- (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163. RESULTS We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T-. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T-. CONCLUSIONS TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.
Collapse
Affiliation(s)
- David J Pinato
- Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
- Division of Oncology, Department of Translational Medicine, Universita del Piemonte Orientale "A. Avogadro", Novara, Italy
| | - Sam M Murray
- Department of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Alejandro Forner
- Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, University of Barcelona, Hospital Clinic, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | | | - Petros Fessas
- Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Department of Medical Area (DAME), University of Udine, Udine, Italy
| | - Beatriz Mínguez
- Liver Unit, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Valentina Cacciato
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy
| | - Claudio Avellini
- Institute of Histopathology, Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia", Udine, Italy
| | - Alba Diaz
- Pathology Department, Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Rosemary J Boyton
- Department of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Daniel M Altmann
- Department of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
| | | | - Ayse U Akarca
- Department of Histopathology, University College London Cancer Institute, London, UK
| | - Teresa Marafioti
- Department of Histopathology, University College London Cancer Institute, London, UK
| | - Francesco A Mauri
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Edoardo Casagrande
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy
| | - Federica Grillo
- Department of Surgical Sciences, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy
| | - Edoardo Giannini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS-Ospedale Policlinico San Martino, Genoa, Italy
| | - Sherrie Bhoori
- Department of Oncology, University of Milan, Milano, Italy
- Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Vincenzo Mazzaferro
- Department of Oncology, University of Milan, Milano, Italy
- Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| |
Collapse
|
|
24
|
Talakić E, Janek E, Mikalauskas S, Schemmer P. Liver Transplantation in Malignancies: A Comprehensive and Systematic Review on Oncological Outcome. Visc Med 2021; 37:302-314. [PMID: 34540947 PMCID: PMC8406343 DOI: 10.1159/000517328] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Liver transplantation (LT) is today's standard treatment for both end-stage liver disease and tumors; however, suitable grafts for LT are a scarce resource and outcome after LT is highly dependent on its underlying indication. Thus, patients must be carefully selected to optimize the number of life years gained per graft. This comprehensive and systematic review critically reflects the most recently published oncological outcome data after LT in malignancies based on the preoperative radiological findings. METHODS A systematic literature search was conducted to detect preferentially most recent high-volume series or large database analysis on oncological outcomes after LT for both primary liver cancer and liver metastases between January 1, 2019, and November 14, 2020. A comprehensive review on the radiological assessment of the reviewed liver malignancies is included and its preoperative value for an outcome-driven indication reflected. RESULTS Twenty most recent high-volume or relevant studies including a total number of 2,521 patients were identified including 4, 4, 4, 4, 3, and 1 publications on oncological outcome after LT for hepatocellular carcinoma, cholangiocellular carcinoma, hepatic epitheloid hemangioendothelioma, hepatoblastoma, and both metastatic neuroendocrine tumors and colorectal cancer, respectively. The overall survival is comparable to patients without tumors if patients with malignancies are well selected for LT; however, this is highly dependent on tumor entity, tumor stage, and both neoadjuvant and concomitant treatment. DISCUSSION/CONCLUSION LT is a promising option for better survival in patients with malignant liver tumors in selected patients; however, the indication must be critically discussed prior to LT in every single case in the context of organ shortage.
Collapse
Affiliation(s)
- Emina Talakić
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Elmar Janek
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Saulius Mikalauskas
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
| | - Peter Schemmer
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
| |
Collapse
|
|
25
|
Ward EM, Sherif AE, O'Neill S, Hughes M, Ireland H, Wigmore SJ, Adair A. Clinical Outcomes of Ablation Compared with Resection for Single Hepatocellular Carcinoma Lesions, as a Primary Treatment or Bridging to Liver Transplantation: A Retrospective Comparative Study. Ann Transplant 2021; 26:e931980. [PMID: 34326301 PMCID: PMC8330445 DOI: 10.12659/aot.931980] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background Ablative therapies (AT) are widely utilized as bridging treatment for liver transplantation (LT) candidates with hepatocellular carcinoma (HCC) who are on the transplant waiting list to minimize dropout rate. We aimed to investigate whether AT could be considered a primary treatment modality for LT candidates with single, small HCC lesions. Material/Methods We retrospectively investigated the outcomes of patients with AT for single HCC lesions as primary treatment or bridging to LT between 2010 and 2017, compared with surgical resection (SR) during the same time period as control. Univariate and multivariate survival analyses were performed. Matched analysis, after propensity score matching (PSM), was performed to minimize the selection bias confounding effect on outcomes. Results Of 162 patients identified, 92 received AT and 70 had SR. PSM identified 38 paired matches in each group. Overall survival (OS) and disease-free survival (DFS) before matching showed comparable outcomes for each treatment after 1, 3, and 5 years. Multivariate analysis using Cox regression models adjusting the study confounders showed lesion size (>30 mm), not treatment received, was associated with worse DFS (hazard ratio, 2.21 [95% confidence interval, 1.14–4.28]). In the matched groups, OS and DFS were equivalent and consistent with the whole-cohort survival outcomes. Explant histopathology of patients having AT as a bridge to LT showed complete pathological response in 85.7% of patients. Conclusions This study supports the use of AT with curative intent for single ≤3-cm HCCs, particularly in LT candidates, with salvage transplantation kept as a backup in case of recurrence.
Collapse
Affiliation(s)
- Elizabeth M Ward
- Department of Hepato-Pancreato-Biliary (HPB)/Transplant Surgery, The University of Edinburgh Clinical Surgery, Edinburgh, United Kingdom
| | - Ahmed Elshawadfy Sherif
- Department of Hepato-Pancreato-Biliary (HPB)/Transplant Surgery, The University of Edinburgh Clinical Surgery, Edinburgh, United Kingdom.,Department of Hepato-Pancreato-Biliary (HPB) Surgery, National Liver Institute, Menoufia University, Shibin Elkom, Egypt
| | - Stephen O'Neill
- Department of Transplant Surgery, Belfast City Hospital, Belfast, United Kingdom
| | - Michael Hughes
- Department of Hepato-Pancreato-Biliary (HPB)/Transplant Surgery, The University of Edinburgh Clinical Surgery, Edinburgh, United Kingdom
| | - Hamish Ireland
- Department of Interventional Radiology, Vascular Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Stephen J Wigmore
- Department of Hepato-Pancreato-Biliary (HPB)/Transplant Surgery, The University of Edinburgh Clinical Surgery, Edinburgh, United Kingdom
| | - Anya Adair
- Department of Hepato-Pancreato-Biliary (HPB)/Transplant Surgery, The University of Edinburgh Clinical Surgery, Edinburgh, United Kingdom
| |
Collapse
|
|
26
|
Koulouris A, Tsagkaris C, Spyrou V, Pappa E, Troullinou A, Nikolaou M. Hepatocellular Carcinoma: An Overview of the Changing Landscape of Treatment Options. J Hepatocell Carcinoma 2021; 8:387-401. [PMID: 34012929 PMCID: PMC8128500 DOI: 10.2147/jhc.s300182] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 04/13/2021] [Indexed: 12/12/2022] Open
Abstract
The last three years have seen remarkable progress in comprehending predisposing factors and upgrading our treatment arsenal concerning hepatocellular carcinoma (HCC). Until recently, there were no means to withstand the progression of viral hepatitis-associated liver cirrhosis to HCC. A deeper understanding of the molecular mechanism of the disease, the use of biomarkers, and the follow-up, allowed us to realize that conventional chemotherapy failing to increase survival in patients with advanced HCC tends to be exiled from clinical practice. Multi-kinase inhibitors (TKIs) such as sorafenib, lenvatinib targeting mainly the vascular endothelial growth factor receptors 1–3 VEGFRs 1–3 provided until recently the standard of care for these patients, as first- or second-line treatment. Since May 2020, the atezolizumab plus bevacizumab combination (immunotherapy plus anti-VEGF) has become the new reference standard in first-line HCC treatment. Additionally, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy can be used as a second-line treatment following first-line treatment’s failure. Phase III clinical trials have recently suggested the efficacy of novel anti-angiogenic factors such as cabozantinib and ramucirumab as a second-line treatment option. With considerations about toxicity arising, clinical trials are investigating combinations of the aforementioned targeted therapies with immunotherapy as first-line treatment. This paper aims to perform a systematic review describing the evolving treatment options for HCC over the last decades, ranging from neoadjuvant treatment to systemic therapy of advanced-stage HCC. With the landscape of HCC treatment shifting towards novel agents the forming of a new therapeutic algorithm for HCC seems to be imperative.
Collapse
Affiliation(s)
- Andreas Koulouris
- Resident of Medical Oncology, University General Hospital of Heraklion, University of Crete, Crete, Greece
| | | | | | - Eleni Pappa
- Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Michail Nikolaou
- 1st Oncology Department, "Saint Savas" Anticancer - Oncology Hospital, Athens, Greece
| |
Collapse
|
|
27
|
Minici R, Ammendola M, Manti F, Siciliano MA, Giglio E, Minici M, Melina M, Currò G, Laganà D. Safety and Efficacy of Degradable Starch Microspheres Transcatheter Arterial Chemoembolization as a Bridging Therapy in Patients with Early Stage Hepatocellular Carcinoma and Child-Pugh Stage B Eligible for Liver Transplant. Front Pharmacol 2021; 12:634084. [PMID: 33897421 PMCID: PMC8062923 DOI: 10.3389/fphar.2021.634084] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/19/2021] [Indexed: 12/12/2022] Open
Abstract
In patients with early-stage hepatocellular carcinoma, awaiting liver transplantation, current guidelines by AASLD and ESMO recommend a bridging therapy with a loco-regional treatment to prevent progression outside transplantation criteria. The standard of care in delaying disease progression has been recognized to be the transarterial chemoembolization. Permanent occlusion of tumor feeding vessels has effects on tumour stromal microenvironment by inducing intra- and intercellular signaling processes counteracting hypoxia, such as the release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumour proliferation and metastatic growth. Among chemoembolization interventions, TACE with degradable starch microspheres represents an alternative to conventional cTACE and DEB-TACE and it minimizes detrimental effects on tumour stromal microenvironment, guaranteeing a transient occlusion of tumour feeding arteries and avoiding VEGF overexpression.Between January 2015 and September 2020, 54 consecutive patients with early-stage hepatocellular carcinoma and Child-Pugh stage B, who had undergone DSM-TACE as a bridging therapy while awaiting liver transplantation, were eligible for the study. A total of 154 DSM-TACE was performed, with a mean number of 2.85 procedures per patient. 18 patients (33.3%) succeeded in achieving liver transplantation, with a mean waiting time-to-transplantation of 11.7 months. The cumulative rates of patients still active on the WL at 6 months were about 91 and 93% when considering overall drop-out and tumour-specific drop-out respectively. Overall survival was about 96% at 6 months and 92% at 12 months. 17 patients experienced adverse events after the chemoembolizations. For patients with HCC in the transplant waiting list and within the Child-Pugh B stage, life expectancy may be dominated by the liver dysfunction, rather than by the tumour progression itself. In this population subset, the choice of LRT is critical because LRT itself could become a dangerous tool that is likely to precipitate liver dysfunction to an extent that survival is shortened rather than prolonged. Hence, the current study demonstrates that DSM-TACE is not far from being an ideal LRT, because it has an excellent safety profile, maintaining an efficacy that guarantees a clear advantage on the dropout rate with respect to the non-operative strategy, thus justifying its use.
Collapse
Affiliation(s)
- Roberto Minici
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Michele Ammendola
- Digestive Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Francesco Manti
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Maria Anna Siciliano
- Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Enrica Giglio
- Medical Oncology Unit, University Hospital-Marche Polytechnic University, Ancona, Italy
| | - Marco Minici
- National Research Council (Cnr), Institute for High Performance Computing and Networking (ICAR), Rende, Italy
| | - Marica Melina
- Department of Medical and Surgical Sciences, Sant’Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giuseppe Currò
- General Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Domenico Laganà
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| |
Collapse
|
|
28
|
Cheung TT, Ma KW, She WH. A review on radiofrequency, microwave and high-intensity focused ultrasound ablations for hepatocellular carcinoma with cirrhosis. Hepatobiliary Surg Nutr 2021; 10:193-209. [PMID: 33898560 DOI: 10.21037/hbsn.2020.03.11] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Hepatocellular carcinoma (HCC) is usually accompanied by liver cirrhosis, which makes treatment of this disease challenging. Liver transplantation theoretically provides an ultimate solution to the disease, but the maximal surgical stress and the scarcity of liver graft make this treatment option impossible for some patients. In an ideal situation, a treatment that is safe and effective should provide a better outcome for patients with the dilemma. Objective This article aims to give a comprehensive review of various types of loco-ablative treatment for HCC. Evidence Review Loco-ablative treatment bridges the gap between surgical resection and transarterial chemotherapy. Various types of ablative therapy have their unique ability, and evidence-based outcome analysis is the most important key to assisting clinicians to choose the most suitable treatment modality for their patients. Findings Radiofrequency ablation (RFA) has a relatively longer history and more evidence to support its effectiveness. Microwave ablation (MWA) is gaining momentum because of its shorter ablation time and consistent ablation zone. High-intensity focused ultrasound (HIFU) ablation is a relatively new technology that provides non-invasive treatment for patients with HCC. It has been carried out at centers of excellence and it is a safe and effective treatment option for selected patients with HCC and liver cirrhosis. Conclusion and Relevance Selective use of different loco-ablative therapies will enhance clinicians' treatment options for treatment of HCC.
Collapse
Affiliation(s)
- Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
| |
Collapse
|
|
29
|
Kim Y, Lee HA, Lee JS, Jeon MY, Kim BK, Park JY, Kim DY, Ahn SH, Um SH, Seo YS, Kim SU. Association Between Curative Treatment after Transarterial Radioembolization and Better Survival Outcomes in Patients with Hepatocellular Carcinoma. Cancer Invest 2021; 39:274-283. [PMID: 33356630 DOI: 10.1080/07357907.2020.1870126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/30/2020] [Accepted: 12/26/2020] [Indexed: 01/27/2023]
Abstract
Transarterial radioembolization (TARE) is one of the therapeutic options for hepatocellular carcinoma (HCC). This study aimed to investigate the predictors and prognostic values of achieving curative treatments after TARE. Overall, 143 patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited from two Korean tertiary institutes. Twenty-seven patients received curative treatments after TARE. Younger age than 65 years and AFP of ≤200 ng/mL independently predicted the increased probability of achieving curative treatment after TARE, and the curative treatment after TARE provided a survival benefit in patients with intrahepatic HCC.
Collapse
Affiliation(s)
- Yuna Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Mi Young Jeon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| |
Collapse
|
|
30
|
Hasan B, Colak Y, Khalid RA, Castillo M, Castaneda D, Tandon K, Shaw JJ, Erim T, Zervos XB, Castro FJ, Al-Khalloufi K. Early Detection of Hepatocellular Carcinoma Recurrence in the Posttransplant Population: A Comparison of RETREAT and Cleveland Clinic Florida Scoring System. Transplant Proc 2021; 53:193-199. [PMID: 33069486 DOI: 10.1016/j.transproceed.2020.09.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 08/10/2020] [Accepted: 09/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Liver transplantation (LT) for hepatocellular carcinoma (HCC) is curative in most cases; however, recurrence is observed in some patients. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score is an externally validated scoring system for prediction of post-LT HCC recurrence. The Cleveland Clinic Florida Scoring System (CCFSS) is a potential new scoring system for prediction of HCC recurrence. Our study aimed to compare the RETREAT and CCFSS. METHODS We conducted a retrospective cohort study of 52 adult patients with HCC who underwent LT at a tertiary care center. Mantel-Haenszel chi-square analyses were conducted to compare the RETREAT and CCFSS classifications for detecting HCC recurrence. RESULTS A total of 52 patients underwent LT. The median follow-up period was 37 months. Four patients had post-LT HCC recurrence, with all recurrences occurring within 2 years of LT. The RETREAT score was better able to detect low, moderate, and high levels of risk (P < .001), compared to the CCFSS score (P = 0.480). Both risk scores had a sensitivity of 75%; the specificity of the RETREAT score was 95.8%, whereas the specificity of the CCFSS was 60.4%. Alpha-fetoprotein level at the time of LT was associated with HCC recurrence (P = .014). CONCLUSIONS This is the first study to evaluate the CCFSS as a potential new scoring system to predict HCC recurrence after LT. The RETREAT score is more specific than the CCFSS. The incorporation of alpha-fetoprotein level at the time of LT improves the estimation of HCC recurrence in the post-LT period.
Collapse
Affiliation(s)
- Badar Hasan
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida.
| | - Yasar Colak
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida
| | - Rumman A Khalid
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida
| | - Michael Castillo
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida
| | - Daniel Castaneda
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida
| | - Kanwarpreet Tandon
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida
| | - Joshua J Shaw
- Department of Transplant Hepatology, Cleveland Clinic Florida, Weston, Florida
| | - Tolga Erim
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida
| | - Xaralambos B Zervos
- Department of Transplant Hepatology, Cleveland Clinic Florida, Weston, Florida
| | - Fernando J Castro
- Department of Gastroenterology, Cleveland Clinic Florida, Weston, Florida
| | - Kawtar Al-Khalloufi
- Department of Transplant Hepatology, Cleveland Clinic Florida, Weston, Florida
| |
Collapse
|
|
31
|
Lee S, Kim KW, Song GW, Kwon JH, Hwang S, Kim KH, Ahn CS, Moon DB, Park GC, Lee SG. The Real Impact of Bridging or Downstaging on Survival Outcomes after Liver Transplantation for Hepatocellular Carcinoma. Liver Cancer 2020; 9:721-733. [PMID: 33442541 PMCID: PMC7768098 DOI: 10.1159/000507887] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 04/14/2020] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION There is no consensus regarding selection criteria on liver transplantation (LT) for hepatocellular carcinoma (HCC), especially for living donor liver transplantation, although emerging evidence has been found for the effectiveness of bridging or downstaging. OBJECTIVE We evaluated the long-term outcomes of patients who underwent LT with or without bridging or downstaging for HCC. METHODS This retrospective study included 896 LT recipients with HCC between June 2005 and May 2015. Recurrence-free survival (RFS), overall survival (OS), and their associated factors were evaluated. RESULTS The 5-year RFS in the full cohort of 896 patients was 82.4%, and the OS was 85.3%. In patients with initial Organ Procurement and Transplantation Network (OPTN) T1 and T2, the 5-year RFS and OS did not significantly differ between LT groups with and without bridging (all p ≥ 0.05). The 5-year RFS and OS of OPTN T3 patients with successful downstaging were not significantly different from those of patients with OPTN T2 with primary LT (p = 0.070 and p = 0.185), but were significantly higher than in patients with OPTN T3 with downstaging failure and initial OPTN T1 or T2 with progression (all p < 0.001). In the multivariate analysis, last alpha-fetoprotein before LT ≥70 ng/mL (hazard ratio [HR]: 1.77, p = 0.001; HR: 1.72, p = 0.004), pretransplant HCC status exceeding the Milan criteria (HR: 5.12, p < 0.001; HR: 3.31, p < 0.001), and positron emission tomography positivity (HR: 2.57, p < 0.001; HR: 2.57, p < 0.001) were independent predictors for worse RFS and OS. CONCLUSIONS The impact of bridging therapy on survival outcomes is limited in patients with early-stage HCC, whereas OPTN T1 or T2 with progression provides worse prognosis. OPTN T3 should undergo LT after successful downstaging, and OPTN T3 with successful downstaging allows for acceptable long-term posttransplant outcomes.
Collapse
Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyoung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,*Kyoung Won Kim, Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology 88, Olympic-Ro 43-Gil, Seoul 05505 (Republic of Korea),
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,**Gi-Won Song, Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology 88, Olympic-Ro 43-Gil, Seoul 05505 (Republic of Korea),
| | - Jae Hyun Kwon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
32
|
Ziogas IA, Hickman LA, Matsuoka LK, Izzy M, Montenovo MI, Rega SA, Feurer ID, Alexopoulos SP. Comparison of Wait-List Mortality Between Cholangiocarcinoma and Hepatocellular Carcinoma Liver Transplant Candidates. Liver Transpl 2020; 26:1112-1120. [PMID: 32475062 DOI: 10.1002/lt.25807] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/28/2020] [Accepted: 05/17/2020] [Indexed: 12/13/2022]
Abstract
Despite the divergent disease biology of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC), wait-list prioritization is identical for both diagnoses. We compared wait-list and posttransplant outcomes between CCA and HCC liver transplantation patients with Model for End-Stage Liver Disease exceptions using Scientific Registry of Transplant Recipients data. The 408 CCA candidates listed between 2003 and mid-2017 were matched to 2 HCC cohorts by listing date (±2 months, n = 816) and by Organ Procurement and Transplantation Network (OPTN) region and date (±6 months, n = 408). Cumulative incidence competing risk regression examined the effects of diagnosis, OPTN region, and center-level CCA listing volume on wait-list removal due to death/being too ill (dropout). Cox models evaluated the effects of diagnosis, OPTN region, center-level CCA volume, and waiting time on graft failure among deceased donor liver transplantation (DDLT) recipients. After adjusting for OPTN region and CCA listing volume (all P ≥ 0.07), both HCC cohorts had a reduced likelihood of wait-list dropout compared with CCA candidates (HCC with period matching only: subdistribution hazard ratio [SHR] = 0.63; 95% CI, 0.43-0.93; P = 0.02 and HCC with OPTN region and period matching: SHR = 0.60; 95% CI, 0.41-0.87; P = 0.007). The cumulative incidence rates of wait-list dropout at 6 and 12 months were 13.2% (95% CI, 10.0%-17.0%) and 23.9% (95% CI, 20.0%-29.0%) for CCA candidates, 7.3% (95% CI, 5.0%-10.0%) and 12.7% (95% CI, 10.0%-17.0%) for HCC candidates with region and listing date matching, and 7.1% (95% CI, 5.0%-9.0%) and 12.6% (95% CI, 10.0%-15.0%) for HCC candidates with listing date matching only. Additionally, HCC DDLT recipients had a 57% reduced risk of graft failure compared with CCA recipients (P < 0.001). Waiting time was unrelated to graft failure (P = 0.57), and there was no waiting time by diagnosis cohort interaction effect (P = 0.47). When identically prioritized, LT candidates with CCA have increased wait-list dropout compared with those with HCC. More granular data are necessary to discern ways to mitigate this wait-list disadvantage and improve survival for patients with CCA.
Collapse
Affiliation(s)
- Ioannis A Ziogas
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Laura A Hickman
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Lea K Matsuoka
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Manhal Izzy
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN
| | - Martin I Montenovo
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Scott A Rega
- Vanderbilt Transplant Center, Vanderbilt University Medical Center, Nashville, TN
| | - Irene D Feurer
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
- Vanderbilt Transplant Center, Vanderbilt University Medical Center, Nashville, TN
| | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| |
Collapse
|
|
33
|
Akbulut S, Sahin TT. Comment on experience with LDLT in patients with hepatocellular carcinoma and portal vein tumor thrombosis postdownstaging. Int J Surg Case Rep 2020; 74:36-37. [PMID: 32777765 PMCID: PMC7417667 DOI: 10.1016/j.ijscr.2020.07.057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 07/18/2020] [Accepted: 07/19/2020] [Indexed: 02/07/2023] Open
Key Words
- ldlt, living donor liver transplantation
- ds, downstaging
- hcc, hepatocellular carcinoma
- pvtt, portal vein tumor thrombus
- lt, liver transplantation
- mdct, multidetector computerized tomography
- mri, magnetic resonance imaging
- afp, alfa-feto protein
- lld, living liver donors
- grwr, graft to recipient weight ratio
- meld, model for end stage liver disease
- bmi, body mass index
- hbv, hepatitis b virus
- hcv, hepatitis c virus
Collapse
Affiliation(s)
- Sami Akbulut
- Department of Surgery and Liver Transplant Institute, Inonu University, Faculty of Medicine, 244280, Malatya, Turkey.
| | - Tevfik Tolga Sahin
- Department of Surgery and Liver Transplant Institute, Inonu University, Faculty of Medicine, 244280, Malatya, Turkey
| |
Collapse
|
|
34
|
Tropea A, Barbara M, Calamia S, Lomaglio L, Bonsignore P, Di Francesco F, Pagano D, Gruttadauria S. Laparoscopic Microwave Thermal Ablation for the Treatment of Hepatocellular Carcinoma in Chronic Hepatic Patients. J Laparoendosc Adv Surg Tech A 2020; 30:1072-1075. [PMID: 32721269 DOI: 10.1089/lap.2020.0513] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: Laparoscopic microwave thermal ablation (LMWTA) is a well-established alternative treatment to liver resection for treatment of liver tumors. The aim of this study was to describe our experience in LMWTA for hepatocellular carcinoma (HCC) in chronic hepatic patients. Materials and Methods: A study group of 61 consecutive HCC patients treated with LMWTA from January, 2013 to May, 2020 were considered for this study. Patient characteristics, liver function test, operational characteristics, and complications were recorded. Results: Of the 61 patients who underwent LMWTA, median age was 64 (interquartile range [IQR]: 58-71) years, mean body mass index was 26.2 (IQR: 23.2-29.4); 44 patients (72%) presented with an hepatitis C virus etiology, 46 (75%) were Child-Pugh Class A, median model for end-stage liver disease (MELD) score was 8.0 (IQR: 7.0-9.4). Viral infection was confirmed to be the most important risk factor in determining progressive cirrhotic evolution with HCC expression. Conclusions: LMWTA is a safe alternative treatment to traditional surgery, and can be combined with surgery.
Collapse
Affiliation(s)
- Alessandro Tropea
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy
| | - Marco Barbara
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy
| | - Sergio Calamia
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy
| | - Laura Lomaglio
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy
| | - Pasquale Bonsignore
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy
| | - Fabrizio Di Francesco
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy
| | - Duilio Pagano
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy
| | - Salvatore Gruttadauria
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy.,Department of Surgery and Surgical Medical Specialties, University of Catania, Catania, Italy
| |
Collapse
|
|
35
|
Hasan S, Abel S, Uemura T, Verma V, Koay EJ, Herman J, Thai N, Kirichenko A. Liver transplant mortality and morbidity following preoperative radiotherapy for hepatocellular carcinoma. HPB (Oxford) 2020; 22:770-778. [PMID: 31685379 DOI: 10.1016/j.hpb.2019.10.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 09/19/2019] [Accepted: 10/01/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Radiotherapy (RT) can be used for tumor downstaging and as a bridge to transplantation in hepatocellular carcinoma (HCC), but its effect on surgical complications is unknown. Therefore, we investigated post-transplant mortality and acute readmission rates in HCC with and without preoperative RT using the National Cancer Database (NCDB). METHODS After exclusion, 11,091 transplant patients were analyzed, 165 of whom received RT prior to transplant. Multivariable binomial logistic regression analysis identified characteristics associated with use of RT, and factors associated with increased 30/90-day mortality and 30-day readmission, following propensity matching. RESULTS Although RT (median 40 Gy in 5 fractions) was more often delivered to larger tumors and advanced stages, it resulted in 59% downstaging rate, 39% pathologic complete response rate, and a median of 4 additional months to transplantation. Crude 30/90-day mortality rates were both 1.2% with preoperative RT, compared to 2.7% and 4.4% without. The 30-day readmission rate was 5.5% with RT and 10.7% without it. Propensity matched analysis demonstrated no statistical differences in 30/90-day mortality and a lower 30-day readmission rate with preoperative RT. Age >58, stage III disease, lack of transarterial chemoembolization, and shorter time to transplant independently predicted higher 90-day mortality. CONCLUSION Preoperative RT for HCC did not increase postoperative mortality or length of stay following liver transplant.
Collapse
Affiliation(s)
| | - Stephen Abel
- Allegheny Health Network Cancer Institute, Division of Radiation OncologyPittsburgh, PA, USA
| | - Tadahiro Uemura
- Allegheny Health Network, Division of Transplant Medicine, Pittsburgh, PA, USA
| | - Vivek Verma
- Allegheny Health Network Cancer Institute, Division of Radiation OncologyPittsburgh, PA, USA
| | - Eugene J Koay
- MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX, USA
| | - Joseph Herman
- MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX, USA
| | - Ngoc Thai
- Allegheny Health Network, Division of Transplant Medicine, Pittsburgh, PA, USA
| | - Alexander Kirichenko
- Allegheny Health Network Cancer Institute, Division of Radiation OncologyPittsburgh, PA, USA
| |
Collapse
|
|
36
|
Locoregional Therapies in the Treatment of 3- to 5-cm Hepatocellular Carcinoma: Critical Review of the Literature. AJR Am J Roentgenol 2020; 215:223-234. [PMID: 32255691 DOI: 10.2214/ajr.19.22098] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE. Treatment options for hepatocellular carcinoma (HCC) continue to expand. However, given the complexity of the patients including factors such as codominant cirrhosis or portal hypertension and transplant status, it can be difficult to know which treatment is most advantageous. The choice of HCC treatment is perhaps most complex in the setting of HCCs that are 3-5 cm. This article reviews the evidence for locoregional therapies in treating 3- to 5-cm HCCs. CONCLUSION. Combination therapy with transarterial chemoembolization (TACE) and ablation has the most robust and highest level of evidence to support its efficacy and therefore should be considered first-line therapy for nonresectable HCCs that measure 3-5 cm. The studies support that TACE followed by ablation is superior to either TACE alone or ablation alone. Data for transarterial radioembolization (TARE) to treat HCCs in this specific size range are very limited. Additional data are needed about the comparative effectiveness of TACE-ablation combination and TARE and how the TACE-ablation combination compares with surgical resection.
Collapse
|
|
37
|
Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma. Ann Surg 2020; 271:616-624. [PMID: 30870180 DOI: 10.1097/sla.0000000000003253] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
38
|
Cools KS, Moon AM, Burke LM, McGinty KA, Strassle PD, Gerber DA. Validation of the Liver Imaging Reporting and Data System Treatment Response Criteria After Thermal Ablation for Hepatocellular Carcinoma. Liver Transpl 2020; 26:203-214. [PMID: 31677319 PMCID: PMC6980979 DOI: 10.1002/lt.25673] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 10/26/2019] [Indexed: 12/17/2022]
Abstract
Single hepatocellular carcinoma (HCC) tumors can be successfully eradicated with thermal ablation (TA). We assessed the validity of the Liver Imaging Reporting and Data System Treatment Response (LR-TR) criteria with a retrospective analysis of a single-center database of patients with small HCC tumors (<3 cm in diameter) who underwent both laparoscopic TA and liver transplantation (LT) from 2004 to 2018. Postablation MRIs were assigned LR-TR categories (nonviable, equivocal, and viable) for ablated lesions and Liver Imaging Reporting and Data System (LI-RADS) categories (probable or definite HCC) for untreated lesions. Interpretations were compared with the histopathology of the post-LT explanted liver. There were 45 patients with 81 tumors (59 ablated and 22 untreated; mean size, 2.2 cm), and 23 (39%) of the ablated tumors had viable HCC on histopathology. The sensitivity/specificity of LR-TR categories (nonviable/equivocal versus viable) of ablated tumors was 30%/99%, with a positive predictive value (PPV)/negative predictive value (NPV) of 93%/69%. The sensitivity varied with residual tumor size. The sensitivity/specificity of LI-RADS 4 and 5 diagnostic criteria at detecting new HCC was 65%/94%, respectively, with a PPV/NPV of 85%/84%. The interrater reliability (IRR) was high for LR-TR categories (90% agreement, Cohen's ĸ = 0.75) and for LI-RADS LR-4 and LR-5 diagnostic categories (91% agreement, Cohen's ĸ = 0.80). In patients with HCC <3 cm in diameter, LR-TR criteria after TA had high IRR but low sensitivity, suggesting that the LR-TR categories are precise but inaccurate. The low sensitivity may be secondary to TA's disruption in the local blood flow of the tissue, which could affect the arterial enhancement phase on MRI. Additional investigation and new technologies may be necessary to improve imaging after ablation.
Collapse
Affiliation(s)
- Katherine S. Cools
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Andrew M. Moon
- Division of Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Lauren M.B. Burke
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Katrina A. McGinty
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Paula D. Strassle
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Department of Epidemiology, University of North Carolina School of Public Health
| | - David A. Gerber
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC
| |
Collapse
|
|
39
|
Voskanyan SE, Sushkov AI, Artemiyev AI, Zabezhinsky DA, Naydenov EV, Bashkov AN, Chuchuev ES, Shabalin MV, Syutkin VE. [Salvage liver transplantation for hepatocellular carcinoma]. Khirurgiia (Mosk) 2019:21-28. [PMID: 31626235 DOI: 10.17116/hirurgia201910121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
OBJECTIVE To analyze clinical course and the results of salvage liver transplantation in patients with recurrent hepatocellular carcinoma (HCC) after liver resection. MATERIAL AND METHODS A 54-year-old man with HCV-infection and HCC and 22-year-old woman with fibrolamellar variant of HCC underwent resection of the right and left liver lobe, respectively. The first patient experienced recurrent HCC four times with an interval of 3-6 months within 2 years after surgery. Repeated liver resection was made in first three cases, right liver lobe transplantation - after the fourth recurrence. In the second patient, HCC recurred in 4 months after resection and was accompanied by subtotal portal vein thrombosis. Therefore, repeated liver resection was excluded and patient underwent right liver lobe transplantation. RESULTS Patients are alive in 5 and 3.5 years after liver resection and in 2.5 and 3 years after transplantation, respectively. There are currently no signs of recurrent HCC in the graft.
Collapse
Affiliation(s)
- S E Voskanyan
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - A I Sushkov
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - A I Artemiyev
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - D A Zabezhinsky
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - E V Naydenov
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - A N Bashkov
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - E S Chuchuev
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - M V Shabalin
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| | - V E Syutkin
- State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency of Russia, Moscow, Russia
| |
Collapse
|
|
40
|
Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol 2019; 25:3704-3721. [PMID: 31391767 PMCID: PMC6676544 DOI: 10.3748/wjg.v25.i28.3704] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/13/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
Collapse
Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Sylvester M Black
- Division of Transplant Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Lanla Conteh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Anne Noonan
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Elliott
- Division of Diagnostic Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| |
Collapse
|
|
41
|
Uemura T, Kirichenko A, Bunker M, Vincent M, Machado L, Thai N. Stereotactic Body Radiation Therapy: A New Strategy for Loco-Regional Treatment for Hepatocellular Carcinoma While Awaiting Liver Transplantation. World J Surg 2019; 43:886-893. [PMID: 30361748 DOI: 10.1007/s00268-018-4829-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Trans-arterial chemoembolization and radiofrequency ablation are commonly used for control of hepatocellular carcinoma (HCC) on liver transplant (LTx) waiting list. Stereotactic body radiation therapy (SBRT) was introduced to our institution for HCC as a bridging or downsizing therapy to LTx. PATIENTS AND METHODS Twenty-five HCC lesions in 22 patients were treated with SBRT while waiting for LTx from January 2010 to December 2015. Nineteen of these patients received deceased donor LTx. SBRT was defined as 40-50 Gy delivered in 4-6 fractions. Pre- and post-liver transplant outcome were analyzed in addition to the dropout rate and tumor response to SBRT. RESULTS Median size of original tumors was 3.2 cm (2.0-8.9), and median size of tumor after SBRT was significantly smaller at 0.9 cm (0-3.2) in the explanted livers (p < 0.01). The dropout rate was 9%, and they were only downsized patients outside of Milan criteria. Liver disease did not progress between pre- and post-SBRT except one patient. Twenty-eight percent of treated HCCs showed complete pathologic response, and 22% had extensive partial response with some residual tumor. No HCC recurrence was experienced after LTx. CONCLUSION SBRT is indicated to be safe, effective treatment for HCC on LTx waiting list, and it leads to satisfactory post-liver transplant outcomes.
Collapse
Affiliation(s)
- Tadahiro Uemura
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA.
| | | | - Mark Bunker
- Pathology, Allegheny General Hospital, Pittsburgh, USA
| | - Molly Vincent
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA
| | - Lorenzo Machado
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA
| | - Ngoc Thai
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA
| |
Collapse
|
|
42
|
Sandow T, Pavlus J, Field D, Lacayo E, Cohen E, Lynskey G, Caridi T, Buckley D, Cardella J, Kallakury B, Spies J, Kim AY. Bridging Hepatocellular Carcinoma to Transplant: Transarterial Chemoembolization Response, Tumor Biology, and Recurrence after Transplantation in a 12-Year Transplant Cohort. J Vasc Interv Radiol 2019; 30:995-1003. [PMID: 31109853 DOI: 10.1016/j.jvir.2018.12.736] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 12/09/2018] [Accepted: 12/18/2018] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To evaluate tumor response to transarterial chemoembolization as well as biologic characteristics of the tumor as predictors of recurrence after transplantation in patients with hepatocellular carcinoma (HCC) who were bridged or down-staged to liver transplantation. MATERIALS AND METHODS An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, single-institution retrospective analysis was performed on all patients with HCC who were treated with the use of conventional transarterial chemoembolization or transarterial chemoembolization with drug-eluting embolics (DEE) over a 12-year period and who subsequently underwent liver transplantation (n = 142). Treatment response was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) imaging criteria and then correlated with tumor characteristics and recurrence. Of the 142 patients followed after transplantation, 127 had imaging after transarterial chemoembolization but before transplantation. Imaging response and post-transplantation recurrence were correlated with patient demographics, liver function, and tumor morphology. HCC recurred in 9 patients (mean time from transplantation, 526 days). Recurrence was analyzed with the use of univariate and multivariate statistics. Kaplan-Meier recurrence-free survival curves were calculated based on immediate imaging response before transplantation with the use of the log-rank test. RESULTS Before transplantation, 57% of patients (72/127) demonstrated complete response (CR) and 24% (31/127) showed partial response (PR). Complete pathologic necrosis occurred in 54% (39/72) of CR patients and 20% (6/31) of PR patients. Poor treatment response, defined as stable disease (SD) or progressive disease (PD), occurred in 18% of patients (24/127) before transplantation and was present in 67% of cases of recurrence (6/9; P < .001). Post-transplantation recurrence was present in 1.4% of patients (1/71) with CR and in 6.5% of patients (2/31) with PR. In patients with SD after transarterial chemoembolization, HCC recurred in 18.8% of transplant patients (3/16) and in 43% of patients (3/7) with PD. Larger pretreatment tumor size (P = .05), higher Child-Pugh score (P = .002), higher tumor grade at explantation (P = .04), and lymphovascular invasion at explantation (P = .008) also were associated with increased incidence of post-transplantation recurrence. CONCLUSIONS Poor tumor response to transarterial chemoembolization before transplantation identifies patients at increased risk for post-transplantation recurrence.
Collapse
Affiliation(s)
- Tyler Sandow
- Department of Radiology, Ochsner Health System, New Orleans, Louisiana
| | - John Pavlus
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - David Field
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Eduardo Lacayo
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Emil Cohen
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - George Lynskey
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Theresa Caridi
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Donna Buckley
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - John Cardella
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Bhaskar Kallakury
- Department of Pathology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - James Spies
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Alexander Y Kim
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007.
| |
Collapse
|
|
43
|
N'Kontchou G, Nault JC, Sutter O, Bourcier V, Coderc E, Grando V, Nahon P, Ganne-Carrié N, Diallo A, Sellier N, Seror O. Multibipolar Radiofrequency Ablation for the Treatment of Mass-Forming and Infiltrative Hepatocellular Carcinomas > 5 cm: Long-Term Results. Liver Cancer 2019; 8:172-185. [PMID: 31192154 PMCID: PMC6547257 DOI: 10.1159/000489319] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 04/16/2018] [Indexed: 02/04/2023] Open
Abstract
AIMS AND BACKGROUND Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm. METHODS Eighty-three consecutive patients with cirrhosis (median age 70 years [37-93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1-9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed. RESULTS Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1-112 months), in naive patients the 3- and 5-year OS was 51% (38-62) and 24% (13-36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33-4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32-6.21], p = 0.008), multinodular form (HR: 2.74 [1.4-5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67-7.01], p = 0.0007) were independent RFS predictors. CONCLUSIONS mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.
Collapse
Affiliation(s)
- Gisele N'Kontchou
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Jean-Charles Nault
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Olivier Sutter
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Valerie Bourcier
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Emmanuelle Coderc
- Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Veronique Grando
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Pierre Nahon
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Nathalie Ganne-Carrié
- Service d'Hépatologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France
| | - Abou Diallo
- Département d'Information Médical de l'Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bobigny, France
| | - Nicolas Sellier
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France
| | - Olivier Seror
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, Paris, France,Service de Radiologie de l'Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bondy, France,*Olivier Seror, Service de Radiologie, Hôpital Jean Verdier, Avenue du 14 juillet, FR–93140 Bondy (France), E-Mail
| |
Collapse
|
|
44
|
More Than Just Wait Time? Regional Differences in Liver Transplant Outcomes for Hepatocellular Carcinoma. Transplantation 2019; 103:747-754. [DOI: 10.1097/tp.0000000000002248] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
|
|
45
|
Abstract
Identifying the optimal allocation policy with regard to hepatocellular carcinoma has been a persistent and evolving challenge. The current criteria for LT for HCC endorsed by the United Network of Organ Sharing (UNOS) are based on the Milan Criteria: a solitary tumor < 5 cm, or maximum of three tumors ≤ 3 cm each, without vascular invasion or evidence of extrahepatic spread. Contraindications to HCC exception points include: stage 1 HCC, ruptured HCC, extrahepatic HCC, and main portal or hepatic vein HCC invasion. Based upon projected waitlist dropout rates due to tumor growth, patients with HCC are assigned MELD standardized exception points. In addition to tumor size and number, AFP levels are an important predictor of recurrence of HCC following liver transplantation. Standardized exception points for HCC patients are not awarded to patients with AFP levels > 1000 ng/mL that do not decrease to < 500 ng/mL with treatment. Appeals for MELD exception points for patients with HCC vary widely between UNOS regions, with success of nonstandardized exception point appeals varying from 3.1 to 21% between regions. In an effort to make prioritization for HCC more consistent, a national liver review board (NLRB)is being convened that will focus on developing a national guidance for assessing common requests and addressing exception points, including for HCC.
Collapse
|
|
46
|
Ogawa K, Kaido T, Okajima H, Fujimoto Y, Yoshizawa A, Yagi S, Hori T, Iida T, Takada Y, Uemoto S. Impact of pretreatments on outcomes after living donor liver transplantation for hepatocellular carcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:73-81. [PMID: 30561147 DOI: 10.1002/jhbp.602] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The purpose of this study was to examine the impact of pretreatments on outcomes after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). METHODS From February 1999 to March 2015, 223 patients underwent LDLT for HCC. Until December 2006, there was no restriction in patient selection criteria regarding the number and size of tumors, following which we implemented the Kyoto criteria (tumor number ≤10, maximal diameter ≤5 cm, and des-gamma-carboxy prothrombin ≤400 mAU/ml) since January 2007. RESULTS Of 223 patients, 156 had a history of pretreatments. Among 101 patients meeting the Milan criteria at the initial diagnosis, 38 progressed to beyond the criteria at liver transplantation (LT). Twenty-two out of 38 met the Kyoto criteria, and their survival and recurrence rates were significantly better than those of patients exceeding the Kyoto criteria (P = 0.004 and 0.035, respectively). Regarding the number of pretreatments (0 vs. 1-4 vs. ≥5), recurrence rate was significantly higher in the ≥5 pretreatments group than the 0 group. However, for patients meeting the Kyoto criteria, there were no significant differences in recurrence rates between these three groups. CONCLUSION Better outcomes will be achieved by performing LT for HCCs meeting the Kyoto criteria even after repeated pretreatments.
Collapse
Affiliation(s)
- Kohei Ogawa
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Yasuhiro Fujimoto
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Atsushi Yoshizawa
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Tomohide Hori
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Taku Iida
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| | - Yasutsugu Takada
- Department of Hepatobiliary Pancreatic and Breast Surgery, Ehime University, Toon, Ehime, Japan
| | - Shinji Uemoto
- Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan
| |
Collapse
|
|
47
|
Zhang L, Zhang SN, Li L, Zhang XB, Wu RC, Liu JH, Huang ZY, Li W, Ran JH. Prolonged warm ischemia aggravates hepatic mitochondria damage and apoptosis in DCD liver by regulating Ca 2+/CaM/CaMKII signaling pathway. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2019; 12:217-228. [PMID: 31933737 PMCID: PMC6944004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 12/14/2018] [Indexed: 06/10/2023]
Abstract
This study was conducted to investigate the effect of warm ischemia duration on hepatocyte mitochondrial damage after liver transplantation, and confirm the role of CaMKIIγ in this process. Rat donation after cardiac death (DCD) liver transplantation model was established by exposing donor liver to 0 (W0 group), 15 (W15 group), and 30 (W30 group) min warm ischemia. Some rats in W15 group were transfected with CaMKIIγ and CaMKIIγ-shRNA lentivirus. On day 1, 3, and 7 post-transplantation, a series of experiments, including HE staining, TEM observation, ALT and AST measurement, flow cytometry analysis, qRT-PCR, and Western blotting were performed to evaluate the extent of hepatic and mitochondria damage. Within 7 days post-transplantation, prolonged ischemia led to an obvious deterioration of hepatic and mitochondria damage, presenting with a marked increase of apoptotic hepatocytes, ALT and AST levels, cells with low MMP, and AIF and Cyt C expression. CaMKIIγ overexpression caused the significant ultrastructural damage of hepatic cells, increase of cells with low MMP, enhancement of AIF and Cyt C expression, and augmented Ca2+/CaM/CaMKIIγ, while blocking CaMKIIγ showed an opposite result. In conclusion, ischemia duration is proportional to the extent of hepatic mitochondria damage, and CaMKIIγ plays a negative regulatory role in this process by regulating the Ca2+/CaM/CaMKII signaling pathway.
Collapse
Affiliation(s)
- Li Zhang
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
- Department of Hepatopancreatobiliary, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and TechnologyKunming, Yunnan Province, China
| | - Sheng-Ning Zhang
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| | - Li Li
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| | - Xi-Bing Zhang
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| | - Rui-Chao Wu
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| | - Jun-Han Liu
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| | - Zhao-Yu Huang
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| | - Wang Li
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| | - Jiang-Hua Ran
- Department of Hepatopancreatobiliary Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People’s Hospital of Kunming, Calmette HospitalKunming, Yunnan Province, China
| |
Collapse
|
|
48
|
Couri T, Pillai A. Goals and targets for personalized therapy for HCC. Hepatol Int 2019; 13:125-137. [PMID: 30600478 DOI: 10.1007/s12072-018-9919-1] [Citation(s) in RCA: 366] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 12/04/2018] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide and its incidence continues to rise. While cirrhosis underlies most cases of HCC, many molecular pathways are implicated in HCC carcinogenesis, including the TERT promoter mutation, Wnt/β-catenin, P53, Akt/mTOR, vascular endothelial growth factor receptor (VEGFR), and endothelial growth factor receptor (EGFR)/RAS/MAPK pathways. While the most widely used staging and treatment algorithm for HCC-the Barcelona Clinic Liver Cancer (BCLC) system-does not recommend systemic molecular therapy for early HCC, a variety of treatment options are available depending upon the stage of HCC at diagnosis. Determining the best treatment options must take into account not only the burden and extent of HCC, but also the patient's performance status, underlying liver function, extra-hepatic disease and co-morbidities. Radiofrequency or microwave ablation, liver resection, or liver transplantation, all potential curative therapies for HCC, should be the first-line treatments when possible. For patients who are not candidates of curative treatments, locoregional therapies such as transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and stereotactic body radiation (SBRT) can improve survival and quality of life. Sorafenib, a multi-kinase VEGF inhibitor, is the most widely used systemic chemotherapy approved as a first-line agent for unresectable or advanced HCC. Clinical trials are underway directed towards molecular therapies that target different aspects of the hepatocellular carcinogenesis cascade. Ideally, the goal of future therapy should be to target multiple pathways in the HCC cascade with combination treatments to achieve personalized care aimed at improving overall survival.
Collapse
Affiliation(s)
- Thomas Couri
- Department of Internal Medicine, University of Chicago Medical Center, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medical Center, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
| |
Collapse
|
|
49
|
Raoul JL, Forner A, Bolondi L, Cheung TT, Kloeckner R, de Baere T. Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence. Cancer Treat Rev 2018; 72:28-36. [PMID: 30447470 DOI: 10.1016/j.ctrv.2018.11.002] [Citation(s) in RCA: 402] [Impact Index Per Article: 57.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 11/09/2018] [Accepted: 11/10/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the sixth leading cause of cancer and the third leading cause of cancer-related mortality. Patient stratification and treatment allocation are based on tumor stage, liver function, and performance status. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate stage HCC, including those with large or multinodular HCC, well-preserved liver function, and no cancer-related symptoms or evidence of vascular invasion or extrahepatic spread. Two TACE techniques have been used since 2004, conventional TACE (cTACE) and TACE with drug-eluting beads (DEB-TACE). cTACE was evidenced first to treat intermediate stage HCC patients. It combines the transcatheter delivery of chemotherapy using Lipiodol-based emulsion plus an embolizing agent to achieve strong cytotoxic and ischemic effects. Drug-eluting beads (DEBs) were developed in order to slowly release chemotherapeutic agents, and to increase ischemia intensity and duration. Recent advances allow TACE treatment of both early stage patients (i.e. those with a solitary nodule or up to 3 nodules under 3 cm) and some advanced stage patients. Here we review recent clinical evidence related to TACE treatment of patients with early, intermediate, and advanced stage HCC. Based on the 2014 TACE algorithm of Raoul et al., this international expert panel proposes an updated TACE algorithm and provides insights into TACE use for patients at any HCC stage.
Collapse
Affiliation(s)
- Jean-Luc Raoul
- Digestive Oncology, Institut de Cancérologie de l'Ouest, Boulevard Professeur Jacques Monod, 44805 Nantes-Saint Herblain, France.
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer Group, Liver Unit, IDIBAPS, Hospital Clínic, University of Barcelona, Calle Villaroel 170, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Avenida Monforte de Lemos, 28029 Madrid, Spain.
| | - Luigi Bolondi
- Unit of Internal Medicine, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Zamboni 33, 40126 Bologna, Italy.
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road 102, Hong Kong Special Administrative Region
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Centre, Langenbeckstraße 1, 55131 Mainz, Germany.
| | - Thierry de Baere
- Gustave Roussy-Cancer Campus, rue Edouard-Vaillant 114, 94 805 Villejuif Cedex, France.
| |
Collapse
|
|
50
|
Kim TH, Choi HI, Kim BR, Kang JH, Nam JG, Park SJ, Lee S, Yoon JH, Lee DH, Joo I, Lee JM. No-Touch Radiofrequency Ablation of VX2 Hepatic Tumors In Vivo in Rabbits: A Proof of Concept Study. Korean J Radiol 2018; 19:1099-1109. [PMID: 30386141 PMCID: PMC6201983 DOI: 10.3348/kjr.2018.19.6.1099] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 07/23/2018] [Indexed: 02/06/2023] Open
Abstract
Objective In a proof of concept study, we compared no-touch radiofrequency ablation (NtRFA) in bipolar mode with conventional direct tumor puncture (DTP) in terms of local tumor control (LTC), peritoneal seeding, and tumorigenic factors, in the rabbit VX2 subcapsular hepatic tumor model. Materials and Methods Sixty-two rabbits with VX2 subcapsular hepatic tumors were divided into three groups according to the procedure: DTP-RFA (n = 25); NtRFA (n = 25); and control (n = 12). Each of the three groups was subdivided into two sets for pathologic analysis (n = 24) or computed tomography (CT) follow-up for 6 weeks after RFA (n = 38). Ultrasonography-guided DTP-RFA and NtRFA were performed nine days after tumor implantation. LTC was defined by either achievement of complete tumor necrosis on histopathology or absence of local tumor progression on follow-up CT and autopsy. Development of peritoneal seeding was also compared among the groups. Serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured via ELISA (Elabscience Biotechnology Co.) after RFA for tumorigenic factor evaluation. Results Regarding LTC, there was a trend in NtRFA (80%, 20/25) toward better ablation than in DTP-RFA (56%, 14/25) (p = 0.069). Complete tumor necrosis was achieved in 54.5% of DTP-RFA (6/11) and 90.9% of NtRFA (10/11). Peritoneal seeding was significantly more common in DTP-RFA (71.4%, 10/14) than in NtRFA (21.4%, 3/14) (p = 0.021) or control (0%). Elevations of HGF, VEGF or IL-6 were not detected in any group. Conclusion No-touch radiofrequency ablation led to lower rates of peritoneal seeding and showed a tendency toward better LTC than DTP-RFA.
Collapse
Affiliation(s)
- Tae-Hyung Kim
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Hyoung In Choi
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Bo Ram Kim
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Ji Hee Kang
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Ju Gang Nam
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Sae Jin Park
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Seunghyun Lee
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul 03080, Korea
| |
Collapse
|